IP Library › Granted Patent US 7,935,693

Granted Patent B2

US 7,935,693 · App. 11/967,163 · Granted May 3, 2011

Polycyclic aryl substituted triazoles and polycyclic heteroaryl substituted triazoles useful as Axl inhibitors

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Quick Facts

Patent No.: US 7,935,693
App. No.: 11/967,163
Granted: May 3, 2011
Kind: B2

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Abstract

Polycyclic aryl and polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl catalytic activity are also disclosed.

Claims (610)

1. A compound of formula (I):

wherein:

R 1 , R 4 and R 5 are independently selected from hydrogen, alkyl, aryl, aralkyl, —C(O)R 9 or —C(O)N(R 6 )R 7 ;

one of R 2 and R 3 is selected from one of the following and the other is selected from the other two of the following:

a) a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where one or two carbons of the alkylene chain is optionally replaced by —NR 9 —, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 8 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which its corresponding R 2 or R 3 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—;

b) a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); or

c) a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 4;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

B 5 , B 6 , B 7 and B 8 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which its corresponding R 2 or R 3 is attached;

each R 6 and R 7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, —R 11 —OR 9 , —R 11 —CN, —R 11 —NO 2 , —R 11 —N(R 9 ) 2 , R 11 —C(O)OR 9 and —R 11 —C(O)N(R 9 ) 2 , or any R 6 and R 7 , together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted N-heterocyclyl;

each R 8 is independently selected from the group consisting of hydrogen, cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2), or two R 8 's on adjacent carbons can combine to form a double bond;

each R 9 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl;

each R 10 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain;

each R 11 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain;

each R 12 is hydrogen, alkyl, cyano, nitro or —OR 9 ; and

each R 13 is independently selected from the group consisting of hydrogen, cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

as an isolated stereoisomer or a mixture thereof, or as a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 which is a compound of formula (Ia):

wherein:

R 1 , R 4 and R 5 are independently selected from hydrogen, alkyl, aryl, aralkyl, —C(O)R 9 or —C(O)N(R 6 )R 7 ;

one of R 2 and R 3 is selected from one of the following and the other is selected from the other two of the following:

a) a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where one or two carbons of the alkylene chain is optionally replaced by —NR 9 —, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

c) a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 4;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

each R 6 and R 7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, —R 11 —OR 9 , —R 11 —CN, —R 11 —NO 2 , —R 11 —N(R 9 ) 2 , —R 11 —C(O)OR 9 and —R 11 —C(O)N(R 9 ) 2 , or any R 6 and R 7 , together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted N-heterocyclyl;

each R 12 is hydrogen, alkyl, cyano, nitro or —OR 9 ; and

as an isolated stereoisomer or a mixture thereof, or as a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where one or two carbons of the alkylene chain is optionally replaced by —NR 9 —, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

4. The compound of claim 3 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

5. The compound of claim 4 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O) R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

6. The compound of claim 5 , which is 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(6-pyrrolidin-1-yl-5,6,7,8,9,10-hexahydrobenzo[8]annulene-3-yl)-1H-1,2,4-triazole-3,5-diamine.

7. The compound of claim 3 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,T-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

8. The compound of claim 7 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— or ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

9. The compound of claim 8 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where at least one carbon is replaced by —N(R 9 )— and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

10. The compound of claim 9 selected from the group consisting of:

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(4(1H)-oxo-2,3,5,6-tetrahydrobenzo[d]azocin-8-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(3-cyclopentyl-1,2,3,4,5,6-hexahydrobenzo[d]azocin-8-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(3-cyclopentyl-1,2,3,4,5,6-hexahydrobenzo[d]azocin-9-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(1(2H)-oxo-3,4,5,6-tetrahydrobenzo[c]azocin-9-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(1,2,3,4,5,6-hexahydrobenzo[c]azocin-9-yl)-1H-1,2,4-triazole-3,5-diamine.

11. The compound of claim 8 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

12. The compound of claim 11 selected from the group consisting of:

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(7-oxo-5,6,8,9,10-pentahydrocycloocta[b]pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(7-(pyrrolidin-1-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(7-(methoxyimino)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(7-hydroxy-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine.

13. The compound of claim 2 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where one or two carbons of the alkylene chain is optionally replaced by —NR 9 —, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O)— (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

14. The compound of claim 13 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—; provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

15. The compound of claim 14 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—; provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

16. The compound of claim 13 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of ═C(R 8 )— and ═N—;

B 5 , B 6 , B 7 and B 8 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one of A 1 , A 3 and A 4 is independently selected from the group consisting of 0, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 ), or A 2 is ═N— or one of B 5 , B 6 , B 7 and B 8 is ═N—, and one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

17. The compound of claim 16 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of ═C(R 8 )— and ═N—;

B 5 , B 6 , B 7 and B 8 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one of A 1 , A 3 and A 4 is independently selected from the group consisting of 0, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 ), or A 3 is ═N— or one of B 5 , B 6 , B 7 and B 8 is ═N—, and one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

18. The compound of claim 13 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

19. The compound of claim 18 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O)— (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

20. The compound of claim 13 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene or alkenylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) P — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )— or ═N—, provided that at least one of A 1 , A 3 and A 4 is independently selected from the group consisting of 0, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 ), or A 3 is ═N— or one of B 5 , B 6 , B 7 and B 8 is ═N—, and one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

21. The compound of claim 20 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

B 5 , B 6 , B 7 and B 8 are each independently selected from the group consisting of ═C(R 13 )— or ═N—, provided that at least one of A 1 , A 3 and A 4 is independently selected from O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 ), or A 2 is ═N— or one of B 5 , B 6 , B 7 and B 8 is ═N—, and one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

22. The compound of claim 21 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

B 5 , B 6 , B 7 and B 8 are each independently selected from the group consisting of ═C(R 13 )— or ═N—, provided that at least one A 2 is ═N— or one of B 5 , B 6 , B 7 and B 8 is ═N—, and one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

23. The compound of claim 22 which is 1-(1,4-ethano-8-pyridin-4-yl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N 3 -(7-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine.

24. The compound of claim 2 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

25. The compound of claim 24 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached.

26. The compound of claim 25 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached.

27. The compound of claim 24 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 3 is a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

28. The compound of claim 27 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 3 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p -(where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

29. The compound of claim 28 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 3 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

30. The compound of claim 29 which is 1-(5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidin-4-yl)-N 3 -(5,6,8,9-tetrahydrospiro[benzo[7]annulene-7,2′-[1,3]dioxolane]-3-yl)-1H-1,2,4-triazole-3,5-diamine.

31. The compound of claim 2 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 3 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) or N;

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )— or ═N—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

32. The compound of claim 31 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[V][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 5 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

33. The compound of claim 32 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 3 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

34. The compound of claim 31 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 3 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

35. The compound of claim 34 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-a]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) or N;

36. The compound of claim 2 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

37. The compound of claim 36 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached.

38. The compound of claim 37 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached.

39. The compound of claim 36 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain or the alkenylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

40. The compound of claim 39 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, and one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

41. The compound of claim 36 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 5 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached.

42. The compound of claim 41 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a bicyclic aryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached.

43. The compound of claim 36 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that at least one carbon in A is replaced with —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) or one of B 1 , B 2 , B 3 and B 4 is ═N—, one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 3 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

44. The compound of claim 43 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

45. The compound of claim 2 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,1′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

46. The compound of claim 45 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

47. The compound of claim 46 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently C(R 8 ) 2 ;

each A 2 is independently C(R 8 );

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7′-dihydro-5H-benzo[2,3]azepino[4,5′-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5′-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]′thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

48. The compound of claim 47 which is 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 3 -(7-pyrrolidin-1-yl-6,8-ethano-6,7,8,9-tetrahydro-5H-benzo[7]annulene-3-yl)-1H-1,2,4-triazole-3,5-diamine.

49. The compound of claim 45 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

50. The compound of claim 49 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is abridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 2;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

51. The compound of claim 1 which is a compound of formula (Ib):

wherein:

R 1 , R 4 and R 5 are independently selected from hydrogen, alkyl, aryl, aralkyl, —C(O)R 9 or —C(O)N(R 6 )R 7 ;

one of R 2 and R 3 is selected from one of the following and the other is selected from the other two of the following:

a) a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where one or two carbons of the alkylene chain is optionally replaced by —NR 9 —, ═N—, —O—, —S(O) p (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

c) a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 4;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

each R 6 and R 7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, —R 11 —OR 9 , —R 11 —NO 2 , —R 11 —N(R 9 ) 2 , —R 11 —C(O)OR 9 and —R 11 —C(O)N(R 9 ) 2 , or any R 6 and R 7 , together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted N-heterocyclyl;

each R 12 is hydrogen, alkyl, cyano, nitro or —OR 9 ; and

as an isolated stereoisomer or a mixture thereof, or as a pharmaceutically acceptable salt thereof.

52. The compound of claim 51 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where one or two carbons of the alkylene chain is optionally replaced by —NR 9 —, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

53. The compound of claim 52 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

54. The compound of claim 53 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six carbons, where each carbon of the alkylene chain may be replaced by —N(R 9 )—, ═N—, —O—, —S(O) p (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

55. The compound of claim 54 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently ═C(R 13 )—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 2 is attached; and

R 3 is selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, each optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

56. The compound of claim 55 which is 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N 5 -(1(2H)-oxo-3,4,5,6-tetrahydrobenzo[c]azocin-9-yl)-1H-1,2,4-triazole-3,5-diamine.

57. The compound of claim 51 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

A is an alkylene chain containing six to ten carbons, where one or two carbons of the alkylene or alkenylene chain is optionally replaced by —NR 9 —, ═N—, —O—, —S(O) p — (where p is 0, 1 or 2) or —P(O) p — (where p is 0, 1 or 2) and where each carbon in the alkylene chain is independently optionally substituted by one or two substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, ═N—O—R 6 , —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to R 2 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—; and

R 3 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

58. The compound of claim 51 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 3 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

59. The compound of claim 51 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2); and

R 3 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) or N;

B 5 , B 6 , B 7 and B 8 are each independently ═C(R 13 )— or ═N—, provided that one of B 5 , B 6 , B 7 and B 8 is a carbon directly bonded to the nitrogen to which R 3 is attached.

60. The compound of claim 51 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a bicyclic aryl of formula (II) or a bicyclic heteroaryl of formula (II):

where:

B 1 , B 2 , B 3 and B 4 are each independently selected from the group consisting of ═C(R 13 )— and ═N—, provided that one of B 1 , B 2 , B 3 and B 4 is a carbon directly bonded to the nitrogen to which R 3 is attached and that only one or two of B 1 , B 2 , B 3 and B 4 can be ═N—.

61. The compound of claim 51 wherein:

R 1 , R 4 and R 5 are each hydrogen;

R 2 is a bridged bicyclic aryl of formula (III) or a bridged bicyclic heteroaryl of formula (III):

where:

m and n are independently 1 to 2;

q and r are independently 0 to 3;

each A 1 , A 3 and A 4 is independently selected from the group consisting of C(R 8 ) 2 , O, S(O) p (where p is 0, 1 or 2), P(O) p (where p is 0, 1 or 2) and N(R 9 );

each A 2 is independently selected from the group consisting of C(R 8 ) and N;

R 3 is a polycyclic heteroaryl containing more than 14 ring atoms selected from the group consisting of 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-yl, 6,7-dihydro-5H-benzo[2,3]azepino[4,5-c]pyridazin-3-yl, (Z)-dibenzo[b,f][1,4]thiazepin-11-yl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[4,5-c]pyridazin-2-yl, 6,7-dihydro-5H-benzo[2,3]oxepino[4,5-c]pyridazin-3-yl, 6,7-dihydro-5H-benzo[2,3]thiepino[4,5-c]pyridazin-3-yl, spiro[chromeno[4,3-c]pyridazine-5,1′-cyclopentane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 5,7,8,9-tetrahydrospiro[cyclohepta[b]pyridine-6,2′-[1,3]dioxolane]-3-yl, 5,6,8,9-tetrahydrospiro[cyclohepta[b]pyridine-7,2′-[1,3]dioxolane]-3-yl, 6,8,9,10-tetrahydro-5H-spiro[cycloocta[b]pyridine-7,2′-[1,3]dioxane]-3-yl, and 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-2-yl, where each polycyclic heteroaryl is optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —R 10 —OR 9 , —R 10 —O—R 11 —OR 9 , —R 10 —O—R 11 —O—R 11 —OR 9 , —R 10 —O—R 11 —CN, —R 10 —O—R 11 —C(O)OR 9 , —R 10 —O—R 11 —C(O)N(R 6 )R 7 , —R 10 —O—R 11 —S(O) p R 9 (where p is 0, 1 or 2), —R 10 —O—R 11 —N(R 6 )R 7 , —R 10 —O—R 11 —C(NR 12 )N(R 12 )H, —R 10 —OC(O)—R 9 , —R 10 —N(R 6 )R 7 , —R 10 —C(O)R 9 , —R 10 —C(O)OR 9 , —R 10 —C(O)N(R 6 )R 7 , —R 10 —N(R 6 )C(O)OR 9 , —R 10 —N(R 6 )C(O)R 9 , —R 10 —N(R 6 )S(O) t R 9 (where t is 1 or 2), —R 10 —S(O) t OR 9 (where t is 1 or 2), —R 10 —S(O) p R 9 (where p is 0, 1 or 2), and —R 10 —S(O) t N(R 6 )R 7 (where t is 1 or 2).

62. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of claim 1 ; as an isolated stereoisomer or a mixture thereof, or as a pharmaceutically acceptable salt thereof.

63. A method of inhibiting Axl catalytic activity in a mammal, wherein the method comprises administering to the mammal a compound of claim 1 ; as an isolated stereoisomer or a mixture thereof, or as a pharmaceutically acceptable salt thereof.

Assignments (3)

SECURITY INTEREST Recorded May 8, 2026

From: RIGEL PHARMACEUTICALS, INC.

To: MIDCAP FUNDING IV TRUST

Reel/Frame 075576/0880 →

SECURITY INTEREST Recorded Aug 25, 2022

From: RIGEL PHARMACEUTICALS, INC.

To: MIDCAP FINANCIAL TRUST

Reel/Frame 061327/0712 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2008

From: SINGH, RAJINDER; GOFF, DANE; YU, JIAXIN; HOLLAND, SACHA; ZHANG, JING; HECKRODT, THILO J.; DING, PINGYU; LITVAK, JOANE

To: RIGEL PHARMACEUTICALS, INC.

Reel/Frame 021415/0791 →