IP Library › Granted Patent US 9,650,391

Granted Patent B2

US 9,650,391 · App. 11/966,894 · Granted May 16, 2017

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Inventors: Pingyu Ding (Foster City, CA); Dane Goff (Redwood City, CA); Jing Zhang (Foster City, CA); Rajinder Singh (Belmont, CA); Sacha Holland (San Francisco, CA); Jiaxin Yu (San Carlos, CA); Thilo J. Heckrodt (San Francisco, CA); Joane Litvak (Oakland, CA)

Assignee: Rigel Pharmaceuticals Inc.

C07D495/04 C07D401/14 C07D403/14 C07D405/12 C07D405/14 C07D407/14 C07D413/14 C07D471/04 C07D487/04 C07D519/00

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Quick Facts

Patent No.: US 9,650,391
App. No.: 11/966,894
Granted: May 16, 2017
Kind: B2

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Abstract

N 3 -Heteroaryl substituted triazoles and N 5 -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 activity are also disclosed.

Claims (277)

1. A compound of formula (Ia):

wherein:

R 1 , R 4 and R 5 are each independently selected from the group consisting of hydrogen and —C(O)N(R 6 )R 7 ;

R 2 is a heteroaryl selected from the group consisting of benzoxazolyl, isoquinolinyl, pyrimidinyl, 4,5-dihydro-1H-benzo[b]azepin-2(3H)-onyl, 6,7,8,9-tetrahydro-5H-pyrido[3,2-d]azepinyl, 5,6,7,8-tetrahydro-1,6-naphthyridinyl, 5,6,7,8-tetrahydroquinolinyl, 1H-pyrrolo[2,3-b]pyridinyl, benzo[b]thiophenyl, 7′,8′-dihydro-5′H-spiro[[1,3]dioxolane-2,6′-quinoline]-3′-yl, 4b,5,6,7,7a,8-hexahydropentaleno[2,1-b]pyridinyl, and 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinyl, each 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 heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —O—R 10 —OR 8 , —R 9 —O—R 10 —O—R 10 —OR 8 , —R 9 —O—R 10 —CN, —R 9 —O—R 10 —C(O)OR 8 , —R 9 —O—R 10 —C(O)N(R 6 )R 7 , —R 9 —O—R 10 —S(O) p R 8 (where p is 0, 1 or 2), —R 9 —O—R 10 —N(R 6 )R 7 , —R 9 —O—R 10 —C(NR 11 )N(R 11 )H, —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

or R 2 is pyridinyl 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 heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —O—R 10 —OR 8 , —R 9 —O—R 10 —O—R 10 —OR 8 , —R 9 —O—R 10 —CN, —R 9 —O—R 10 —C(O)OR 8 , —R 9 —O—R 10 —C(O)N(R 6 )R 7 , —R 9 —O—R 10 —S(O) p R 8 (where p is 0, 1 or 2), —R 9 —O—R 10 —N(R 6 )R 7 , —R 9 —O—R 10 —C(NR 11 )N(R 11 )H, —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2)

R 3 is heteroaryl selected from the group consisting of pyrimidinyl, quinazolinyl, isoquinolinyl, furo[3,2-c]pyridinyl, phenanthridinyl, thieno[3,2-d]pyridazinyl, thieno[3,2-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —O—R 14 —N(R 12 ) 2 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —C(O)N(R 12 )—R 14 —N(R 12 )R 13 , —R 13 —C(O)N(R 12 )—R 14 —OR 12 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 6 and R 7 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 10 —OR 8 , —R 10 —CN, —R 10 —NO 2 , —R 10 —N(R 8 ) 2 , —R 10 —C(O)OR 8 and —R 10 —C(O)N(R 8 ) 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, alkyl, alkenyl, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 11 is hydrogen, alkyl, cyano, nitro or —OR 8 ;

each R 12 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl, or two R 12's , together with the common nitrogen to which they are both attached, may optionally form an optionally substituted N-heterocyclyl or an optionally substituted N-heteroaryl;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and

each R 14 is independently an optionally substituted straight or branched alkylene chain;

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

2. The compound of claim 1 , wherein:

R 1 , R 4 and R 5 are each independently selected from the group consisting of hydrogen and —C(O)N(R 6 )R 7 ;

R 2 is a heteroaryl selected from the group consisting of benzoxazolyl, isoquinolinyl, pyrimidinyl, 4,5-dihydro-1H-benzo[b]azepin-2(3H)-onyl, 6,7,8,9-tetrahydro-5H-pyrido[3,2-d]azepinyl, 5,6,7,8-tetrahydro-1,6-naphthyridinyl, 5,6,7,8-tetrahydroquinolinyl, 1H-pyrrolo[2,3-b]pyridinyl, benzo[b]thiophenyl, 7′,8′-dihydro-5′H-spiro[[1,3]dioxolane-2,6′-quinoline]-3′-yl, 4b,5,6,7,7a,8-hexahydropentaleno[2,1-b]pyridinyl, and 6,7,8,9-tetrahydrocyclohepta[b]pyridinyl, each 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 heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —O—R 10 —OR 8 , —R 9 —O—R 10 —O—R 10 —OR 8 , —R 9 —O—R 10 —CN, —R 9 —O—R 10 —C(O)OR 8 , —R 9 —O—R 10 —C(O)N(R 6 )R 7 , —R 9 —O—R 10 —S(O) p R 8 (where p is 0, 1 or 2), —R 9 —O—R 10 —N(R 6 )R 7 , —R 9 —O—R 10 —C(NR 11 )N(R 11 )H, —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is selected from the group consisting of pyrimidinyl, isoquinolinyl, quinazolinyl, phenanthridinyl, thieno[3,2-d]pyrimidinyl, thieno[3,2-d]pyridazinyl, 6,7dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, and furo[3,2-c]pyridinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —O—R 14 —N(R 12 ) 2 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —C(O)N(R 12 )—R 14 —N(R 12 )R 13 , —R 13 —C(O)N(R 12 )—R 14 —OR 12 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 11 is hydrogen, alkyl, cyano, nitro or —OR 8 ;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and

each R 14 is independently an optionally substituted straight or branched alkylene chain.

3. The compound of claim 2 , wherein:

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

R 2 is selected from the group consisting of benzo[b]thiophenyl, 4,5-dihydro-1H-benzo[b]azepin-2(3H)-onyl, and benzoxazolyl optionally substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is selected from the group consisting of isoquinolinyl, quinazolinyl and thieno[3,2-d]pyrimidinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

4. The compound of claim 3 selected from the group consisting of:

1-(isoquinolin-1-yl)-N 3 -(2-(pyrrolidin-1-ylmethyl)benzo[d]oxazol-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6-chloroquinazolin-4-yl)-N 3 -(2-(pyrrolidin-1-ylmethyl)benzo[d]oxazol-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(4,5-dihydro-1H-benzo[b]azepin-2(3H)-on-8-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(2-(1-(4-(2-(dimethylamino)ethyl)piperazin-1-yl)oxomethyl)benzo[b]thiophen-5-yl)-1H-1,2,4-triazole-3,5-diamine.

5. The compound of claim 2 , wherein:

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

R 2 is pyridinyl substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is pyrimidinyl optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

6. The compound of claim 5 which is 1-(6-phenylpyrimidine-4-yl)-N 3 (3-methyl-2-(4-pyrrolidin-1-ylpiperdin-1-yl)pyridine-5-yl)-1H-1,2,4-triazole-3,5-diamine.

7. The compound of claim 2 , wherein:

R 1 , R 4 and R 5 are each independently selected from the group consisting of hydrogen and —C(O)N(R 6 )R 7 ;

R 3 is quinazolinyl optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

8. The compound of claim 7 selected from the group consisting of:

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-cyclopentyl-1,4-diazepan-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-pyrrolidin-1-ylpiperidin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-piperidin-1-ylpiperidin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-(pyrrolidin-1-ylmethyl)piperidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(diethylaminoethylmethylamino)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(2-diethylaminomethylpyrrolidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-diethylaminopyrrolidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(4-(bicyclo[2.2.1]heptan-2-yl)-1,4-diazepan-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-methylquinazolin-4-yl)-N 3 -(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6-fluoroquinazolin-4-yl)-N 3 -(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-bromopyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)propenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-(4-piperidin-1-ylpiperidin-1-yl)propenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-(4-dimethylaminopiperidin-1-yl)propenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-(3-(diethylamino)pyrrolidin-1-yl)propenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-(3-(dimethylamino)pyrrolidin-1-yl)propenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-piperidin-1-ylpropenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-(4-pyrrolidin-1-ylpiperidin-1-yl)propenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(6-(3-(4-cyclopentylpiperazin-1-yl)propenyl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(2-(3-(4-isopropylpiperazin-1-yl)propen-1-yl)pyridine-5-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(2-(4-cyclopropylmethyl-3-(S)-methylpiperazin-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine.

9. The compound of claim 2 , wherein:

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

R 2 is pyridinyl substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is selected from the group consisting of isoquinolinyl and phenanthridinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

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

1-(isoquinolin-1-yl)-N 3 -(6-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(isoquinolin-1-yl)-N 3 -(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(phenanthridin-6-yl)-N 3 -(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine.

11. The compound of claim 2 , wherein:

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

R 2 is 1H-pyrrolo[2,3-b]pyridinyl optionally substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

or R 2 is pyridinyl substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is selected from the group consisting of thieno[3,2-d]pyrimidinyl and thieno[3,2-d]pyridazinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

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

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-cyclopentyl-1,4-diazepan-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-(bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-piperidin-1-ylpiperidin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(1H-pyrrolo [2,3-b]pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-(pyrrolidin-1-ylmethyl)piperidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-(azepan-1-yl)piperidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(diethylaminoethylmethylamino)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(2-diethylaminomethylpyrrolidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(3-diethylaminopyrrolidin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-(bicyclo[2.2.1]heptan-2-yl)-1,4-diazepan-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-cyclopropylmethylpiperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(5-bicyclo[2.2.1]heptan-2-yloctahydropyrrol[3,4-c]pyrrolyl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-cyclopropylpiperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(5-methyl-6-(4-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(5-methyl-6-(4-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl)piperazin-1-yl)pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(1-bicyclo[2.2.1]heptan-2-ylpiperidin-4-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(1-bicyclo[2.2.1]heptan-2-ylpiperidin-4-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(1-(bicyclo[2.2.1]heptan-2-yl)-5-methylpiperidin-4-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-(cyclopropylmethyl)piperazin-1-yl)pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(4-(cyclopropylmethyl)piperazin-1-yl)-5-methylpyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-(cyclopropylmethyl)piperazin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(S)-methyl-4-(1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)-3-methylpyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(S)-methyl-4-(2S)-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)-3-methylpyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(thieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(S)-methyl-4-(2S)-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)-3-methylpyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-(2S)-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)-3-chloropyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-(2S)-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)-3-chloropyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-(2S)-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)-3-methylpyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(4-methylthieno[3,2-d]pyridazine-7-yl)-N 3 -(2-(4-(1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylpiperazin-1-yl)-3-methylpyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-cyclopropylmethyl-3-(S)-methylpiperazin-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-cyclopropylmethyl-3-(S)-methylpiperazin-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-cyclopropylmethyl-3-(S)-methylpiperazin-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-bromopyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(pyrrolidin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(3-dimethylaminopyrrolidin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(3-diethylaminopyrrolidin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(4-pyrrolidin-1-yl-piperidin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(4-methylpiperazin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(4-isopropylpiperazin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(4-cyclopentylpiperazin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(morpholin-4-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(piperidin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)propen-1-yl)pyridin-5-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(3-(4-piperidin-1-ylpiperidin-1-yl)propen-1-yl)pyridin-5-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 3 is selected from the group consisting of furo[3,2-c]pyridinyl and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

14. The compound of claim 13 selected from the group consisting of:

1-(furo[3,2-c]pyridine-4-yl)-N3-(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-N3-(6-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-methylpyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine.

15. The compound of claim 2 , wherein:

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

R 2 is 6,7,8,9-tetrahydro-5H-pyrido[3,2-d]azepinyl optionally substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is selected from the group consisting of thieno[3,2-d]pyrimidinyl and quinazolinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

16. The compound of claim 15 selected from the group consisting of:

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N3-(7-cyclopentyl-6,7,8,9-tetrahydro-5H-pyrido[3,2-d]azepin-3-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(6,7-dimethoxyquinazoline-4-yl)-N3-(7-cyclopentyl-6,7,8,9-tetrahydro-5H-pyrido[3,2-d]azepin-3-yl)-1H-1,2,4-triazole-3,5-diamine.

17. The compound of claim 2 , wherein:

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

R 2 is 5,6,7,8-tetrahydro-1,6-naphthyridinyl optionally substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is selected from the group consisting of isoquinolinyl and thieno[3,2-d]pyrimidinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

18. The compound of claim 17 selected from the group consisting of:

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(isoquinolin-1-yl)-N 3 -(6-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-benzyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(ethylcarboxy)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(dimethylaminomethylcarbonyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(dimethylaminomethylcarbonyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(2-dimethylaminoethyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-cyclopentyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(1-methylpiperidin-4-ylcarbonyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(1-methylpiperidin-4-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(piperidin-4-ylcarbonyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(1-methylpiperidin-4-yl)carbonyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-cyclopentyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-cyclopropylmethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-bicyclo[2.2.1]heptan-2-yl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(dimethylaminomethyl)carbonyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine.

19. The compound of claim 2 , wherein:

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

R 2 is selected from the group consisting of 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridinyl, 4b,5,6,7,7a,8-hexahydropentaleno[2,1-b]pyridinyl, 5,6,7,8-tetrahydroquinolinyl, and 7′,8′-dihydro-5′H-spiro[[1,3]dioxolane-2,6′-quinoline]-3′-yl, each optionally substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is thieno[3,2-d]pyrimidinyl optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

20. The compound of claim 19 selected from the group consisting of:

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(pyrrolidin-1ylcarbonyl)-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(2-(dimethylamino)-1-oxyethylamino)-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-amino-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(6-(1-methylpiperidin-4-ylamino)-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(7′,8′-dihydro-5′H-spiro[[1,3]dioxolane-2,6′-quinoline]-3′-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(pyrrolidin-1-yl)-4b,5,6,7,7a,8-hexahydropentaleno[2,1-b]pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(4-methylpiperazin-1-yl)-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-cyclopentylamino-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidine-4-yl)-N 3 -(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-pyrrolidin-1-yl-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(1-methylpiperidin-4-ylamino)-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-pyrrolidin-1-yl-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-(1-methylpiperidin-4-yl)carbonylamino-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-cyclopentylamino-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-cyclohexylamino-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-bicyclo[2.2.1]heptan-2-yl-amino-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(6-bis-(cyclopropylmethyl)amino-5,6,7,8-tetrahydroquinolin-3-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-yl)-1H-1,2,4-triazole-3,5-diamine.

21. The compound of claim 2 , wherein:

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

R 2 is pyrimidinyl optionally substituted by one or more substituents selected from the group consisting of cyano, nitro, halo, haloalkyl, alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, —R 9 —OR 8 , —R 9 —OC(O)—R 8 , —R 9 —C(O)R 8 , —R 9 —C(O)OR 8 , —R 9 —C(O)N(R 6 )R 7 , —R 9 —C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )R 7 , —R 9 —N(R 6 )—R 10 N(R 6 )R 7 , —R 9 —N(R 6 )C(O)OR 8 , —R 9 —N(R 6 )C(O)—R 10 —N(R 6 )R 7 , —R 9 —N(R 6 )C(O)R 8 , —R 9 —N(R 6 )S(O) t R 8 (where t is 1 or 2), —R 9 —S(O) t OR 8 (where t is 1 or 2), —R 9 —S(O) p R 8 (where p is 0, 1 or 2), and —R 9 —S(O) t N(R 6 )R 7 (where t is 1 or 2);

R 3 is selected from the group consisting of quinazolinyl and thieno[3,2-d]pyrimidinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain.

22. The compound of claim 21 selected from the group consisting of:

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(2-(4-pyrrolidin-1-ylpiperidin-1-yl)pyrimidin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(6,7-dimethoxyquinazoline-4-yl)-N 3 -(2-(4-piperidin-1-ylmethylpiperidin-1-yl)pyrimidin-5-yl)-1H-1,2,4-triazole-3,5-diamine;

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-pyrrolidin-1ylpiperidin-1-yl)pyrimidin-5-yl)-1H-1,2,4-triazole-3,5-diamine; and

1-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)-N 3 -(2-(4-(piperidin-1-ylmethyl)piperidin-1-yl)pyrimidin-5-yl)-1H-1,2,4-triazole-3,5-diamine.

23. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (Ia):

wherein:

R 1 , R 4 and R 5 are each independently selected from the group consisting of hydrogen and —C(O)N(R 6 )R 7 ;

R 3 is heteroaryl selected from the group consisting of pyrimidinyl, quinazolinyl, isoquinolinyl, furo[3,2-c]pyridinyl, phenenthridinyl, thieno[3,2-d]pyridazinyl, thieno[3,2-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, each optionally substituted by one or more substitutents selected from the group consisting of alkyl, alkenyl, halo, haloalkyl, haloalkenyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 13 —OR 12 , —R 13 —OC(O)—R 12 , —R 13 —O—R 14 —N(R 12 ) 2 , —R 13 —N(R 12 ) 2 , —R 13 —C(O)R 12 , —R 13 —C(O)OR 12 , —R 13 —C(O)N(R 12 ) 2 , —R 13 —C(O)N(R 12 )—R 14 —N(R 12 )R 13 , —R 13 —C(O)N(R 12 )—R 14 —OR 12 , —R 13 —N(R 12 )C(O)OR 12 , —R 13 —N(R 12 )C(O)R 12 , —R 13 —N(R 12 )S(O) t R 12 (where t is 1 or 2), —R 13 —S(O) t OR 12 (where t is 1 or 2), —R 13 —S(O) p R 12 (where p is 0, 1 or 2), and —R 13 —S(O) t N(R 12 ) 2 (where t is 1 or 2);

each R 9 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain;

each R 10 is independently an optionally substituted straight or branched alkylene chain;

each R 11 is hydrogen, alkyl, cyano, nitro or —OR 8 ;

each R 13 is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; and

each R 14 is independently an optionally substituted straight or branched alkylene chain;

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

24. A method of inhibiting Axl catalytic activity in a mammal, wherein the method comprises administering to the mammal an effective amount of 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: DING, PINGYU; GOFF, DANE; ZHANG, JING; SINGH, RAJINDER; HOLLAND, SACHA; YU, JIAXIN; HECKRODT, THILO J.; LITVAK, JOANE

To: RIGEL PHARMACEUTICALS, INC.

Reel/Frame 021414/0805 →

Continuity (3)

Provisional Application 60975443 · Sep 26, 2007

Provisional Application 60882875 · Dec 29, 2006

Related Publication 20080182862A1 · Jul 31, 2008