IP Library › Granted Patent US 8,026,237

Granted Patent B2

US 8,026,237 · App. 11/572,962 · Granted Sep 27, 2011

Pyrrole derivatives as pharmaceutical agents

Assignee: Exelixis, Inc.

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Quick Facts

Patent No.: US 8,026,237
App. No.: 11/572,962
Granted: Sep 27, 2011
Kind: B2

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Abstract

Compounds, compositions and methods for modulating the activity of receptors are provided. In particular compounds and compositions are provided for modulating the activity of receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder directly or indirectly related to the activity of the receptors.

Claims (239)

1. The compound of formula (III);

wherein:

R 1 is optionally substituted alkyl;

R 3 is independently hydrogen or optionally substituted alkyl;

R 4 is aryl, optionally substituted by one or more substituents selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 8 —OR 9 , —R 8 —SR 9 , —R 8 —S(O) t R 10 (where t is 1 or 2), —R 8 —N(R 9 ) 2 , —R 8 —CN, —R 8 —C(O)R 9 , —R 8 —C(S)R 9 , —R 8 —C(NR 9 )R 9 , —R 8 —C(O)OR 9 , —R 8 —C(S)OR 9 , —R 8 —C(NR 9 )OR 9 , —R 8 —C(O)N(R 9 ) 2 , —R 8 —C(S)N(R 9 ) 2 , —R 8 —C(NR 9 )N(R 9 ) 2 , —R 8 —C(O)SR 9 , —R 8 —C(S)SR 9 , —R 8 —C(NR 9 )SR 9 , —R 8 —S(O) t OR 9 (where t is 1 or 2), —R 8 —S(O) t N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )N═C(R 9 ) 2 , —R 8 —S(O) t N(R 9 )C(O)R 10 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )C(O)N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )C(NR 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 —N(R 9 )C(O)R 10 , —R 8 —N(R 9 )C(O)OR 10 , —R 8 —N(R 9 )C(O)SR 10 , —R 8 —N(R 9 )C(NR 9 )SR 10 , —R 8 —N(R 9 )C(S)SR 10 , —R 8 —N(R 9 )C(O)N(R 9 ) 2 , —R 8 —N(R 9 )C(NR 9 )N(R 9 ) 2 , —R 8 —N(R 9 )C(S)N(R 9 ) 2 , —R 8 —N(R 9 )S(O) t R 10 (where t is 1 or 2), —R 8 —OC(O)R 10 , —R 8 —OC(NR 9 )R 10 , —R 8 —OC(S)R 10 , —R 8 —OC(O)OR 10 , —R 8 —OC(NR 9 )OR 10 , —R 8 —OC(S)OR 10 , —R 8 —OC(O)SR 9 , —R 8 —OC(O)N(R 9 ) 2 , —R 8 —OC(NR 9 )N(R 9 ) 2 , —R 8 —OC(S)N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(O)R 9 , —R 8 -C(O)—R 11 —C(S)R 9 , —R 8 -C(O)—R 11 —C(NR 9 )R 9 , —R 8 -C(O)—R 11 —C(O)OR 9 , —R 8 -C(O)—R 11 —C(S)OR 9 , —R 8 -C(O)—R 11 —C(NR 9 )OR 9 , —R 8 —C(O)—R 11 —C(O)N(R 9 ) 2 , —R 8 -C(O)—R 11 —C(S)N(R 9 ) 2 , —R 8 -C(O)—R 11 —C(NR 9 )N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(O)SR 9 , —R 8 —C(O)—R 11 —C(S)SR 9 and —R 8 —C(O)—R 11 —C(NR 9 )SR 9 ;

R 5 is alkyl optionally substituted by one or more substituents selected from the group consisting of halo, haloalkyl, haloalkoxy, nitro, —OR 9 , —SR 9 , —S(O) t R 10 (where t is 1 or 2), —N(R 9 ) 2 , —CN, —C(O)R 9 , —C(S)R 9 , —C(NR 9 )R 9 , —C(O)OR 9 , —C(S)OR 9 , —C(NR 9 )OR 9 , —C(O)N(R 9 ) 2 , —C(S)N(R 9 ) 2 , —C(NR 9 )N(R 9 ) 2 , —C(O)SR 9 , —C(S)SR 9 , —C(NR 9 )SR 9 , —S(O) t OR 9 (where t is 1 or 2), —S(O) t N(R 9 ) 2 (where t is 1 or 2), —S(O) t N(R 9 )N(R 9 ) 2 (where t is 1 or 2), —S(O) t N(R 9 )N═C(R 9 ) 2 , —S(O) t N(R 9 )C(O)R 10 (where t is 1 or 2), —S(O) t N(R 9 )C(O)N(R 9 ) 2 (where t is 1 or 2), —R 8 -S(O) t N(R 9 )C(NR 9 )N(R 9 ) 2 (where t is 1 or 2), —N(R 9 )C(O)R 10 , —N(R 9 )C(O)OR 10 , —N(R 9 )C(O)SR 10 , —N(R 9 )C(NR 9 )SR 10 , —N(R 9 )C(S)SR 10 , —N(R 9 )C(O)N(R 9 ) 2 , —N(R 9 )C(NR 9 )N(R 9 ) 2 , —N(R 9 )C(S)N(R 9 ) 2 , —N(R 9 )S(O) t R 10 (where t is 1 or 2), —OC(O)R 10 , —OC(NR 9 )R 10 , —OC(S)R 10 , —OC(O)OR 10 , —OC(NR 9 )OR 10 , —OC(S)OR 10 , —OC(O)SR 9 , —OC(O)N(R 9 ) 2 , —OC(NR 9 )N(R 9 ) 2 , —OC(S)N(R 9 ) 2 , —C(O)—R 11 —C(O)R 9 , —C(O)—R 11 —C(S)R 9 , —C(O)—R 11 —C(NR 9 )R 9 , —C(O)—R 11 —C(O)OR 9 , —C(O)—R 11 —C(S)OR 9 , —C(O)—R 11 —C(NR 9 )OR 9 , —C(O)—R 11 —C(O)N(R 9 ) 2 , —C(O)—R 11 —C(S)N(R 9 ) 2 , —C(O)—R 11 —C(NR 9 )N(R 9 ) 2 , —C(O)—R 11 —C(O)SR 9 , —C(O)—R 11 —C(S)SR 9 and —C(O)—R 11 —C(NR 9 )SR 9 ;

R 6 is hydrogen or optionally substituted alkyl;

R 7 is aryl, optionally substituted by one or more substituents selected from the group consisting of optionally substituted alkenyl, optionally substituted alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, dioxo, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 13 —OR 14 , —R 13 —SR 14 , —R 13 —S(O) t R 18 (where t is 1 or 2), —R 13 —N(R 14 ) 2 , —R 13 —CN, —R 13 —C(O)R 14 , —R 13 —C(S)R 14 , —R 13 —C(NR 14 )R 14 , —R 13 —C(S)OR 14 , —R 13 —C(NR 14 )OR 14 , —R 13 —C(S)N(R 14 ) 2 , —R 13 —C(NR 14 )N(R 14 ) 2 , —R 13 —C(O)SR 14 , —R 13 —C(S)SR 14 , —R 13 —C(NR 14 )SR 14 , —R 13 —S(O) t OR 14 (where t is 1 or 2), —R 13 —S(O) t N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )N═C(R 14 ) 2 , —R 13 —S(O) t N(R 14 )C(O)R 18 , —R 13 —S(O) t N(R 14 )C(O)N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(NR 14 )N(R 14 ) 2 (where t is 1 or 2), —R 13 —N(R 14 )C(O)R 15 , —R 13 —N(R 14 )C(O)OR 18 , —R 13 —N(R 14 )C(O)SR 15 , —R 13 —N(R 14 )C(NR 14 )SR 15 , —R 13 —N(R 14 )C(S)SR 15 , —R 13 —N(R 14 )C(O)N(R 14 ) 2 , —R 13 —N(R 14 )C(NR 14 )N(R 14 ) 2 , —R 13 —N(R 14 )C(S)N(R 14 ) 2 , —R 13 —N(R 14 )S(O) t R 18 (where t is 1 or 2), —R 13 —OC(O)R 15 , —R 13 —OC(NR 14 )R 15 , —R 13 —OC(S)R 15 , —R 13 —OC(O)OR 18 , —R 13 —OC(NR 14 )OR 18 , —R 13 —OC(S)OR 18 , —R 13 —OC(O)SR 14 , —R 13 —OC(O)N(R 14 ) 2 , —R 13 —OC(NR 14 )N(R 14 ) 2 , —R 13 —OC(S)N(R 14 ) 2 —R 13 —C(O)—R 16 —C(O)R 14 , —R 13 —C(O)—R 16 —C(S)R 14 , —R 13 —C(O)—R 16 —C(NR 14 )R 14 , —R 13 C(O)—R 18 —C(O)OR 14 , —R 13 —C(O)—R 18 —C(S)OR 14 , —R 13 —C(O)—R 18 —C(NR 14 )OR 14 , —R 13 —C(O)—R 16 —C(O)N(R 14 ) 2 , —R 13 —C(O)—R 16 —C(S)N(R 14 ) 2 , —R 13 —C(O)—R 16 C(NR 14 )N(R 14 ) 2 , —R 13 —C(O)—R 16 —C(O)SR 14 , —R 13 —C(O)—R 16 —C(S)SR 14 and —R 13 —C(O)—R 16 —C(NR 14 )SR 14 ;

where each R 8 and R 13 are independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where each R 9 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; or

where two R 9 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R 14 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; or

where two R 14 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R 10 and R 15 are independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and

where each R 11 and R 16 are independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain; or as a pharmaceutically acceptable salt thereof.

2. The compound of claim 1

wherein:

R 1 is optionally substituted alkyl;

R 3 is hydrogen;

R 4 is aryl optionally substituted by one or more substituents selected from the group consisting of halo, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 8 —OR 9 , —R 8 —SR 9 , —R 8 —S(O) t R 10 (where t is 1 or 2), —R 8 —N(R 9 ) 2 , —R 8 —CN, —R 8 —C(O)R 9 , —R 8 —C(S)R 9 , —R 8 —C(NR 9 )R 9 , —R 8 —C(O)OR 9 , —R 8 —C(S)OR 9 , —R 8 —C(NR 9 )OR 9 , —R 8 —C(O)N(R 9 ) 2 , —R 8 —C(S)N(R 9 ) 2 , —R 8 —C(NR 9 )N(R 9 ) 2 , —R 8 —C(O)SR 9 , —R 8 —C(S)SR 9 , —R 8 —C(NR 9 )SR 9 , —R 8 —S(O) t OR 9 (where t is 1 or 2), —R 8 —S(O) t N(R 9 ) 2 (where t is 1 or 2), —R 8 -S(O) t N(R 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 -S(O) t N(R 9 )N═C(R 9 ) 2 , —R 8 —S(O) t N(R 9 )C(O)R 10 (where t is 1 or 2), —R 8 -S(O) t N(R 9 )C(O)N(R 9 ) 2 (where t is 1 or 2), —R 8 -S(O) t N(R 9 )C(NR 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 -N(R 9 )C(O)R 10 , —R 8 -N(R 9 )C(O)OR 10 , —R 8 -N(R 9 )C(O)SR 10 , —R 8 -N(R 9 )C(NR 9 )SR 10 , —R 8 -N(R 9 )C(S)SR 10 , —R 8 —N(R 9 )C(O)N(R 9 ) 2 , —R 8 —N(R 9 )C(NR 9 )N(R 9 ) 2 , —R 8 —N(R 9 )C(S)N(R 9 ) 2 , —R 8 -N(R 9 )S(O) t R 10 (where t is 1 or 2), —R 8 —OC(O)R 10 , —R 8 —OC(NR 9 )R 10 , —R 8 —OC(S)R 10 , —R 8 —OC(O)OR 10 , —R 8 —OC(NR 9 )OR 10 , —R 8 —OC(S)OR 10 , —R 8 —OC(O)SR 9 , —R 8 —OC(O)N(R 9 ) 2 , —R 8 —OC(NR 9 )N(R 9 ) 2 , —R 8 —OC(S)N(R 9 ) 2 ; —R 8 —C(O)—R 11 —C(O)R 14 , —R 8 —C(O)—R 11 —C(S)R 14 , —R 8 C(O)—R 11 —C(NR 14 )R 14 , —R 8 —C(O)—R 11 —C(O)OR 14 , —R 8 —C(O)—R 11 —C(S)OR 14 , —R 8 —C(O)—R 11 —C(NR 14 )OR 14 , —R 8 —C(O)—R 11 —C(O)N(R 14 ) 2 , —R 8 —C(O)—R 11 —C(S)N(R 14 ) 2 , —R 8 —C(O)—R 11 —C(NR 14 )N(R 14 ) 2 , —R 8 —C(O)—R 11 —C(O)SR 14 , —R 8 —C(O)—R 11 —C(S)SR 14 and —R 8 —C(O)—R 11 —C(NR 14 )SR 14 ;

R 5 is alkyl, optionally substituted by one or more substituents selected from the group consisting of halo, nitro, —OR 9 , —SR 9 , —S(O) t R 10 (where t is 1 or 2), —N(R 9 ) 2 , —CN, —C(O)R 9 , —C(S)R 9 , —C(NR 9 )R 9 , —C(O)OR 9 , —C(S)OR 9 , —C(NR 9 )OR 9 , —C(O)N(R 9 ) 2 , —C(S)N(R 9 ) 2 , —C(NR 9 )N(R 9 ) 2 , —C(O)SR 9 , —C(S)SR 9 , —C(NR 9 )SR 9 , —S(O) t OR 9 (where t is 1 or 2), —S(O) t N(R 9 ) 2 (where t is 1 or 2), —S(O) t N(R 9 )N(R 9 ) 2 (where t is 1 or 2), —S(O) t N(R 9 )N═C(R 9 ) 2 , —S(O) t N(R 9 )C(O)R 10 (where t is 1 or 2), —S(O) t N(R 9 )C(O)N(R 9 ) 2 (where t is 1 or 2), —R 8 -S(O) t N(R 9 )C(NR 9 )N(R 9 ) 2 (where t is 1 or 2), —N(R 9 )C(O)R 10 , —N(R 9 )C(O)OR 10 , —N(R 9 )C(O)SR 10 , —N(R 9 )C(NR 9 )SR 10 , —N(R 9 )C(S)SR 10 , —N(R 9 )C(O)N(R 9 ) 2 , —N(R 9 )C(NR 9 )N(R 9 ) 2 , —N(R 9 )C(S)N(R 9 ) 2 , —N(R 9 )S(O) t R 10 (where t is 1 or 2), —OC(O)R 10 , —OC(NR 9 )R 10 , —OC(S)R 10 , —OC(O)OR 10 , —OC(NR 9 )OR 10 , —OC(S)OR 10 , —OC(O)SR 9 , —OC(O)N(R 9 ) 2 , —OC(NR 9 )N(R 9 ) 2 , —OC(S)N(R 9 ) 2 , —C(O)—R 11 —C(O)R 9 , —C(O)—R 11 —C(S)R 9 , —C(O)—R 11 —C(NR 9 )R 9 , —C(O)—R 11 —C(O)OR 9 , —C(O)—R 11 —C(S)OR 9 , —C(O)—R 11 —C(NR 9 )OR 9 , —C(O)—R 11 —C(O)N(R 9 ) 2 , —C(O)—R 11 —C(S)N(R 9 ) 2 , —C(O)—R 11 —C(NR 9 )N(R 9 ) 2 , —C(O)—R 11 —C(O)SR 9 , —C(O)—R 11 —C(S)SR 9 and —C(O)—R 11 —C(NR 9 )SR 9 ;

R 6 is hydrogen or optionally substituted alkyl;

R 7 is aryl optionally substituted by one or more substituents selected from the group consisting of halo, nitro, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 13 —OR 14 , —R 13 —SR 14 , —R 13 —S(O) t R 18 (where t is 1 or 2), —R 13 —N(R 14 ) 2 , —R 13 —CN, —R 13 —C(O)R 14 , —R 13 —C(S)R 14 , —R 13 —C(NR 14 )R 14 , —R 13 —C(S)OR 14 , —R 13 —C(NR 14 )OR 14 , —R 13 —C(S)N(R 14 ) 2 , —R 13 —C(NR 14 )N(R 14 ) 2 , —R 13 —C(O)SR 14 , —R 13 —C(S)SR 14 , —R 13 —C(NR 14 )SR 14 , —R 13 —S(O) t OR 14 (where t is 1 or 2), —R 13 —S(O) t N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )N═C(R 14 ) 2 , —R 13 —S(O) t N(R 14 )C(O)R 18 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(O)N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(NR 14 )N(R 14 ) 2 (where t is 1 or 2) and —R 13 —N(R 14 )S(O) t R 18 (where t is 1 or 2);

where each R 8 and R 13 are independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where two R 9 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl; and

optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; or

where two R 14 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R 11 is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain;

or as a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 wherein R 7 is aryl, substituted by R 26 and optionally substituted by R 25 ;

wherein:

R 25 is selected from the group consisting of halo, nitro, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkenyl, —R 13 —OR 14 ; —R 13 —SR 14 , —R 13 —S(O) t R 15 (where t is 1 or 2), —R 13 —N(R 14 ) 2 , —R 13 —CN, —R 13 —C(O)R 14 , —R 13 —S(O) t N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(O)R 15 , (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(O)N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(NR 14 )N(R 14 ) 2 (where t is 1 or 2), —R 13 —N(R 14 )C(O)R 15 , —R 13 —N(R 14 )S(O) t R 15 (where t is 1 or 2), —R 13 —C(O)—R 16 —C(O)R 14 , —R 13 —C(O)—R 16 —C(S)R 14 and —R 13 —C(O)—R 16 —C(O)N(R 14 ) 2 ;

R 26 is selected from the group consisting of —R 13 —C(O)R 14 , —R 13 —S(O) t R 15 (where t is 1 or 2), —R 13 —S(O) t N(R 14 ) 2 (where t is 1 or 2) and —R 13 —S(O) t N(R 14 )C(O)R 15 (where t is 1 or 2);

where each R 13 is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where two R 14 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R 15 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and

where each R 16 is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain.

4. The compound of claim 3 wherein R 7 is:

wherein:

m is 0 to 1;

R 25 is selected from the group consisting of halo, nitro, optionally substituted cycloalkyl, optionally substituted heteroaralkenyl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —R 13 —OR 14 ; —R 13 —SR 14 , —R 13 —S(O) t R 15 (where t is 1 or 2), —R 13 —N(R 14 ) 2 , —R 13 —CN, —R 13 —C(O)R 14 , —R 13 —S(O) t N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(O)R 15 , (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(O)N(R 14 ) 2 (where t is 1 or 2), —R 13 —S(O) t N(R 14 )C(NR 14 )N(R 14 ) 2 (where t is 1 or 2), —R 13 —N(R 14 )C(O)R 15 , and —R 13 —N(R 14 )S(O) t R 15 (where t is 1 or 2); and

R 26 is selected from the group consisting of —R 13 —S(O) t R 15 (where t is 1 or 2), —R 13 —C(O)R 14 and —R 13 —S(O) t N(R 14 ) 2 (where t is 1 or 2);

where each R 13 is independently a direct bond or an optionally substituted straight or branched alkylene chain;

where two R 14s , together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

and where each R 16 is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain.

5. The compound of claim 4 wherein R 26 is in the para position.

6. The compound of claim 4 wherein R 7 is aryl except phenyl, substituted by R 26 and optionally substituted by R 25 wherein:

R 26 is selected from the group consisting of —S(O) t R 15 (where t is 1 or 2), —N(R 14 ) 2 , —C(O)R 14 and —S(O) t N(R 14 ) 2 (where t is 1 or 2);

where each R 13 is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where two R 14 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl; and

7. The compound of claim 1 wherein R 1 and R 5 are each alkyl.

8. The compound of claim 1 wherein R 4 is aryl optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 8 —OR 9 , —R 8 —SR 9 , —R 8 —S(O) t R 10 (where t is 1 or 2), —R 8 —N(R 9 ) 2 , —R 8 —CN, —R 8 —C(O)R 9 , —R 8 —C(S)R 9 , —R 8 —C(NR 9 )R 9 , —R 8 —C(O)OR 9 , —R 8 —C(S)OR 9 , —R 8 —C(NR 9 )OR 9 , —R 8 —C(O)N(R 9 ) 2 , —R 8 —C(S)N(R 9 ) 2 , —R 8 —C(NR 9 )N(R 9 ) 2 , —R 8 —C(O)SR 9 , —R 8 —C(S)SR 9 , —R 8 —C(NR 9 )SR 9 , —R 8 —S(O) t OR 9 (where t is 1 or 2), —R 8 —S(O) t N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )N═C(R 9 ) 2 , —R 8 —S(O) t N(R 9 )C(O)R 10 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )C(O)N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )C(NR 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 —N(R 9 )C(O)R 10 , —R 8 —N(R 9 )C(O)OR 10 , —R 8 —N(R 9 )C(O)SR 10 , —R 8 —N(R 9 )C(NR 9 )SR 10 , —R 8 —N(R 9 )C(S)SR 10 , —R 8 —N(R 9 )C(O)N(R 9 ) 2 , —R 8 —N(R 9 )C(NR 9 )N(R 9 ) 2 , —R 8 —N(R 9 )C(S)N(R 9 ) 2 , —R 8 —N(R 9 )S(O) t R 10 (where t is 1 or 2), —R 8 —OC(O)R 10 , —R 8 —OC(NR 9 )R 10 , —R 8 —OC(S)R 10 , —R 8 —OC(O)OR 10 , —R 8 —OC(NR 9 )OR 10 , —R 8 —OC(S)OR 10 , —R 8 —OC(O)SR 9 , —R 8 —OC(O)N(R 9 ) 2 , —R 8 —OC(NR 9 )N(R 9 ) 2 , —R 8 —OC(S)N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(O)R 9 , —R 8 —C(O)—R 11 —C(S)R 9 , —R 8 —C(O)—R 11 —C(NR 9 )R 9 , —R 8 —C(O)—R 11 —C(O)OR 9 , —R 8 —C(O)—R 11 —C(S)OR 9 , —R 8 —C(O)—R 11 —C(NR 9 )OR 9 , —R 8 —C(O)—R 11 —C(O)N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(S)N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(NR 9 )N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(O)SR 9 , —R 8 —C(O)—R 11 —C(S)SR 9 and —R 8 —C(O)—R 11 —C(NR 9 )SR 9 ;

where each R 5 is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where two R 9 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R 19 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and

where each R 11 is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain.

9. The compound of claim 8 wherein said compound is selected from the group consisting of:

5-(1H-Indol-5-yl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Acenaphthen-5-yl-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Biphenyl-2-yl-1-(2-diethylamino-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Biphenyl-2-yl-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

5-Biphenyl-2-yl-4-methyl-1-(2-morpholin-4-yl-ethyl)-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-4-fluoro-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-4-fluoro-phenyl)-1-(2-dimethylamino-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-4-fluoro-phenyl)-4-methyl-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(2-morpholin-4-yl-ethyl)-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Diethylamino-ethyl)-4-methyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-5-(2-phenoxy-phenyl)-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-5-(2-phenoxy-phenyl)-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3-Dimethylamino-propyl)-4-methyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-ethyl)-4-methyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

5-(4-Benzyloxy-2-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(4-Hydroxy-2-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-[2-methyl-4-(3-morpholin-4-yl-propoxy)-phenyl]-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-[4-(3-morpholin-4-yl-propoxy)-2-trifluoromethyl-phenyl]-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide, or

a pharmaceutically acceptable salt of any of the foregoing.

10. The compound of claim 8 wherein R 4 is:

wherein:

n is 0 to 4;

R 18 is halo, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted aralkenyl;

R 19 is selected from the group consisting of haloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —R 8 —OR 9 or —R 8 —C(O)N(R 9 ) 2 ;

where R 8 is a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain; and

where two R 9 s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl.

11. The compound of claim 1 selected from the group consisting of:

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid [4-(2-fluoro-benzoyl)-phenyl]-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-3-trifluoromethyl-phenyl)-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-sulfamoyl-phenyl)-amide;

5-(4-fluoro-2-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (3-chloro-4-sulfamoyl-phenyl)-amide;

5-(4-fluoro-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(4-fluoro-2-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (3-chloro-4-sulfamoyl-phenyl)-amide;

5-(4-fluoro-2-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-sulfamoyl-3-trifluoromethyl-phenyl)-amide;

1,4-Dimethyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-(4-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Isopropoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-5-fluoro-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Butoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Benzyloxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Bromo-2-methoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Bromo-2-butoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

3-[4-(4-Methanesulfonyl-phenylcarbamoyl)-1,3-dimethyl-1H-pyrrol-2-yl]-benzoic acid methyl ester;

5-(3,5-Bis-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Isopropoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Butoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Benzylcarbamoyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide; and

5-(3-Carbamoyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

N-[4-(aminosulfonyl)-3-chlorophenyl]-5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-1-(pyridin-3-ylmethyl)-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-1H pyrrole-3-carboxamide;

1-[3-(dimethylamino)propyl]-5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-2-ylmethyl)-1H-pyrrole-3-carboxamide;

1-[3-(dimethylamino)propyl]-5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide;

4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-3-ylmethyl)-1H-pyrrole-3-carboxamide;

4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide;

1-[2-(diethylamino)ethyl]-4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[(6-chloropyridin-2-yl)methyl]-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-1,4-dimethyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[(6-aminopyridin-2-yl)methyl]-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[2-(diethylamino)ethyl]-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

1-[(6-aminopyridin-2-yl)methyl]-4-methyl-N[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-[(6-pyrrolidin-1-ylpyridin-2-yl)methyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-4-methyl-1-[(6-methylpyridin-2-yl)methyl]-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

methyl (6-{[2-(2,4-difluorophenyl)-3-methyl-4-({[4-(methylsulfonyl)phenyl]amino}carbonyl)-1H-pyrrol-1-yl]methyl}pyridin-2-yl)carbamate;

1-{[6-(acetylamino)pyridin-2-yl]methyl}-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-{2-hydroxy-3-[(2-methylpropyl)amino]propyl}-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-{2-hydroxy-3-[(phenylmethyl)amino]propyl}-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(3-amino-2-hydroxypropyl)-5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-1-{2-[(2-methylpropyl)amino]-2-oxoethyl}-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(2-amino-2-oxoethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[2-(butylamino)-2-oxoethyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1,4-dimethyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-fluorophenyl)-1,4-dimethyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-piperidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-2-ylmethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-piperidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[3-(dimethylamino)propyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[2-(diethylamino)ethyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[(6-chloropyridin-2-yl)methyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-ethyl-1-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-Fluoro-phenyl)-4-methyl-1-pyridin-2-ylmethyl-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

5-(2-Fluoro-phenyl)-1-(2-hydroxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-4-methyl-1-pyrazin-2-ylmethyl-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

1-(3-Fluoro-pyridin-2-ylmethyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(tetrahydro-furan-2-ylmethyl)-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(1-Hydroxy-2-methoxy-ethyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3,3-Dimethyl-2-oxo-butyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-Furan-2-ylmethyl-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (3-chloro-4-sulfamoyl-phenyl)-amide;

1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-2-ylmethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[2-(diethylamino)ethyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-piperidin-1-ylethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[2-hydroxy-3-(phenyloxy)propyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-(2,3-dihydroxypropyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-prop-2-en-1-yl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(3-hydroxypropyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-{(2S)-3-[(4-fluorophenyl)oxy]-2-hydroxypropyl}-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(4-hydroxybutyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

N-[4-(aminosulfonyl)-3-chlorophenyl]-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chloro-phenyl)-1-(2-Methoxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-prop-2-en-1-yl-1H-pyrrole-3-carboxamide;

5-(2,6-Dimethyl-phenyl)-1-(2-hydroxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-pyridin-3-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-pyridin-2-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-[3-(4-Fluoro-phenoxy)-2-(R)-hydroxy-propyl]-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-Cyclopropylmethyl-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-prop-2-ynyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-[3-(4-fluoro-phenoxy)-2-(S)-hydroxy-propyl]-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-[3-(4-fluoro-phenoxy)-2-(R)-hydroxy-propyl]-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-cyclopropylmethyl-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl-1(2-piperidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-Methoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-methyl-amide;

5-(2-Methoxy-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Diethylamino-ethyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(2-pyrrolidin-1-yl-ethyl)-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-pyridin-2-yl-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3-Dimethylamino-propyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(2-piperidin-1-yl-ethyl)-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(2-morpholin-4-yl-ethyl)-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-3-phenoxy-propyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

1-(2-Diethylamino-ethyl)-5-(2,6-difluoro-phenyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-ethyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Difluoro-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Difluoro-phenyl)-4-methyl-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Difluoro-phenyl)-4-methyl-1-pyridin-2-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-(2-trifluoromethoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-3-phenyl-propyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-2-phenyl-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-3-methoxy-propyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-4-methyl-1-(3,3,3-trifluoro-2-hydroxy-propyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3-tert-Butoxy-2-hydroxy-propyl)-5-(2-chloro-phenyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-3-isopropoxy-propyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-ethyl)-5-(4-methoxy-2-trifluoromethyl-phenyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide, or

a pharmaceutically acceptable salt of any of the foregoing.

12. The compound of claim 8 wherein R 4 is naphthyl optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 8 —OR 9 , —R 8 —SR 9 , —R 8 —S(O) t R 10 (where t is 1 or 2), —R 8 —N(R 9 ) 2 , —R 8 —CN, —R 8 —C(O)R 9 , —R 8 —C(S)R 9 , —R 8 —C(NR 9 )R 9 , —R 8 —C(O)OR 9 , —R 8 —C(S)OR 9 , —R 8 —C(NR 9 )OR 9 , —R 8 —C(O)N(R 9 ) 2 , —R 8 —C(S)N(R 9 ) 2 , —R 8 —C(NR 9 )N(R 9 ) 2 , —R 8 —C(O)SR 9 , —R 8 —C(S)SR 9 , —R 8 —C(NR 9 )SR 9 , —R 8 —S(O) t OR 9 (where t is 1 or 2), —R 8 —S(O) t N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )N═C(R 9 ) 2 , —R 8 —S(O) t N(R 9 )C(O)R 10 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )C(O)N(R 9 ) 2 (where t is 1 or 2), —R 8 —S(O) t N(R 9 )C(NR 9 )N(R 9 ) 2 (where t is 1 or 2), —R 8 —N(R 9 )C(O)R 10 , —R 8 —N(R 9 )C(O)OR 10 , —R 8 —N(R 9 )C(O)SR 10 , —R 8 —N(R 9 )C(NR 9 )SR 10 , —R 8 —N(R 9 )C(S)SR 10 , —R 8 —N(R 9 )C(O)N(R 9 ) 2 , —R 8 —N(R 9 )C(NR 9 )N(R 9 ) 2 , —R 8 —N(R 9 )C(S)N(R 9 ) 2 , —R 8 —N(R 9 )S(O) t R 10 (where t is 1 or 2), —R 8 —OC(O)R 10 , —R 8 —OC(NR 9 )R 10 , —R 8 —OC(S)R 10 , —R 8 —OC(O)OR 10 , —R 8 —OC(NR 9 )OR 10 , —R 8 —OC(S)OR 10 , —R 8 —OC(O)SR 9 , —R 8 —OC(O)N(R 9 ) 2 , —R 8 —OC(NR 9 )N(R 9 ) 2 , —R 8 —OC(S)N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(O)R 9 , —R 8 —C(O)—R 11 —C(S)R 9 , —R 8 —C(O)—R 11 —C(NR 9 )R 9 , —R 8 —C(O)—R 11 —C(O)OR 9 , —R 8 —C(O)—R 11 —C(S)OR 9 , —R 8 —C(O)—R 11 —C(NR 9 )OR 9 , —R 8 —C(O)—R 11 —C(O)N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(S)N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(NR 9 )N(R 9 ) 2 , —R 8 —C(O)—R 11 —C(O)SR 9 , —R 8 —C(O)—R 11 —C(S)SR 9 and —R 8 —C(O)—R 11 —C(NR 9 )SR 9 .

13. The compound of claim 12 wherein said compound is selected from the group consisting of:

1,4-dimethyl-5-naphthalen-1-yl-1H-pyrrole-3-carboxylic acid (4-methane sulfonyl-phenyl)-amide; and

1,4-dimethyl-5-(4-methyl-naphthalen-1-yl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide, or a pharmaceutically acceptable salt of any of the foregoing.

14. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

15. The pharmaceutical composition of claim 14 , further comprising one or more additional active ingredients.

16. The pharmaceutical composition of claim 15 wherein said one or more additional active ingredients are selected from the group consisting of ACE inhibitors, Angiotensin II blockers, anti-coagulants, anti-cancer agents, anti-arrhythmics, anti-inflammatory agents, beta blockers, calcium channel antagonists, lipid-modulating agents, cytokine antagonists, digitalis medicines, diuretics, endothelin blockers, vasodilators, immune-suppressants, and glucose lowering agents.

17. The compound of claim 11 wherein said compound is 1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition comprising a compound of claim 17 .

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2007

From: CANNE BANNEN, LYNNE; CHEN, JEFF; DALRYMPLE MEYR, LISA ESTHER; FLATT, BRENTON T.; FORSYTH, TIMOTHY PATRICK; GU, XIAO-HUI; MAC, MORRISON B.; MANN, LARRY W.; MANN, GRACE; MARTIN, RICHARD; MOHAN, RAJU; MURPHY, BRETT; NYMAN, MICHAEL CHARLES; STEVENS, WILLIAM C., JR.; WANG, TIE-LIN; WANG, YONG; WU, JASON H.

To: EXELIXIS, INC.

Reel/Frame 019261/0736 →

Continuity (3)

Provisional Application 60592469 · Jul 30, 2004

Provisional Application 60592439 · Jul 30, 2004

Related Publication 20080234270A1 · Sep 25, 2008