Pyrazolopyridines and pyrazolopyrimidines
A compound having the structure: or a pharmaceutically acceptable salt or solvate thereof, wherein A and A′ are C or N, where C may be substituted by halo or C 1 -C 6 alkyl; R and R 0 are selected from the group consisting of H, C 1 -C 6 alkyl, —(CH 2 ) n —W, etc., where W is 5- or 6-membered heteroaryl or heterocyclic containing N, S and/or O atoms, —NR″SO 2 —R′, etc., where R′ and R″ are C 1 -C 6 alkyl, etc.; wherein each alkyl, etc., may be substituted; or, R and Ro and the N atom to which they are bonded together to form a monocyclic or bicyclic heterocyclic ring, etc.; R 1 is H, halo or cyano; R 2 and R 2′ are H, C 1 -C 6 alkyl, etc.; X is a bond, etc.; R 3 is H, C 1 -C 4 alkyl, etc.; Y is a bond, —(CH 2 ) m —, etc. The invention also relates to compositions and uses in the treatment of various diseases.
1. A method of treating a disease or condition selected from inflammation, neuroinflammation, arthritis, rheumatoid arthritis, spondyloarthropathies, systemic lupus erythematous arthritis, osteoarthritis, gouty arthritis, pulmonary sarcoisosis, silicosis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, nephritis, retinitis, autoimmune disease, fibrosis, polymyositis, eczema, psoriasis, and atopic dermatitis, comprising administering to the subject a therapeutically effective amount of a compound having the structure:
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein:
A and A′ are independently C or N, where C may be unsubstituted or substituted by halo or C 1 -C 6 alkyl;
R and R 0 are independently selected from the group consisting of H, C 1 -C 6 alkyl, hydroxy(C 1 -C 6 alkyl), phenyl(C 1 -C 6 alkyl), and —(CH 2 ) n —W, where W is C 3 -C 8 cycloalkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1-3 N, S and/or O atoms, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ and SR′, where R′ and R″ are independently C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, phenyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, heterocyclic, halo, cyano, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryloxy, —SO 2 —R′, —CONR′R″, NR′COR″, —NR′CONR′R″, —NR′CO 2 R″, —(CH 2 ) n —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, phenyl, amino, hydroxyalkylamino, heterocyclic, or —(CH 2 ) n —W′, where W′ is hydroxy, C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, or 5- or 6-membered heteroaryl containing 1-3 N, S and/or O atoms;
or, R and R 0 and the N atom to which they are bonded together form a monocyclic or bicyclic heterocyclic ring which may be unsubstituted or substituted by (a) halo, hydroxy, heteroaryl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, (C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, aryl(C 1 -C 6 alkoxy), aryloxy, amino, aminoacyl, C 1 -C 6 alkylaminoacyl, arylalkylaminoacyl, di(C 1 -C 6 alkyl)aminoacyl, —SO 2 —R′, —SO 2 —NR″—(CH 2 ) n —W, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ is independently amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, or (b) —(CH 2 ) n —W, where W is C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N atoms, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′, where R′ and R″ is independently alkyl or cycloalkyl; wherein each of said phenyl, aryl, or heteroaryl may be unsubstituted or substituted by halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, cyano, or hydroxy;
R 1 is H, halo or cyano;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
X is a bond, —CO—, —CONH—, —SO 2 —, —SONH—, or —(CH 2 ) m —;
R 3 is H, C 1 -C 4 alkyl, phenyl, naphthyl, 6-membered heteroaryl or heterocyclic containing 1-3 N atoms, a 5-membered heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, a 10-membered bicyclic heteroaryl or heterocyclic containing 1-4 N atoms, a 9-membered bicyclic heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, or an 8-membered bicyclic heteroaryl or heterocyclic containing (a) 1-4 N atoms or (b) 1 O or S atom and 1-3 N atoms or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent —Y—R 4 and/or 1-4 substituents each independently selected from R 5 ; with the proviso that when X is —CO— or —SO 2 —, R 3 is not H;
Y is a bond, —(CH 2 ) m — or —O—;
R 4 is (a) H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, cyano, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, cyano, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ;
R 5 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, cyano, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 or —NR 6 SO 2 NR 7 R 8 ;
R 6 is H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, said C 1 -C 6 alkyl is optionally substituted by —NR 7 R 8 or a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, hydroxy and cyano;
R 7 and R 8 are each independently H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1-2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C 1 -C 6 alkyl is optionally substituted by C 3 -C 8 cycloalkyl, halo, hydroxy, amino, (C 1 -C 6 alkyl)amino or di(C 1 -C 6 alkyl)amino and said heterocyclic ring being optionally substituted by one or more C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl groups;
R 9 is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and, m and n are independently 0, 1, 2 or 3.
2. The method of claim 1 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein:
A, A″ and A′″ are independently C or N, where C may be unsubstituted or substituted by halo or C 1 -C 6 alkyl;
R 1 is H, cyano or halo;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
R 3 is H, C 1 -C 4 alkyl, phenyl, naphthyl, 6-membered heteroaryl or heterocyclic containing 1-3 N atoms, a 5-membered heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, a 10-membered bicyclic heteroaryl or heterocyclic containing 1-4 N atoms, a 9-membered bicyclic heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, or an 8-membered bicyclic heteroaryl or heterocyclic containing (a) 1-4 N atoms or (b) 1 O or S atom and 1-3 N atoms or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent —Y—R 4 and/or 1-4 substituents each independently selected from R 5 ;
Y is a bond, —(CH 2 ) m — or —O—;
R 4 is (a) H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, —CN, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ;
R 5 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, —CN, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 or —NR 6 SO 2 NR 7 R 8 ;
R 6 is H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, said C 1 -C 6 alkyl is optionally substituted by —NR 7 R 8 or a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, hydroxy and cyano;
R 7 and R 8 are each independently H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1-2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C 1 -C 6 alkyl is optionally substituted by C 3 -C 8 cycloalkyl, halo, hydroxy, amino, (C 1 -C 6 alkyl)amino or di(C 1 -C 6 alkyl)amino and said heterocyclic ring being optionally substituted by one or more C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl groups;
R 9 is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 10 is —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, phenyl, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, heterocyclic, —(CH 2 ) n —W′, where W′ is hydroxy, C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N and/or O atoms; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, heterocyclic, halo, cyano, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryloxy, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently phenyl, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 11 and R 12 are each independently H, hydroxy, halo, cyano, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and, m and n are independently 0, 1, 2, or 3.
3. The method of claim 1 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein:
A″ and A′″ are independently C or N, where C may be unsubstituted or substituted by halo or C 1 -C 6 alkyl;
R 1 is H, cyano or halo;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
R 3 is H, C 1 -C 4 alkyl, phenyl, naphthyl, 6-membered heteroaryl or heterocyclic containing 1-3 N atoms, a 5-membered heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, a 10-membered bicyclic heteroaryl or heterocyclic containing 1-4 N atoms, a 9-membered bicyclic heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, or an 8-membered bicyclic heteroaryl or heterocyclic containing (a) 1-4 N atoms or (b) 1 O or S atom and 1-3 N atoms or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent —Y—R 4 and/or 1-4 substituents each independently selected from R 5 ;
Y is a bond, —(CH 2 ) m — or —O—;
R 4 is (a) H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, —CN, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ;
R 5 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, —CN, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 or —NR 6 SO 2 NR 7 R 8 ;
R 6 is H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, said C 1 -C 6 alkyl is optionally substituted by —NR 7 R 8 or a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, hydroxy and cyano;
R 7 and R 8 are each independently H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1-2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C 1 -C 6 alkyl is optionally substituted by C 3 -C 8 cycloalkyl, halo, hydroxy, amino, (C 1 -C 6 alkyl)amino or di(C 1 -C 6 alkyl)amino and said heterocyclic ring being optionally substituted by one or more C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl groups;
R 9 is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 10 is —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, phenyl, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, heterocyclic, —(CH 2 ) n —W′, where W′ is hydroxy, C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N and/or O atoms; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, heterocyclic, halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryloxy, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently phenyl, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 11 and R 12 are each independently H, hydroxy, halo, cyano, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and, m and n are independently 0, 1, 2 or 3.
4. The method of claim 1 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein:
R 1 is H, cyano or halo;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
R 3 is H, C 1 -C 4 alkyl, phenyl, naphthyl, 6-membered heteroaryl or heterocyclic containing 1-3 N atoms, a 5-membered heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, a 10-membered bicyclic heteroaryl or heterocyclic containing 1-4 N atoms, a 9-membered bicyclic heteroaryl or heterocyclic containing either (a) 1-4 N atoms or (b) 1 O or S atom and 0-3 N atoms, or an 8-membered bicyclic heteroaryl or heterocyclic containing (a) 1-4 N atoms or (b) 1 O or S atom and 1-3 N atoms or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent —Y—R 4 and/or 1-4 substituents each independently selected from R 5 ;
Y is a bond, —(CH 2 ) m — or —O—;
R 4 is (a) H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, —CN, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, oxo, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 and —NR 6 SO 2 NR 7 R 8 ;
R 5 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, —CN, —OR 6 , —NR 7 R 8 , —SR 6 , —SOR 9 , —SO 2 R 9 , —COR 6 , —OCOR 6 , —COOR 6 , —NR 6 COR 6 , —CONR 7 R 8 , —NR 6 SO 2 R 9 , —SO 2 NR 7 R 8 , —NR 6 CONR 7 R 8 , —NR 6 COOR 9 or —NR 6 SO 2 NR 7 R 8 ;
R 6 is H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, said C 1 -C 6 alkyl is optionally substituted by —NR 7 R 8 or a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, containing 1 or 2 heteroatoms selected from O and N, said heteroaryl being optionally substituted by 1-5 substituents selected from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo, hydroxy and cyano;
R 7 and R 8 are each independently H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1-2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C 1 -C 6 alkyl is optionally substituted by C 3 -C 8 cycloalkyl, halo, hydroxy, amino, (C 1 -C 6 alkyl)amino or di(C 1 -C 6 alkyl)amino and said heterocyclic ring being optionally substituted by one or more C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl groups;
R 9 is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 10 is —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, phenyl, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, heterocyclic, —(CH 2 ) n —W′, where W′ is hydroxy, C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N and/or O atoms; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, heterocyclic, halo, cyano, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryloxy, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently phenyl, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 11 and R 12 are each independently H, hydroxy, halo, cyano, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and, m and n are independently 0, 1, 2 or 3.
5. The method of claim 1 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein:
A and A′ are independently C or N, where C may be unsubstituted or substituted by C 1 -C 6 alkyl;
R and R 0 are independently selected from the group consisting of H, C 1 -C 6 alkyl, hydroxy(C 1 -C 6 alkyl), phenyl(C 1 -C 6 alkyl), and —(CH 2 ) n —W, where W is C 3 -C 8 cycloalkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1-3 N, S and/or O atoms, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ and SR′, where R′ and R″ are independently C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, phenyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, heterocyclic, halo, cyano, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryloxy, —SO 2 —R′, —CONR′R″, NR′COR″, —NR′CONR′R″, —NR′CO 2 R″, —(CH 2 ) n —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, phenyl, amino, hydroxyalkylamino, heterocyclic, or —(CH 2 ) n —W′, where W′ is hydroxy, C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, or 5- or 6-membered heteroaryl containing 1-3 N, S and/or O atoms;
or, R and R 0 and the N atom to which they are bonded together form a monocyclic or bicyclic heterocyclic ring which may be unsubstituted or substituted by (a) halo, hydroxy, heteroaryl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, (C 1 -C 6 alkoxy)C 1 -C 6 alkoxy, aryl(C 1 -C 6 alkoxy), aryloxy, amino, aminoacyl, C 1 -C 6 alkylaminoacyl, arylalkylaminoacyl, di(C 1 -C 6 alkyl)aminoacyl, —SO 2 —R′, —SO 2 —NR″—(CH 2 ) n —W, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ is independently amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, or (b) —(CH 2 ) n —W, where W is C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N atoms, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′, where R′ and R″ is independently alkyl or cycloalkyl; wherein each of said phenyl, aryl, or heteroaryl may be unsubstituted or substituted by halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, cyano, or hydroxy;
R 1 is halo;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms; and, n is 0, 1, 2 or 3.
6. The method of claim 1 wherein the compound has the structure:
wherein:
A, A′, A″ and A′″ are independently C or N, where C may be unsubstituted or substituted by halo or C 1 -C 6 alkyl;
R 1 is H, cyano or halo;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
R 10 is —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ is independently C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and
R 11 and R 12 are each independently H, hydroxy, halo, cyano, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl.
7. The method of claim 1 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein:
A″ and A′″ are independently C or N, where C may be unsubstituted or substituted by halo or C 1 -C 6 alkyl;
R 1 is H, cyano or halo;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
R 10 is —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, phenyl, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, heterocyclic, —(CH 2 ) n —W′, where W′ is hydroxy, C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N and/or O atoms; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, heterocyclic, halo, cyanohydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryloxy, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently phenyl, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;
R 11 and R 12 are each independently H, hydroxy, halo, cyano, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and, m and n are independently 0, 1, 2 or 3.
8. The method of claim 1 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein:
R 1 is H, cyano or halo;
R 2 and R 2′ are independently H, C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, or C 3 -C 8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
R 10 is —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, phenyl, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, heterocyclic, —(CH 2 ) n —W′, where W′ is hydroxy, C 3 -C 8 cycloalkyl, phenyl, naphthyl, heterocyclic, 5- or 6-membered heteroaryl containing 1-3 N and/or O atoms; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, heterocyclic, halo, cyano, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryloxy, —SO 2 —R′, —NHSO 2 —R′, —NR″SO 2 —R′ or SR′ where R′ and R″ are independently phenyl, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl; and, n is 0, 1, 2 or 3.
9. The method of claim 1 wherein the compound is selected from the group consisting of:
4-({2-[ethyl(ethylsulfonyl)amino]benzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)-phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[ethyl(ethylsulfonyl)amino]benzyl}amino)-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({2-[(ethylsulfonyl)(methyl)amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-{[2-(4-hydroxyphenyl)ethyl]amino}-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[(2-methylpropyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({5-chloro-2-[methyl(methylsulfonyl)amino]benzyl}amino)-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({5-fluoro-2-[methyl(methylsulfonyl)amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({2-fluoro-6-[methyl(methylsulfonyl)amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({2-[ethyl(methylsulfonyl)amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[(cyclopentylmethyl)amino]-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-({5-methyl-2-[methyl(methylsul-fonyl)amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[ethyl(methylsulfonyl)amino]benzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoro-ethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[(ethylsulfonyl)(methyl)amino]benzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-fluoro-2-[methyl(methylsulfon-yl)amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({5-chloro-2-[methyl(methylsulfonyl)amino]benzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[(2-methylpropyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[(cyclopentylmethyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({2-fluoro-6-[methyl(methylsulfonyl)-amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-({2-[methyl(methylsulfonyl)amino]benzyl}-amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-({2-[methyl(methylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-({5-methyl-2-[methyl(methylsulfonyl)amino]-benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-({2-[methyl(phenylsulfonyl)-amino]benzyl}am-ino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[(2-{4-[(phenylsulfonyl)amino]-phenyl}ethyl)-amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({2-[(2-hydroxyethyl)(methylsulfonyl)-amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({2-[methyl(phenylsulfonyl)amino]benzyl}-amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({2-[(2-hydroxyethyl)(methylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({4-hydroxy-2-[methyl(methylsulfonyl)amino]benzyl}-amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({4-hydroxy-2-[methyl(methylsulfonyl)amino]benzyl}-amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({5-hydroxy-2-[methyl(methylsulfonyl)amino]benzyl}-amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[(2-{[(3-hydroxyphenyl)sulfonyl](methyl)-amino}benzyl)amino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({4-hydroxy-2-[methyl(methylsulfonyl)-amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[ethyl(methylsulfonyl)amino]-5-hydroxybenzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-hydroxy-2-[methyl(phenylsulfonyl)-amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[ethyl(phenylsulfonyl)amino]-5-hydroxybenzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-cyclopropyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-({2-[methyl(methylsulfonyl)amino]-benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-{[(1R)-1-{2-[methyl(methylsulfonyl)amino]-phenyl}ethyl]amino}-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-{[(1 S)-1-{2-[methyl(methylsulfonyl)-amino]phenyl}ethyl]amino}-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({2-[methyl(phenylsulfonyl)amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({4-hydroxy-2-[methyl(methylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-hydroxy-2-[methyl(phenylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[ethyl(phenylsulfonyl)amino]-5-hydroxybenzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[({3-[methyl(phenylsulfonyl)-amino]pyrazin-2-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({3-[ethyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
N-ethyl-4-[({3-[ethyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-cyclopropyl-5-fluoro-4-hydroxyphenyl)-4-({2-[methyl(methylsulfonyl)amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[({4-[methyl(methylsulfonyl)-amino]pyridin-3-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-cyclopropyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[({2-[methyl(methylsulfonyl)amino]-pyridin-3-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-methoxy-2-[methyl(methylsulfonyl)-amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[({3-[methyl(methylsulfonyl)am-ino]pyrazin-2-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({2-[ethyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,22-trifluoroethyl)phenyl]-N-methyl-4-[({2-[methyl(methylsulfonyl)-amino]pyridin-3-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-hydroxy-2-[methyl(pyridin-3-ylsulfonyl)amino]benzyl}amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[({3-[methyl(methylsulfonyl)-amino]pyridin-2-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-({2-[methyl(methylsulfonyl)amino]benzyl}amino)-N-(6-methylpyridin-3-yl)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-4-((1,3,3-trimethylureido)benzyl)-amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-4-((2-(N-methyl-1H-pyrazole-4-sulfonamido)benzyl)amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-((2-N, 1-dimethyl-1H-imidazole-4-sulfonamido)benzyl)amido)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[(2-{[(2-methoxyethyl)sulfonyl]-(methyl)amino}benzyl)amino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({2-[methyl(pyridin-3-ylsulfonyl)amino]ben-zyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({2-[ethyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-{[2-(sulfamoylmethyl)benzyl]-amino}-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-{[2-(methyl{[6-(morpholin-4-yl)pyridin-3-yl]sulfonyl}amino)benzyl]amino}-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-{[2-(methyl{[3-(morpholin-4-yl)propyl]sulfonyl}amino)benzyl]amino}-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[({5-methyl-2-[methyl(methyl-sulfonyl)amino]pyridin-3-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-({2-[methyl(pyridin-3-ylsulfonyl)amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[(2-{methyl[(6-methylpyridin-3-yl)sulfonyl]amino}benzyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[(2-{methyl[(6-methylpyridin-3-yl)sulfonyl]amino}benzyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({5-chloro-2-[ethyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({5-chloro-2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-({2-[methyl(sulfamoyl)amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((N-(2-hydroxyethyl)sulfamoyl)(methyl)-aminobenzyl)amino)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,22-trifluoroethyl)phenyl]-N-{6-[(2-hydroxyethyl)amino]pyridin-3-yl}-4-({5-hydroxy-2-[methyl(methylsulfonyl)amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,22-trifluoroethyl)phenyl]-4-({2-[methyl(methylsulfonyl)amino]ben-zyl}amino)-N-(6-methylpyridin-3-yl)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({2-[methyl(methylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,22-trifluoroethyl)phenyl]-4-[({5-fluoro-2-[methyl(methylsulfonyl)-amino]pyridin-3-yl}methyl)amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({2-[ethyl(methylsulfonyl)amino]-5-fluoropyridin-3-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({3-[ethyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,22-trifluoroethyl)phenyl]-4-({5-methyl-2-[methyl(methylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-((2-(N-ethylethylsulfonamido)benzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-((2-(N-ethylmethylsulfonamido)-5-fluorobenzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoro-ethyl)phenyl)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-((5-chloro-2-(N-ethylmethylsulfonamido)benzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoro-ethyl)phenyl)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((2-(N-methylethyl-sulfonamido)benzyl)-amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-(((5-methyl-2-(N-methylmethylsulfonam-ido)pyridin-3-yl)methyl)amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-[({2-[ethyl(methylsulfonyl)amino]-5-methylpyridin-3-yl}methyl)amino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-fluoro-2-[methyl(methylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({5-chloro-2-[methyl(methylsulfonyl)amino]benzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[ethyl(methylsulfonyl)amino]benzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)-phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
4-({2-[ethyl(methylsulfonyl)amino]-5-methylbenzyl}amino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-hydroxy-2-[methyl(methylsulfonyl)-amino]benzyl}amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-((2-(N-methylmethylsulfonamido)benzyl)-amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-4-((2-(N-methylmethylsulfon-amido)benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-((2-(N-methylphenylsulfonamido)benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((2-(N-methylphenylsulfonamido)-benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((5-hydroxy-2-(N-methylmethylsulfon-amido)benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((2-(N-methylmethylsulfon-amido)benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((5-hydroxy-2-(N-methylmethylsulfon-amido)benzyl)amino)-N-(6-((2-hydroxyethyl)amino)pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,22-trifluoroethyl)phenyl)-N-methyl-4-(((3-(N-methylmethyl-sulfonamido)pyrazin-2-yl)methyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((2-(N-(2-hydroxyethyl)methyl-sulfonamido)benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-4-((2-(N-(2-hydroxyethyl)methylsulfon-amido)benzyl)amino)-N-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
4-((2-(N-ethylmethylsulfonamido)benzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)-phenyl)-N-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
4-((5-fluoro-2-(N-methylmethylsulfonamido)benzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
4-((2-(N-ethylphenylsulfonamido)-5-hydroxybenzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
4-((2-(N-methylphenylsulfonamido)-5-hydroxybenzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
4-((2-(N-ethylphenylsulfonamido)-5-hydroxybenzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
4-((2-(N-methylphenylsulfonamido)-5-hydroxybenzyl)amino)-6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-4-((2-(methyl(sulfamoyl)amino)-benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
6-(5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl)-N-methyl-4-((2-(methyl(N-methylsulfamoyl)amino)benzyl)amino)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide;
4-[4-(7,8-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-ethylphenol formate;
3-ethyl-4-[4-(3-phenoxyazetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol formate;
3-ethyl-4-{4-[6-(4-methyl-1H-imidazol-1-yl)-3,4-dihydroisoquinolin-2(1H)-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}phenol formate;
3-ethyl-4-{4-[6-(2-methoxyethoxy)-3,4-dihydroisoquinolin-2(1H)-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}phenol formate;
1-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-3-methylazetidin-3-ol formate;
2-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-N-[2-(pyrrolidin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide formate;
N-benzyl-2-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-1,2,3,4-tetrahydroiso-quinoline-5-carboxamide formate;
4-{4-[7-(benzyloxy)-6-methoxy-3,4-dihydroisoquinolin-2(1H)-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}-3-ethylphenol formate;
4-[4-(5-chloro-3,4-dihydroisoquinolin-2(1H)-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-ethylphenol formate;
4-chloro-3-({1-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]azetidin-3-yl}oxy)benzonitrile formate;
3-ethyl-4-[4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol formate;
3-ethyl-4-[4-(8-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol formate;
N-{2-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-1,2,3,4-tetrahydroisoquinolin-5-yl}methanesulfonamide formate;
4-(4-{[2-(biphenyl-4-yl)ethyl]amino}-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-ethylphenol formate;
N-[2-({[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide hydrochloride;
1-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-N, N-dimethylpyrrolidine-3-sulfon-amide (racemic);
N-[2-({[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)-3-methylphenyl]-N-methylmethanesulfonamide diethylamine salt;
3-ethyl-4-[4-(4-methoxypiperidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol diethylamine salt;
N-[2-({[2-(3,4-dim ethoxyphenyl)ethyl][6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide hydrochloride;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl](2-{4-[(methylsulfon-yl)amino]phenyl}ethyl)amino}methyl)phenyl]-N-methylmethanesulfonamide hydrochloride;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)-phenyl]-N-methylmethanesulfonamide;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)-4-methylphenyl]-N-methylmethanesulfonamide hydrochloride;
N-[4-chloro-2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide hydrochloride;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)-3-fluorophenyl]-N-methylmethanesulfonamide hydrochloride;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)-phenyl]-N-methylethanesulfonamide hydrochloride;
N-ethyl-N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}-methyl)phenyl]ethanesulfonamide hydrochloride;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-propylmethanesulfonamide;
N-ethyl-N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}-methyl)phenyl]methanesulfonamide;
N-butyl-N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}-methyl)phenyl]methanesulfonamide;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl][2-(morpholin-4-yl)ethyl]amino}methyl)phenyl]-N-methylmethanesulfonamide;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl][2-(morpholin-4-yl)ethyl]amino}methyl)phenyl]-N-methylmethanesulfonamide;
N-ethyl-N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4 yl](methyl)-amino}methyl)-4-methylphenyl]methanesulfonamide;
N-[2-({ethyl[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)-4-methylphenyl]-N-methylmethanesulfonamide;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl](propyl)amino}-methyl)-4-methylphenyl]-N-methylmethanesulfonamide;
N-ethyl-N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4 yl](methyl)am-ino}methyl)phenyl]methanesulfonamide hydrochloride;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl](methyl)amino}-methyl)phenyl]-N-methylmethanesulfonamide hydrochloride;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-(2-hydroxyethyl)methanesulfonamide;
N-{2-[({6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridin-4-yl}amino)methyl]phenyl}-N-methylmethanesulfonamide;
N-(2-{[{6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridin-4-yl}(methyl)amino]methyl}phenyl)-N-methylmethanesulfonamide;
N-{2-[({6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridin-4-yl}amino)methyl]-4-methylphenyl}-N-methylmethanesulfonamide;
4-{4-[(cyclopropylmethyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-2-fluoro-5-(2,2,2-trifluoroethyl)phenol;
4-{4-[(2-cyclopropylethyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-2-fluoro-5-(2,2,2-trifluoroethyl)phenol;
2-fluoro-4-{4-[(2-methylpropyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5-(2,2,2-trifluoro-ethyl)phenol;
4-[4-(butylamino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-2-fluoro-5-(2,2,2-trifluoroethyl)phenol;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino}methyl)-phenyl]-N-methylmethanesulfonamide hydrochloride;
N-(2-(((6-(2-ethyl-4-hydroxy-6-methylphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl)amino)methyl)-phenyl)-N-methylmethanesulfonamide;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-3-(1H-imidazol-2-yl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide;
N-[2-({[3-(4,5-dimethyl-1H-imidazol-2-yl)-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-3-(4-methyl-1H-imidazol-2-yl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide;
4-[3-(5-benzyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)-4-{[2-(methylsulfanyl)ethyl]-amino}-1H-pyrazolo[4,3-c]pyridin-6-yl]-2-fluoro-5-(2,2,2-trifluoroethyl)phenol;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-3-(1H-pyrazol-1-yl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide;
N-{2-[({6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-3-(1H-pyrazol-1-yl)-1H-pyrazolo[4,3-c]pyridin-4-yl}amino)methyl]phenyl}-N-methylmethanesulfonamide;
N-{2-[({6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-3-(5-methyl-4H-1,2,4-triazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-4-yl}amino)methyl]phenyl}-N-methylmethanesulfonamide;
N-[2-({[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-3-(5-methyl-4H-1,2,4-triazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino}methyl)phenyl]-N-methylmethanesulfonamide;
N-{2-[({6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-3-[5-(6-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl]-1H-pyrazolo[4,3-c]pyridin-4-yl}amino)methyl]phenyl}-N-methylmethanesulfonamide;
4-(5-{6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-hydroxy-2-[methyl(methyl-sulfonyl)amino]benzyl}amino)-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-4H-1,2,4-triazol-3-yl)piperidine-1-carboxamide;
N-(2-{[(6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-3-{5-[1-(pyrrolidin-1-ylacetyl)piperid-in-4-yl]-4H-1,2,4-triazol-3-yl}-1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino]methyl}phenyl)-N-methyl-methanesulfonamide;
N-{2-[({6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-3-(4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl}amino)methyl]-4-hydroxyphenyl}-N-methylmethanesulfonamide;
N-{2-[({3-(5-acetyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yl}amino)methyl]-4-hydroxyphenyl}-N-methylmethanesulfonamide;
N-[2-(dimethylamino)ethyl]-2-{6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-({5-hydroxy-2-[methyl(methylsulfonyl)amino]benzyl}amino)-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxamide; and,
4-(3-(5-benzyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)-4-((3-hydroxy-2-methylpropyl)-amino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2-fluoro-5-(2,2,2-trifluoroethyl)phenol.