US 9,518,052 B2 · Pyrazolopyridines and pyrazolopyrimidines

Abstract

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 C1-C6 alkyl; R and R0 are selected from the group consisting of H, C1-C6 alkyl, —(CH2)n—W, etc., where W is 5- or 6-membered heteroaryl or heterocyclic containing N, S and/or O atoms, —NR″SO2—R′, etc., where R′ and R″ are C1-C6 alkyl, etc.; wherein each alkyl, etc., may be substituted; or, R and R0 and the N atom to which they are bonded together to form a monocyclic or bicyclic heterocyclic ring, etc.; R1 is H, halo or cyano; R2 and R2′ are H, C1-C6 alkyl, etc.; X is a bond, etc.; R3 is H, C1-C4 alkyl, etc.; Y is a bond, —(CH2)m—, etc. The invention also relates to compositions and uses in the treatment of various diseases.

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, A″ and A′″ are independently C or N, where C may be unsubstituted or substituted by halo or C1-C6 alkyl;
R1 is H, cyano or halo;
R2 and R2′ are independently H, C1-C6 alkyl, cyano, C1-C6 alkoxy, C1-C6 alkylthio, or C3-C8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms;
R3 is H, C1-C4 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—R4 and/or 1-4 substituents each independently selected from R5;
Y is a bond, —(CH2)m— or —O—;
R4 is (a) H, C1-C6 alkyl, C3-C8 cycloalkyl, halo, oxo, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 and —NR6SO2NR7R8;
(b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C1-C6 alkyl, C3-C8 cycloalkyl, halo, —CN, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 and —NR6SO2NR7R8;
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 C1-C6 alkyl, C3-C8 cycloalkyl, halo, oxo, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 and —NR6SO2NR7R8;
R5 is C1-C6 alkyl, C3-C8 cycloalkyl, halo, —CN, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —COOR6, —NR6COR6, —CONR7R8, —NR6SO2R9, —SO2NR7R8, —NR6CONR7R8, —NR6COOR9 or —NR6SO2NR7R8;
R6 is H, C1-C6 alkyl or C3-C8 cycloalkyl, said C1-C6 alkyl is optionally substituted by —NR7R8 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 C1-C6 alkyl, C3-C8 cycloalkyl, halo, hydroxy and cyano;
R7 and R8 are each independently H, C1-C6 alkyl or C3-C8 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 C1-C6 alkyl is optionally substituted by C3-C8 cycloalkyl, halo, hydroxy, amino, (C1-C6 alkyl)amino or di(C1-C6 alkyl)amino and said heterocyclic ring being optionally substituted by one or more C1-C6 alkyl or C3-C8 cycloalkyl groups;
R9 is C1-C6 alkyl or C3-C8 cycloalkyl;
R10 is —NHSO2—R′, —NR″SO2—R′ or SR′ where R′ and R″ are independently hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, phenyl, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino, heterocyclic, —(CH2)n—W′, where W′ is hydroxy, C3-C8 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, C1-C6 alkyl, C1-C6 alkoxy, aryloxy, —SO2—R′, —NHSO2—R′, —NR″SO2—R′ or SR′ where R′ and R″ are independently phenyl, C1-C6 alkyl or C3-C8 cycloalkyl;
R11 and R12 are each independently H, hydroxy, halo, cyano, C1-C6 alkyl or C3-C8 cycloalkyl;
and, m and n are independently 0, 1, 2, or 3.

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Pyrazolopyridines and pyrazolopyrimidines

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Pyrazolopyridines and pyrazolopyrimidines

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Abstract

Claims12