Compounds and use thereof as hdac6 inhibitors

A compound of formula (I)

• or a pharmaceutically acceptable salt and/or solvate thereof;
• wherein
• Y1 is a 9- or 10-membered bicyclic heteroaryl selected from the following formulae
• wherein
• A1, A2, A3, A4, A5, A6 and A7 are each independently selected from C—R7 and N;
• A8, A9, A10 and A11 are each independently selected from C—R7 and N, provided that at least one of A8, A9, A10, or A11 is N;
• G1 is selected from C—R3 and N;
• G2 is selected from O and N—R4;
• B is selected from O, S and N—R5,
• provided that when A5, A6 and A7 are C—R7, then B is not S;
• and
• R2 is selected from hydrogen, halogen, cyano, amino, hydroxy, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl, heteroaryl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —OR1, —(C1-C6) alkylene-OR15, —O—(C2-C6) alkylene-OR15, —NR16(C2-C6) alkylene-OR15, —NR17R18, —(C1-C6) alkylene-NR17R18, —O—(C2-C6) alkylene-NR17R18, —NR16—(C2-C6) alkylene-NR17R18, —(C1-C6) alkylene-SO2—NR17R18, —NR16—SO2—R15, —(C1-C6) alkylene-NR16—SO2—R15, —O—(C2-C6)alkylene-NR16—SO2—R15, —NR16—(C2-C6) alkylene-NR11—SO2—R15, —C(O)—NR17R18, —(C1-C6) alkylene-C(O)—NR17R18, —O—(C1-C6) alkylene-C(O)—NR17R18, —NR16—(C1-C6) alkylene-C(O)—NR17R1B, —NR16C(O)—R15, —(C1-C6) alkylene-NR16C(O)—R15, —O—(C2-C6) alkylene-NR16C(O)—R15, —NR16—(C2-C6) alkylene-NR16C(O)—R15, —C(O)—R15, —C(O)OR15, —(C1-C6) alkylene-C(O)OR15, —O—(C1-C6) alkylene-C(O)OR15, —NR16—(C1-C6) alkylene-C(O)OR15;
• R3 is selected from halogen, cyano, amino, hydroxy, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl, heteroaryl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —OR15, —(C1-C6) alkylene-OR15, —O—(C2-C6)alkylene-OR15, —NR16(C2-C6) alkylene-OR15, —NR17R18, —(C1-C6) alkylene-NR17R18, —O—(C2-C6) alkylene-NR17R18, —NR16—(C2-C6) alkylene-NR17R18, —(C1-C6) alkylene-SO2—NR17R18, —NR16—SO2—R15, —(C1-C6) alkylene-NR16—SO2—R15, —O—(C2-C6) alkylene-NR16—SO2—R15, —NR16—(C2-C6) alkylene-NR17—SO2—R15, —C(O)—NR17R18, —(C1-C6) alkylene-C(O)—NR17R18, —O—(C1-C6) alkylene-C(O)—NR17R18, —NR16—(C1-C6) alkylene-C(O)—NR17R18, —NR16C(O)—R15, —(C1-C6) alkylene-NR16C(O)—R15, —O—(C2-C6) alkylene-NR16C(O)—R15, —NR16—(C2-C6) alkylene-NR16C(O)—R5, —C(O)—R15, —C(O)OR15, —(C1-C6) alkylene-C(O)OR15, —O—(C1-C6) alkylene-C(O)OR15, —NR16—(C1-C6) alkylene-C(O)OR15;
• R4 is selected from hydrogen, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —(C1-C6) alkylene-aryl, —(C1-C6) alkylene-heteroaryl, —(C1-C6) alkylene-OR15, —(C1-C6) alkylene-NR17R18, —(C1-C6) alkylene-C(O)—NR17R18, —(C1-C6) alkylene-NR16C(O)—R15, —(C1-C6) alkylene-C(O)OR15, and —(C1-C6) alkylene-OC(O)—R15;
• R5 is selected from hydrogen, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl, heteroaryl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —(C1-C6) alkylene-aryl, —(C1-C6) alkylene-heteroaryl, —(C1-C6) alkylene-OR15, —(C1-C6) alkylene-NR17R's, —(C1-C6) alkylene-C(O)—NR17R18, —(C1-C6) alkylene-NR16C(O)—R15, —(C1-C6) alkylene-C(O)OR15, and —(C1-C6) alkylene-OC(O)—R15;
• R7 is independently selected from hydrogen, halogen, amino, hydroxy, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —(C3-C7) heterocycloalkyl, aryl, heteroaryl, —OR15, —(C1-C6) alkylene-OR15, —O—(C2-C6) alkylene-OR15, —NR16(C2-C6) alkylene-OR15, —NR17R18, —(C1-C5) alkylene-NR17R18, —O—(C2-C6) alkylene-NR17R18, —NR16—(C2-C6) alkylene-NR17R18, —SO—R15, —SO2—R15, —SO2NR17R18, —(C1-C6) alkylene-SO2—NR17R18, —NR16—SO2—R15, —(C1-C6) alkylene-NR16—SO2—R15, —O—(C2-C6) alkylene-NR16—SO2—R15, —NR16—(C2-C6) alkylene-NR17—SO2—R15, —C(O)—NR17R18, —(C1-C6) alkylene-C(O)—NR17R18, —O—(C1-C6) alkylene-C(O)—NR17R18, —NR16—(C1-C6) alkylene-C(O)—NR17R18, —NR16C(O)—R15, —(C1-C6) alkylene-NR16C(O)—R15, —O—(C2-C6) alkylene-NR16C(O)—R15, —NR16—(C2-C6) alkylene-NR17C(O)—R15, —C(O)—R15, —C(O)—OR15, —(C1-C6) alkylene-C(O)—OR15, —O—(C1-C6) alkylene-C(O)—OR15, —NR16—(C1-C5) alkylene-C(O)—OR15, —OC(O)—R15, —(C1-C6) alkylene-OC(O)—R15, —O—(C2-C6) alkylene-OC(O)—R15, —NR16—(C2-C6) alkylene-OC(O)—R15 or —NR16—C(O)—OR15;
• wherein
• each of said —(C1-C6) alkyl or —(C1-C6) alkylene in R2, R3, R4, R5 or R7 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• each of said —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl or heteroaryl in R2, R3, R4, R5 or R7 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —H—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• R15, R16, R17 and R18 are each independently selected from hydrogen, —(C1-C6)haloalkyl, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl, heteroaryl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —(C1-C6) alkylene-heteroaryl, and —(C1-C6) alkylene-aryl;
• and/or two groups selected from R15, R16, R17 and R18 form together a cycle selected from —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl and heteroaryl;
• wherein
• each of said —(C1-C6) alkyl or —(C1-C6) alkylene in R15, R16, R17 or R18 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• each of said —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl or heteroaryl in R15, R16, R17 or R18 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• Y2 is a 5-membered heteroaryl selected from the following formulae
• wherein R12, R13 and R14 are each independently selected from hydrogen, halogen, cyano, hydroxy, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl), —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C5) alkyl) and —N—((C1-C6) alkyl)2;
• wherein each of said —(C1-C6) alkyl in R12, R13 or R14 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• L is selected from —(CR10R11)n, —(C4-C7) cycloalkyl and (C4-C7) heterocycloalkyl;
• wherein
• n is an integer selected from 1 or 2;
• R10 and R11 are independently selected from hydrogen, halogen, hydroxy, amino, —(C1-C3) alkyl, —(C1-C2) haloalkyl, —(C1-C2) hydroxyalkyl, —(C1-C2) aminoalkyl, —O—(C1-C4) alkyl, —NH—(C1-C3) alkyl and —N—((C1-C3) alkyl)2;
• each of said —(C3-C7) cycloalkyl or (C3-C7) heterocycloalkyl in L is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C5) alkyl)2;
• Z1 is selected from —C(O)—R9 and —SO2—R9;
• wherein R9 is selected from amino, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl, heteroaryl, —(C1-C6) alkylene-(C3—C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —(C1-C6) alkylene-aryl, —(C1-C6) alkylene-heteroaryl, —(C1-C6) alkylene-OR21, —(C1-C6) alkylene-NR23R24, —(C1-C6) alkylene-C(O)—NR23R24, —(C1-C6) alkylene-C(O)—NR23R24, —(C1-C6) alkylene-NR22—C(O)—R21, —(C1-C6) alkylene-C(O)OR21, —OR21, —NR23R24, —NR22—(C2-C6) alkylene-OR21, —NR22—(C2-C6) alkylene-NR23R24, —NR22—(C1-C6) alkylene-C(O)OR21;
• wherein
• each of said —(C1-C6) alkyl or —(C1-C6) alkylene in R9 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• each of said —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl or heteroaryl in R9 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• R21, R22, R23 and R24 are each independently selected from hydrogen, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) halocycloalkyl, —(C3-C7) heterocycloalkyl, aryl, heteroaryl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —(C1-C6) alkylene-heteroaryl, and —(C1-C6) alkylene-aryl;
• and/or two groups selected from R21, R22, R23 and R24 form together a cycle selected from —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl and heteroaryl;
• wherein
• each of said —(C1-C6) alkyl or —(C1-C6) alkylene in R1, R22, R23 or R24 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• each of said —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, aryl or heteroaryl in R21, R22, R23 or R24 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• and
• R1 is selected from hydrogen, —(C1-C6) alkyl, —(C3-C7) cycloalkyl, —(C3-C7) heterocycloalkyl, —(C1-C6) alkylene-(C3-C7) cycloalkyl, —(C1-C6) alkylene-(C3-C7) heterocycloalkyl, —(C1-C6) alkylene-OR19 and —(C1-C6) alkylene-NR19R20,
• wherein
• R19 and R20 are each independently selected from hydrogen, —(C1-C6) alkyl and —(C3-C7) cycloalkyl;
• or R19 and R20 form together a cycle selected from —(C3-C7) cycloalkyl and —(C3-C7)heterocycloalkyl;
• each of said —(C1-C6) alkyl or —(C1-C6) alkylene in R1, R19 and R20 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• each of said —(C3-C7) cycloalkyl or —(C3-C7) heterocycloalkyl in in R15, R16, R17 or R18 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl, and —N—((C1-C6) alkyl)2;
• R1 and one of R10 or R11 from together a (C3-C7) heterocycloalkyl comprising at least one nitrogen atom;
• wherein said (C3-C7) heterocycloalkyl in R1 and R10 or R11 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• or
• R1 and R9 form together a (C3-C7) heterocycloalkyl comprising at least one nitrogen atom;
• wherein said (C3-C7) heterocycloalkyl in R1 and R9 is optionally substituted with at least one group selected from halogen, cyano, hydroxy, oxo, amino, —(C1-C6) alkyl, —CH2—O—(C1-C6) alkyl, —CH2—NH—(C1-C6) alkyl, —CH2—N—((C1-C6) alkyl)2, —O—(C1-C6) alkyl, —NH—(C1-C6) alkyl and —N—((C1-C6) alkyl)2;
• provided that
• when Y1 is quinazolinyl and R1 is hydrogen, then Z1 is not selected from —C(O)-methyl and —S(O)2-methyl;
• when Y1 is 1H-pyrazolo[3,4-d]pyrimidinyl and R1 is hydrogen, then Z1 is not selected from —C(O)-methyl, —C(O)-t-butyl and —SO2-methyl;
• and
• the compound of formula (I) is not N-(2-(5-(2-((5-methyloxazolo[4,5-b]pyridin-2-yl)thio)acetyl)thiophen-2-yl)ethyl)acetamide.