JNK inhibitors

A compound of formula (I) or a pharmaceutically acceptable salt thereof

• wherein R1 is an optionally substituted C3-12 carbocyclyl or C3-12 heterocyclyl group, Y is N or C and Z is lone electron pair, hydrogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C3-12 carbocyclyl, C3-12 heterocyclyl, (CH2)nOR2, (CH2)nNR22, CO2R2, COR2, CONR22, wherein the C1-12 alkyl group optionally contains one or more insertions selected from —O—, —N(R2) —S—, —S(O)— and —S(O2)—;
• and each substitutable nitrogen atom in Z is optionally substituted by R3, COR3, SO2R3 or CO2R3;
• wherein n is 1 to 6, preferably n is 1, 2 or 3;
• wherein R2 is hydrogen, C1-12 alkyl, C3-12 carbocyclyl, C3-12 heterocyclyl, C1-12alkylC3-12carbocyclyl or C1-12alkylC3-12heterocyclyl optionally substituted by one or more of C1-6 alkyl, halogen, C1-6 haloalkyl, OR4, SR4, NO2, CN, NR4R4, NR4COR4, NR4CONR4R4, NR4COR4, NR4CO2R4, CO2R4, COR4, CONR42, S(O)2R4, SONR42, S(O)R4, SO2NR4R4, NR4S(O)2R4, wherein the C1-12 alkyl group optionally incorporates one or two insertions selected from the group consisting of —O—, —N(R4)—, —S(O)— and —S(O2)—, wherein each R4 may be the same or different and is as defined below;
• wherein two R2 in NR22 may form a partially saturated, unsaturated or fully saturated five to seven membered ring containing one to three heteroatoms, optionally and independently substituted with one or more of halogen, C1-12 alkyl, C1-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C3-12 carbocyclyl, C3-12 heterocyclyl, OR5, SR5, NO2, CN, NR52, NR5COR5, NR5CONR52, NR5COR5, NR5CO2R5, CO2R5, COR5, CONR52, S(O)2R5, SONR52, S(O)R5, SO2NR52, or NR5S(O)2R5;
• and each saturated carbon in the optional ring is further optionally and independently substituted by ═O, ═S, NNR62, ═N—OR6, ═NNR6COR6, ═NNR6CO2R6, ═NNSO2R6, or ═NR6;
• wherein R3 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, or C6-12 aryl;
• wherein R4 is hydrogen, C1-6 alkyl, C1-6 haloalkyl or C6-12 aryl;
• wherein R5 is hydrogen, C1-12 alkyl, C3-12 carbocyclyl or C3-12 heterocyclyl, optionally substituted by one or more of C1-6 alkyl, halogen, C1-6 haloalkyl, OR7, SR7, NO2, CN, NR7R7, NR7COR7, NR7CONR7R7, NR7COR7, NR7CO2R7, CO2R7, COR7, CONR72, S(O)2R7, SONR72, S(O)R7, SO2NR7R7, NR7S(O)2R7, wherein the C1-12 alkyl group optionally incorporates one or two insertions selected from the group consisting of —O—, —N(R7)—, —S(O)— and —S(O2)—, wherein each R7 may be the same or different and is as defined below;
• wherein R6 is hydrogen, C1-12 alkyl, C3-12 carbocyclyl or C3-12 heterocyclyl, optionally substituted by one or more of C1-6 alkyl, halogen, C1-6 haloalkyl, OR7 SR7, NO2, CN, NR7R7, NR7COR7, NR7CONR7R7, NR7COR7, NR7CO2R7, CO2R7, COR7, CONR72, S(O)2R7, S(O)R7, SO2NR7R7, NR7S(O)2R7, wherein the C1-12 alkyl group optionally incorporates one or two insertions selected from the group consisting of —O—, —N(R7)—, —S(O)— and —S(O2)—, wherein each R7 may be the same or different and is as defined below;
• wherein R7 is hydrogen, C1-6 alkyl, or C1-6 haloalkyl;
• wherein the optionally substituted carbocyclyl or heterocyclyl group in R1 and Z is optionally and independently fused to a partially saturated, unsaturated or fully saturated five to seven membered ring containing zero to three heteroatoms, and each substitutable carbon atom in R1 or Z, including the optional fused ring, is optionally and independently substituted by one or more of halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C3-12 carbocyclyl, C3-12 heterocyclyl, (CH2)nOR12, (CH2)nNR122, OR12, SR12, NO2, CN, NR122, NR12COR12, NR12CONR122, NR12COR12, NR12CO2R12, CO2R12, COR12, CONR122, S(O)2R12, SONR122, S(O)R12, SO2NR122, or NR12S(O)2R12 wherein the C1-12 alkyl group optionally contains one or more insertions selected from —O—, —N(R12)— —S—, —S(O)— and —S(O2)—;
• and each saturated carbon in the optional fused ring is further optionally and independently substituted by ═O, ═S, NNR132, ═N—OR13, ═NNR13COR13, ═NNR13CO2R13, ═NNSO2R13, or ═NR13;
• and each substitutable nitrogen atom in R1 is optionally substituted by R14, COR14, SO2R14 or CO2R14;
• wherein n is 1 to 6, preferably n is 1, 2 or 3;
• wherein R12 is hydrogen , C1-12 alkyl, C3-12 carbocyclyl or C3-12 heterocyclyl, optionally substituted by one or more of C1-6 alkyl, halogen, C1-6 haloalkyl, OR15, SR15, NO2, CN, NR15R15, NR15COR15, NR15CONR15R15, NR15COR15, NR15CO2R15, CO2R15, COR15, CONR152, S(O)2R15, SONR152, S(O)R15, SO2NR15R15, NR15S(O)2R15, wherein the C1-12 alkyl group optionally incorporates one or two insertions selected from the group consisting of —O—, —N(R15)—, —S(O)— and —S(O2)—, wherein each R15 may be the same or different and is as defined below;
• wherein two R12 in NR122 may form a partially saturated, unsaturated or fully saturated five to seven membered ring containing one to three heteroatoms, optionally and independently substituted with one or more of halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C3-12 carbocyclyl, C3-12 heterocyclyl, OR16, SR16, NO2, CN, NR162, NR16COR16, NR16CONR162, NR16COR16, NR16CO2R16, CO2R16, COR16, CONR162, S(O)2R16, SONR162, S(O)R16, SO2NR162, or NR16S(O)2R16;
• and each saturated carbon in the optional ring is further optionally and independently substituted by ═O, ═S, NNR172, ═N—OR17, ═NNR17COR17, ═NNR17CO2R17, ═NNSO2R17, or ═NR17;
• wherein R13 is hydrogen, C1-12 alkyl, C3-12 carbocyclyl or C3-12 heterocyclyl, optionally substituted by one or more of C1-6 alkyl, halogen, C1-6 haloalkyl, OR15 SR15, NO2, CN, NR15R15, NR15COR15, NR15CONR15R15, NR15COR15, NR15CO2R15, CO2R15, COR15, CONR152,S(O)2R15, S(O)R15, SO2NR15R15, NR15S(O)2R15, wherein the C1-12 alkyl group optionally incorporates one or two insertions selected from the group consisting of —O—, —N(R15)—, —S (O)— and —S(O2)—,
• wherein each R15 may be the same or different and is as defined below;
• wherein R14 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, or C6-12 aryl;
• wherein R15 is hydrogen, C1-6 alkyl, or C1-6 haloalkyl;
• wherein R16 is hydrogen, C1-12 alkyl, C3-12 carbocyclyl or C3-12 heterocyclyl, optionally substituted by one or more of C1-6 alkyl, halogen, C1-6 haloalkyl, OR18, SR18, NO2, CN, NR18R18, NR18COR18, NR18CONR18R18, NR18COR18, NR18CO2R18, CO2R18, COR18, CONR182, S(O)2R18, SONR182, S(O)R18, SO2NR18R18, NR18S(O)2R18, wherein the C1-12 alkyl group optionally incorporates one or two insertions selected from the group consisting of —O—, —N(R18)—, —S(O)— and —S(O2)—, wherein each R18 may be the same or different and is as defined below;
• wherein R17 is hydrogen, C1-12 alkyl, C3-12 carbocyclyl or C3-12 heterocyclyl, optionally substituted by one or more of C1-6 alkyl, halogen, C1-6 haloalkyl, OR18, SR18, NO2, CN, NR18R18, NR18COR18, NR18CONR18R18, NR18COR18, NR18CO2R18, CO2R18, COR18, CONR182, S(O)2R18, S(O)R18, SO2NR18R18, NR18S(O)2R18, wherein the C1-12 alkyl group optionally incorporates one or two insertions selected from the group consisting of —O—, —N(R18)—, —S(O)— and —S(O2)—,
• wherein each R18 may be the same or different and is as defined below;
• and
• wherein R18 is hydrogen, C1-6 alkyl, or C1-6 haloalkyl.