发明名称 SUBSTITUTED PYRAZOLES AND USES THEREOF
摘要 The present invention provides for compounds of formula 0 and various embodiments thereof, and compositions comprising compounds of formula 0 and various embodiments thereof.;;In compounds of formula 0, the groups R1A, R1B, R1C, R1D, R2, R3, R4, R5 and R6 have the meaning as described herein. The present invention also provides for methods of using compounds of formula 0 and compositions comprising compounds of formula 0 as DLK inhibitors and for treating neurodegeneration diseases and disorders.
申请公布号 US2015175619(A1) 申请公布日期 2015.06.25
申请号 US201414576890 申请日期 2014.12.19
申请人 Genentech, Inc. 发明人 Siu Michael;Estrada Anthony;Liu Wen;Lyssikatos Joseph P.;Patel Snahel;Liang Guibai;Chen Kevin
分类号 C07D491/107;C07D401/04;C07D491/08;C07D471/04;C07D401/14;C07D413/14;C07D407/14 主分类号 C07D491/107
代理机构 代理人
主权项 1. A compound of formula 0:and salts thereof; wherein in formula 0 R1A is selected from the group consisting of H, —F, —Cl, a 3 to 12 membered heterocycloalkyl, 5 or 6 membered) heteroaryl, —(X1A)0-1—OR1A-1, —(X1A)0-1—SR1A-1, —(X1A)0-1—S(O)R1A-1, —(X1A)0-1—S(O)2R1A-1 and —(X1A)0-1—N(R1A-1)2, each X1A is independently selected from the group consisting of C1-4 alkylene, C1-4 haloalkylene, C1-4 heteroalkylene, C2-4 alkenylene and C2-4 alkynylene, R1A-1 at each occurrence is each independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, 3-7 membered cycloalkyl, 3-7 membered cycloalkyl-C1-4 alkyl-, 3-7 membered heterocycloalkyl, 3-7 membered heterocycloalkyl-C1-4 alkyl-, 5-6 membered heteroaryl, 5-6 membered heteroaryl-C1-4 alkyl-, phenyl and phenyl-C1-4 alkyl-, or any two R1A-1 groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring optionally comprising 1 to 2 additional heteroatom selected from N, O and S, and wherein a R1A group at each occurrence is independently optionally further substituted with 1 to 5 R1A-2 substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO2, —SF5, —NH2, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, oxo, —S(═O)1-2—C1-6 alkyl and 3 to 7 membered heterocycloalkyl; R1B is selected from the group consisting of H, —OH, —F, —Cl, —Br, —I, —CN, —NH2, —N(CH3)C(O)CH3, C1-6 alkylamino, C1-6 dialkylamino, C1-6 alkoxy, C1-6 alkyl, C1-6 haloalkyl and C1-6 heteroalkyl; or R1A and R1B together form an oxo group or a 3 to 7 membered heterocycloalkyl comprising 1 to 2 heteroatoms selected from N, O and S and wherein said 3 to 7 membered heterocycloalkyl is optionally further substituted with 1 to 5 R1A-2 substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO2, —SF5, —NH2, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, oxo, —S(═O)1-2—C1-6 alkyl and 3 to 7 membered heterocycloalkyl; R1C at each occurrence is independently selected from the group consisting of hydrogen, —F, —Cl, —Br, —I, C1-4 alkyl and C1-4 haloalkyl; R1D at each occurrence is independently selected from the group consisting of hydrogen, —F, —Cl, —Br, —I, —OH, C1-4 alkyl, C1-4 haloalkyl, 3 to 7 membered heterocycloalkyl; or R1A and R1D together form a 3-7 membered cycloalkyl or 3-7 membered heterocycloalkyl, each optionally substituted by C1-4 alkyl; R2 is selected from the group consisting of hydrogen, —F, —Cl, —Br, —I, —NO2, —CN, C1-6 alkyl and C1-6 haloalkyl; R3 is N(R3A)2, wherein each R3A is independently selected from the group consisting of hydrogen, C1-6 alkyl, and C1-6 haloalkyl; R4 is selected from the group consisting of C1-12 alkyl, C1-12 haloalkyl, C2-12 alkenyl, C2-12 alkynyl, —F, —Cl, —Br, —I, —(X4)0-1—CN, —(X4)0-1—NO2, —(X4)0-1—SF5, —(X4)0-1—OSF5, —(X4)0-1—OR4A, —(X4)0-1—N(R4A)2, —(X4)0-1—SR4A, —(X4)0-1—CF3, 3 to 7 membered cycloalkyl-(X4)0-1—, 3 to 7 membered heterocycloalkyl-(X4)0-1—, 5 to 6 membered heteroaryl-(X4)0-1—, phenyl-(X4)0-1—, —(X4)0-1—C(═O)N(R4A)(R4A), —(X4)0-1—C(═O)OR4A, —(X4)0-1—N(R4A)C(═O)(R4A), —(X4)0-1—N(R4A)C(═O)OR4A, —(X4)0-1—S(═O)1-2—R4A, —(X4)0-1—N(R4A)S(═O)1-2—R4A, —(X4)0-1—S(═O)1-2N(R4A)2, —(X4)0-1—C(═O)R4A, —(X4)0-1—C(═NOR4A)R4A, —(X4)0-1—N(R4A)C(═O)N(R4A)2, —(X4)0-1—OC(═O)R4A, —(X4)0-1—OP(═O)(OR4A)2, —(X4)—SC(═O)OR4A and —(X4)—SC(═O)N(R4A)2, each X4 is independently selected from the group consisting of C1-4 alkylene, C1-4 haloalkylene, C1-4 heteroalkylene, C2-4 alkenylene and C2-4 alkynylene, R4A at each occurrence is each independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl and C1-6 heteroalkyl, or any two R4A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring optionally comprising 1 to 2 additional heteroatoms selected from N, O and S, and wherein a R4 group is independently optionally further substituted with 1 to 5 R4A-1 substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO2, —SF5, —NH2, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkyl and C1-6 dialkylamino; or R3 and R4 together with the atoms to which they are attached form a 5 or 6 membered heteroaryl wherein the 5 or 6 membered heteroaryl is optionally substituted with 1 to 3 R3/4cy substituents selected from the group consisting of C1-12 alkyl, C1-12 haloalkyl, C2-12 alkenyl, C2-12 alkynyl, —F, —Cl, —Br, —I, —(X3/4)0-1—CN, —(X3/4)0-1—NO2, —(X3/4)0-1—SF5, —(X3/4)0-1—OSF5, —(X3/4)0-1—OR3/4A, —(X3/4)0-1—N(R3/4A)2, —(X3/4)0-1—SR3/4A, —(X3/4)0-1—CF3, 3 to 12 membered cycloalkyl-(X3/4)0-1-, 3 to 12 membered heterocycloalkyl-(X3/4)0-1—, 5 to 6 membered heteroaryl-(X3/4)0-1—, phenyl-(X3/4)0-1—, —(X3/4)0-1—C(═O)N(R3/4A)(R3/4A), —(X3/4)0-1—C(═O)OR3/4A, —(X3/4)0-1—N(R3/4A)C(═O)(R3/4A), —(X3/4)0-1—N(R3/4A)C(═O)OR3/4A, —(X3/4)0-1—S(═O)1-2—R3/4A, —(X3/4)0-1—N(R3/4A)S(═O)1-2—R3/4A, —(X3/4)0-1—S(═O)1-2N(R3/4A)2, —(X3/4)0-1—C(═O)R3/4A, —(X3/4)0-1—C(═NOR3/4A)R3/4A, —(X3/4)0-1—N(R3/4A)C(═O)N(R3/4A)2 and —(X3/4)0-1—OC(═O)R3/4A, —(X3/4)0-1—OP(═O)(OR3/4A)2, —(X3/4)—SC(═O)OR3/4A and (X3/4)—SC(═O)N(R3/4A)2, each X3/4 is independently selected from the group consisting of C1-4 alkylene, C1-4 haloalkylene, C1-4 heteroalkylene, C2-4 alkenylene and C2-4 alkynylene, R3/4A at each occurrence is each independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl and C1-6 heteroalkyl, or any two R3/4A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring optionally comprising 1 to 2 additional heteroatom selected from N, O and S, and wherein a R3/4cy substituent at each occurrence is independently optionally further substituted with 1 to 5 R3/4cy-1 substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO2, —SF5, —NH2, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkyl and C1-6 dialkylamino; R5 is hydrogen, —F, —Cl, —Br or —I; and R6 is selected from the group consisting of C1-12 alkyl, C1-12 haloalkyl, C1-12 heteroalkyl-(L)0-1-, C2-12 alkenyl-(L)0-1-, C2-12 alkynyl-(L)0-1-, 3 to 12 membered cycloalkyl-(L)0-1- and 3 to 12 membered heterocycloalkyl-(L)0-1-, wherein L is selected from the group consisting of C1-4 alkylene, C1-4 haloalkylene, C1-4 heteroalkylene, C2-4 alkenylene and C2-4 alkynylene, wherein a R6 group is optionally further substituted with 1 to 5 R6A substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO2, —SF5, —OSF5, —NH2, C1-6 alkyl, C1-6 haloalkyl, 3 to 5 membered cycloalkyl, 3 to 5 membered heterocycloalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylamino and C1-6 dialkylamino.
地址 South San Francisco CA US