| CPC C07D 401/14 (2013.01) [C07D 405/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01)] | 10 Claims |
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1. A compound of formula (I)
 wherein
R1 is selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, cyano, nitro, —NRARB, —C(O)—C1-4alkyl, C3-6cycloalkyl, phenyl and 5 to 6 membered heterocyclyl;
wherein the C3-6cycloalkyl, phenyl or 5 to 6 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, cyano, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, —C(O)OH, —C(O)O—(C1-4alkyl), —NRARB, —(C1-4alkyl)-NRARB, C3-7cycloalkyl and 5 to 6 membered heterocyclyl; and
wherein RA and RB are each independently selected from the group consisting of hydrogen and C1-4alkyl;
a is an integer from 0 to 3;
each R2 is independently selected from the group consisting of chloro, fluoro, methyl and methoxy;
R3 is selected from the group consisting of hydrogen, fluoro, chloro and methyl;
R4 is 5 membered heterocyclyl; wherein the 5 membered heterocyclyl contains at least one heteroatom selected from the group consisting of O, N and S; optionally contains 1 to 3 additional heteroatoms independently selected from the group consisting of O, N and S; wherein the 5 membered heterocyclyl is saturated, partially unsaturated, or aromatic;
and wherein the 5 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, C3-7cycloalkyl, —C(O)OH, —C(O)—O—C1-4alkyl, —C1-2alkyl-C(O)—O—C1-4alkyl, cyano, —NRERF, —C(O)—NRERF, pyrrolidin-2-yl-5-one, pyrrolidin-3-yl-2,5-dione, pyrrol-3-yl-2,5-dione, 1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-5-yl, 1,2,4-oxadiazol-3-yl-5-one, oxazolidin-5-yl-2,4-dione, 1H-imidazol-5-yl-2,5-dione, thiazol-5-yl-2,4-dione, isoxazol-5-yl-3-ol, isothiazol-5-yl-3-ol, 3-chloro-4-hydroxy-phenyl, —C(O)—NH—CN, —C(O)—NH—SO2—CH3, —SO2—NH—CF3, and —SO2—NH—CF2CF3;
wherein RE is selected from the group consisting of hydrogen, C1-4alkyl, cyclopropyl, 3-hydroxy-cycloprop-1-yl, —C(O)—C1-4alkyl, —C(O)-cyclopropyl, —C(O)—O—C1-4alkyl and —SO2—C1-4alkyl; and
RF is selected from the group consisting of hydrogen and C1-4alkyl;
R5 is selected from the group consisting of
(a) C1-4alkyl; wherein the C1-4alkyl is optionally substituted with one or more halogen, and further optionally substituted with a substituent selected from the group consisting of hydroxy, C1-4alkoxy, fluorinated C1-4alkoxy, —C(O)OH, —C(O)—O—(C1-4alkyl), —C(O)—O-(fluorinated C1-4alkyl), —C(O)-(fluorinated C1-4alkyl), and —C(O)—NRLRM; wherein RL and RM are each independently selected from the group consisting of hydrogen and C1-2alkyl;
(b) —CH2—C3-8cycloalkyl or —CH2-adamant-1-yl; wherein the C3-8cycloalkyl is optionally substituted with one or more halogen or C1-4alkyl; and further optionally substituted with a substituent selected from the group consisting of —C(O)OH, —C(O)—O—C1-4alkyl, —C(O)-(5 to 6 membered saturated heterocyclyl), —C(O)-(isoindolin-2-yl), —C(O)-(azaspiro[2.4]heptan-5-yl), —C(O)-(carboxy substituted azaspiro[2.4]heptan-5-yl), —C(O)—(NRPRQ substituted azaspiro[2.4]heptan-5-yl), phenyl, 1,1′-biphen-4-yl and —C(O)—NRPRQ;
wherein the —C(O)-(5 to 6 membered saturated heterocyclyl) substituent on the —CH2—C3-8cycloalkyl is further optionally substituted on the (5 to 6 membered heterocyclyl) with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, cyano, —C(O)OH, —C(O)—O—C1-4alkyl, —NRPRQ, phenyl and C3-8cycloalkyl;
wherein the phenyl substituent on the —CH2—C3-8cycloalkyl is further optionally substituted with one or more substituents independently selected form the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, cyano, —NRPRQ, and C3-8cycloalkyl;
and wherein RP and RQ are each independently selected from the group consisting of hydrogen and C1-4alkyl;
(c) -L1-(5 to 6 membered saturated heterocyclyl); wherein L1 is selected from the group consisting of —CH2— and —CH2—C(O)—; wherein, when L1 is —CH2—C(O)—, then the (5 to 6 membered saturated heterocyclyl) is bound to the —C(O)— portion of L1; - and wherein the (5 to 6 membered saturated heterocyclyl) is optionally substituted with one to two oxo group;
(d) —C1-2alkyl-phenyl; wherein the phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, —OCH2—C(O)—NRSRT, phenyl and phenoxy; and
wherein RS and RT are each independently selected from the group consisting of hydrogen and C1-4alkyl;
(e) 1,2,3-triazol-4-yl, 1,2,5-triazol-3-yl, —CH2-1,2,3-triazol-4-yl and —CH2-1,2,5-triazol-3-yl;
wherein the 1,2,3-triazol-4-yl or 1,2,5-triazoly-3-yl, whether alone or as part of the substituent group is optionally substituted with a substituent selected from the group consisting of C1-4alkyl, fluorinated C1-4alkyl, phenyl and piperidinyl; wherein the piperidinyl is optionally substituted with —C(O)—C1-4alkyl;
(f) —CH2-(5 to 6 membered or 9 to 10 membered heterocyclyl); wherein the (5 to 6 membered or 9 to 10 membered heterocyclyl) is other than triazolyl;
wherein the (5 to 6 membered or 9 to 10 membered heterocyclyl) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, cyano, —C(O)OH, —C(O)—O—C1-4alkyl, —C1-2alkyl-O—C1-4alkyl, —C1-2alkyl-O-(fluorinated C1-4alkyl), —C(O)—NRVRW, —C1-2alkyl-C(O)—NRVRW, -(5 to 6 membered saturated heterocyclyl), —C(O)-(5 to 6 membered saturated heterocyclyl), —C(O)-(carboxy substituted 5 to 6 membered saturated heterocyclyl), —C1-2alkyl-C(O)-(5 to 6 membered saturated heterocyclyl), phenyl and pyridinyl;
wherein the pyridinyl substituent on the —CH2-(5 to 6 membered or 9 to 10 membered heterocyclyl) is further optionally substituted with one or more substituents independently selected from the group consisting of halogen and fluorinated C1-4alkyl;
and wherein RV and RW are each independently selected from the group consisting of hydrogen and C1-4alkyl;
and (g) —CH2—NR8R9; wherein R8 is selected from the group consisting of hydrogen and C1-4alkyl; R9 is selected from the group consisting of C1-4alkyl, fluorinated C1-4alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, —C(O)—C1-4alkyl, —C(O)—C1-2alkyl-O—C1-4alkyl, —C(O)-phenyl, —C(O)—C1-2alkyl-phenyl, —C(O)—O—C1-4alkyl, —C(O)—O-phenyl, —C(O)—O—C1-2alkyl-phenyl, —C(O)—C3-7cycloalkyl, —C(O)-(1-methyl-cycloprop-1-yl), —C(O)-(5 to 6 membered saturated heterocyclyl), —C(O)—C1-2alkyl-C(O)-(5 to 6 membered saturated heterocyclyl), —O—C1-2alkyl-C(O)-(5 to 6 membered saturated heterocyclyl), —C(O)-(1-methyl-pyridinyl-one) and —C(O)—NRXRY; and
wherein RX and RY are each independently selected from the group consisting of hydrogen and C1-4alkyl;
R6 and R7 are each independently selected from the group consisting of hydrogen, halogen, C1-4alkyl and C1-4alkoxy;
provided that at least one of R6 or R7 is hydrogen;
or a stereoisomer, isotopologue, isotopomer, or pharmaceutically acceptable salt or solvate thereof.
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