发明名称 sGC STIMULATORS
摘要 Compounds of Formula I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.;
申请公布号 US2015274712(A1) 申请公布日期 2015.10.01
申请号 US201314428844 申请日期 2013.09.18
申请人 IM G-Yoon Jamie;IYENGAR Rajesh;MOORE Joel;FRETZEN Angelika 发明人 Im G-Yoon Jamie;Iyengar Rajesh;Moore Joel;Fretzen Angelika
分类号 C07D413/14;A61K31/506;A61K31/513 主分类号 C07D413/14
代理机构 代理人
主权项 1. A compound according to Formula I, or a pharmaceutically acceptable salt thereof, wherein: ring B is a 5-membered heteroaryl ring selected from furan or thiophene; n is an integer selected from 0 to 3; each JB is independently selected from halogen, —CN, a C1-6 aliphatic, —ORB or a C3-8 cycloaliphatic group; wherein each said C1-6 aliphatic and each said C3-8 cycloaliphatic group is optionally and independently substituted with up to 3 instances of R3; each RB is independently selected from hydrogen, a C1-6 aliphatic or a C3-8 cycloaliphatic ring; wherein each said C1-6 aliphatic and each said C3-8 cycloaliphatic ring is optionally and independently substituted with up to 3 instances of R3a; each R3 is independently selected from halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4haloalkyl); each R3a is independently selected from halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4haloalkyl); X is selected from N, C-JD or C—H; o is an integer selected from 0 to 3; each JD is independently selected from halogen, —NO2, —ORD, —SRD, —C(O)RD, —C(O)ORD, —C(O)N(RD)2, —CN, —N(RD)2, —N(Rd)C(O)RD, —N(Rd)C(O)ORD, —SO2RD, —SO2N(RD)2, —N(Rd)SO2RD, a C1-6 aliphatic, —(C1-6 aliphatic)-RD, a C3-8 cycloaliphatic ring, a 6 to 10-membered aryl ring, a 4 to 8-membered heterocyclic ring or a 5 to 10-membered heteroaryl ring; wherein each said 4 to 8-membered heterocylic ring and each said 5 to 10-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C1-6 aliphatic, each said C34 cycloaliphatic ring, each said 6 to 10-membered aryl ring, each said 4 to 8-membered heterocyclic ring and each said 5 to 10-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R5; each RD is independently selected from hydrogen, a C1-6 aliphatic, —(C1-6 aliphatic)-Rf, a C3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said 4 to 8-membered heterocylic ring and each said 5 to 6-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C1-6 aliphatic, each said C3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R5a; each Rd is independently selected from hydrogen, a C1-6 aliphatic, —(C1-6 aliphatic)-Rf, a C3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said heterocylic ring and each said heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C1-6 aliphatic, each said C3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R5b; each Rf is independently selected from a C3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said heterocylic ring and each said heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C1-6 aliphatic, each said C3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R5c; when JD is —C(O)N(RD)2, —N(RD)2 or —SO2N(RD)2, the two instances of RD together with the nitrogen atom attached to the RD, alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R5; or when JD is —N(Rd)C(O)RD, the RD group together with the carbon atom attached to the RD group, with the nitrogen atom attached to the Rd group and with the Rd group alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R5; when JD is —N(Rd)C(O)ORD, the RD group together with the oxygen atom attached to the RD group, with the carbon atom of the —C(O)— portion of the —N(Rd)C(O)ORD group, with the nitrogen atom attached to the Rd group, and with the Rd group alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R5; when JD is —N(Rd)SO2RD, the RD group together with the oxygen atom attached to the RD group, with the sulfur atom attached to said oxygen atom in the —SO2RD portion of the —N(Rd)SO2RD group, with the nitrogen atom attached to the Rd group, and with the Rd group alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R5; each R5 is independently selected from halogen, —CN, —NO2, C1-4 alkyl, a C7-12 aralkyl, C3-8 cycloalkyl ring, C1-4 haloalkyl, C1-4 cyanoalkyl, —OR6, —SR6, —OCOR6, —COR6, —C(O)OR6, —C(O)N(R6)2, —N(R6)C(O)R6, —N(R6)2, —SO2R6, —SO2N(R6)2, —N(R6)SO2R6, phenyl or an oxo group; wherein each said phenyl group is optionally and independently substituted with up to 3 instances of halogen, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —NO2, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4haloalkyl); and wherein each said C7-12 aralkyl and each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; each R5a is independently selected from halogen, —CN, —NO2, C1-4 alkyl, a C7-12 aralkyl, C3-8 cycloalkyl ring, C1-4 haloalkyl, C1-4 cyanoalkyl, —OR6, —SR6, —OCOR6, —COR6, —C(O)OR6, —C(O)N(R6)2, —N(R6)C(O)R6, —N(R6)2, —SO2R6, —SO2N(R6)2, —N(R6)SO2R6, phenyl or an oxo group; wherein each said phenyl group is optionally and independently substituted with up to 3 instances of halogen, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —NO2, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4 haloalkyl); and wherein each said C7-12 aralkyl and each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; each R5b is independently selected from halogen, —CN, —NO2, C1-4 alkyl, a C7-12 aralkyl, C3-8 cycloalkyl ring, C1-4 haloalkyl, C1-4 cyanoalkyl, —OR6, —SR6, —OCOR6, —COR6, —C(O)OR6, —C(O)N(R6)2, —N(R6)C(O)R6, —N(R6)2, —SO2R6, —SO2N(R6)2, —N(R6)SO2R6, phenyl or an oxo group; wherein each said phenyl group is optionally and independently substituted with up to 3 instances of halogen, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —NO2, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4 haloalkyl); and wherein each said C7-12 aralkyl and each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; each R5c is independently selected from halogen, —CN, —NO2, C1-4 alkyl, a C7-12 aralkyl, C3-8 cycloalkyl ring, C1-4 haloalkyl, C1-4 cyanoalkyl, —OR6, —SR6, —OCOR6, —COR6, —C(O)OR6, —C(O)N(R6)2, —N(R6)C(O)R6, —N(R6)2, —SO2R6, —SO2N(R6)2, —N(R6)SO2R6, phenyl or an oxo group; wherein each said phenyl group is optionally and independently substituted with up to 3 instances of halogen, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —NO2, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4haloalkyl); and wherein each said C7-12 aralkyl and each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; each R6 is independently selected from hydrogen, a C1-4 alkyl, a C2-4 alkenyl, phenyl, a C7-12 aralkyl or a C3-8 cycloalkyl ring; wherein each said C1-4 alkyl, each said C2-4 alkenyl, each said phenyl, each said C7-12 aralkyl and each said C3-8 cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; alternatively, two instances of R6 linked to the same nitrogen atom of R5, together with said nitrogen atom of R5, form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S; or alternatively, one instance of R6 linked to a nitrogen atom of R5 and one instance of R6 linked to a carbon or sulfur atom of the same R5, together with said nitrogen and said carbon or sulfur atom of the same R5, form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S; or, alternatively, two JD groups attached to two vicinal ring D atoms, taken together with said two vicinal ring D atoms, form a 5 to 7-membered heterocycle resulting in a fused ring D wherein said 5 to 7-membered heterocycle contains from 1 to 3 heteroatoms independently selected from N, O or S; and wherein said 5 to 7-membered heterocycle is optionally and independently substituted by up to 3 instances of halogen, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl), —O(C1-4 haloalkyl), oxo or phenyl; wherein said phenyl is optionally and independently substituted by up to three instances of halogen, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —NO2, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4 haloalkyl); RC is a ring C; ring C is a phenyl ring, a monocyclic 5 or 6-membered heteroaryl ring, a bicyclic 8 to 10-membered heteroaryl ring, a monocyclic 3 to 10-membered cycloaliphatic ring, or a monocyclic 4 to 10-membered heterocycle; wherein said monocyclic 5 or 6-membered heteroaryl ring, said bicyclic 8 to 10-membered heteroaryl ring, or said monocyclic 4 to 10-membered heterocycle contain between 1 and 4 heteroatoms selected from N, O or S; wherein said monocyclic 5 or 6-membered heteroaryl ring is not a 1,3,5-triazinyl ring; and wherein said phenyl, monocyclic 5 to 6-membered heteroaryl ring, bicyclic 8 to 10-membered heteroaryl ring, or monocyclic 4 to 10-membered heterocycle is optionally and independently substituted with up to 3 instances of JC; each JC is independently selected from halogen, —CN, —NO2, a C1-6 aliphatic, —ORH, —SRH, —N(RH)2, a C3-8 cycloaliphatic ring or a 4 to 8-membered heterocyclic ring; wherein said 4 to 8-membered heterocyclic ring contains 1 or 2 heteroatoms independently selected from N, O or S; wherein each said C1-6 aliphatic, each said C3-8 cycloaliphatic ring and each said 4 to 8-membered heterocyclic ring, is optionally and independently substituted with up to 3 instances of R7; or alternatively, two f groups attached to two vicinal ring C atoms, taken together with said two vicinal ring C atoms, form a 5 to 7-membered heterocycle resulting in a fused ring C; wherein said 5 to 7-membered heterocycle contains from 1 to 2 heteroatoms independently selected from N, O or S; each RH is independently selected from hydrogen, a C1-6 aliphatic, a C3-8 cycloaliphatic ring or a 4 to 8-membered heterocyclic ring; wherein each said 4 to 8-membered heterocylic ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C1-6 aliphatic, each said C3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, is optionally and independently substituted with up to 3 instances of R7a; alternatively, two instances of RH linked to the same nitrogen atom of JC, together with said nitrogen atom of JC, form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R7b; or each R7 is independently selected from halogen, —CN, —NO2, C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl ring, —OR8, —SR8, —N(R8)2, or an oxo group; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; each R7a is independently selected from halogen, —CN, —NO2, C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl ring, —OR8, —SR8, —N(R8)2, or an oxo group; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; each R7b is independently selected from halogen, —CN, —NO2, C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl ring, —OR8, —SR8, —N(R8)2, or an oxo group; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; each R8 is independently selected from hydrogen, a C1-4 alkyl, C1-4 haloalkyl or a C3-8 cycloalkyl ring; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen; alternatively, two instances of R8 linked to the same nitrogen atom of R7, together with said nitrogen atom of R7, form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S; and RA is selected from hydrogen, halogen, C1-4 alkyl or C1-4 haloalkyl.
地址 Cambridge MA US