发明名称 CERTAIN AMINO-PYRIDAZINES, COMPOSITIONS THEREOF, AND METHODS FOR THEIR USE
摘要 Provided are compounds of Formula I:;;or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X and m are as defined herein.;Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof.;Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.
申请公布号 US2015322018(A1) 申请公布日期 2015.11.12
申请号 US201514594274 申请日期 2015.01.12
申请人 Ashcraft Luke W.;Bergnes Gustave;Collibee Scott;Chuang Chihyuan;Gardina Jeff;Morgan Bradley P.;Muci Alex R.;Qian Xiangping;Warrington Jeffrey;Yang Zhe;Lu Pu-Ping;Romero Antonio 发明人 Ashcraft Luke W.;Bergnes Gustave;Collibee Scott;Chuang Chihyuan;Gardina Jeff;Morgan Bradley P.;Muci Alex R.;Qian Xiangping;Warrington Jeffrey;Yang Zhe;Lu Pu-Ping;Romero Antonio
分类号 C07D237/20;C07D413/04;C07D401/12;C07D513/04;C07D401/14;C07D417/14;C07D409/14;C07D403/04;C07D401/04 主分类号 C07D237/20
代理机构 代理人
主权项 1. A compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from hydrogen, halogen, CN, C1-6 alkyl, C1-6 haloalkyl, C(O)ORa, C(O)NRbRc, ORa, NRbRc, C6-10 aryl and 5-10 membered heteroaryl; R2 is selected from C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, 5-10 membered heteroaryl and NRbRc, wherein each of the C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen, CN, oxo, (CH2)nORa, (CH2)nOC(O)Ra, (CH2)nOC(O)ORa, (CH2)nOC(O)NRbRc, (CH2)nNRbRc, (CH2)nNRdC(O)Ra, (CH2)nNRdC(O)ORa, (CH2)nNRdC(O)NRbRc, (CH2)nNRdC(O)C(O)NRbRc, (CH2)nNRdC(S)Ra, (CH2)nNRdC(S)ORa, (CH2)nNRdC(S)NRbRc, (CH2)nNRdC(NRe)NRbRc, (CH2)nNRdS(O)Ra, (CH2)nNRdSO2Ra, (CH2)nNRdSO2NRbRc, (CH2)nC(O)Ra, (CH2)nC(O)ORa, (CH2)nC(O)NRbRc, (CH2)nC(S)Ra, (CH2)nC(S)ORa, (CH2)nC(S)NRbRc, (CH2)nC(NRe)NRbRc, (CH2)nSRa, (CH2)nS(O)Ra, (CH2)nSO2Ra, (CH2)nSO2NRbRc, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)nC3-8 cycloalkyl, (CH2)n3-8 membered heterocycloalkyl, (CH2)nC6-10 aryl and (CH2)n5-10 membered heteroaryl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)nC3-8 cycloalkyl, (CH2)n3-8 membered heterocycloalkyl, (CH2)nC6-10 aryl and (CH2)n5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 Rf substituents; R3 is selected from hydrogen, halogen, CN, C1-6 alkyl, C1-6 haloalkyl, C(O)ORa, C(O)NRbRc, ORa, NRbRc, C6-10 aryl and 5-10 membered heteroaryl; R4 is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C(O)Ra, C(O)ORa, C(O)NRbRc and SO2Ra; R5 and R6 are each independently C1-6 alkyl; R7 is selected from C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl and 5-10 membered heteroaryl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen, ON, oxo, ORa, OC(O)Ra, OC(O)ORa, OC(O)NRbRc, NRbRc, NRdC(O)Ra, NRdC(O)ORa, NRdC(O)NRbRc, NRdC(O)C(O)NRbRc, NRdC(S)Ra, NRdC(S)ORa, NRdC(S)NRbRc, NRdC(NRe)NRbRc, NRdS(O)Ra, NRdSO2Ra, NRdSO2NRbRc, C(O)Ra, C(O)ORa, C(O)NRbRc, C(S)Ra, C(S)ORa, C(S)NRbRc, C(NRe)NRbRc, SRa, S(O)Ra, SO2Ra, SO2NRbRc, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 Rf substituents; R8 and R9, at each occurrence, are each independently selected from hydrogen, halogen and C1-6 alkyl; X is selected from a bond, —(CH2)p—, —(CH2)pC(O)(CH2)q—, —(CH2)pO(CH2)q—, —(CH2)pS(CH2)q—, —(CH2)pNRd(CH2)q—, —(CH2)pC(O)O(CH2)q—, —(CH2)pOC(O)(CH2)q—, —(CH2)pNRdC(O)(CH2)q—, —(CH2)pC(O)NRd(CH2)q—, —(CH2)pNRdC(O)NRd(CH2)q—, —(CH2)pNRdSO2(CH2)q—, and —(CH2)pSO2NRd(CH2)q—; or alternatively, X, R2 and R3, together with the carbon atoms to which they are bound, form a 5-6 membered ring optionally containing one or more heteroatoms selected from oxygen nitrogen and sulfur, and optionally containing one or more double bonds, and optionally substituted with 1, 2, 3, 4 or 5 Rf substituents; Ra, at each occurrence, is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 Rf substituents; Rb and Rc, at each occurrence, are each independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl, 5-10 membered heteroaryl, C(O)Rg, C(O)ORg, C(O)NRiRj and SO2Rg, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 Rf substituents; Rd, at each occurrence, is independently selected from hydrogen and C1-6 alkyl; Re, at each occurrence, is independently selected from hydrogen, CN, OH, C1-6 alkoxy, C1-6 alkyl and C1-6 haloalkyl; Rf, at each occurrence, is independently selected from halogen, CN, ORh, OC(O)Rh, OC(O)ORh, OC(O)NRiRj, NRiRj, NRdC(O)Rh, NRdC(O)ORh, NRdC(O)NRiRj, NRdC(O)C(O)NRiRj, NRdC(S)Rh, NRdC(S)ORh, NRdC(S)NRiR, NRdC(NRe)NRiRj, NRdS(O)Rh, NRdSO2Rh, NRdSO2NRiRj, C(O)Rh, C(O)ORh, C(O)NRiRj, C(S)Rh, C(S)ORh, C(S)NRiR, C(NRe)NRiR, SRh, S(O)Rh, SO2Rh, SO2NRiR, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 Rk substituents; or two Rf substituents bound to a single carbon atom, together with the carbon atom to which they are both bound, form a group selected from carbonyl, C3-8 cycloalkyl and 3-8 membered heterocycloalkyl; Rg, at each occurrence, is independently selected from C1-6 alkyl, C1-6 haloalkyl, phenyl, naphthyl, and C7-11 aralkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-6 alkoxy, C1-6 alkyl and C1-6 haloalkyl; Rh, at each occurrence, is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 Rk substituents; Ri and Rj, at each occurrence, are each independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl, 5-10 membered heteroaryl, C(O)Rg, and C(O)ORg, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C6-10 aryl, C7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-6 alkoxy, C1-6 alkyl and C1-6 haloalkyl; Rk, at each occurrence, is independently selected from halogen, CN, OH, C1-6 alkoxy, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NHC(O)C1-6 alkyl, NHC(O)C7-11 aralkyl, NHC(O)OC1-6 alkyl, NHC(O)OC7-11 aralkyl, OC(O)C1-6 alkyl, OC(O)C7-11 aralkyl, OC(O)OC1-6 alkyl, OC(O)OC7-11 aralkyl, C(O)C1-6 alkyl, C(O)C7-11 aralkyl, C(O)OC1-6 alkyl, C(O)OC7-11 aralkyl, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C7-11 aralkyl substituent is optionally substituted with 1, 2 or 3 substituents selected from OH, C1-6 alkoxy, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NHC(O)C1-6 alkyl, NHC(O)C7-11 aralkyl, NHC(O)OC1-6 alkyl, and NHC(O)OC7-11 aralkyl; or two Rk substituents bound to a single carbon atom, together with the carbon atom to which they are both bound, form a carbonyl group; m is 0, 1 or 2; n, at each occurrence, independently is 0, 1 or 2; p is 0, 1 or 2; and q is 0, 1 or 2; provided the compound is not 6-(4-chlorophenyl)-5-methyl-N-(2-methyl-2-(piperidin-1-yl)propyl)pyridazin-3-amine, N-(2-methyl-2-(piperidin-1-yl)propyl)-6-phenyl-5-propylpyridazin-3-amine or N-(2-methyl-2-morpholinopropyl)-6-phenyl-5-propylpyridazin-3-amine.
地址 San Francisco CA US