| 主权项 |
1. Compounds of formula (I)or pharmaceutically acceptable salts thereof; wherein
Y is absent or is selected from the group consisting
of —C(═O)—, —N(H)C(═O)—, —N(Ra)C(═O)—, —O—C(═O)—, —N(H)S(O)1-2—, —N(Ra)S(O)1-2— and —S(O)2—, wherein Ra is selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 heteroalkyl, C2-6 alkenyl and C2-6 alkynyl; R2 is —(Xb)0-1—Rb, wherein Xb is selected from the group consisting of C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C1-6 heteroalkylene, 3-6 membered cycloalkylene and 3-6 membered heterocycloalkylene, Rb is selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocycloalkyl, 6-10 membered aryl and 5-10 membered heteroaryl, wherein the aliphatic and aromatic portions of Xb and Rb are each independently optionally substituted with 1 to 5 Rb1 substituents selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, F, Cl, Br, I, —OH, —NH2, —SH, —CN, —NO2, —N3, —C(═O)OH, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, —(C1-4 alkenylene)0-1-C(═O)—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)O—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)N(H)—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)N(C1-4 alkyl)2, —(C1-4 alkenylene)0-1-S(O)2—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)—(C1-4 heteroalkyl) and —(C1-4 alkenylene)0-1-C(═O)—(C3-6 heterocycloalkyl), and wherein if Rb is a 6 membered aryl or a 5-6 membered heteroaryl then any two substituents attached to adjacent atoms said aryl or heteroaryl are optionally combined to from a 3-6 membered carbocyclic or a 3-6 membered heterocyclic ring comprising 1-3 heteroatoms selected from N, O and S, and optionally substituted with 1 to 3 Rb1 substituents; X1 is N or N+—O−; X2, X3 and X4 are each C, or one of X2, X3 and X4 is N or N+—O− and the remainder of X2, X3 and X4 are each C; R3 is selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, F, Cl, Br, I, —CN, —CF3, —OCF3, —SF5 and —N3; R4 is selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, F, Cl, Br, I, —CN, —NO2, —N3, —SH, —OH, C1-6 alkoxy, —CF3, —OCF3, —SF5, C1-6 alkylamino and C1-6 dialkylamino, or is absent if X4 is N or N+—O; R5 is (Xe)0-1—Rc, wherein Xc is selected from the group consisting of C1-6 alkylene, C2-6 alkenylene, C2-6 heteroalkylene, C2-6alkynylene, —N(H)—, —N(Rxc)—, —O—, —S(O)2—, —C(═O)—, —C(═O)O—, —C(═O)N(H)—, —N(H)C(═O)— and —OC(═O)—, wherein Rxc is selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, and wherein Rc is selected from the group consisting of hydrogen, F, Cl, Br, I, —CN, —NO2, —NH2, —OH, —CF3, —OCF3, —SF5, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocycloalkyl, 6 membered aryl and 5-6 membered heteroaryl, wherein the aliphatic and aromatic portions of Xc and Rc are optionally substituted with 1 to 5 Rc1 substituents selected from the group consisting of C1-6 alkyl, C1-6 heteroalkyl, F, Cl, Br, I, —OH, —NH2, —SH, —CN, —NO2, —N3, —C(═O)OH, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), —O(C1-6 alkyl), alkenylene)0-1-C(═O)—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)O—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)N(H)—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)N(C1-4 alkyl)2, —(C1-4 alkenylene)0-1-S(O)2—(C1-4 alkyl), —(C1-4 alkenylene)0-1-C(═O)—(C1-4 heteroalkyl) and —(C1-4 alkenylene)0-1-C(═O)—(C3-6 heterocycloalkyl), or R5 is absent if X3 is N or N+—O−; R6 is selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, C2-6 alkenyl, C2-6 alkynyl, F, Cl, Br, I, —OH, —NH2, —SH, —CN, —NO2, —CF3, —OCF3, —SF5 and —N3, or R6 is absent if X2 is N or N+—O−; A is absent or is selected from the group consisting of —O—, —N(H)—, —N(Rd)—, —S(O)2—, —S(O)—, —S—, —(Xd)0-1—N(H)C(═O)—, —(Xd)0-1—N(Rd)C(═O)—, —Xd—, —(Xd)0-1—C(═O)N(H)—, —(Xd)0-1—C(═O)N(Rd)—, —(Xd)0-1—C(═O)—, —C(═O)—(Xd)0-1—, —(Xd)0-1—OC(═O)— and —(Xd)0-1C(═O)O—, wherein Xd is selected from the group consisting of C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C1-6 heteroalkylene, 6-10 membered arylene, 5-10 membered heteroarylene, 3-10 membered cycloalkylene, 3-10 membered heterocycloalkylene, and Rd at each occurrence is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C1-6 heteroalkyl and C1-6 haloalkyl, wherein the aliphatic or aromatic portions of Xd and Rd are each independently optionally substituted with 1 to 5 Rd1 substituents selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylamino, C1-6 dialkylamino, F, Cl, Br, I, —OH, —NH2, —SH, —CN, —NO2, —CF3, —OCF3, —SF5, and —N3; B is selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, 3-6 membered cycloalkyl, 4-9 membered heterocycloalkyl, 6-10 membered aryl and 5-6 membered heteroaryl, wherein the aliphatic or aromatic portions of B are independently optionally substituted with 1 to 5 RB1 substituents selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, C3-6 heterocycloalkyl, F, Cl, Br, I, —OH, —NH2, —SH, —CF3, —SF5, —(Xe)0-1—CN, —(Xe)0-1—N3, —(Xe)0-1—OH, —(Xe)0-1—H, —(Xe)0-1—N(H)Re, —(Xe)0-1—N(Re)2, —(Xe)0- 1—SRe, —(Xe)0-1—C(O)Re, —(Xe)0-1—S(O)Re, —N(H)S(O)2Re, —N(Re)S(O)2Re, —(Xe)0-1—C(═O)ORe, —(Xe)0-1—C(═O)OH, —(Xe)0-1—C(═O)N(H)Re, —(Xe)0-1—C(═O)N(Re)Re, —(Xe)0-1—N(H)C(═O)Re, —(Xe)0-1—N(Re)C(═O)Re, wherein if B is a 6 membered aryl or a 5-6 membered heteroaryl then any two substituents attached to adjacent atoms of said aryl or heteroaryl are optionally combined to from a 3-6 membered carbocyclic or a 3-6 membered heterocyclic ring optionally comprising 1-3 heteroatoms selected from N, O and S, and optionally substituted with 1 to 3 RB1 substituents; wherein Xe is selected from the group consisting of C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C1-6 heteroalkylene, C3-6 cycloalkylene and C3-6 heterocycloalkylene, and Re at each occurrence is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, wherein the aliphatic or aromatic portions of Xe and Re are each independently optionally substituted with 1 to 5 Re1 substituents selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylamino, C1-6 dialkylamino, F, Cl, Br, I, —OH, —NH2, —SH, —CN, —NO2, —CF3, —OCF3, —SF5 and —N3, and wherein any two Re groups attached to the same nitrogen atom are optionally combined to form a 3-7 membered heterocyclic or 5-10 membered heteroaryl ring comprising 1-3 heteroatoms selected from N, O and S; and wherein if X3 is N, R3 is H, R4 is H or NH2, R6 is —OH and —Y—R2 is other than H, then -A-B is not thiazol-4-yl substituted with 2-thiophenyl-S(O)2CH2—, phenyl-S(O)2—CH2—, 4-pyridyl, or pyridyl-S(O)2CH2—, if X3 is N, R3 is H or Cl, R4 is H, R6 is —OH, —NH2, or —NHCH3 and —Y—R2 is hydrogen, 4-tetrahydropyranyl, 4-((CH3CH2)2N(CH2)3-4O)-phenyl, (CH3CH2)2N(CH2)4—, 3-(4-methylpiperazinyl)-propyl or trifluoroacetyl, then -A-B is not 2-chlorophenyl, 2-methylphenyl, 2,6-dichlorophenyl, 3,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, phenyl, 2-chloro-6-(2-ethoxyethoxy)phenyl, if X3 is N, R3, R4 and R6 are each H, and —Y—R2 is hydrogen, cyclohexyl, (CH3CH2)2NCH2CH2—, CH3N(H)CH2CH2—, (CH3)2NCH2CH2—, (CH3)3CC(═O)— or 2-(4-morpholinyl)ethyl, then -A-B is not 3,4-dimethoxyphenyl or optionally substituted pyridine-2-on-3-yl, if X4 is N, R3 is H, R5 is isopropyl, R6 is methoxy, -A-B is propyl or isopropyl, then —Y—R2 is other than optionally substituted pyridyl, if X4 is N, R3, R5, R6 are each H, -A-B is methyl, then —Y—R2 is other than hydrogen, if R3, R4, R5 and R6 are each H, and —Y—R2 is hydrogen, cyclohexyl, (CH3CH2)2NCH2CH2—, CH3N(H)CH2CH2—, (CH3)2NCH2CH2—, (CH3)3CC(═O)— or 2-(4-morpholinyl)ethyl, then -A-B is not 3,4-dimethoxyphenyl or optionally substituted pyridine-2-on-3-yl, if R3, R4 and R5 are each hydrogen, —Y—R2 is other than hydrogen, then one of R6 and -A-B is other than ethoxy. |
