| 主权项 |
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof or mixture of stereoisomers thereof, wherein R1 is optionally substituted piperidinyl, optionally substituted pyridyl, optionally substituted pyrrolyl, optionally substituted pyrroldinyl, 1,4-dimethylthiazolyl, 2-ethyl-4-methylthiazolyl, 2-isopropylthiazol-5-yl, thiazolyl, 3-ethylthiazol-5-yl, 1-methylsulfonylpiperidin-4-yl, or
R1 is —C(O)Z, where Z is piperazinyl, (S)-2-(3-ethylpiperazin-1-yl), optionally substituted pyrrolopyrrolyl, piperidin-3-ylamino, or,R1 is where R13 is H, methylpyrazolyl, methylimidazolyl, benzyl, 3-hydroxybutyl, 3-(dimethylamino)-2,2-dimethylpropyl, ethylamide, methylpyridyl, methylsulfonyl, (1-methylimidazol-2-yl)methyl, (1,5-dimethylimidazol-4-yl)methyl, (1-methylpyrrol-2-yl)methyl, or where R13 is C(O)W, where W is —N(CH3)2, piperidinyl, piperazinyl, or morpholinyl, or,R1 is where R14 is —C(O)CH3, H, or (1-methylpyrrol-2-yl)methyl, or, R1 is where A, B, and D may all be carbon, or where two of A, B, and D are carbon and the other is nitrogen, or where one of A, B, and D is carbon and the remaining two are nitrogen; and when A is nitrogen R4 is absent, when B is nitrogen R2 is absent, and when D is nitrogen R3 is absent; and wherein R2 is H, —CH3, or F, or, with R3 and the atoms at positions a and b, forms an optionally substituted pyridine or a pyrazole; and wherein R3 is H, F, Cl, —CN, —CH3, —OCH3, —OH, —NH2, methylsulfonyl, or, with R4 and the atoms at b and c, forms an optionally substituted benzene, optionally substituted imidazole, optionally substituted pyrazole, optionally substituted pyrazolidine, optionally substituted imidazolidine, optionally substituted isothiazole, or, with R2 and the atoms at a and b, forms an optionally substituted pyridine or optionally substituted pyrazole; and wherein R4 is F, —CN, —OCH3, —OEt, H, Cl, Br, —NH—C(O)—CH—(CH3)2, —N(CH3)2, —CH3, —CH2OH, optionally substituted piperazinyl, 4-hydroxypiperizin-1-yl, optionally substituted piperidinyl not attached to a phenyl group through a nitrogen, or, with R3 and the atoms at b and c, forms an optionally substituted pyrazole ring or or, with R5 and the atoms at c and d, forms an optionally substituted pyrazole ring or an optionally substituted pyrrole ring, or, R4 is -(q)-C(O)X, where q is a bond, is —NH—, or is —CH2—, and
where X is —NR11R12,
where R11 and R12 are both H, both —CH2CH3, or both —CH3, or where one of R11 and R12 is H and the other is 1,1-dimethylethyl, cyclobutyl, cyclopropyl, lower alkyl, methyl alcohol, ethyl alcohol, propyl alcohol, cyclobutylmethyl; 2,3-dihydroxypropyl, benzyl, optionally substituted azetidinyl, pyrrolidinyl, piperidinyl, methylazetidinyl, optionally substituted pyrrolyl, —CH2—NH—CH3, pyrazolyl, piperazinyl, alcohol, —OCH3, or orwhere X is optionally substituted pyrrolidinyl attached through a nitrogen to the carbonyl group of R4, optionally substituted piperidinyl not attached through a nitrogen to the carbonyl group of R4, optionally substituted piperazinyl attached through a nitrogen to the carbonyl group of R4, or optionally substituted morpholinyl attached through a nitrogen to the carbonyl group of R4, and wherein R5 is H, F, Cl, —CH3, —OCH3, pyrrolyl, —CH2OH, —NH2, —OH, or, with R4 and the atoms at c and d, forms an optionally substituted benzene, an optionally substituted pyrazole, or an optionally substituted pyrrole, or, with R6 and the atoms at d and e, forms an optionally substituted pyridine, or R5 is C(O)Y, where Y is —NH2, —N(CH3)2, optionally substituted piperazinyl, optionally substituted piperidinyl, and wherein R6 is H, F, —CH3, —CF3, or, with R5 and the atoms at c and d, forms an optionally substituted benzene or an optionally substituted pyrazole; and wherein R7 is —CF3 or —CHF2; and wherein R8 is and wherein R9 is Br, Cl, F, I, or H; with the following provisos:
when R4 is F: R2 is not —CH3 or F; R3 is not —CH3, —CN, F, Cl, or —OCH3; R5 is not —CH3, F, Cl, or —OCH3; and R6 is not —CH3 or F;when R4 is Cl: R2 is not F; R3 is not F or —CN; R5 is not F, —CN, or —C(O)N(CH3)2, R6 is not —CF3 or F; D is not nitrogen; and either R5 is —C(O)NH2 or one of R2, R3, R5, and R6 is —CH3;when R4 is —CH3: R3 is not F; R5 is not F; and R5 and R6 do not form a pyrimidine together with the atoms at d and e;when R4 is —OCH3: R2 is not F; R3 is not Cl or —OCH3, R5 is not Cl or —OCH3; and R6 is not F or —CF3;when R4 is —CN: R2 is not F; R3 is not Cl, F, or —OCH3, R5 is not Cl, F, or —OCH3; and R6 is not F;when R4 is —OCH2CH3: R3 is not Cl or F; R5 is not Cl or F; and R6 is not —CF3;when R4 is R3 is not H or F; and R5 is not H or F;when R4 is at least one of R2, R3, R5, and R6 is not H;when R4 is R3 is not F; and R5 is not F;when R2 is F: R3 is not —OCH3 or F; R5 is not —CN; and at least one of R3, R4, R5, and R6 is not H;when R2 is Cl: R3 is not F;when R2 is —CH3: R3 is not Cl; at least one of R3, R4, R5, and R6 is not —CH3; and R4 and R5 do not form a pyrazolyl with the atoms at c and d;when R3 is —OCH3: R2 is not F; and R6 is not F;when R3 is F: R2 is not —OCH3; and X is not when R3 is Cl: R5 is not Cl; R11 is not benzyl; and R12 is not benzyl;when R5 is Cl, R6 is not —CH3; R11 is not benzyl; and R12 is not benzyl;when R5 is F or —OCH3: R6 is not F;when R6 is F: at least one of R2, R3, R4, and R5 is not H;when R3 and R5 are H: R11 is not cyclopropyl; and R12 is not cyclopropyl;when R9 is Cl, R1 is not an amide group;when B is nitrogen and A and D are carbon: R4 may not be —CN or when R7 is —CHF2 and R4 is then R4 does not have the absolute stereochemistry and wherein, when R8 is then the following provisos are in effect:
when R4 is F: at least one of R2, R3, R5, and R6 is not H; R3 is not C(O)N(CH3)2; and R5 is not C(O)N(CH3)2;when R4 is Cl: at least one of R2, R3, R5, and R6 is not H;when R3 is F: R4 is not C(O)NHCH2CH2CH2CH3, C(O)N(CH3)2, C(O)NHCH2CH2CH3, or C(O)NHC(CH3)3;R4 is not C(O)NHCH2CH2CH2OH, C(O)NHCH(CH3)2, —CN, or R5 is not R3 is not when R2 is F: R5 is not —C(O)NH2;when R2 is —CH3, R4 and R5 do not form a pyrazole with atoms at c and d; andwhen B is nitrogen, R3 and R4 do not form an optionally substituted imidazole with the atoms at b and c; and wherein, when R8 is then following provisos are in effect:
R4 is not —CH3, —C(O)NHCH2CH2OH, —NHC(O)CH(CH3)2, or when R4 is C(O)NHCH3, at least one of R2, R3, R5, and R6 is not H;when R4 is —OCH3: R3 is not F or —CH3; and R5 is not F or —CH3;when R4 is R3 is not Cl; and R5 is not Cl;when R4 is —C(O)NHCH(CH3)2 or —C(O)N(CH2CH3)2: at least one of R3 and R5 is not H;R5 is not —C(O)NH2; andR6 is not —CF3. |
