主权项 |
1. A compound of Formula I:or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein
A1 is CR6 or N; A2 is CR5 or N; A3 is CR4 or N; A4 is CR3 or N; A5 is CR1 or N; A6 is CR8 or N, provided that no more than one of A1, A2, A3, A4, A5 and A6 is N; L is —C(═O)NH—, —C(═O)N(CH3)—, —NH—, —N(CH3)— or —O—; each of R1, R4, R5 and R8, independently, is H, F, Cl, Br, CF3, OCF3, C1-6-alkyl, CN, OH, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein the C1-6-alkyl and C1-6-alkyl portion of —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-3 substituents of F, oxo or OH; each of R2 and R7, independently, is F, Cl, Br, I, haloalkyl, haloalkoxyl, C1-6-alkyl, C2-6alkenyl, C2-6alkynyl, CN, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NH-phenyl, —NH-benzyl, —Si(CH3)3 or a ring selected from the group consisting of phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, diazolyl, triazolyl, tetrazolyl, pyranyl, dihydropyranyl, tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, pyrrolyl, dihydropyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azetidinyl, 8-oxo-3-aza-bicyclo[3.2.1]oct-3-yl, aza-bicyclo[2.2.1]hept-5-yl, 2-oxo-7-aza-[3,5]-spironon-7-yl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, wherein the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NH-phenyl, —NH-benzyl and ring are optionally substituted, independently, with 1-3 substituents of R9; each of R3 and R6, independently, is H, halo, haloalkyl, haloalkoxyl, C1-6-alkyl, CN, OH, OC1-6-alkyl, S(O)oC1-6-alkyl, NHC1-6-alkyl or C(O)C1-6-alkyl; each R9, independently, is halo, haloalkyl, haloalkoxyl, CN, OH, NO2, NH2, acetyl, —C(O)NHCH3, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, piperazinyl, oxetanyl or dioxolyl, wherein each of the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetanyl or dioxolyl, is optionally substituted independently with 1-5 substituents of F, Cl, CN, NO2, NH2, OH, oxo, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, isopropoxyl, cyclopropyl, cyclopropylmethoxyl, butyl, butoxyl, isobutoxyl, tert-butoxyl, isobutyl, sec-butyl, tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl, or oxetanyl; X is —CR10R10—, —O— or —S—, wherein each R10, independently, is H, halo, haloalkyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl or a ring selected from the group consisting of morpholinyl, piperidinyl, piperizinyl, tetrahydrofuranyl, furanyl, thienyl, phenyl, pyrdinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl, dihydropyranyl, tetrahydropyranyl, pyrrolyl, dihydropyrrolyl, tetrahydropyrrolyl and oxetanyl; Y is —O—, —S— or —CH2—, provided that (1) when X is —O— or —S—, then Y is —CH2—, or (2) when X is —CR10R10—, then Y is —O— or —S—; and Z is CH2, CHF, CF2, CH(CH3), C(CH3)2 or CH(CF3). |