Isoxazolines as therapeutic agents

摘要

The present invention provides compound of Formula (I);
biologically active metabolites, pro-drugs, isomers, stereoisomers, solvates, hydrates and pharmaceutically acceptable salts thereof wherein the variables are defined herein. The compounds of the invention are useful for treating immunological conditions.

主权项

1. A compound of Formula (I)stereoisomers, and pharmaceutically acceptable salts thereof wherein
A is X is phenyl, benzo[1,4]oxazin-3-onyl, benzoxazolyl, 2,3-dihydrobenzo[1,4]dioxinyl, 2,3-dihydrobenzo furanyl, pyrazinonyl, pyridinyl, pyridonyl, or quinolinyl, each of which is optionally substituted with one or more substituents independently selected from Br, Cl, F, CF3, CN, COOH, OCF3, OH, (C1-C6)alkyl, or (C1-C6)alkoxy; Y is pyridazinonyl, pyridinyl, or pyrimidinyl, each of which is optionally substituted by one or more substituents independently selected from CF3, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, Z is —C(O)NH2, CN, —C(O)-morpholinyl, —C(O)-pyrrolidinyl, —C(O)—N(H)CH2CH2OH, (C3-C6)cycloalkyl, 1,4-dioxanyl, imidazolyl, morpholinyl, phenyl, piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyrazolo[3,4-b]pyridinyl, pyridazinyl, pyridazinonyl, pyridinyl, pyridonyl, pyrimidinyl, pyrrolidinyl, tetrahydropyranyl, tetrazolyl, or thienyl, each of which is optionally substituted by one or more substituents independently selected from Br, Cl, F, CF3, CN, —C(O)OH, —C(O)OCH3, —C(O)CH3, —C(O)CH2OC(O)CH3, —C(O)C(CH3)3, —C(O)C(H)(CH3)2, —C(O)CH2CN, —C(O)CH2OH, —C(O)CH2OCH3, —C(O)CH2CH2N(CH3)2, —C(O)C(CH3)2OH, —C(O)OC(CH3)3, —C(O)N(H)CH2CH3, —C(O)CH2N(CH3)2, —C(O)CH2N(H)S(O)2CH3, —C(O)CH2N(H)C(O)CH3, —C(O)CH2N(H)C(O)N(H)CH3, —C(O)CH2OCH3, —C(O)CH2S(O)2CH3, —C(O)NH2, —C(O)N(CH3)2, —C(O)N(H)CH3, —C(O)N(H)CH2CH3, —C(O)N(H)CH(CH3)2, —C(O)N(H)CH2CH2OH, —C(O)N(H)-isoxazolyl, —C(O)N(H)thiazolyl, —C(O)N(CH3)CH2CH2OH, —C(O)-cyclopropyl, —C(O)-cyclobutyl, —OCH2CH2OH, —OC(CH3)3, —NH2, —N(CH3)2, —N(H)C(O)CH3—, —N(H)C(O)CH2OH, —N(H)C(O)CH2CN, —N(H)C(O)C(CH3)2OH, —N(H)C(O)C(H)(OH)CH3, —N(H)C(O)CH2N(CH3)2, —N(H)C(O)CH2N(H)CH3, —N(H)C(O)(OH)CH3, —N(Rc)C(O)N(Rc)(Rc), —N(H)C(O)N(CH3)2, —N(H)C(O)N(H)CH3—N(H)C(O)N(H)CH2CH2OH, —N(H)C(O)N(H)C(H)(CH2OH)2, —N(H)C(O)N(CH3)CH2CH2OH, —N(H)C(O)N(CH3)CH2C(H)(OH)CH2OH, —N(H)C(O)O(CH3)3, —N(H)S(O)2NH2, —N(H)S(O)2CH3, —N(Rc)S(O)2N(Rc)(Rc), —NO2, 1,2,4-oxadiazolyl, oxo, —OH, —S(O)2(Rc), —S(O)CH3, —S(O)CH2CH3, —S(O)CH2CH2CH3, —S(O)2C(H)(CH3)2, —S(O)2cyclopropyl, —S(O)2-imidazolyl, —S(O)2-isoxazolyl, —CH2CN, —CH2C(O)N(H)CH3, —CH2C(O)N(H)-cyclopropyl, —CH2OCH3, —CH2OH, —CH2CH2OH, —CH2OS(O)2-phenyl, —C(CH3)OH, —C(H)(CH2)2OH, —CH2NH2, —CH2N(CH3)2, —CH2N(H)C(O)CH3, —CH2N(H)C(O)C(H)(OH)CH3, —CH2N(H)C(O)CH2CN, —CH2N(H)C(O)CH2OH, —CH2N(H)C(O)C(CH3)2OH, —CH2N(H)C(O)N(H)CH3, —CH2N(H)C(O)N(CH3)2, —CH2S(O)2CH3, —CH2-morpholinyl, —CH2-thiomorpholinyl, —CH2-thiomorpholinyl 1,1-dioxide, morpholinyl, oxadiazolyl, oxazolyl, piperidinyl, (C1-C6)alkyl, (C1-C6)alkoxy, or (C3-C6)cycloalkyl; Rc is independently H, (C1-C3)alkyl or (C3-C6)cycloalkyl; Re is H, —C(O)Rc, (C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C3-C6)cycloalkyl, heteroaryl optionally substituted with (C1-C3)alkyl, or heterocyclyl; or Ra is independently H, (C1-C3)alkyl or (C3-C6)cycloalkyl, Rb is independently H, CF3, (C1-C3)alkyl or (C3-C6)cycloalkyl; R1 is independently Br, Cl, F, (C1-C3)alkyl or (C3-C6)cycloalkyl; m is 0, 1 or 2; n is 0; and p is 0 or 1.