OXEPAN-2-YL-PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE

摘要

Oxepan-2-yl pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein X is thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.;

主权项

1. A compound selected from Formula I: and stereoisomers, geometric isomers, tautomers, or pharmaceutically acceptable salts thereof, wherein: R1 is selected from H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C6-C20 aryl, C3-C12 carbocyclyl, C2-C20 heterocyclyl, C1-C20 heteroaryl, and —(C1-C12 alkylene)-(C2-C20 heterocyclyl); R2 is independently selected from F, Cl, Br, I, —CH3, —CH2CH3, —CH(CH3)2, —C(CH3)3, —CH2CH(CH3)2, —CH═CH2, —CH═C(CH3)2, ═CH2, —CHF2, —CF3, —CH2OH, —CH2OCH3, —CH2NH2, —CH2NHCH3, —CH2CH2NH2, —CH2CHCH2NH2, —CH2CH(CH3)NH2, —CH2OH, —CH2CH2OH, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CN, —CO2H, —COCH3, —COCH2NH2, —CO2CH3, —CO2C(CH3)3, —COCH(OH)CH3, —CONH2, —CONHCH3, —CON(CH3)2, —C(CH3)2CONH2, —NO2, —NH2, —NHCH3, —N(CH3)2, —NHCH2CHF2, —NHCH2CF3, —NHCH2CH2OH, —NHCOCH3, —N(CH3)COCH3, —NHC(O)OCH2CH3, —NHC(O)OCH2Cl3, —NHC(O)OC6H5, —NHS(O)2CH3, —N(CH3)C(CH3)2CONH2, —N(CH3)CH2CH2S(O)2CH3, ═O, —OH, —OCH3, —OCHF2, —OCH2F, —OCH2CH3, —OCH(CH3)2, —OCH2CH(CH3)2, —OC(CH3)3, —S(O)2N(CH3)2, —SCH3, —CH2OCH3, —S(O)2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, azetidinyl, azepanyl, oxetanyl, oxetan-3-ylmethylamino, (3-methyloxetan-3-yl)methylamino, pyrrolidinyl, piperazinyl, piperidinyl, (piperidin-4-yl)ethyl), pyranyl, (piperidin-4-ylmethyl), morpholinomethyl, and morpholino; n is 1, 2, 3, 4, 5, or 6; X is selected from the structures: where the wavy line indicates the site of attachment; and R3 is selected from H, Cl, Br, C1-C12 alkyl, —O—(C1-C12 alkyl), —(C1-C12 alkylene)-(C3-C12 carbocyclyl), —(C1-C12 alkylene)-(C2-C20 heterocyclyl), —(C2-C8 alkenylene)-(C3-C12 carbocyclyl), —(C2-C8 alkenylene)-(C2-C20 heterocyclyl), C6-C20 aryl, —(C6-C20 arylene)-(C2-C20 heterocyclyl), —(C6-C20 arylene)-(C6-C20 arylene), —(C6-C20 arylene)-(C1-C12 alkylene)-(C2-C20 heterocyclyl), —(C6-C20 arylene)-O—(C2-C20 heterocyclyl), —(C6-C20 arylene)-O—(C1-C12 alkyl), C3-C12 carbocyclyl, C2-C20 heterocyclyl, C1-C20 heteroaryl, —(C1-C20 heteroaryl)-(C2-C20 heterocyclyl), and —(C1-C20 heteroaryl)-(C1-C12 alkyl); where alkyl, alkenyl, alkynyl, alkylene, carbocyclyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CH3, —CH2CH3, —CH(CH3)2, —CH2CH(CH3)2, —CH2NH2, —CH2CH2NH2, —CH2CHCH2NH2, —CH2CH(CH3)NH2, —CH2OH, —CH2CH2OH, —CH(CH2OH)2, —C(CH2OH)3, —CH(CH3)OH, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CN, —CF3, —CHF2, —CH2F, —CO2H, —COCH3, —COCH(CH3)2, —CO2CH3, —CO2C(CH3)3, —COCH(OH)CH3, —CONHCH3, —CON(CH3)2, —C(CH3)2CONH2, —NO2, —NHCH3, —N(CH3)2, —NHCOCH3, —N(CH3)COCH3, —NHS(O)2CH3, —N(CH3)C(CH3)2CONH2, —N(CH3)CH2CH2S(O)2CH3, ═O, —OH, —OCH3, —OCF3, —OCH(CH3)2, —S(O)2N(CH3)2, —SCH3, —CH2OCH3, —S(O)2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, azetidinyl, azepanyl, oxetanyl, phenyl, pyrrolidinyl, piperazinyl, piperidinyl, (piperidin-4-yl)ethyl), pyranyl, (piperidin-4-ylmethyl), morpholinomethyl, and morpholino.