| 摘要 |
This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in therapy and in the regulation of metabolism, especially lowering blood glucose levels. The compounds referred to are compounds according to the formula 1: wherein X is selected from: CH2 , CHYR7, CHYC(O)R7, C=O, C=S, and C=NOR8,; Y is selected from: O, S, and NR8; R1 is selected from: COOH and heteroaryl; R2 and R3 are independently of each other selected from: hydrogen, halogen, and C1-6 alkyl, provided that one of R2 or R3 is other than hydrogen; R4 is selected from: C1-6-alkyl, C2-6 alkenyl, C2-6-alkynyl, halogen, (R9)(R10)N, R8C(Z)N(R11), R8OC(Z)N(R11), (R9)(R10)NC(Z)N(R11),R8S(O)2N(R11), (R9)(R10)NS(O)2N(R11), and R8SC (Z)N(R11);R5 is selected from: (i) C1-6-alkyl which is substituted by a grou p selected from A, provided that A is not halogen; (ii) C7-12-alkyl, C2-12- alkenyl and C2-12-alkynyl; (iii) C1-12-alkyl, where one or more carbon atoms are replaced by Y, and where one or more carbons are optionally substituted by a group selected from A, provided that if more than one carbon is replaced b y Y, the said Y groups are not directly connected to each other; R6 is selecte d from: C1-12-alkyl, C3-8-cycloalkyl, C3-8-heterocycloalkyl, C2-6-alkenyl, and C2-6-alkynyl, aryl, and heteroaryl; R7 is optionally selected from hydrogen; R8, R9, R10 and R11 are independently of each other selected from: hydrogen, C1-6-alkyl, C3-8-cycloalkyl, C2-6-alkenyl, C2-6-alkynyl, and C3-8- heterocycloalkyl, aryl and heteroaryl; or where any pair of R8, R9, R10 and R11 together with the atom or atoms to which they are bound form a ring havi ng 3-7 ring members; or pharmaceutically acceptable salts, stereoisomers or prodrugs thereof.
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