| 摘要 |
<p>The 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 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)(R11), (R9)(R10)NC(Z)N(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 group selected from A, provided that A is not halogen; (ii) C7-C12 alkyl, C2-C12 alkenyl and C2-C12 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 by Y, the said Y groups are not directly connected to each other; R6 is selected from C1-12 alkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C2-6alkenyl, and C2-6 alkynyl, aryl and heteroaryl; R7 is optionally selected from hydrogen; R8, R9, R10 and R11 are independently from 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 when any pair of R8, R9, R10 and R11 together with the atom or atoms to which they are bound from a ring having 3-7 ring members; or pharmaceutically acceptable salts, stereoisomers or prodrugs thereof. 23 claims</p> |
