3-(SUBSTITUTED-4-OXOQUINAZOLIN-3(4H)-YL)-3-DEUTERO-PIPERIDINE-2,6-DIONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

摘要

The invention provides 3-deuterium-enriched 3-(6-, 7-, or 8-substituted-4-oxoquinazolin-3(4H)-yl)-piperidine-2,6-diones, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same.

主权项

1. A deuterium-enriched compound of formula I: and pharmaceutically acceptable salts, solvates, and stereoisomers thereof, wherein: Z is H or D, provided that the abundance of deuterium in Z is at least 30%; R1, R2, R3, R4, R5, and R10 are independently selected from H and D; R6 is selected from: H; D; —(CH2)nOH; phenyl; —O(C1-C6)alkyl; and (C1-C6)alkyl optionally substituted with one or more halo; R7, R8, and R9 are independently selected from: H; D; halo; —(CH2)nOH; (C1-C6)alkyl optionally substituted with one or more halo; (C1-C6)alkoxy optionally substituted with one or more halo; and —(CH2)nNHRa; alternatively, two of R7, R8, R9, and R10 are taken together with the atoms to which they are attached to form a 5-6 membered ring optionally substituted with one or more groups independently selected from halo, (C1-C6)alkyl optionally substituted with one or more halo; and (C1-C6)alkoxy optionally substituted with one or more halo; Ra is selected from: H; D; (C1-C6)alkyl optionally substituted with one or more halo; —(CH2)n-(6 to 10 membered aryl); —C(O)(CH2)n-(6 to 10 membered aryl); —C(O)(CH2)n-(6 to 10 membered heteroaryl); —C(O)(C1-C8)alkyl optionally substituted with one or more halo; C(O)(CH2)n—(C3-C10-cycloalkyl); —C(O)(CH2)n—NRbRc, —C(O)(CH2)n—O—(C1-C6)alkyl; and, —C(O)(CH2)n—O—(CH2)n-(6 to 10 membered aryl); wherein the aryl and heteroaryl are optionally substituted with one or more groups independently selected from: halo; —SCF3; (C1-C6)alkyl optionally substituted with one or more halo; and (C1-C6)alkoxy optionally substituted with one or more halo; Rb and Rc are each independently selected from: H; D; (C1-C6)alkyl optionally substituted with one or more halo; (C1-C6)alkoxy optionally substituted with one or more halo; and 6 to 10 membered aryl; the aryl being optionally substituted with one or more groups independently selected from: halo; (C1-C6)alkyl optionally substituted with one or more halo; and (C1-C6)alkoxy optionally substituted with one or more halo; n is independently selected from selected from 0, 1, and 2; and a hydrogen atom present in any substituent is optionally replaced by D.