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US 2014/0228382 A1Published application
3-(5-substituted-4-oxoquinazolin-3(4h)-yl)-3-deutero-piperidine-2,6-dione derivatives and compositions comprising and methods of using the same
AssigneeDeuteRx, LLC
InventorSheila DeWitt
Life of this patent
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Abstract
The invention provides 3-deuterium-enriched 3-(5-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, such as in the treatment of cancer, an immune-related disease, or an inflammatory disease.
Claims27
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, R7, R8, and R9 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;
- R10 is selected from:
- H;
- D;
- halo;
- —(CH2)nH;
- (C1-C6)alkyl optionally substituted with one or more halo;
- (C1-C6)alkoxy optionally substituted with one or more halo;
- and —(CH2)nNHRa;
- 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 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 selected from:
- halo;
- (C1-C6)alkyl optionally substituted with one or more halo;
- and (C1-C6)alkoxy optionally substituted with one or more halo;
- alternatively, R10 is selected from R10a, R10b, and R10c;
- R10aa is selected from:
- H;
- D;
- halo;
- —(CH2)nOH;
- (C1-C6)alkyl optionally substituted with one or more halo;
- and (C1-C6)alkoxy optionally substituted with one or more halo;
- R10b=—(CH2)n—NHRd;
- R10c=—(CH2)n—NHRg;
- Rd is selected from:
- H;
- D;
- —(C1-C6)alkyl optionally substituted with one or more halo;
- —C(O)(C1-C8)alkyl optionally substituted with one or more halo;
- —C(O)(CH2)n(C3-C10-cycloalkyl);
- —C(O)(CH2)nNReRf;
- and, —C(O)(CH2)nO(C1-C6)alkyl.
- Re and Rf are each independently selected from:
- hydrogen;
- (C1-C6)alkyl optionally substituted with one or more halo;
- and (C1-C6)alkoxy optionally substituted with one or more halo;
- Rg is selected from:
- —C(O)(CH2)1NHRh;
- —(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);
- and, —C(O)(CH2)nO(CH2)n-(6 to 10 membered aryl), wherein the aryl and heteroaryl are optionally substituted with one or more groups selected from:
- halo;
- —SCF3;
- (C1-C6)alkyl optionally substituted with one or more halo;
- and, (C1-C6)alkoxy substituted with one or more halo;
- Rh is selected from:
- 6 to 10 membered aryl optionally substituted with one or more groups 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.
81 more elements
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23-26. (canceled)
Dependencies are inferred from the claim text.