Methods of treatment using selective Bcl-2 inhibitors
AssigneeAbbVie Inc.
InventorsSteven Elmore, Andrew Souers, Lichun Wang, Tariq Ghayur, Stuart J. Perper
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Abstract
This invention pertains to methods of treating systemic lupus erythematosus and Sjogren's Syndrome with compounds that selectively inhibit the activity of Bcl-2 anti-apoptotic proteins. Specifically, the current invention is directed to treatment with compounds that selectively inhibit the activity of Bcl-2 proteins, with a lesser affinity for inhibiting the activity of other BCL-2 family proteins, including Bcl-XL.
Claims20
A method of treating systemic lupus erythematosus and lupus nephritis in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound comprising a selective Bcl-2 inhibitor, wherein the selective Bcl-2 inhibitor is a compound of Formula (I),
- wherein
- A1 is N or CH;
- B1 is OR1 or NHR1;
- Y1 is CN, NO2, CF3, F or Cl;
- R1 is (CH2)nR2;
- R2 is cycloalkyl or heterocyclyl;
- wherein the heterocyclyl and cycloalkyl are optionally substituted with one or more independently selected R4, OR4, OH, CN, or F;
- R3 is heteroaryl;
- wherein the heteroaryl is optionally substituted with one or more independently selected NH2, Cl, or F;
- R4 is alkyl, cycloalkyl, heterocyclyl, or spiroheterocyclyl;
- wherein the alkyl is optionally substituted with one or more F;
- R5 is deuterium;
- each R6 is independently selected from CH3, spirocyclopropyl and OH;
- m is 0, 1, 2, 3, 4, 5, or 6;
- n is 0 or 1;
- and
- p is 0, 1, or 2,
- or a pharmaceutically acceptable salt or prodrug thereof.
A method of treating Sjogren's Syndrome in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound comprising a selective Bcl-2 inhibitor, wherein the selective Bcl-2 inhibitor is a compound of Formula (I),
- wherein
- A1 is N or CH;
- B1 is OR′ or NHR1;
- Y1 is CN, NO2, CF3, F or Cl;
- R1 is (CH2)nR2;
- R2 is cycloalkyl or heterocyclyl;
- wherein the heterocyclyl and cycloalkyl are optionally substituted with one or more independently selected R4, OR4, OH, CN, or F;
- R3 is heteroaryl;
- wherein the heteroaryl is optionally substituted with one or more independently selected NH2, Cl, or F;
- R4 is alkyl, cycloalkyl, heterocyclyl, or spiroheterocyclyl;
- wherein the alkyl is optionally substituted with one or more;
- R5 is deuterium;
- each R6 is independently selected from CH3, spirocyclopropyl and OH;
- m is 0, 1, 2, 3, 4, 5, or 6;
- n is 0 or 1;
- and
- p is 0, 1, or 2,
- or a pharmaceutically acceptable salt or prodrug thereof.
Dependencies are inferred from the claim text.