BIR domain binding compounds

A method of inhibiting apoptosis in a cell comprising contacting the cell with a compound of Formula 1.2a,

• wherein:
• n is 0 or 1;
• m is 0, 1, or 2;
• Y is NH, O or S;
• R1 is C1-C6 optionally substituted with one R6 substituent,
• R1a is
• 1) H, or
• 2) C1-C6 alkyl optionally substituted with one R6 substituent;
• R2 is C1-C6 optionally substituted with one or more halogens;
• R3 is C1-C6 alkyl optionally substituted with one R6 substituent;
• R4 is
• 1) H
• 2) —C(O)(O)n—R11,
• 3) —C(═Y)NR8R9, or
• 4) —S(O)2—R11
• R5 is
• 1) C1-C6 alkyl,
• 2) aryl,
• 3) heteroaryl,
• 4) C1-C7 cycloalkyl, or
• 5) heterocyclyl;
• wherein the alkyl and cycloalkyl are optionally substituted with one or more R6 substituents;
• and wherein the aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more R10 substituents;
• R6 is:
• 1) halogen,
• 2) haloalkyl,
• 3) C1-C6 alkyl,
• 4) C3-C7 cycloalkyl,
• 5) aryl,
• 6) heteroaryl,
• 7) heterocyclyl,
• 8) —OR7,
• 9) —S(O)mR7,
• 10) —NR8R9,
• 11) —COR7,
• 12) —C(O)OR7
• 13) —OC(O)R7,
• 14) —SC(O)R7,
• 15) —CONR8R9,
• 16) —S(O)2NR8R9, or
• 17) —NC(═Y)NR8R9
• wherein the aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more R10 substituents;
• R7 is:
• 1) H,
• 2) haloalkyl,
• 3) C1-C6 alkyl,
• 4) C3-C7 cycloalkyl,
• 5) aryl,
• 6) heteroaryl,
• 7) heterocyclyl, or
• 8) —C(═Y)NR8R9,
• wherein the alkyl and cycloalkyl are optionally substituted with one or more R6 substituents,
• and the aryl, heteroaryl, and heterocyclyl, are optionally substituted with one or more R10 substituents;
• R8 and R9 are each independently
• 1) H,
• 2) haloalkyl,
• 3) C1-C6 alkyl,
• 4) C3-C7 cycloalkyl,
• 5) aryl,
• 6) heteroaryl,
• 7) heterocyclyl,
• 8) —C(O)R11,
• 9) —C(O)YR11, or
• 10) —SO2R11,
• wherein the alkyl and cycloalkyl are optionally substituted with one or more R6 substituents, and wherein the aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more R10 substituents;
• or R8 and R9 together with the nitrogen atom to which they are bonded form a five, six, or seven membered heterocyclic ring optionally substituted with one or more R6 substituents;
• R10 is
• 1) halogen,
• 2) NO2,
• 3) CN,
• 4) C1-C6 alkyl,
• 5) C3-C7 cycloalkyl,
• 6) haloalkyl,
• 7) —OR7,
• 8) —NR8R9,
• 9) —SR7,
• 10) —COR7,
• 11) —C(O)OR7,
• 12) —S(O)mR7,
• 13) —CONR8R9, or
• 14) —SO2NR8R9,
• wherein the alkyl is optionally substituted with one or more R6 substituents;
• and R11 is
• 1) haloalkyl,
• 2) C1-C6 alkyl,
• 3) C3-C7 cycloalkyl,
• 4) aryl,
• 5) heteroaryl,
• 6) heterocyclyl, or
• 7) heterobicyclyl,
• wherein the alkyl and cycloalkyl are optionally substituted with one or more R6 substituents;
• and wherein the aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more R10 substituents;
• or a salt thereof
• wherein the cell is a breast cancer cell, lung cancer cell, or ovarian cancer cell.