Pyrazol-3-ones that activate pro-apoptotic bax

A pharmaceutical composition, comprising:

• a pharmaceutically acceptable carrier;
• and
• a compound of Formula I:
• or a pharmaceutically acceptable salt thereof, wherein:
• A is N or CH;
• X is heteroaryl, which comprises 5 ring atoms and is optionally substituted with 1 Ra, wherein 1 or 2 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), O, and S;
• Y is unsubstituted phenyl;
• R1 is selected from the group consisting of:
• (i) heteroaryl comprising from 5-10 ring atoms, wherein 1, 2, 3, or 4 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), O, and S;
• (ii) —C(O)-(heteroaryl), wherein the heteroaryl contains from 5-10 ring atoms, wherein 1, 2, 3, or 4 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), O, and S);
• and
• (iii) hydrogen;
• R2 is phenyl optionally substituted with from 1-4 Re, or heteroaryl containing from 5-6 ring atoms, wherein from 1-4 of the ring atoms is independently selected from the group consisting of N, NH, N(C1-C3 alkyl), NC(O)(C1-C6 alkyl), O, and S;
• and wherein the heteroaryl is optionally substituted with from 1-3 Re;
• Ra is C1-C8 alkyl;
• and
• Re is C1-C6 alkyl.

A pharmaceutical composition, comprising:

• a pharmaceutically acceptable carrier;
• and
• a compound of formula (I-A), or a pharmaceutically acceptable salt thereof:
• wherein:
• X′ is S;
• X′″ is unsubstituted phenyl,
• X″ is H or C1-C4 alkyl;
• R2 is C1-C4 alkyl;
• phenyl that is optionally substituted with from 1-4 Re;
• or heteroaryl containing from 5-6 ring atoms, wherein from 1-4 of the ring atoms is independently selected from the group consisting of N, NH, N(C1-C3 alkyl), NC(O)(C1-C6 alkyl), O, and S;
• and wherein the heteroaryl is optionally substituted with from 1-3 Re;
• R12 is —C(O)OH;
• C2-C6 alkoxy that is optionally substituted with —NH2;
• or heterocyclyl containing from 5-7 ring atoms, wherein from 1-2 of the ring atoms of the heterocyclyl is independently selected from the group consisting of N, NH, N(C1-C6 alkyl), NC(O)(C1-C6 alkyl), NC(O)O(C1-C6 alkyl), O, and S;
• and each of which is optionally substituted with from 1-3 independently selected C1-C4 alkyl groups;
• each of R13 and R14 is H;
• and
• each occurrence of Re is, independently, halo;
• cyano;
• —C(O)(C1-C6 alkyl);
• C(O)OH;
• —C(O)O(C1-C6 alkyl);
• —NH2;
• —NH(C1-C6 alkyl), N(C1-C6 alkyl)2, —NHC(O)(C1-C6 alkyl), C1-C6 alkoxy;
• C1-C6 haloalkoxy;
• C1-C6 thioalkoxy;
• C1-C6 thiohaloalkoxy;
• C1-C6 alkyl, C3-C6 cycloalkyl;
• or C1-C6 haloalkyl.