METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION

A method of preparing a pharmaceutical composition, the method comprising contacting a compound with a pharmaceutically-acceptable carrier selected from water, ethanol, isopropanol, saline, physiological saline, DMSO, dimethylformamide, potassium phosphate buffer, phosphate buffer saline (PBS), sodium phosphate buffer, 4-2-hydroxyethyl-1-piperazineethanesulfonic acid buffer (HEPES), 3-(N-morpholino) propanesulfonic acid buffer (MOPS), piperazine-N,N′-bis(2-ethanesulfonic acid) buffer (PIPES), and saline sodium citrate buffer (SSC), wherein the compound is of the formula:

• wherein:
• each is independently a single bond or a double bond;
• X1 is CR5, CR5R6, N, NR5, O, S, C═O, C═S, or a carbon atom connected to Q1;
• X2 is CR7, CR7R8, N, NR7, O, S, C═O, C═S, or a carbon atom connected to Q1;
• X3 is CR9, CR9R10, N, NR9, O, S, C═O, C═S, or a carbon atom connected to Q1;
• X4 is CR11, CR11R12, N, NR11, O, S, C═O, C═S, or a carbon atom connected to Q1;
• X5 is CR13, N, or NR13;
• wherein at least one of X1, X2, X3, and X4 is a carbon atom connected to Q1;
• Q1 is C═O, C═S, C═CR14R15, C═NR14, alkylene, alkenylene, or alkynylene, each of which is independently substituted or unsubstituted, or a bond;
• m is 1, 2, 3, or 4;
• Y is N, O, or absent;
• R1 is —C(O)R16, —C(O)OR16, —C(O)NR16R17, —OR16, —SR16, —NR16R17, —NR16C(O)R16, —OC(O)R16, C═O, C═S, —CN, —SiR16R17R18, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen;
• each R3 and R4 is independently, —C(O)R19, —C(O)OR19, —C(O)NR19R20, —SOR19, —SO2R19, alkyl, alkylene, alkenyl, alkenylene, alkynyl, aryl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen, or R3 and R4 together with the Y atom to which R3 and R4 are bound form a ring, wherein the ring is substituted or unsubstituted, or R3 is absent;
• each R2, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, and R18 is independently —C(O)R21, —C(O)OR21, —C(O)NR21R22, —OR21, —SR21, —NR21R22, —NR21C(O)R22, —OC(O)R21, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
• each R19 and R20 is C(O)R23, —C(O)OR23, —C(O)NR23R24, —OR23, —SR23, —NR23R24, —NR23C(O)R24, —OC(O)R23, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen or halogen;
• each R21 and R22 is independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen;
• and
• each R23 and R24 is independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl, each of which is independently substituted or unsubstituted, or hydrogen,
• or a pharmaceutically-acceptable salt thereof, wherein the compound is not a compound of Table 1.