Naphthoquinones for disease therapies

摘要

The present invention discloses novel naphtho[2,3-b]furan-4,9-diones and naphtho[2,3-b]thiophene-4,9-diones and methods of making and using the same. The present invention also discloses pharmaceutical compositions comprising novel naphtho[2,3-b]furan-4,9-dione or naphtho[2,3-b]thiophene-4,9-diones for the treatment of various indications including proliferative diseases.

主权项

1. A compound of formula I:or a pharmaceutically acceptable salt thereof;wherein:
n is 0-4; m is 0-2; X is O or S; each R1 is independently halogen; —NO2; —CN; —OR; —SR; —N+(R)3; —N(R)2; —C(O)R; —CO2R; —C(O)C(O)R; —C(O)CH2C(O)R; —S(O)R; —S(O)2R; —C(O)N(R)2; —SO2N(R)2; —OC(O)R; —N(R)C(O)R; —N(R)N(R)2; —N(R)C(═NR)N(R)2; —C(═NR)N(R)2; —C═NOR; —N(R)C(O)N(R)2; —N(R)SO2N(R)2; —N(R)SO2R; —OC(O)N(R)2; or an optionally substituted group selected from C1-12 aliphatic; a 3- to 14-membered carbocycle; a 3- to 14-membered heterocycle; a 6- to 14-membered aryl ring; or a 5- to 14-membered heteroaryl ring, or: two R1 groups on adjacent carbon atoms are taken together with their intervening atoms to form an optionally substituted ring selected from 3- to 14-membered carbocycle; 3- to 14-membered heterocycle; a 6- to 14-membered aryl ring; or a 5- to 14-membered heteroaryl ring; each R2, R3, and R4 is independently hydrogen; halogen; —NO2; —CN; —OR; —SR; —N+(R)3; —N(R)2; —C(O)R; —CO2R; —C(O)C(O)R; —C(O)CH2C(O)R; —S(O)R; —S(O)2R; —C(O)N(R)2; —SO2N(R)2; —OC(O)R; —N(R)C(O)R; —N(R)N(R)2; —N(R)C(═NR)N(R)2; —C(═NR)N(R)2; —C═NOR; —N(R)C(O)N(R)2; —N(R)SO2N(R)2; —N(R)SO2R; —OC(O)N(R)2; or an optionally substituted group selected from C1-12 aliphatic; a 3- to 14-membered carbocycle; a 3- to 14-membered heterocycle; a 6- to 14-membered aryl ring; or a 5- to 14-membered heteroaryl ring; R′ is —S(O)R5; —S(O)2R5; or —NO2, wherein when m is O, R′ is —S(O)R5 or —S(O)2R5; R5 is —OR; —SR; —N(R)2; or an optionally substituted group selected from C1-12 aliphatic; a 3- to 14-membered carbocycle; a 3- to 14-membered heterocycle; a 6- to 14-membered aryl ring; or a 5- to 14-membered heteroaryl ring; and each R is independently hydrogen or an optionally substituted group selected from C1-12 aliphatic; a 3- to 14-membered carbocycle; a 3- to 14-membered heterocycle; a 6- to 14-membered aryl ring; or a 5- to 14-membered heteroaryl ring; wherein when m is 1 or 2, each double bond independently has Z or E stereochemistry; Provided that either R3 or R4 is not hydrogen when R′ is —NO2; Further provided that R2 is not methyl when R′ is —S(O)2OH.