HETEROCYCLO COMPOUNDS AS APOPTOTIC INDUCERS AND USES THEREOF

摘要

Disclosed are heterocyclo compounds that have a formula represented by the following: and wherein X, R1, R2, R3, R4, R5, R6 and n are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of cancer conditions in mammals including humans, including by way of non-limiting example, prostate, colon, bladder, melanoma, liver, breast, cervical, ovarian, esophagi, glialblastoma, pancreatic and lung cancer.

主权项

1. A compound according to formula 1′:or a pharmaceutically acceptable salt, solvate or prodrug thereof; and stereoisomers, isotopic variants and tautomers thereof; wherein X is —O—, or —NRx—; Rx is H or C1-C6 alkyl; R1 is H, OH, —OC(O)—Ry1, NH2, —NRz1Rz2, or —N(RZ3)—C(O)—RZ4; R2 is H, OH, —OC(O)—Ry2, NH2, —NRz5Rz6, —N(Rz7)—C(O)—Rz8; each Ry1, Ry2, Rz2, Rz4, Rz6, and Rz8 is independently substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted cycloalkyl; each Rz1, Rz3, Rz5, and Rz7 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted cycloalkyl; or Rz5 and Rz6 together with the N they are attached to form a heterocycle; or R1 and R2 are joined together to form —O—CRw1Rw2—O—, —O—C(O)—O—, —NH—C(O)—NH—, or —NH—C(S)—NH—; each Rw1, and Rw2 is independently H, or substituted or unsubstituted alkyl; R3 is H or halo; R4 is independently selected from H, OH, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, substituted or unsubstituted amino, substituted or unsubstituted arylalkyl, sulfo, substituted sulfo, substituted sulfonyl, substituted sulfinyl, substituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, azido, substituted or unsubstituted carbamoyl, carboxyl, cyano, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted dialkylamino, substituted or unsubstituted dialkylamido, halo, nitro, and thiol; each R5 and R6 is independently H; or R5 and R6 together with the Cs they are attached to form a carbocycle or heterocycle; n is 1, 2, 3, 4 or 5; and each dotted bond is independently a single or a double bond; provided that i) when R2 is H; then R3 is halo; and ii) the compound is other than