6-substituted estradiol derivatives and methods of use

Abstract

Disclosed are compounds of the formula: wherein R, R, Rand Rare independently hydrogen, C-Calkyl, halo, a sulfate, a glucuronide, —OH, a bulky group, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, —N(CH); a phosphate group, and a phosphinate group; Ris hydrogen, halogen or alkyl; Ris selected from the group consisting of H, C-Calkyl, halogen, a sulfate, a glucoronide, —SONH, —COOH, —CN, —CHCN—, —NHCN—, —CHO, ═CHOCH, —COO salt, —OSOalkyl, —NH, and —NHCO(CH); Ris selected from the group consisting of H, a C-Calkyl, a sulfate, a glucoronide, a bulky group, aryl, cycloalkyl, heteroaryl and heterocycloalkyl; X is selected from the group consisting of C-Calkyl, C-Calkenyl, C-Calkynyl, halogen, a glucoronide, —NH, —SONH, —COOH, —CN, —CHCN, —NHCN, —CHO, —COOsalt, —OSOalkyl, —SH, —SCH, —CH[(CH)CH]COOCH, —(CH)COOCH, —(CH)—O—CH, —(CH)—O—(CH)CH, (CH)—S—CH, —(CH)—S—(CH)CH, —(CH)—NH—(CH)CH, —C-Calkenyl-O—(CH)CH, —C-Calkenyl-S—(CH)CH, —C-Calkenyl-N—(CH)CH, —C-Calkynyl-O—(CH)CH, —C-Calkynyl-S—(CH)CH, —C-Calkynyl-N—(CH)CH, —(CH)—OH, —(CH)—O—NH, —(CH)—S—NH, —NH(CH)CH, —NH(CH)OCH, —NH(CH)CHOH—COOH, —N(CH), —(CH)(NH)CHOH, —NHCOOH, —(CH)NHCOOH, —NO, —SCN, —SOalkyl, —B(OH), —(CH)N(CH)—SO—NH, —(CH)—NH—SO—NH, —NHC(═S) CH, and —NHNH; and Y is selected from hydrogen, ═O, —OCO(R) and —OH; wherein m is an integer between 0-20, n is an integer between 0-8, thesymbol represents either a single or a double bond capable of forming a keto group at position 3 or 17; and thesymbol represents any type of bond regardless of the stereochemistry; and the respective enantiomers, other stereochemical isomers, hydrates, solvates, tautomers and pharmaceutically acceptable salts of said compounds. The compounds are useful in the treatment of various types of cancer.