6-SUBSTITUTED ESTRADIOL DERIVATIVES AND METHODS OF USE

摘要

Disclosed are compounds of the formula (I): where in R1, R2, R3 and R4 are independent l y hydrogen, C1 -C6 alkyl, halo, a sulfate, a glucuronide, -OH, a bulky group, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, N ( CH2 ) n; a phosphate group, and a phosphinate group; R9 is hydrogen, halogen or alkyl; R11 i s selected from the group consisting of H, C1 -C6 alkyl, halogen, a sulfate, a glucoronide, - SO2NH2, -COOH, -CN, -CH2CN-, -NHCN-, -CHO, =CHOCH3, -COO salt, -0S02alkyl, -NH2, and -NHCO ( CH2 ) n; R12 is selected from the group consisting o f H, a C1 -C6 alkyl, a sulfate, a glucoronide, a bulky group, aryl, cycloalkyl, heteroaryl and heterocycloalkyl; X i s selected from the group consisting of C1 -C12 alkyl, C2 -C12 alkenyl, C2 -C12 alkynyl, halogen, a glucoronide, -NH2, - SO2NH2, -COOH, -CN, -CH2CN, -NHCN, -CHO, -COOsalt, -0S02alkyl, - SH, - SCH3, -CH [ ( CH2 ) nCH3 ] COOCH3, - ( CH2 ) mCOOCH3, - ( CH2 U-O-CH3, - ( CH2 ) m-0- ( CH2 ) nCH3, ( CH2 ) m- S -CH3, - ( CH2 U- S - ( CH2 ) nCH3, - ( CH2 ) m-NH- ( CH2 ) nCH3, -C2 -C8 alkenyl -0- ( CH2 ) nCH3, - C2 -C8 alkenyl - S - ( CH2 ) nCH3, -C2 -C8 alkenyl -N- ( CH2 ) nCH3, -C2 -C8 alkynyl -O- ( CH2 ) nCH3, -C2 -C8 alkynyl - S - ( CH2 ) nCH3, -C2 -C8 alkynyl -N- ( CH2 ) nCH3, - ( CH2 U-OH, - ( CH2 ) m-O-NH2, - ( CH2 ) m- S -NH2 , -NH ( CH2 ) mCH3, -NH ( CH2 ) mOCH3, -NH ( CH2 ) mCHOH-COOH, -N ( CH3 ) 2, - ( CH2 ) m (NH ) CH2OH, -NHCOOH, - ( CH2 ) mNHCOOH, -NO2, - SCN, - S02alkyl, -B ( OH ) 2, - ( CH2 ) m N ( CH3 ) - SO2 -NH3, - ( CH2 ) m-NH- SO2 -NH2,-NHC ( = S) CH3, and -NHNH2; and Y is selected from hydrogen, =0, -OCO(R6) and -OH; wherein m is an integer between 0-20, n is an integer between 0-8, the symbol represents either a single or a double bond capable of forming a keto group at position 3 or 17; and the ?/WV symbol 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.