Methods for reducing the uterotrophic effect of tamoxifen and tamoxifen analogs

摘要

The present invention provides a method of minimizing the uterotrophic effect of non-steroidal antiestrogen compounds of formula II CHEM wherein either R4 is H or a lower alkyl radical and R5 is a lower alkyl radical, or R4 and R5 are joined together with the adjacent nitrogen atom to form a heterocyclic radical; R6 is H or a lower alkyl radical; R7 is H, halo, OH, a lower alkyl radical, or is a buta-1,3-dienyl radical which together with the adjacent benzene ring forms a naphthyl radical; R8 is H or OH; and n is 2; or a pharmaceutically acceptable salt thereof, wherein said formula II compound is administered to a woman for the treatment or prevention of breast carcinoma, comprising concurrently or sequentially administering to said woman a compound of formula I CHEM wherein R1 is -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), or -OSO2(C4-C6 alkyl); R2 is -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), or -OSO2(C4-C6 alkyl); n is 2 or 3; and R3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof. The present invention further provides pharmaceutical compositions comprising a compound of formula I and a compound of formula II together with a pharmaceutically acceptable carrier, excipient, or diluent.