Design and synthesis of norendoxifen analogues with dual aromatase inhibitory and estrogen receptor modulatory activities.

ABSTRACT: Both selective estrogen receptor modulators and aromatase inhibitors are widely used for the treatment of breast cancer. Compounds with both aromatase inhibitory and estrogen receptor modulatory activities could have special advantages for treatment of breast cancer. Our previous efforts led to the discovery of norendoxifen as the first compound with dual aromatase inhibitory and estrogen receptor binding activities. To optimize its efficacy and aromatase selectivity versus other cytochrome P450 enzymes, a series of structurally related norendoxifen analogues were designed and synthesized. The most potent compound, 4'-hydroxynorendoxifen (10), displayed elevated inhibitory potency against aromatase and enhanced affinity for estrogen receptors when compared to norendoxifen. The selectivity

SUBMITTER: Lv W 

PROVIDER: S-EPMC4687028 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature