Design and synthesis of triarylacrylonitrile analogues of tamoxifen with improved binding selectivity to protein kinase C.

ABSTRACT: The clinical selective estrogen receptor modulator tamoxifen is also a modest inhibitor of protein kinase C, a target implicated in several untreatable brain diseases such as amphetamine abuse. This inhibition and tamoxifen's ability to cross the blood brain barrier make it an attractive scaffold to conduct further SAR studies toward uncovering effective therapies for such diseases. Utilizing the known compound 6a as a starting template and guided by computational tools to derive physicochemical properties known to be important for CNS permeable drugs, the design and synthesis of a small series of novel triarylacrylonitrile analogues have been carried out providing compounds with enhanced potency and selectivity for PKC over the estrogen receptor relative to tamoxifen. Shortened synthetic

SUBMITTER: Carpenter C 

PROVIDER: S-EPMC5696786 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature