Synthesis and pharmacological evaluation of novel cis-3,4-diaryl-hydroxychromanes as high affinity partial agonists for the estrogen receptor.

Abstract The syntheses and in vitro pharmacological evaluation of a number of cis -3,4-diaryl-hydroxy-chromanes are reported, along with the results of a thorough in vivo profiling of the tissue-selective estrogen partial-agonist NNC 45-0781 [ 3 , (−)-(3 S ,4 R )-7-hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane]. These studies showed that NNC 45-0781 is a very promising candidate for the prevention of post-menopausal osteoporosis, and the treatment of other health issues related to the loss of endogenous estrogen production.