Analogs of methyl-piperidinopyrazole (MPP): antiestrogens with estrogen receptor alpha selective activity

  • Bioorg Med Chem Lett. 2009 Jan 1;19(1):108-10. doi: 10.1016/j.bmcl.2008.11.006.
Hai-Bing Zhou  1 ,  Kathryn E Carlson ,  Fabio Stossi ,  Benita S Katzenellenbogen ,  John A Katzenellenbogen
Affiliations
  • 1. Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.
PMID: 19014882 DOI: 10.1016/j.bmcl.2008.11.006
Abstract

Methyl-piperidino-pyrazole (MPP), an Estrogen receptor alpha (ERalpha)-selective antagonist we developed, has a basic side chain (BSC) attached to an ERalpha-selective agonist ligand, methyl-pyrazole-triol (MPT) through an ether linkage. To remove the possibility that metabolic cleavage of the BSC in MPP would regenerate MPT, we have replaced the N-piperidinylethoxy moiety with an N-piperidinylpropyl group, giving MPrP. This new analog retains the high ERalpha-selective binding affinity and antagonist potency of MPP.