2. Academic Validation
  3. The discovery of (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1- azabicyclo[2.2.2]-octan-3-amine as a novel, nonpeptide substance P antagonisst

The discovery of (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1- azabicyclo[2.2.2]-octan-3-amine as a novel, nonpeptide substance P antagonisst

  • J Med Chem. 1992 Jul 10;35(14):2591-600. doi: 10.1021/jm00092a009.
J A Lowe 3rd 1,  S E Drozda,  R M Snider,  K P Longo,  S H Zorn,  J Morrone,  E R Jackson,  S McLean,  D K Bryce,  J Bordner
Affiliations

Affiliation

  • 1 Department of Exploratory Medicinal Chemistry, Central Research Division, Pfizer, Inc., Groton, Connecticut 06340.
PMID: 1378901 DOI: 10.1021/jm00092a009
Abstract

We describe the structure-activity relationship development of a series of quinuclidines which culminated in the first potent, selective, nonpeptide substance P (SP) antagonist, (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxy-phenyl)methyl]-1- azabicyclo[2.2.2]octan-3-amine, 3 (CP-96,345). Compound 3 is a potent displacer of [3H]SP binding in human IM-9 cells and blocks SP-induced and capsaicin-induced plasma extravasation, as well as SP-induced salivation in the rat in vivo. This compound may both help to further our understanding of the interactions of small molecules with peptide receptors and serve to evaluate the therapeutic potential of a SP antagonist.

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