Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine

  • Lipids. 1991 Dec;26(12):1172-4. doi: 10.1007/BF02536525.
M M Billah  1 ,  R W Egan ,  A K Ganguly ,  M J Green ,  W Kreutner ,  J J Piwinski ,  M I Siegel ,  F J Villani ,  J K Wong
Affiliations
  • 1. Department of Chemistry, Schering-Plough Research, Schering-Plough Corporation, Bloomfield, New Jersey 07003.
PMID: 1819703 DOI: 10.1007/BF02536525
Abstract

From a series of amide analogs of the histamine H1 antagonist, azatadine, a potent, orally active, dual platelet-activating factor (PAF) and histamine antagonist, Sch 37370, namely 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo- [5,6]cyclohepta[1,2-b]pyridin-11-ylidine)piperidine, was discovered. Sch 37370 selectively inhibits PAF-induced aggregation of human platelets in vitro (IC50 = 0.6 microM), and in vivo inhibits PAF- and histamine-induced bronchospasm in guinea pigs with ED50 values of 6.0 and 2.4 mg/kg p.o., respectively. Sch 37370 is expected to be more efficacious than single mediator antagonists in allergic diseases, such as asthma.

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