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

  • PAF Receptor and Antagonists
  • Published:
Lipids

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 plateletsin vitro (IC50=0.6 μM), andin 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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Abbreviations

BSA:

bovine serum albumin

PAF:

platelet-activating factor

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Authors and Affiliations

  1. Department of Chemistry Schering-Plough Research, Schering-Plough Corporation, 07003, Bloomfield, New Jersey

    Ashit K. Ganguly, Michael J. Green, John J. Piwinski, Frank J. Villani & Jesse K. Wong

  2. Department of Allergy and Inflammation Biology Schering-Plough Research, Schering-Plough Corporation, 07003, Bloomfield, New Jersey

    M. Motasim Billah, Robert W. Egan, William Kreutner & Marvin I. Siegel

Authors
  1. M. Motasim Billah
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  2. Robert W. Egan
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  3. Ashit K. Ganguly
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  4. Michael J. Green
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  5. William Kreutner
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  6. John J. Piwinski
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  7. Marvin I. Siegel
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  8. Frank J. Villani
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  9. Jesse K. Wong
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Motasim Billah, M., Egan, R.W., Ganguly, A.K. et al. Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine. Lipids 26, 1172–1174 (1991). https://doi.org/10.1007/BF02536525

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  • DOI: https://doi.org/10.1007/BF02536525

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