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

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.

• Authors: M M Billah, R W Egan, A K Ganguly, M J Green, W Kreutner, J J Piwinski, M I Siegel, F J Villani, J K Wong
• Journal: Lipids (Lipids) Vol. 26 Issue 12 Pg. 1172-4 (Dec 1991) ISSN: 0024-4201 [Print] United States
• PMID: 1819703 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Histamine Antagonists
• Piperidines
• Platelet Activating Factor
• Platelet Aggregation Inhibitors
• Loratadine
• N-acetyldesloratadine

Topics

• Histamine Antagonists (pharmacology)
• Humans
• Kinetics
• Loratadine (analogs & derivatives)
• Male
• Piperidines (chemical synthesis, pharmacology)
• Platelet Activating Factor (antagonists & inhibitors, pharmacology)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (pharmacology)
• Structure-Activity Relationship