Design and discovery of RWJ 22108 - A novel bronchoselective calcium channel blocker

John H. Dodd, Charles F. Schwender, John B. Moore, David M. Ritchie, Yolanda Gray-Nunez, Deborah Loughney, Thomas Kirchner, William C. Miller, Sandra Mockoviak

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

A series of cyclic sulfone dihydropyridines ranging in sulfone ring size from five to nine membered have been evaluated for calcium antagonist activity. Increasing the sulfone ring size from 5 to 8 membered resulted in a two orders of magnitude in vitro potency increase. Aromatic substitution which favored tracheal effects over aortic effects was found to be 2-NO2 and 2-Cl, 6-F. The ester side chain which was found to maximize in vivo activity was the N-benzyl-N-methyl aminoethyl moiety. Combination of all these structural features resulted in RWJ 22108, a bronchoselective calcium channel blocker which preclinically exhibits an antiasthmatic profile.

Original languageEnglish (US)
Pages (from-to)135-148
Number of pages14
JournalDrug Design and Discovery
Volume15
Issue number3
StatePublished - Jul 14 1998

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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    Dodd, J. H., Schwender, C. F., Moore, J. B., Ritchie, D. M., Gray-Nunez, Y., Loughney, D., Kirchner, T., Miller, W. C., & Mockoviak, S. (1998). Design and discovery of RWJ 22108 - A novel bronchoselective calcium channel blocker. Drug Design and Discovery, 15(3), 135-148.