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 language | English (US) |
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Pages (from-to) | 135-148 |
Number of pages | 14 |
Journal | Drug Design and Discovery |
Volume | 15 |
Issue number | 3 |
State | Published - 1998 |
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery