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Imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyrazines: the role of nitrogen position in inotropic activity.

Authors
  • Spitzer, W A
  • Victor, F
  • Pollock, G D
  • Hayes, J S
Type
Published Article
Journal
Journal of medicinal chemistry
Publication Date
Aug 01, 1988
Volume
31
Issue
8
Pages
1590–1595
Identifiers
PMID: 3397997
Source
Medline
License
Unknown

Abstract

Congestive heart failure is a major medical problem for which existing medicaments have provided limited benefit. Recent new experimental drugs, including imidazo[4,5-b]- and imidazo[4,5-c]pyridines, have both inotropic and vasodilatory properties. Subtle changes in nitrogen position of these compounds have been shown to dramatically affect potency. We have synthesized a series of imidazo[4,5-b]- and -[4,5-c]pyridine analogues having an imidazo nitrogen relocated at the bridgehead position. The superior inotropic activity of the [4,5-c]pyridines as compared to [4,5-b]pyridines is reaffirmed by the activity of our analogues. The biological equivalence of imidazo[4,5-b]pyridines with imidazo[1,2-a]pyrimidines and imidazo[4,5-c]pyridines with imidazo[1,2-a]pyrazines is demonstrated. Further, 2-[2-methoxy-4-(methylsulfenyl)phenyl]imidazo[1,2-a]pyrazine and 2-[2-methoxy-4-(methylsulfonyl)phenyl]-imidazo[1,2-a]pyrazine are potent inotropic agents both in vitro and in vivo.

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