2,4-Diamino-5-cyano-6-halopyridines

A new class of cyclic AMP phosphodiesterase inhibitors with therapeutic potential

Christoph de Haën, Bernhard J. Nist, R. Scott Hansen, David G Johnson, W. Joseph Thompson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

2,4-Diamino-5-cyano-6-halopyridines have been described previously as oral insulinotropic agents and have been found recently to have bronchodilatory properties. In the present report the synthesis of the iodo compound is newly described, and it is established that HI- or HBr-mediated condensation and cyclization of malononitrile in 1,2-dichloroethane yield selectively the 5-cyanopyridine derivatives. The pyridine derivatives were found to constitute a new class of potent cyclic AMP phosphodiesterase inhibitors. Inhibition of purified dog kidney cyclic AMP phosphodiesterase was of the mixed type. Since cyclic AMP phosphodiesterase inhibitors are known to enhance glucose-induced insulin secretion and to activate glucose production by the liver, the finding that the pyridine derivatives described here inhibited cyclic AMP phosphodiesterase opens new avenues of interpretation for their insulinotropic actions as well as for the paradoxical lack of improvement of glucose disposal by elevation of insulin after oral drug administration. Cyclic AMP phosphodiesterase inhibition also has the potential of explaining the bronchodilatory effects of these drugs.

Original languageEnglish (US)
Pages (from-to)2109-2113
Number of pages5
JournalBiochemical Pharmacology
Volume33
Issue number13
DOIs
StatePublished - Jul 1 1984

Fingerprint

Phosphodiesterase Inhibitors
Cyclic AMP
Phosphoric Diester Hydrolases
Derivatives
Glucose
Insulin
Therapeutics
Cyclization
Pharmaceutical Preparations
Liver
Oral Administration
Condensation
Dogs
Kidney

ASJC Scopus subject areas

  • Pharmacology

Cite this

2,4-Diamino-5-cyano-6-halopyridines : A new class of cyclic AMP phosphodiesterase inhibitors with therapeutic potential. / de Haën, Christoph; Nist, Bernhard J.; Scott Hansen, R.; Johnson, David G; Joseph Thompson, W.

In: Biochemical Pharmacology, Vol. 33, No. 13, 01.07.1984, p. 2109-2113.

Research output: Contribution to journalArticle

de Haën, Christoph ; Nist, Bernhard J. ; Scott Hansen, R. ; Johnson, David G ; Joseph Thompson, W. / 2,4-Diamino-5-cyano-6-halopyridines : A new class of cyclic AMP phosphodiesterase inhibitors with therapeutic potential. In: Biochemical Pharmacology. 1984 ; Vol. 33, No. 13. pp. 2109-2113.
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