Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors

David Rotella, Z. Sun, Y. Zhu, J. Krupinski, R. Pongrac, L. Seliger, D. Normandin, J. E. Macor

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34 Citations (Scopus)

Abstract

A previous report from these laboratories identified the N-3-benzylimidazoquinazolinone nucleus as a more selective PDE5 inhibitor template compared to the pyrazolopyrimidine of sildenafil. This paper describes in detail the structure-activity relationships of a set of sulfonamide analogues, several of which are both more potent and more selective PDE5 inhibitors in vitro than sildenafil. The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described.

Original languageEnglish
Pages (from-to)5037-5043
Number of pages7
JournalJournal of Medicinal Chemistry
Volume43
Issue number26
DOIs
StatePublished - 28 Dec 2000

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Phosphodiesterase 5 Inhibitors
Sulfonamides
Structure-Activity Relationship
Pharmacokinetics
Enzymes
In Vitro Techniques
Sildenafil Citrate

Cite this

Rotella, David ; Sun, Z. ; Zhu, Y. ; Krupinski, J. ; Pongrac, R. ; Seliger, L. ; Normandin, D. ; Macor, J. E. / Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors. In: Journal of Medicinal Chemistry. 2000 ; Vol. 43, No. 26. pp. 5037-5043.
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abstract = "A previous report from these laboratories identified the N-3-benzylimidazoquinazolinone nucleus as a more selective PDE5 inhibitor template compared to the pyrazolopyrimidine of sildenafil. This paper describes in detail the structure-activity relationships of a set of sulfonamide analogues, several of which are both more potent and more selective PDE5 inhibitors in vitro than sildenafil. The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described.",
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Rotella, D, Sun, Z, Zhu, Y, Krupinski, J, Pongrac, R, Seliger, L, Normandin, D & Macor, JE 2000, 'Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors', Journal of Medicinal Chemistry, vol. 43, no. 26, pp. 5037-5043. https://doi.org/10.1021/jm000336j

Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors. / Rotella, David; Sun, Z.; Zhu, Y.; Krupinski, J.; Pongrac, R.; Seliger, L.; Normandin, D.; Macor, J. E.

In: Journal of Medicinal Chemistry, Vol. 43, No. 26, 28.12.2000, p. 5037-5043.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Macor, J. E.

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