Structure-activity relationships of PDE5 inhibitors

D. Eros, Cs Szántai-Kis, R. Kiss, Gy Kéri, B. Hegymegi-Barakonyi, I. Kövesdi, L. Orfi

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

cGMP has a short-term effect on smooth muscle tone and a longer-term effect on responses to chronic drug treatment or proliferative signals. cGMP-Phosphodiesterase type 5 (PDE5) hydrolizes cGMP, and the result is smooth muscle contraction. PDE5 is a relatively novel therapeutic target of various diseases, such as erectile dysfunction and pulmonary hypertension. The most intensively examined and marketed PDE5 inhibitor was sildenafil (Viagra) but recently vardenafil (Levitra) and tadalafil (Cialis) were launched with beneficial ADME parameters and PDE5 selectivity. The increasing interest in PDE5 inhibition made it reasonable to collect the available inhibitory data from the scientific literature and set up a structure-activity relationship study. Chemical structures of 438 compounds and their cGMP-PDE5 inhibitory data (IC50) were collected from recently published articles. In this paper physiology, regulation and inhibition of PDE5 (and briefly other PDE-s) are discussed and inhibitors are tabulated by the core structures. Finally, a general QSAR model built from these data is presented. All data used in the QSAR study were summarized in a Supplement (for description please see the online version of the article).

Original languageEnglish
Pages (from-to)1570-1585
Number of pages16
JournalCurrent medicinal chemistry
Volume15
Issue number16
DOIs
Publication statusPublished - Jul 1 2008

Keywords

  • PDE5
  • QSAR
  • Virtual sceening

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Eros, D., Szántai-Kis, C., Kiss, R., Kéri, G., Hegymegi-Barakonyi, B., Kövesdi, I., & Orfi, L. (2008). Structure-activity relationships of PDE5 inhibitors. Current medicinal chemistry, 15(16), 1570-1585. https://doi.org/10.2174/092986708784911524