Document Detail

Structure -activity relationships of PDE5 inhibitors.
MedLine Citation:
PMID:  18673225     Owner:  NLM     Status:  MEDLINE    
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).
D Eros; Cs Szántai-Kis; R Kiss; Gy Kéri; B Hegymegi-Barakonyi; I Kövesdi; L Orfi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current medicinal chemistry     Volume:  15     ISSN:  0929-8673     ISO Abbreviation:  Curr. Med. Chem.     Publication Date:  2008  
Date Detail:
Created Date:  2008-08-04     Completed Date:  2008-09-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9440157     Medline TA:  Curr Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1570-85     Citation Subset:  IM    
Vichem Chemie Ltd., Herman Ottó u. 15., Budapest, 1022, Hungary.
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MeSH Terms
Cyclic Nucleotide Phosphodiesterases, Type 5 / antagonists & inhibitors*,  classification,  metabolism
Models, Biological
Phosphodiesterase Inhibitors / chemistry*,  pharmacology*
Structure-Activity Relationship
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; EC Nucleotide Phosphodiesterases, Type 5

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