Linked Life Data

18616237

Source:http://linkedlifedata.com/resource/pubmed/id/18616237

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2008-8-7
pubmed:abstractText
To find selective inhibitor of phosphodiesterase type 5 (PDE5), the essential structure elements of clinically used drugs sildenafil, vardenafil, and tadalafil were combined and a tetracyclic parent was constructed to which in 2-positions substituted acetic acid methylesters were introduced to form 17 novel vasodilators, methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]- pyridin[3,4-b]indol-2-substituted acetates. By molecular field analysis (MFA), an equation of three-dimensional quantitative structure-activity relationship (3D QSAR) was established, which not only revealed the dependence of the in vitro vasorelaxation activities on the structures but also pointed out the way to design new lead compounds properly. Docking these novel vasodilators into the hydrophobic pocket of phosphodiesterase type 5 (PDE5) revealed that their adaptabilities to this pocket did significantly affect on their vasorelaxation activity. Actually, the docking adaptabilities of these novel vasodilators to PDE5 were consistent with the conformational requirements of them to MFA and with the crystal conformation of two representatives.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4715-23
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo-[3',4':1,2]pyridin[3,4-b]indol-2-substituted acetates: synthesis and three-dimensional quantitative structure-activity relationship investigation as a class of novel vasodilators.
pubmed:affiliation
College of Pharmaceutical Sciences, Capital Medical UniVersity, Beijing 100069, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't