Linked Life Data

2066995

Source:http://linkedlifedata.com/resource/pubmed/id/2066995

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1991-8-14
pubmed:abstractText
Three analogues with restricted flexibility were designed to study the active conformation of verapamil during interaction with the slow calcium channel. Thus cis- and trans-1-(3,4-dimethoxyphenyl)-4-[N-[2-(3,4-dimethoxy-phenyl)ethyl]-N- methylamino]-r-1-cyclohexanecarbonitrile (5a and 5b), and 4-(3,4-dimethoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-4-cyanopiper idine, in which the verapamil structure is inserted into a cyclohexane or piperidine ring, were synthesized. Conformational analysis was performed with NMR and theoretical methods, and slow calcium channel antagonism was tested on guinea pig aorta strips. The compounds are some 100 times less potent than the parent compound even if they are able to reach conformations that are quite close to the lowest energy conformation proposed for verapamil and similar compounds. It appears that the flexibility to rotate around the bond between the quaternary atom and the adjacent methylene, a property which is lost in compounds 5a, 5b, and 6, is a major requisite for the calcium antagonism of verapamil.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2219-25
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Verapamil analogues with restricted molecular flexibility.
pubmed:affiliation
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't