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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
15
|
| pubmed:dateCreated |
1995-9-12
|
| pubmed:abstractText |
The synthesis and pharmacological activities of the four stereoisomers of methyl tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylate(furnidipine) are reported. The four isomers were synthesized by a modified Hantzsch synthesis by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 3-aminocrotonate and methyl 2-[(2'-nitrophenyl)methylene]acetoacetate or, alternatively, by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 2-[(2'-nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate. The 1:1 diastereomeric mixtures thus obtained were separated by chromatography, using poly(D-phenylglycine) as the chiral stationary phase. The enantiomeric purity of the stereoisomers was determined by a high-performance liquid chromatography-chiral stationary phase technique (HPLC-CSP). Attempts to obtain crystals of a single stereoisomer failed in different solvents, while methanol crystallization of the product obtained from (+/-)-tetrahydrofuran-2-ylmethyl 2-[(2'-nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate yielded good-quality crystals of the most insoluble racemate which proved to be a mixture of the (SS)/(RR) enantiomers by X-ray crystallography. Conformational analysis of the stereoisomers, assuming rotation of the aryl substituent and ester groups, shows small energy differences (about 4 kcal.mol-1) between the most and the least favorable conformations. Binding studies were performed using [3H]isradipine as a reference ligand. The results showed stereospecificity of the furnidipine isomers in brain, ileum, and cardiac tissues, the (SS)- and (SR)-isomers clearly being more potent than their (RR)- and (RS)-enantiomers. The (SS)- and (SR)-isomers were also more selective on cerebral tissue when compared with ileal and cardiac preparations.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydropyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Isradipine,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/furnidipine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
21
|
| pubmed:volume |
38
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2830-41
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:7636844-Animals,
pubmed-meshheading:7636844-Binding, Competitive,
pubmed-meshheading:7636844-Brain,
pubmed-meshheading:7636844-Calcium Channel Blockers,
pubmed-meshheading:7636844-Chemistry, Physical,
pubmed-meshheading:7636844-Crystallography, X-Ray,
pubmed-meshheading:7636844-Dihydropyridines,
pubmed-meshheading:7636844-Drug Evaluation, Preclinical,
pubmed-meshheading:7636844-Guinea Pigs,
pubmed-meshheading:7636844-Heart,
pubmed-meshheading:7636844-Isradipine,
pubmed-meshheading:7636844-Kinetics,
pubmed-meshheading:7636844-Molecular Conformation,
pubmed-meshheading:7636844-Molecular Structure,
pubmed-meshheading:7636844-Muscle, Smooth, Vascular,
pubmed-meshheading:7636844-Muscle Contraction,
pubmed-meshheading:7636844-Myocardial Contraction,
pubmed-meshheading:7636844-Myocardium,
pubmed-meshheading:7636844-Physicochemical Phenomena,
pubmed-meshheading:7636844-Rats,
pubmed-meshheading:7636844-Rats, Sprague-Dawley,
pubmed-meshheading:7636844-Stereoisomerism,
pubmed-meshheading:7636844-Structure-Activity Relationship,
pubmed-meshheading:7636844-Tritium
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Synthesis, structure, and pharmacological evaluation of the stereoisomers of furnidipine.
|
| pubmed:affiliation |
Departamento de Química Orgánica, Universidad de Alcalá, Madrid, Spain.
|
| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|