Linked Life Data

8687280

Source:http://linkedlifedata.com/resource/pubmed/id/8687280

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-8-22
pubmed:abstractText
A group of racemic 3-[2-nitrooxyethyl (1,3-dinitrooxy-2-propyl or 4-nitrophenylethyl)] 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-[2- trifluoromethylphenyl (2-nitrophenyl or 3-nitrophenyl)]-3,5-pyridinedicarboxylates 13-15 were prepared using the Hantzsch reaction that involved the condensation of 2-nitrooxyethyl 9a, 1,3-dinitrooxy-2-propyl 9b or 4-nitrophenylethyl 9c acetoacetate with isopropyl 3-aminocrotonate 11 and 2-trifluoromethyl 12a, 2-nitro 12b or 3-nitro 12c benzaldehyde. In vitro calcium channel antagonist activities were determined using a guinea pig ileum longitudinal smooth muscle assay. Compounds 13-15 exhibited superior, or equipotent, calcium channel antagonist activity (10(-8) to 10(-10) M range) relative to the reference drug nifedipine (IC50 = 1.43 x 10(-8) M). The R1 C-3 ester substituent was a determinant of calcium channel antagonist activity where the potency order was CH2CH2ONO2 > CH2CH2-C6H4-4-NO2 > or = CH(CH2ONO2)2. In contrast, the C-4 R2-aryl substituent (2-CF3-C6H4-, 2-O2N-C6H4- or 3-O2N-C6H4-) was not a major determinant of activity. Compounds 13a-15a, which possess a 3-(2-nitrooxyethyl) ester substituent exhibit superior calcium channel antagonist smooth muscle relaxant activity (IC50 = 10(-10) M range) relative to nifedipine, could serve as potential probes to investigate the in vivo release of nitric oxide (NO) which induces vascular muscle relaxation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0365-6233
pubmed:author
pubmed:issnType
Print
pubmed:volume
329
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Synthesis and smooth muscle calcium channel antagonist effects of dialkyl 1,4-dihydro-2,6-dimethyl-4-aryl-3,5-pyridinedicarboxylates containing a nitrooxy or nitrophenyl moiety in the 3-alkyl ester substituent.
pubmed:affiliation
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't