Linked Life Data

11472211

Source:http://linkedlifedata.com/resource/pubmed/id/11472211

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2001-7-26
pubmed:abstractText
A series of 6-substituted 2-alkylaminoquinazolin-4(3H)-ones structurally related to 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested as putative K(ATP) channel openers on isolated pancreatic endocrine tissue as well as on isolated vascular, intestinal, and uterine smooth muscle. Most of the 6-halogeno-2-alkylaminoquinazolin-4(3H)-ones were found to inhibit insulin release from pancreatic B-cells and to exhibit vasorelaxant properties. In contrast to their pyridothiadiazine dioxide isosteres previously described as more active on the endocrine than on the smooth muscle tissue, quinazolinones cannot be considered as tissue selective compounds. Biological investigations, including measurements of (86)Rb, (45)Ca efflux from pancreatic islet cells and measurements of vasodilator potency in rat aortic rings exposed to 30 or 80 mM KCl in the presence or the absence of glibenclamide, were carried out with 6-chloro- and 6-iodo-3-isopropylaminoquinazolin-4(3H)-ones. Such experiments showed that, depending on the tissue, these new compounds did not always express the pharmacological profile of pure K(ATP) channel openers. Analyzed by X-ray crystallography, one example of quinazolinones appeared to adopt a double conformation. This only suggests a partial analogy between the 2-alkylaminoquinazolin-4(3H)-ones and the 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides. In conclusion, the newly synthesized quinazolinones interfere with insulin secretion and smooth muscle contractile activity. Most of the compounds lack tissue selectivity, and further investigations are required to fully elucidate their mechanism(s) of action.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2575-85
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11472211-Adenosine Triphosphate, pubmed-meshheading:11472211-Animals, pubmed-meshheading:11472211-Aorta, pubmed-meshheading:11472211-Calcium, pubmed-meshheading:11472211-Crystallography, X-Ray, pubmed-meshheading:11472211-Female, pubmed-meshheading:11472211-Glyburide, pubmed-meshheading:11472211-Guinea Pigs, pubmed-meshheading:11472211-Ileum, pubmed-meshheading:11472211-Insulin, pubmed-meshheading:11472211-Islets of Langerhans, pubmed-meshheading:11472211-Muscle, Smooth, pubmed-meshheading:11472211-Muscle Contraction, pubmed-meshheading:11472211-Potassium Channels, pubmed-meshheading:11472211-Potassium Chloride, pubmed-meshheading:11472211-Quinazolines, pubmed-meshheading:11472211-Rats, pubmed-meshheading:11472211-Rats, Wistar, pubmed-meshheading:11472211-Rubidium, pubmed-meshheading:11472211-Structure-Activity Relationship, pubmed-meshheading:11472211-Uterine Contraction, pubmed-meshheading:11472211-Uterus
pubmed:year
2001
pubmed:articleTitle
Original 2-alkylamino-6-halogenoquinazolin-4(3H)-ones and K(ATP) channel activity.
pubmed:affiliation
Laboratoire de Chimie Pharmaceutique, Université de Liège, 1, Avenue de l'Hôpital, B-4000 Liège, Belgium.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't