Linked Life Data

12852765

Source:http://linkedlifedata.com/resource/pubmed/id/12852765

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2003-7-10
pubmed:abstractText
3-(Alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides were synthesized, and their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the K(ATP) channel activators diazoxide and pinacidil. Structure-activity relationships indicated that an improved potency and selectivity for the pancreatic tissue was obtained by introducing a fluorine atom in the 7-position and a short linear (preferably ethyl) or cyclic (preferably cyclobutyl) hydrocarbon chain on the nitrogen atom in the 3-position. By contrast, strong myorelaxant activity was gained by the introduction of a halogen atom different from the fluorine atom in the 7-position and a bulky branched alkylamino chain in the 3-position. Thus, 3-(ethylamino)-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide (11) expressed a marked inhibitory activity on pancreatic B-cells (IC(50) = 1 microM) associated with a weak vasorelaxant effect (ED(50) > 300 microM), whereas 7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide (27), which was only slightly active on insulin-secreting cells (IC(50) > 10 microM), was found to be very potent on vascular smooth muscle cells (ED(50) = 0.29 microM). Radioisotopic and electrophysiological investigations performed with 7-chlorinated, 7-iodinated, and 7-fluorinated 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides confirmed that the drugs activated K(ATP) channels. The present data revealed that subtle structural modifications of 3-(alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides can generate original compounds activating K(ATP) channels and exhibiting different in vitro tissue selectivity profiles.
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:day
17
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3342-53
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12852765-Adenosine Triphosphate, pubmed-meshheading:12852765-Animals, pubmed-meshheading:12852765-Aorta, pubmed-meshheading:12852765-Benzothiadiazines, pubmed-meshheading:12852765-Diazoxide, pubmed-meshheading:12852765-Female, pubmed-meshheading:12852765-Glucose, pubmed-meshheading:12852765-Insulin, pubmed-meshheading:12852765-Ion Channel Gating, pubmed-meshheading:12852765-Islets of Langerhans, pubmed-meshheading:12852765-Isomerism, pubmed-meshheading:12852765-Molecular Conformation, pubmed-meshheading:12852765-Muscle, Smooth, Vascular, pubmed-meshheading:12852765-Muscle Relaxation, pubmed-meshheading:12852765-Oocytes, pubmed-meshheading:12852765-Organ Specificity, pubmed-meshheading:12852765-Patch-Clamp Techniques, pubmed-meshheading:12852765-Potassium Channels, pubmed-meshheading:12852765-Rats, pubmed-meshheading:12852765-Rats, Wistar, pubmed-meshheading:12852765-Structure-Activity Relationship, pubmed-meshheading:12852765-Xenopus laevis
pubmed:year
2003
pubmed:articleTitle
Toward tissue-selective pancreatic B-cells KATP channel openers belonging to 3-alkylamino-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides.
pubmed:affiliation
Centre de Recherche en Pharmacochimie des Substances Naturelles et Synthétiques, Laboratoire de Chimie Pharmaceutique, Université de Liège, 1, Avenue de l'Hôpital, CHU, Tour 4, B-4000 Liège, Belgium.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't