Quantitative structure-activity relationship study of ATP-sensitive potassium channel openers: derivatives of 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide.
The inhibitory activity of glucose-induced insulin secretion on isolated rat pancreatic islets and the contractile activity of KCl-depolarized rat aorta rings of the derivatives of 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide are quantitatively analyzed using multiple regression analysis. The study has helped to ascertain the role of different substituents in explaining these observed inhibitory activities. From a derived most significant correlation equation, it was concluded that a less hydrophobic 3-substituent and a less bulky 7-substituent in addition to a 3-aminoisopropyl and a 6-chloro substituent are advantageous to enhance the inhibitory action of a compound towards rat pancreatic islets. On the other hand, the more hydrophobic 6- and 7-substituents augment the contractile activity. The analysis, in this way, provided the grounds for rationalizing the substituent selection in designing the improved potency compounds in the series.
Sharma
B K
BK
Department of Chemistry, S. K. Government College, Sikar, India.
Sharma
S K
SK
Singh
P
P
Sharma
Susheela
S
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
D001581:Benzothiadiazines; D015221:Potassium Channels; D011189:Potassium Chloride; D000255:Adenosine Triphosphate