Quantitative structure-activity relationship study of ATP-sensitive potassium channel openers: Derivatives of 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide

Abstract

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.

Keywords::

• 3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide derivatives
• inhibitory and contractile activity
• QSAR analysis
• physicochemical parameters

Acknowledgements

We are grateful to the Department of Chemistry, S. K. Government College and Department of Engineering Chemistry, Sobhasaria Engineering College for providing the facilities to complete this work.