Synthesis and evaluation of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives as K(ATP) channel agonists |
| |
Authors: | Peat Andrew J Townsend Claire Worley Jennings F Allen Scott H Garrido Dulce Mertz Robert J Pfohl Jeffrey L Terry Christopher M Truax Jim F Veasey Robert L Thomson Stephen A |
| |
Institution: | GlaxoSmithKline Research and Development, 5Moore Drive, Research Triangle Park, NC 27709, USA. ajp25551@gsk.com |
| |
Abstract: | A series of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives has been synthesized and evaluated as K(ATP) channel agonists using the inside-out excised patch clamp technique. The most active compounds were approximately 20-fold more potent than diazoxide in opening K(ATP) channels. A linear relationship exists between the potency of the compound and the sigma value of the 7-substituent with electron-withdrawing groups exhibiting higher activity. These compounds may be useful in modulating insulin release from pancreatic beta-cells and in diseases associated with hyperinsulinemia. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|