Synthesis and evaluation of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives as KATP channel agonists
| Autor: | Scott H. Allen, Jeffrey L. Pfohl, Claire Townsend, Jim F Truax, Christopher M. Terry, Andrew J. Peat, Robert J. Mertz, Robert L Veasey, Jennings F. Worley, Stephen A. Thomson, Dulce Garrido |
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| Rok vydání: | 2002 |
| Předmět: |
Patch-Clamp Techniques
Potassium Channels Stereochemistry medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Electrons Benzothiadiazines Biochemistry Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound KATP Channels Drug Discovery medicine Diazoxide Hyperinsulinemia Humans Insulin Structure–activity relationship Lymphocytes Patch clamp Potassium Channels Inwardly Rectifying Molecular Biology Chemistry Organic Chemistry medicine.disease Potassium channel Electrophysiology Benzothiadiazine Molecular Medicine ATP-Binding Cassette Transporters Spectrophotometry Ultraviolet Protons medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 12:2977-2980 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(02)00617-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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