Synthesis of Benzofuran, Benzothiophene, and Benzothiazole-Based Thioamides and their Evaluation as K(ATP) Channel Openers.
Summary of "Synthesis of Benzofuran, Benzothiophene, and Benzothiazole-Based Thioamides and their Evaluation as K(ATP) Channel Openers."
Several series of benzofurans, benzothiophenes, and benzothiazoles, all featuring the thioamide group, were synthesized and tested as novel K(ATP) channel openers in artificial cell systems: CHO cells transfected with SUR1/Kir6.2, and HEK 293 cells transfected with SUR2B/Kir6.1; these served as model systems for insulin-secreting pancreatic β cells and smooth muscle cells, respectively. All compounds were investigated with respect to their binding affinity for the SUR2B-type K(ATP) channels using [(3)H]P1075 as radioligand. Selected compounds were also tested as agonists in intact cells using DiBAC(4)(3) and DyeB (R7260) as membrane potential dyes. Remarkable affinity for SUR2B/Kir6.1 channels in the single-digit micromolar range was observed. In addition, benzothiazole-derived thioamides with sterically demanding, lipophilic substituents showed >100-fold selectivity in favor of SUR2B/Kir6.1. A one-carbon spacer between the heterocyclic skeleton and the thioamide moiety was observed to be crucial for affinity and selectivity. Two of the most potent and selective compounds were studied by crystal structure analyses.
Affiliation
Institute of Organic & Macromolecular Chemistry, University of Düsseldorf, Universiätsstr. 1, 40225 Düsseldorf (Germany), Fax: (+49) 211-81-15079.
Journal Details
This article was published in the following journal.
Name: ChemMedChem
ISSN: 1860-7187
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20845362
- DOI: http://dx.doi.org/10.1002/cmdc.201000297
Medical and Biotech [MESH] Definitions
Thioamides
Organic compounds containing the radical -CSNH2.
Evaluation Studies As Topic
Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.
Holtzman Inkblot Test
Personality evaluation based on the scoring of several variables as a result of the subject's responses in perceiving 47 inkblot plates.
Dithiazanine
3-Ethyl-2-(5-(3-ethyl-2-benzothiazolinylidene)-1,3- pentadienyl)benzothiazolium. A benzothiazole that was formerly used as an antinematodal agent and is currently used as a fluorescent dye.
Program Evaluation
Studies designed to assess the efficacy of programs. They may include the evaluation of cost-effectiveness, the extent to which objectives are met, or impact.
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