Advertisement

Topics

Synthesis of Benzofuran, Benzothiophene, and Benzothiazole-Based Thioamides and their Evaluation as K(ATP) Channel Openers.

06:00 EDT 17th September 2010 | BioPortfolio

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

DeepDyve research library

PubMed Articles [25806 Associated PubMed Articles listed on BioPortfolio]

New hybrid molecules combining benzothiophene or benzofuran with rhodanine as dual COX-1/2 and 5-LOX inhibitors: Synthesis, biological evaluation and docking study.

New molecular hybrids combining benzothiophene or its bioisostere benzofuran with rhodanine were synthesized as potential dual COX-2/5-LOX inhibitors. The benzothiophene or benzofuran scaffold was lin...

On-surface synthesis of self-assembled monolayers of benzothiazole derivatives studied by STM and XPS.

On-surface synthesis has gradually become a prevalent approach to construct two-dimensional functional monolayers on various substrates. In the present work, the synthesis of self-assembled monolayers...

Diversity-oriented Synthesis of Libraries Based on Benzofuran and 2,3-Dihydrobenzofuran Scaffolds.

Benzofuran and 2,3-dihydrobenzofuran scaffolds are core components in a large number of biologically active natural and synthetic compounds including approved drugs. Herein, we report efficient synthe...

Variation in toxicity during the biodegradation of various heterocyclic and homocyclic aromatic hydrocarbons in single and multi-substrate systems.

In the present study, an attempt was made to understand the variation in the toxicity during the biodegradation of aromatic hydrocarbons in single and multi-substrate system. The bacterial bioassay ba...

Biologically Active Heterocyclic Hybrids Based on Quinazolinone, Benzofuran and Imidazolium Moieties: Synthesis, Characterization, Cytotoxic and Antibacterial Evaluation.

Cytotoxic and antimicrobial agents structurally based on quinazolinone, benzofuran and imidazole pharmacophores, have been designed and synthesized. Spectral (IR, (1) H NMR) and elemental analysis dat...

Clinical Trials [3612 Associated Clinical Trials listed on BioPortfolio]

A Study Evaluating the Effects of Lipid Lowering Treatment on Steroid Synthesis

Cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids. Both adrenal and non-adrenal (ovarian + testicular) all steroid hormones are primarily synthesized usi...

Effect of Nutrition on Muscle Protein Synthesis

The present proposal is designed to examine the effect of carbohydrate and protein co-ingestion on muscle protein synthesis during endurance type exercise activities. We hypothesize that m...

Muscle Glycogen Synthesis When Caffeine and Protein is Co-Ingested With Carbohydrates

The aim of the present study is to investigate the effect of added protein+leucine or caffeine to 1.2 g/kg/h CHO on the rate of post-exercise muscle glycogen re-synthesis in healthy, recre...

Evaluation of 3-V Bioscience-2640 to Reduce de Novo Lipogenesis in Subjects With Characteristics of Metabolic Syndrome

Metabolic syndrome increases the risk for development of heart disease. Another condition associated with metabolic syndrome is fatty liver disease which is also referred to as nonalcoholi...

Open Label, Continuation Study of Cholic Acid in Subjects With Inborn Errors of Bile Acid Synthesis

The primary purpose of the study is to evaluate the therapeutic efficacy and safety of cholic acid in subjects with identified inborn errors of bile acid synthesis.

Medical and Biotech [MESH] Definitions

An internationally recognized set of published rules used for evaluation of cancer treatment that define when tumors found in cancer patients improve, worsen, or remain stable during treatment. These criteria are based specifically on the response of the tumor(s) to treatment, and not on the overall health status of the patient resulting from treatment.

Organic compounds containing the radical -CSNH2.

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.

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.

Personality evaluation based on the scoring of several variables as a result of the subject's responses in perceiving 47 inkblot plates.

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topic

Pancreatitis
Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake.  Diagnosis is based on clinical presentation...


Searches Linking to this Article