A small series of benzisoxazole analogs that effectively activate glycogen synthase (GS) was prepared in WO2011057956. These novel GS activators are claimed to be beneficial for the treatment or prophylaxis of metabolic disease and disorders. The 1,2-benzisoxazole-3-ol moiety is utilized in the present patent as a bioisoster of benzoic acid, which has often been employed in prior examples of the GS activators.
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http://dx.doi.org/10.1517/13543776.2012.681303 | DOI Listing |
Chem Biodivers
August 2023
Advanced Catalysis laboratory, Vellore Institute of Technology (VIT), 632014, Vellore, India.
An efficient metal-free approach for site selective C-N coupling reaction of benzo[d]isoxazole and 2H-chromene derivatives has been designed and developed against AchE. This nitrogen containing organo-base promoted methodology, which is both practical and environmentally friendly, provides an easy and suitable pathway for synthesizing Benzisoxazole-Chromene (BC) possessing poly heteroaryl moieties. The synthesized BC derivatives 4 a-n was docked into the active sites of AChE to obtain more perception into the binding modes of the compounds.
View Article and Find Full Text PDFJ Antibiot (Tokyo)
June 2021
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA.
The emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. Most pressing is an immediate need for the development of novel antibacterial agents to treat Gram-negative multi-drug resistant infections, including the opportunistic, hospital-derived pathogen, Acinetobacter baumannii. Herein we report a naturally occurring 1,2-benzisoxazole with minimum inhibitory concentrations as low as 6.
View Article and Find Full Text PDFJ Med Chem
October 2020
Department of Chemistry, Infection Innovative Medicines, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
Herein, we report spiropyrimidinetriones (SPTs) incorporating N-linked azole substituents on a benzisoxazole scaffold with improved Gram-positive antibacterial activity relative to previously described analogues. SPTs have an unusual spirocyclic architecture and represent a new antibacterial class of bacterial DNA gyrase and topoisomerase IV inhibitors. They are not cross-resistant to fluoroquinolones and other DNA gyrase/topoisomerase IV inhibitors used clinically.
View Article and Find Full Text PDFBioorg Med Chem Lett
July 2020
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address:
Aminobenzyloxyarylamide derivatives 1a-i and 2a-t were designed and synthesized as novel selective κ opioid receptor (KOR) antagonists. The benzoyl amide moiety of LY2456302 was changed into N-hydroxybenzamide and benzisoxazole-3(2H)-one to investigate whether it could increase the binding affinity or selectivity for KOR. All target compounds were evaluated in radioligand binding assays for opioid receptor binding affinity.
View Article and Find Full Text PDFFront Mol Biosci
February 2019
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, United States.
The kynurenine pathway is the major route for tryptophan metabolism in mammals. Several of the metabolites in the kynurenine pathway, however, are potentially toxic, particularly 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid. Quinolinic acid (QUIN) is an excitotoxic agonist at the NMDA receptor, and has been shown to be elevated in neurodegenerative diseases such as Alzheimer's Disease and Huntington's Disease.
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