73647-50-4Relevant articles and documents
Cobalt-Catalyzed, Directed Intermolecular C-H Bond Functionalization for Multiheteroatom Heterocycle Synthesis: The Case of Benzotriazine
Wu, Weiping,Fan, Shuaixin,Li, Tielei,Fang, Lili,Chu, Benfa,Zhu, Jin
supporting information, p. 5652 - 5657 (2021/08/01)
Transition-metal-catalyzed, directed intermolecular C-H bond functionalization is synthetically useful but heavily underexplored in multiheteroatom heterocycle synthesis. Herein we report a cobalt catalytic method for the formation of a three-nitrogen-bearing benzotriazine scaffold via the coupling of arylhydrazine and oxadiazolone. This synthetic protocol features a low-cost base metal catalyst, a maximum number of heteroatoms built into a heterocycle, a distinct synthetic logic for benzotriazines, a superior step economy, and a broad substrate scope.
KCNT1 INHIBITORS AND METHODS OF USE
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Paragraph 000700, (2020/11/23)
The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
Synthesis and evaluation of new 1,2,4-oxadiazole based trans- acrylic acid derivatives as potential PPAR-alpha/gamma dual agonist
Bhat, Sana,Bhat, Zahid Rafiq,Gupta, Jeena,Kaur, Jaskiran,Kaur, Paranjeet,Khatik, Gopal L.,Khurana, Navneet,Kumar, Rajan,Kumar, Rakesh,Tikoo, Kulbhushan
, (2020/04/29)
Diabetes is a ubiquitously a metabolic disorder and life-threatening disease. Peroxisome proliferator-activated receptors (PPARs) belong to the class of nuclear receptors which acts as transcription factors to regulate lipid and glucose metabolism. PPAR alpha/gamma dual agonists tend to corroborate the functions of both thiazolidinediones and fibrates and they hold substantial promise for ameliorating the type 2 diabetic treatments and providing potential therapeutic diabetic interventions. New 1,2,4-oxadiazole based trans- acrylic acid derivatives compounds possessing aryl/methylene linker in between pharmacophore head and lipophilic tail for dual PPAR-alpha/gamma agonists are studied. AutoDock Vina used for potential PPAR alpha/gamma dual agonists and 6 compounds 9a, 9g, 9 m, 9n, 9o, and 9r were identified comparable to PPAR gamma agonist Pioglitazone on the basis of their affinity scores and further their in-silico toxicity and in-silico ADME properties. The selected compounds showed better-calculated lipophilicity (iLogP) was found to be 0.92 to 3.19. Compound 9n and 9a were found to be most potent on both PPAR alpha and gamma receptors with EC50 of 0.07 ± 0.0006 μM, 0.06 ± 0.0005 μM and 0.781 ± 0.008 μM, 3.29 μM ± 0.03 respectively as better to pioglitazone having EC50 of 32.38 ± 0.2 and 38.03 ± 0.13 for both receptors. The in-vivo evaluation found to reduce the plasma glucose level and total cholesterol level significantly in diabetic rats compared to pioglitazone at 5 mg/kg/day dose for 7 days of treatment. Thus, trans- acrylic acid derivatives can be further developed as oral therapeutic agents for diabetic interventions as PPAR alpha/gamma dual agonists.
