Design, synthesis and in silico evaluation of benzoxazepino(7,6-b)quinolines as potential antidiabetic agents
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Medicinal Chemistry Research https://doi.org/10.1007/s00044-020-02606-4
ORIGINAL RESEARCH
Design, synthesis and in silico evaluation of benzoxazepino(7,6-b) quinolines as potential antidiabetic agents Pandurangan Thiyagamurthy1 Chitrala Teja1 Kondapalli Naresh2 K. Gomathi3 Fazlur-Rahman Nawaz Khan ●
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Received: 16 May 2020 / Accepted: 23 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The second-generation XPhos palladium preformed catalyst-based C–N cross-coupling through Buchwald–Hartwig amination with primary and secondary amines towards functionalized benzoxazepino(7,6-b)quinolines is accounted for. The microwave irradiation in dioxane provided the desired highly functionalized oxazepino quinolines, 5, in high yield and purity from the corresponding 2-chloro-3-formyl quinolines, 1, via intermediate, 4, in a sequential cyclization/Buchwald amination strategy. Besides, functional group tolerance, low catalyst loading, microwave assistance, and a wide scope of reactions are the advantages. Compounds 5a, 5b, 5c, 5d, 5e, and 6j showed 50% inhibition in antioxidant potency, whereas compounds 5f, 5g, 5m, 6h, 6j, and 6k showed potent activity alongside 70% inhibition of alpha-amylase and 50% inhibition of alpha-glucosidase, respectively. The results were supported by molecular docking studies of the active compounds with acarvostatin as a standard drug for antidiabetic activity. Keywords Antidiabetic Benzoxazepines C–N bond formation Docking Microwave-assisted Pd-precatalyst ●
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Introduction Benzoxazepines is a wide class that attributed attention in the past many years owing to their biological and pharmaceutical properties. Some benzoxazepines derivatives shown potent biological activities considered as lead molecules for future drug development. Benzoxazepines derivatives is an effective medicinally potent agents, like orexin receptor antagonists. (Ai et al. 2010; Bajaj et al. 2004; Gijsen et al. 2010; Greene et al. 2016; Kamei et al. 2006; Youssef and Said 1996) have attracted huge attention in the past few years. The
Supplementary information The online version of this article (https:// doi.org/10.1007/s00044-020-02606-4) contains supplementary material, which is available to authorized users. * Fazlur-Rahman Nawaz Khan [email protected] 1
Organic and Medicinal Chemistry Research Laboratory, School of Advanced Sciences, Vellore Institute of Technology, Vellore 632 014 Tamil Nadu, India
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Department of Pharmaceutical Chemistry, G. Pulla Reddy College of Pharmacy, Hyderabad 500 028 Telangana, India
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Dr. MGR Educational Research Institute, Chennai 600095 Tamil Nadu, India
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N-substituted dibenzo[1, 4]oxazepin-11(10H)-ones were reported to exhibit antidepressant, calcium antagonist, anticancer, and squalene synthase inhibiting activities (DíazGavilán et al. 2008a, 2008b; Greenwood et al. 2006) diuretic activities (Conejo-García et al. 2011; Ramírez et al. 2018). Likewise benzoxazepines structural moiety is eminen
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