Publication: Synthesis of Benzoazepine Derivatives via Azide Rearrangement and Evaluation of Their Antianxiety Activities
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Issued Date
2021-09-09
Resource Type
ISSN
19485875
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2-s2.0-85114637286
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Mahidol University
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SCOPUS
Bibliographic Citation
ACS Medicinal Chemistry Letters. Vol.12, No.9 (2021), 1449-1458
Suggested Citation
Onrapak Reamtong, Sarawut Lapmanee, Jumreang Tummatorn, Nitwaree Palavong, Charnsak Thongsornkleeb, Somsak Ruchirawat Synthesis of Benzoazepine Derivatives via Azide Rearrangement and Evaluation of Their Antianxiety Activities. ACS Medicinal Chemistry Letters. Vol.12, No.9 (2021), 1449-1458. doi:10.1021/acsmedchemlett.1c00275 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/76028
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Title
Synthesis of Benzoazepine Derivatives via Azide Rearrangement and Evaluation of Their Antianxiety Activities
Abstract
A new synthetic method for the construction of benzoazepine analogues has been developed employing ortho-arylmethylbenzyl azide derivatives as precursors using an azide rearrangement reaction. In this work, 14 benzoazepine compounds were successfully synthesized in moderate to excellent yields. All synthetic benzoazepines were evaluated for their cytotoxicity against normal human kidney cell line (HEK cell). The results showed that compound 18c had the lowest cytotoxicity (IC50 = 65.68 μM) among tested compounds, which was comparable with the antianxiety drug diazepam (IC50 = 87.90 μM). Based on the cytotoxicity results, five benzoazepine analogues (compounds 18c, 18h, 18j, 18n, and 18p) were selected to determine the antianxiety effect on stressed rats using elevated plus maze (EPM) and open field test (OFT) methods. Interestingly, compound 18c showed better anxiolytic activity than diazepam without a sedative effect by showing superior hyperlocomotor activity. Therefore, this discovery could pave the way for drug development to treat patients with anxiety disorder.