Discovery of N-methylbenzo[d]oxazol-2-amine as new anthelmintic agent through scalable protocol for the synthesis of N-alkylbenzo[d]oxazol-2-amine and N-alkylbenzo[d]thiazol-2-amine derivatives
Issued Date
2023-02-01
Resource Type
ISSN
00452068
eISSN
10902120
Scopus ID
2-s2.0-85145581405
Pubmed ID
36455482
Journal Title
Bioorganic Chemistry
Volume
131
Rights Holder(s)
SCOPUS
Bibliographic Citation
Bioorganic Chemistry Vol.131 (2023)
Suggested Citation
Laohapaisan P., Reamtong O., Tummatorn J., Thongsornkleeb C., Thaenkham U., Adisakwattana P., Ruchirawat S. Discovery of N-methylbenzo[d]oxazol-2-amine as new anthelmintic agent through scalable protocol for the synthesis of N-alkylbenzo[d]oxazol-2-amine and N-alkylbenzo[d]thiazol-2-amine derivatives. Bioorganic Chemistry Vol.131 (2023). doi:10.1016/j.bioorg.2022.106287 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/81675
Title
Discovery of N-methylbenzo[d]oxazol-2-amine as new anthelmintic agent through scalable protocol for the synthesis of N-alkylbenzo[d]oxazol-2-amine and N-alkylbenzo[d]thiazol-2-amine derivatives
Other Contributor(s)
Abstract
We discovered a lead compound, N-methylbenzo[d]oxazol-2-amine (2a), which had comparable potency to albendazole, an orally administered anthelmintic drug, against Gnathostoma spinigerum, Caenorhabditis elegans and Trichinella spiralis. Compound 2a showed about 10 times lower cytotoxicity towards normal human cell line (HEK293) than albendazole. Moreover, we have developed new processes for the synthesis of N-alkylbenzo[d]oxazol-2-amine and N-alkylbenzo[d]thiazol-2-amine derivatives via metal-free conditions. This protocol could serve as a robust and scalable method, especially, to synthesize N-methylbenzo[d]oxazol-2-amine and N-methylbenzo[d]thiazol-2-amine derivatives which were difficult to prepare using other metal-free conditions. The method employed benzoxazole-2-thiol or benzothiazole-2-thiol as the substrate. The reaction was triggered by methylation of the thiol functional group to form the methyl sulfide intermediate, a crucial tactic, which facilitated in a smooth nucleophilic addition–elimination reaction with gaseous methylamine generated in situ from N-methylformamide. In addition, the proteomic analysis of compound 2a was also studied in this work.