Anti -Schistosomal activity and ADMET properties of 1,2,5-oxadiazinane-containing compound synthesized by visible-light photoredox catalysis.

Autor:	Itoh K; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp.; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan., Nakahara H; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp., Takashino A; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp., Hara A; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp., Katsuno A; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp., Abe Y; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp., Mizuguchi T; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp.; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan., Karaki F; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp.; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan., Hirayama S; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp.; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan., Nagai K; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan., Seki R; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan., Sato N; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan., Okuyama K; Department of Material Science, Graduate School of Science, Josai University 1-1 Keyakidai Sakado Saitama 350-0295 Japan., Hashimoto M; Department of Material Science, Graduate School of Science, Josai University 1-1 Keyakidai Sakado Saitama 350-0295 Japan., Tokunaga K; Division of Liberal Arts, Center for Promotion of Higher Education, Kogakuin University 2665-1 Nakano-machi Hachioji Tokyo 192-0015 Japan., Ishida H; Graduate School of Science and Engineering, Department of Chemistry, Materials and Bioengineering, Kansai University 3-3-35 Yamate-cho Suita Osaka 564-8680 Japan., Mikami F; Department of Parasitology and Tropical Medicine, Kitasato University School of Medicine 1-15-1 Kitazato, Minami-ku Sagamihara Kanagawa 252-0374 Japan., Kwofie KD; Department of Parasitology and Tropical Medicine, Kitasato University School of Medicine 1-15-1 Kitazato, Minami-ku Sagamihara Kanagawa 252-0374 Japan., Kawada H; Department of Parasitology and Tropical Medicine, Kitasato University School of Medicine 1-15-1 Kitazato, Minami-ku Sagamihara Kanagawa 252-0374 Japan., Lin B; Drug Innovation Center Lead Exploration Unit, Graduate School of Pharmaceutical Sciences, Osaka University 1-6 Yamadagaoka Suita Osaka 565-0871 Japan., Nunomura K; Drug Innovation Center Lead Exploration Unit, Graduate School of Pharmaceutical Sciences, Osaka University 1-6 Yamadagaoka Suita Osaka 565-0871 Japan., Kanai T; Drug Innovation Center Lead Exploration Unit, Graduate School of Pharmaceutical Sciences, Osaka University 1-6 Yamadagaoka Suita Osaka 565-0871 Japan., Hatta T; Department of Parasitology and Tropical Medicine, Kitasato University School of Medicine 1-15-1 Kitazato, Minami-ku Sagamihara Kanagawa 252-0374 Japan., Tsuji N; Department of Parasitology and Tropical Medicine, Kitasato University School of Medicine 1-15-1 Kitazato, Minami-ku Sagamihara Kanagawa 252-0374 Japan., Haruta J; Drug Innovation Center Lead Exploration Unit, Graduate School of Pharmaceutical Sciences, Osaka University 1-6 Yamadagaoka Suita Osaka 565-0871 Japan., Fujii H; Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan itok@pharm.kitasato-u.ac.jp.; Medicinal Research Laboratories, School of Pharmacy, Kitasato University 5-9-1 Shirokane Minato-ku Tokyo 108-8641 Japan.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2024 Sep 26. Date of Electronic Publication: 2024 Sep 26.
DOI:	10.1039/d4md00599f
Abstrakt:	The incorporation of saturated nitrogen-containing heterocycle 1,2,5-oxadiazinane into small molecules represents a compelling avenue in drug discovery due to its unexplored behavior within biological systems and incomplete protocols for synthesis. In this study, we present 1,2,5-oxadiazinane, an innovative heterocyclic bioisostere of piperizin-2-one and novel chemotype of the anti -schistosomal drug praziquantel (PZQ), which has been the only clinical drug available for three decades. PZQ is associated with significant drawbacks, including poor solubility, a bitter taste, and low metabolic stability. Therefore, the discovery of a new class of anti -schistosomal agents is imperative. To address this challenge, we introduce a pioneering method for the synthesis of 1,2,5-oxadiazinane derivatives through the cycloaddition of nitrones with N , N , N' , N' -tetraalkyldiaminomethane in the presence of an Ir III complex photosensitizer. This transformative reaction offers a streamlined route to various kinds of 1,2,5-oxadiazinanes that is characterized by mild reaction conditions and broad substrate scope. Mechanistic investigations suggest that the photoredox pathway underlies the [3 + 3] photocycloaddition process. Thus, based on bioisosteric replacement, we identified a remarkable molecule as a new chemotype of a potent anti -schistosomal compound that not only exhibits superior solubility, but also retains the potent biological activity inherent to PZQ. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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