Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery

Ogasahara, Riku; Ban, Kazuho; Mae, Miyu; Akai, Shuji; Sawama, Yoshinari

doi:https://doi.org/10.1002/cmdc.202400201

Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery

Ogasahara, Riku; Ban, Kazuho; Mae, Miyu et al.

ChemMedChem, 2024

アクセス数:37件（2025-04-10 08:31 集計）

固定URL: https://hdl.handle.net/11094/97148

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タイトル	Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery
著者	著者名 Ogasahara, Riku
	著者名 Ban, Kazuho
	著者名 Mae, Miyu
	NRID 1000060192457 1000060192457 researchmap permalink shuji_akai shuji_akai Scopus Author ID 7006001526 7006001526 ORCID 0000-0001-9149-8745 0000-0001-9149-8745 著者名 Akai, Shuji
	NRID 1000080552413 1000080552413 researchmap permalink sawama sawama Scopus Author ID 6505798196 6505798196 ORCID 0000-0002-9923-2412 0000-0002-9923-2412 著者名 Sawama, Yoshinari
キーワード等	Alkylation
	Deuteration
	Heavy drugs
	Kinetic isotope effect
	Sulfonium salt
内容	Ogasahara R., Ban K., Mae M., et al. Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery. ChemMedChem , (2024); https://doi.org/10.1002/cmdc.202400201.
抄録	Deuterated drugs (heavy drugs) have recently been spotlighted as a new modality for small-molecule drugs because the pharmacokinetics of pharmaceutical drugs can be enhanced by replacing C−H bonds with more stable C−D bonds at metabolic positions. Therefore, deuteration methods for drug candidates are a hot topic in medicinal chemistry. Among them, the H/D exchange reaction (direct transformation of C−H bonds to C−D bonds) is a useful and straightforward method for creating novel deuterated target molecules, and over 20 reviews on the synthetic methods related to H/D exchange reactions have been published in recent years. Although various deuterated drug candidates undergo clinical trials, approved deuterated drugs possess CD3 groups in the same molecule. However, less diversification, except for the CD3 group, is a problem for future medicinal chemistry. Recently, we developed various deuterated alkyl (dn-alkyl) sulfonium salts based on the H/D exchange reaction of the corresponding hydrogen form using D2O as an inexpensive deuterium source to introduce CD3, CH3CD2, and ArCH2CD2 groups into drug candidates. This concept summarises recent reviews related to H/D exchange reactions and novel reagents that introduce the CD3 group, and our newly developed electrophilic dn-alkyl reagents are discussed.
出版者	John Wiley and Sons Ltd
収録物名	ChemMedChem
刊行年月	2024-06-25
言語	英語
ハンドルURL	https://hdl.handle.net/11094/97148
PISSN	18607179
eISSN	18607187
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1002/cmdc.202400201
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	ChemMedChem. 2024
DC.title	Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery
DC.creator	Ogasahara, Riku
	Ban, Kazuho
	Mae, Miyu
	Akai, Shuji
	Sawama, Yoshinari
DC.publisher	John Wiley and Sons Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-06-25
DC.identifier	https://doi.org/10.1002/cmdc.202400201
DC.subject	Alkylation
	Deuteration
	Heavy drugs
	Kinetic isotope effect
	Sulfonium salt
DC.description	Ogasahara R., Ban K., Mae M., et al. Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery. ChemMedChem , (2024); https://doi.org/10.1002/cmdc.202400201.
DCTERMS.abstract	Deuterated drugs (heavy drugs) have recently been spotlighted as a new modality for small-molecule drugs because the pharmacokinetics of pharmaceutical drugs can be enhanced by replacing C−H bonds with more stable C−D bonds at metabolic positions. Therefore, deuteration methods for drug candidates are a hot topic in medicinal chemistry. Among them, the H/D exchange reaction (direct transformation of C−H bonds to C−D bonds) is a useful and straightforward method for creating novel deuterated target molecules, and over 20 reviews on the synthetic methods related to H/D exchange reactions have been published in recent years. Although various deuterated drug candidates undergo clinical trials, approved deuterated drugs possess CD3 groups in the same molecule. However, less diversification, except for the CD3 group, is a problem for future medicinal chemistry. Recently, we developed various deuterated alkyl (dn-alkyl) sulfonium salts based on the H/D exchange reaction of the corresponding hydrogen form using D2O as an inexpensive deuterium source to introduce CD3, CH3CD2, and ArCH2CD2 groups into drug candidates. This concept summarises recent reviews related to H/D exchange reactions and novel reagents that introduce the CD3 group, and our newly developed electrophilic dn-alkyl reagents are discussed.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	97148
citation_title	Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery
citation_author	Ogasahara, Riku
	Ban, Kazuho
	Mae, Miyu
	Akai, Shuji
	Sawama, Yoshinari
citation_publisher	John Wiley and Sons Ltd
citation_language	英語
citation_date	2024-06-25
citation_journal_title	ChemMedChem
citation_doi	https://doi.org/10.1002/cmdc.202400201
citation_public_url	https://hdl.handle.net/11094/97148

Deuterated Alkyl Sulfonium Salt Reagents; Importance of H/D Exchange Methods in Drug Discovery

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