title: Biological evaluation of sphingomyelin analogues as inhibitors of sphingomyelinase.
abstract: Seeking neutral sphingomyelinase inhibitors, we designed and synthesized hydrolytically stable analogues of sphingomyelin. These novel analogues replace the phosphodiester moiety of sphingomyelin with carbamate and urea moiety, resulting in inhibition of neutral sphingomyelinase. Compound 1 prevented ceramide generation and apoptotic neuronal cell death in a model of ischemia based on organotypic hippocampal slice cultures.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. minoru.taguchi@po.rd.taisho.co.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Taguchi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Goda
authors.forename: Kikuo
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Akama
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Taizo
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Tomishima
authors.forename: Mariko
authors.initials: M
authors.lastname: Nishiguchi
authors.forename: Koshi
authors.initials: K
authors.lastname: Arai
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takeo
authors.initials: T
authors.lastname: Kobori
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology; D002518:Ceramides / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D008861:Microsomes / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009924:Organ Culture Techniques; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D013109:Sphingomyelins / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002518:Ceramides; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase