title: Synthesis and evaluation of novel phosphate ester analogs as neutral sphingomyelinase inhibitors.
abstract: A novel sphingomyelin inhibitor RY221B-a, which contains a bipyridyl moiety as a metal coordination site was designed based upon the mechanism of phosphate ester hydrolysis. RY221B-a was synthesized from N-Boc-sphingosine in three steps via selective etherification using stannyl acetal. Synthesized RY221B-a exhibited relatively-strong inhibitory activity against Bc-SMase (IC(50)=1.2microM).
authors.affiliation: Tokushima Bunri University, Japan. imagawa@ph.bunri-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imagawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Oda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takemoto
authors.forename: Rieko
authors.initials: R
authors.lastname: Yamauchi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Mugio
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Manabu
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Kenta
authors.initials: K
authors.lastname: Yabiku
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagahama
authors.forename: Jun
authors.initials: J
authors.lastname: Sakurai
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001409:Bacillus cereus / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; C554926:RY221B-a; D015082:2,2'-Dipyridyl; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine