Synthesis and evaluation of novel phosphate ester analogs as neutral sphingomyelinase inhibitors.
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).
Imagawa
Hiroshi
H
Tokushima Bunri University, Japan. imagawa@ph.bunri-u.ac.jp
Oda
Masataka
M
Takemoto
Takayuki
T
Yamauchi
Rieko
R
Yoshikawa
Tomomi
T
Yamamoto
Hirofumi
H
Nishizawa
Mugio
M
Takahashi
Hironobu
H
Hashimoto
Manabu
M
Yabiku
Kenta
K
Nagahama
Masahiro
M
Sakurai
Jun
J
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
D004791:Enzyme Inhibitors; C554926:RY221B-a; D015082:2,2'-Dipyridyl; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine