Sphingomyelin analogues as inhibitors of sphingomyelinase.
To search for neutral sphingomyelinase inhibitors we designed and synthesized hydrolytically stable analogues of sphingomyelin. The novel compounds 8 and 9 which were replaced the phosphodiester moiety of sphingomyelin with the carbamate moiety showed inhibitory activity with an IC(50) value of micro M on neutral sphingomyelinase in rat brain microsomes. Compound 8i showed a selective neutral sphingomyelinase inhibitory activity.
Taguchi
Minoru
M
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama-shi, 331-9530, Saitama, Japan. minoru.taguchi@po.rd.taisho.co.jp
Sugimoto
Kikuo
K
Goda
Ken-ichi
K
Akama
Tomoko
T
Yamamoto
Kyoko
K
Suzuki
Taizo
T
Tomishima
Yasumitsu
Y
Nishiguchi
Mariko
M
Arai
Koshi
K
Takahashi
Kenzo
K
Kobori
Takeo
T
D000818:Animals; D001921:Brain / Q000378:metabolism; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008861:Microsomes / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013109:Sphingomyelins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002219:Carbamates; D010726:Phosphodiesterase Inhibitors; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase