Biological evaluation of sphingomyelin analogues as inhibitors of sphingomyelinase |
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| Authors: | Taguchi Minoru Goda Ken-ichi Sugimoto Kikuo Akama Tomoko Yamamoto Kyoko Suzuki Taizo Tomishima Yasumitsu Nishiguchi Mariko Arai Koshi Takahashi Kenzo Kobori Takeo |
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| Institution: | 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 |
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| 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. |
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