Ogawa Seiichiro, Fujieda Shigeo, Sakata Yuko, Ishizaki Masahiro, Hisamatsu Seiichi, Okazaki Kensuke, Ooki Yoriko, Mori Midori, Itoh Masayoshi, Korenaga Takashi
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Bioorg Med Chem. 2004 Dec 15;12(24):6569-79. doi: 10.1016/j.bmc.2004.09.023.
In the course of chemical modification of alpha-fucosidase inhibitors of 5a-carba-fucopyranosylamine type, an N-dodecyl derivative of the enantiomer 6-deoxy-5a-carba-beta-D-galactopyranosylamine demonstrated very strong inhibition of beta-galactosidase and beta-glucosidase. This finding led us to synthesize corresponding 6-hydroxy compounds, in order to elucidate structure-activity relationships for inhibitors of this type. Among four N-alkyl-5a-carba-beta-D-galactopyranosylamines prepared, the N-octyl derivative could be demonstrated to possess moderate activity toward alpha- and beta-galactosidases, and beta-glucosidase.
在对5a-碳杂-岩藻糖胺型α-岩藻糖苷酶抑制剂进行化学修饰的过程中,对映体6-脱氧-5a-碳杂-β-D-吡喃半乳糖胺的N-十二烷基衍生物对β-半乳糖苷酶和β-葡萄糖苷酶表现出非常强的抑制作用。这一发现促使我们合成相应的6-羟基化合物,以阐明这类抑制剂的构效关系。在所制备的四种N-烷基-5a-碳杂-β-D-吡喃半乳糖胺中,N-辛基衍生物对α-和β-半乳糖苷酶以及β-葡萄糖苷酶具有中等活性。