Hikishima Sadao, Isobe Machiko, Koyanagi Satoru, Soeda Shinji, Shimeno Hiroshi, Shibuya Shiroshi, Yokomatsu Tsutomu
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Bioorg Med Chem. 2006 Mar 1;14(5):1660-70. doi: 10.1016/j.bmc.2005.10.017. Epub 2005 Nov 2.
9-(5',5'-Difluoro-5'-phosphonopentyl)guanine (DFPP-G) and its hypoxanthine analogue (DFPP-H) were modified by introducing a methyl group to all possible positions of the linker connecting a purine and difluoromethylenephosphonic acid moiety to evaluate the effects of the methyl group on inhibition against purine nucleoside phosphorylase. The methyl group on the linker affected the inhibition in a positional-dependent manner. Inhibitory potency of alpha-methyl and beta-methyl-substituted analogues of DFPP-H increased by about 600- to 1000-fold upon converting to cyclopropane nucleotide analogue (+/-)-4.
9-(5',5'-二氟-5'-膦酰戊基)鸟嘌呤(DFPP-G)及其次黄嘌呤类似物(DFPP-H)通过在连接嘌呤和二氟亚甲基膦酸部分的连接子的所有可能位置引入甲基进行修饰，以评估甲基对嘌呤核苷磷酸化酶抑制作用的影响。连接子上的甲基以位置依赖性方式影响抑制作用。将DFPP-H的α-甲基和β-甲基取代类似物转化为环丙烷核苷酸类似物(±)-4后，其抑制效力提高了约600至1000倍。
