Synthesis of 1,1-difluoro-5-(1<i>H</i>-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues. Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues. Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase

Authors:	Tsutomu Yokomatsu Hiroshi Abe Mutsumi Sato Kenji Suemune Taro Kihara Shinji Soeda Hiroshi Shimeno Shiroshi Shibuya

Affiliation:	^a School of Pharmacy, Tokyo University of Pharmacy & Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan ^b Faculty of Pharmaceutical Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract:	A series of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids, (E)-2a,b and (Z)-2a,b, as well as the related methano analogues (±)-3a,b and (±)-4a,b were prepared for evaluation of their PNP inhibitory activities. The cyclopopane ring and the hypoxanthine residue were found to increase the profile of inhibitory activity. The IC₅₀ and K_i values of difluoro{(1R,2S)-2-[2-(6-oxo-6,9-dihydro-1H9-purinyl)ethyl]cyclopropyl}methylphosphonic acid (±)-3b toward PNP purified from Cellulomonas sp. were determined to be 70 nM and 8.8nM, respectively.

Keywords:	enzyme inhibitors mimetics nucleotides phosphonic acids and derivs.
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