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

Authors
Yokomatsu, T Abe, H Sato, M Suemune, K Kihara, T Soeda, S Shimeno, H Shibuya, S
Citation
T. Yokomatsu et al., Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues. Remarkable effect of the nucleobases and thecyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase, BIO MED CH, 6(12), 1998, pp. 2495-2505
Citations number
25
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
09680896 → ACNP
Volume
6
Issue
12
Year of publication
1998
Pages
2495 - 2505
Database
ISI
SICI code
0968-0896(199812)6:12<2495:SO1AAT>2.0.ZU;2-E
Abstract
A series of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids, (E)-2 a,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 th e profile of inhibitory activity. The IC50 and K-i values of difluoro({1R*, 2S*)-2-[2-(6-oxo-6,9-dihydro-1H-9-purinyl)ethyl]cyclopropyl)methylphosphoni c acid (+/-)3b toward PNP purified from Cellulomonas sp. were determined to be 70 nM and 8.8 nM, respectively. (C) 1998 Elsevier Science Ltd. All righ ts reserved.