SYNTHESIS, HYDROLYTIC BEHAVIOR, AND ANTI-HIV ACTIVITY OF SELECTED ACYLOXYALKYL ESTERS OF TRISODIUM PHOSPHONOFORMATE (FOSCARNET SODIUM)

Authors
IYER RP BOAL JH PHILLIPS LR THAKKER DR EGAN W
Citation
Rp. Iyer et al., SYNTHESIS, HYDROLYTIC BEHAVIOR, AND ANTI-HIV ACTIVITY OF SELECTED ACYLOXYALKYL ESTERS OF TRISODIUM PHOSPHONOFORMATE (FOSCARNET SODIUM), Journal of pharmaceutical sciences, 83(9), 1994, pp. 1269-1273
Citations number
27
Categorie Soggetti
Chemistry,"Pharmacology & Pharmacy
Journal title
Journal of pharmaceutical sciences → ACNP
ISSN journal
00223549
Volume
83
Issue
9
Year of publication
1994
Pages
1269 - 1273
Database
ISI
SICI code
0022-3549(1994)83:9<1269:SHBAAA>2.0.ZU;2-N
Abstract
The synthesis and anti-HIV activity of selected (acyloxy)alkyl esters of trisodium phosphonoformate (foscarnet sodium) are described. The co nversion of bis(trimethylsilyl) (alkoxycarbonyl)phosphonates 11a-d to the corresponding disilver salts 12a-d and their subsequent reaction w ith iodoalkyl acrylates 4a-c gave the desired bis(acyloxyalkyl) phosph onates 6-9(a-c). Of the analogs tested, only the dichlorophenyl analog 9a showed a dose-dependent inhibition of HIV activity in H9 cells. Us ing P-31-NMR, bioreversibility has been investigated in an attempt to rationalize these results.