C32-O-IMIDAZOL-2-YL-METHYL ETHER DERIVATIVES OF THE IMMUNOSUPPRESSANTASCOMYCIN WITH IMPROVED THERAPEUTIC POTENTIAL

Authors
GOULET MT MCALPINE SR STARUCH MJ KOPRAK S DUMONT FJ CRYAN JG WIEDERRECHT GJ ROSA R WILUSZ MB PETERSON LB WYVRATT MJ PARSONS WH
Citation
Mt. Goulet et al., C32-O-IMIDAZOL-2-YL-METHYL ETHER DERIVATIVES OF THE IMMUNOSUPPRESSANTASCOMYCIN WITH IMPROVED THERAPEUTIC POTENTIAL, Bioorganic & medicinal chemistry letters, 8(16), 1998, pp. 2253-2258
Citations number
21
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
16
Year of publication
1998
Pages
2253 - 2258
Database
ISI
SICI code
0960-894X(1998)8:16<2253:CEDOTI>2.0.ZU;2-M
Abstract
A series of C32-O-aralkyl ether derivatives of the FK-506 related macr olide ascomycin have been prepared based on an earlier reported C32-O- cinnamyl ether design. In the present study, the nature of the aryl te thering group was varied in an attempt to improve oral activity. An im idazol-2-yl-methyl tether was found to be superior among those investi gated and has resulted in an ascomycin analog, L-733,725, with in vivo immunosuppressive activity comparable to FK-506 but with an improved therapeutic index. (C) 1998 Elsevier Science Ltd. All rights reserved.