RAPID OPTIMIZATION OF AN ICE INHIBITOR SYNTHESIS USING MULTIPLE REACTION CONDITIONS IN A PARALLEL ARRAY

Authors
WARMUS JS RYDER TR HODGES JC KENNEDY RM BRADY KD
Citation
Js. Warmus et al., RAPID OPTIMIZATION OF AN ICE INHIBITOR SYNTHESIS USING MULTIPLE REACTION CONDITIONS IN A PARALLEL ARRAY, Bioorganic & medicinal chemistry letters, 8(17), 1998, pp. 2309-2314
Citations number
7
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
17
Year of publication
1998
Pages
2309 - 2314
Database
ISI
SICI code
0960-894X(1998)8:17<2309:ROOAII>2.0.ZU;2-O
Abstract
Optimization of a 2-step reaction sequence was accomplished in 3-4 day s, with over 200 different reaction conditions evaluated. Combinatoria l arrays were performed using the optimized conditions to synthesize 5 90 new compounds which were tested for inhibition against N-His (D381E ) ICE. Thirty-five compounds showed at least a tenfold improvement in activity compared to an initial standard. (C) 1998 Elsevier Science Lt d. All rights reserved.