SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF MACROCYCLIC FKBP LIGANDS

Authors
LUENGO JI KONIALIANBECK A LEVY MA BRANDT M EGGLESTON DS HOLT DA
Citation
Ji. Luengo et al., SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF MACROCYCLIC FKBP LIGANDS, Bioorganic & medicinal chemistry letters, 4(2), 1994, pp. 321-324
Citations number
15
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
4
Issue
2
Year of publication
1994
Pages
321 - 324
Database
ISI
SICI code
0960-894X(1994)4:2<321:SASOMF>2.0.ZU;2-P
Abstract
A number of pipecolinate dilactones have been synthesized as simplifie d macrocyclic mimics of the binding domains in rapamycin (1) and FK506 (2). Crystallographic studies of these compounds indicate that the co nformation of the pipecolinyl alpha-ketoamide region is preorganized f or binding to FKBP. This is confirmed by the ability of these analogs to inhibit the FKBP cis-trans peptidyl-prolyl isomerase activity.