Affordable Access

Synthesis and evaluation of asperlicin analogues as non-peptidal cholecystokinin-antagonists.

Authors
  • Lattmann, E
  • Billington, D C
  • Poyner, D R
  • Howitt, S B
  • Offel, M
Type
Published Article
Journal
Drug design and discovery
Publication Date
Jan 01, 2001
Volume
17
Issue
3
Pages
219–230
Identifiers
PMID: 11469752
Source
Medline
License
Unknown

Abstract

The SAR of Asperlicin analogues is reported, leading to bioactive 1,4-benzodiazepine-2-ones, which were prepared in a 3 step reaction sequence. The Asperlicin substructure was built up using Tryptophan and readily available 2-amino-acetophenones. This template, containing a 1,4-benzodiazepin-2-one moiety with a 3-indolmethyl side chain, was transformed into mono- and di-substituted 3-indol-3'-yl-methyl-1,4-benzodi-azepine-2-ones by selective alkylation and acylation reactions. The SAR optimization of the 1,4-benzodiazepine scaffold has included variations at the 5-, 7-, 8-position, at the N1, N-indole nitrogen and the configuration of the C3-position. The most active Asperlicin analogue, having an IC50 of 1.6 microM on the CCKA receptor subtype, was obtained from Tryptophan in only 3 steps in an overall yield of 48%.

Report this publication

Statistics

Seen <100 times