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

Eric Lattmann, David C. Billington, David Poyner, Stephen B. Howitt, Michael Offel

Research output: Contribution to journalArticlepeer-review


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%.
Original languageEnglish
Pages (from-to)219-230
Number of pages12
JournalDrug Design and Discovery
Issue number3
Publication statusPublished - 25 Jul 2001


  • animals
  • benzodiazepinones
  • cholecystokinin
  • guinea pigs
  • male receptors
  • cholecystokinin structure-activity relationship


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