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

Lattmann, Eric, Billington, David C., Poyner, David, Howitt, Stephen B. and Offel, Michael (2001). Synthesis and evaluation of asperlicin analogues as non-peptidal cholecystokinin-antagonists. Drug Design and Discovery, 17 (3), pp. 219-230.


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%.

Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Uncontrolled Keywords: animals,benzodiazepinones,cholecystokinin,guinea pigs,male receptors,cholecystokinin structure-activity relationship
Published Date: 2001-07-25
Authors: Lattmann, Eric
Billington, David C.
Poyner, David ( 0000-0003-1590-112X)
Howitt, Stephen B.
Offel, Michael


Item under embargo.

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