Synthesis and evaluation of N1-substituted-3-propyl-1,4-benzodiazepine-2-ones as cholecystokinin (CCK2) receptor ligands

Lattmann, Eric, Sattayasai, Jintana, Billington, David C., Poyner, David R., Puapairoj, Prapawadee, Tiamkao, Siriporn, Airarat, Wanchai, Singh, Harjit, Offel, Michael and Poyner, David (2002). Synthesis and evaluation of N1-substituted-3-propyl-1,4-benzodiazepine-2-ones as cholecystokinin (CCK2) receptor ligands. Journal of Pharmacy and Pharmacology, 54 (6), pp. 827-834.


A novel synthetic approach towards N1-alkylated 3-propyl-1,4-benzodiazepines was developed in five synthetic steps from 2-amino-4-chlorobenzophenone, in which the N-oxide 4 served as a key intermediate. The structure-activity relationship optimization of this 3-prophyl-1,4-benzodiazepine template was carried out on the N1-position by selective alkylation reactions and resulted in a ligand with an improved affinity on the cholecystokinin (CCK2) receptor. The N-allyl-3-propyl-benzodiazepine 6d displayed an affinity towards the CCK2 (CCK-B) receptor of 170 nM in a radiolabelled receptor-binding assay. The anxiolytic activity of this allyl-3-propyl-1,4-benzodiazepine 6d was subsequently determined in in-vivo psychotropic assays. This novel ligand had ED50 values of 4.7 and 5.2 mg kg-1 in the black and white box test and the x-maze, respectively, and no significant sedation/muscle relaxation was observed.

Publication DOI:
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Applied Health Research Group
Uncontrolled Keywords: Pharmacology,Pharmaceutical Science
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Related URLs: (Scopus URL)
Published Date: 2002-06-24
Authors: Lattmann, Eric
Sattayasai, Jintana
Billington, David C.
Poyner, David R. ( 0000-0003-1590-112X)
Puapairoj, Prapawadee
Tiamkao, Siriporn
Airarat, Wanchai
Singh, Harjit
Offel, Michael
Poyner, David ( 0000-0003-1590-112X)

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