Analgesic effects of 5-alkyloxy-4-amino-2(5H)-furanones as cholecystokinin-2 antagonists


4-Amino-2(5H)-furanones were synthesized in high yields over two synthetic steps from readily available mucochloric acid. These 5-alkyloxy-4-amino-2(5H)-furanones were screened in a ([125]) I-CCK-8 radioligand receptor binding assay for CCK2 affinity and novel active ligands in the nanomolar range were identified. SAR was optimized leading to the cyclohexyl derivative 25 with an IC50 of 27 nM. Furanone 18 was obtained as a stable crystalline material with an IC50 of 85 nM, but had a higher CCK2 selectivity. It was subsequently tested in the isolated guinea pig ileum assay with sulfated CCK8 , and the CCK antagonizing properties of the ligand were confirmed. The CCK2 selective antagonist 18 was found to potentiate analgesia in the tail flick assay in mice, for the strong opiate morphine, the partial opiate agonist tramadol and the tricyclic antidepressant desimipramine.

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Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
Additional Information: This is the peer reviewed version of the following article: Lattmann, E., Sattayasai, J., Schwalbe, C. H., Boonprakob, Y., Dunn, S., Fajana, F., & Lattmann, P. (2016). Analgesic effects of 5-alkyloxy-4-amino-2(5H)-furanones as cholecystokinin-2 antagonists. Archiv der Pharmazie, 349(6), 456-465, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Uncontrolled Keywords: 2(5H)-Furanones,analgesia potentiation,CCK antagonists,isolated tissue preparations,radioligand binding
Publication ISSN: 1521-4184
Last Modified: 13 Jun 2024 07:12
Date Deposited: 03 May 2017 08:45
PURE Output Type: Article
Published Date: 2016-06-01
Published Online Date: 2016-05-03
Accepted Date: 2016-04-11
Authors: Lattmann, Eric
Sattayasai, Jintana
Schwalbe, Carl H.
Boonprakob, Yodchai
Dunn, Simon
Fajana, Feyisayo
Lattmann, Pornthip



Version: Accepted Version

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