Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: tuning of receptor selectivity and in vivo efficacy

Marna Pippel; Kristen Boyce; Hariharan Venkatesan; Victor K Phuong; Wen Yan; Terrance D Barrett; Guy Lagaud; Lina Li; Magda F Morton; Clodagh Prendergast; Xiaodong Wu; Nigel P Shankley; Michael H Rabinowitz

doi:10.1016/j.bmcl.2009.09.065

Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: tuning of receptor selectivity and in vivo efficacy

Bioorg Med Chem Lett. 2009 Nov 15;19(22):6376-8. doi: 10.1016/j.bmcl.2009.09.065. Epub 2009 Sep 23.

Authors

Marna Pippel¹, Kristen Boyce, Hariharan Venkatesan, Victor K Phuong, Wen Yan, Terrance D Barrett, Guy Lagaud, Lina Li, Magda F Morton, Clodagh Prendergast, Xiaodong Wu, Nigel P Shankley, Michael H Rabinowitz

Affiliation

¹ Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.

PMID: 19815410
DOI: 10.1016/j.bmcl.2009.09.065

Abstract

In the previous article we demonstrated how certain CCK2R-selective anthranilic amides could be structurally modified to afford high-affinity, selective CCK1R activity. We now describe our efforts at modulating and optimizing the CCK1R and CCK2R affinities aimed at producing compounds with good pharmacokinetics properties and in vivo efficacy in rat models of gastric acid and pancreatic amylase secretion.

MeSH terms

Amino Acid Substitution
Animals
Isoxazoles / chemistry*
Models, Molecular
Rats
Rats, Wistar
Receptor, Cholecystokinin A / antagonists & inhibitors*
Receptor, Cholecystokinin B / antagonists & inhibitors*
Signal Transduction / drug effects*
Sulfonamides / pharmacology*
Treatment Outcome

Substances

Isoxazoles
Receptor, Cholecystokinin A
Receptor, Cholecystokinin B
Sulfonamides
anthranil