Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists I: discovery of CCKR1 selectivity in a previously CCKR2-selective lead series.
A series of CCK2R-selective anthranilic amides is shown to derive CCK1R affinity via selective substitution of the amide side chain. Thus, extending the length of the original benzamide side chain by a single methylene unit imparts CCK1R affinity to the series, and further fine tuning of the affinity results in CCK1R selectivity of greater than 100-fold.
Pippel
Marna
M
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
Allison
Brett D
BD
Phuong
Victor K
VK
Li
Lina
L
Morton
Magda F
MF
Prendergast
Clodagh
C
Wu
Xiaodong
X
Shankley
Nigel P
NP
Rabinowitz
Michael H
MH
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003001:Cloning, Molecular; D004353:Drug Evaluation, Preclinical; D005838:Genotype; D007555:Isoxazoles / Q000737:chemistry*; D018782:Maze Learning; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*
D001549:Benzamides; D007555:Isoxazoles; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D013449:Sulfonamides; C033962:anthranil; C037689:benzamide