Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: tuning of receptor selectivity and in vivo efficacy.
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.
Pippel
Marna
M
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
Boyce
Kristen
K
Venkatesan
Hariharan
H
Phuong
Victor K
VK
Yan
Wen
W
Barrett
Terrance D
TD
Lagaud
Guy
G
Li
Lina
L
Morton
Magda F
MF
Prendergast
Clodagh
C
Wu
Xiaodong
X
Shankley
Nigel P
NP
Rabinowitz
Michael H
MH
D019943:Amino Acid Substitution; D000818:Animals; D007555:Isoxazoles / Q000737:chemistry*; D008958:Models, Molecular; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors*; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D016896:Treatment Outcome
D007555:Isoxazoles; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D013449:Sulfonamides; C033962:anthranil