Pyrazole CCK(1) receptor antagonists. Part 2: SAR studies by solid-phase library synthesis and determination of Free-Wilson additivity.
High-throughput screening revealed compound 1 as a potent antagonist of the CCK(1) receptor. Here, we disclose the synthesis of combinatorial libraries by solid-phase synthesis on Kenner 'safety catch' resin. Additive QSAR models were used to determine a lack of consistent additive SAR within the matrix.
Sehon
Clark
C
Johnson and Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
McClure
Kelly
K
Hack
Michael
M
Morton
Magda
M
Gomez
Laurent
L
Li
Lina
L
Barrett
Terrance D
TD
Shankley
Nigel
N
Breitenbucher
J Guy
JG
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002766:Cholecystokinin / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D015233:Models, Statistical; D019151:Peptide Library; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry*; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors*; D012044:Regression Analysis; D013329:Structure-Activity Relationship
D019151:Peptide Library; D004364:Pharmaceutical Preparations; D011720:Pyrazoles; D043886:Receptor, Cholecystokinin A; D002766:Cholecystokinin