title: Pyrazole CCK(1) receptor antagonists. Part 1: Solution-phase library synthesis and determination of Free-Wilson additivity.
abstract: High throughput screening revealed compound 1 as a potent antagonist of the CCK(1) receptor. Evaluation of the CCK(1) SAR in a series of these diarylpyrazole antagonists was conducted in a matrix synthesis format revealing additive (Free-Wilson) and non-additive SAR. This use of additive QSAR modeling in conjunction with combinatorial libraries represents a unique approach to the evaluation of SAR interactions between the variables of any combinatorial matrix.
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: McClure
authors.forename: Michael
authors.initials: M
authors.lastname: Hack
authors.forename: Liming
authors.initials: L
authors.lastname: Huang
authors.forename: Clark
authors.initials: C
authors.lastname: Sehon
authors.forename: Magda
authors.initials: M
authors.lastname: Morton
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.forename: Terrance D
authors.initials: TD
authors.lastname: Barrett
authors.forename: Nigel
authors.initials: N
authors.lastname: Shankley
authors.forename: J Guy
authors.initials: JG
authors.lastname: Breitenbucher
mesh_terms: 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*; D013329:Structure-Activity Relationship
chemical_list: D019151:Peptide Library; D004364:Pharmaceutical Preparations; D011720:Pyrazoles; D043886:Receptor, Cholecystokinin A; D002766:Cholecystokinin