193626-34-5Relevant articles and documents
Rapid parallel synthesis applied to the optimization of a series of potent nonpeptide neuropeptide Y-1 receptor antagonists
Siegel, Miles G.,Chaney, Michael O.,Bruns, Robert F.,Clay, Michael P.,Schober, Douglas A.,Van Abbema, Anne M.,Johnson, Douglas W.,Cantrell, Buddy E.,Hahn, Patric J.,Hunden, David C.,Gehlert, Donald R.,Zarrinmayeh, Hamideh,Ornstein, Paul L.,Zimmerman, Dennis M.,Koppel, Gary A.
, p. 11619 - 11639 (1999)
This study describes the integrated application of parallel synthesis and computational chemistry to the design of potent nonpeptide antagonists for the neuropeptide Y-1 (NPY1) receptor. A lead molecule was modeled in the active site of the NPY1 receptor, and a potentially fruitful region for analog construction was identified. Synthesis of suitable scaffolds followed by solution phase generation of a small library of analogs produced a compound with 5-fold improvement in binding over the already potent lead. This new compound was shown to be an unanticipated side product of the parallel synthesis reaction.
Structure-activity relationships of a series of 1-substituted-4-methylbenzimidazole neuropeptide Y-1 receptor antagonists
Zimmerman, Dennis M.,Cantrell, Buddy E.,Smith, Edward C.R.,Nixon, James A.,Bruns, Robert F.,Gitter, Bruce,Hipskind, Philip A.,Ornstein, Paul L.,Zarrinmayeh, Hamideh,Britton, Thomas C.,Schober, Douglas A.,Gehlert, Donald R.
, p. 473 - 476 (2007/10/03)
The characterization of a novel series of NPY-1 receptor antagonists derived from the 4-methylbenzimidazole 4 is described. Appropriate substitution on the piperidyl nitrogen of 4 led to systematic increases in Y-1 receptor affinity, to approximately 50-fold, and to the discovery of the importance of a second basic substituent.
