gw-803430 has been researched along with Weight-Loss* in 2 studies
2 other study(ies) available for gw-803430 and Weight-Loss
| Article | Year |
|---|---|
Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup.
Our investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in vivo efficacy. The in vitro and exposure profiles of dihydropyrrolopyrazol-6-ones 1b and 1e were comparable to that of the thienopyrimidinone counterparts 41 and 43 except for a much faster MCHR1 apparent off-rate. The greatly diminished dihydropyrrolopyrazol-6-one anti-obesity response may be the consequence of this rapid off-rate. Topics: Animals; Anti-Obesity Agents; Half-Life; Humans; Obesity; Protein Binding; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Somatostatin; Structure-Activity Relationship; Weight Loss | 2015 |
Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation.
A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body weight in a chronic study. However no clear correlation between the pharmacodynamic effect and the pharmacokinetic data with respect to brain concentration was discernible leading us to conclude that the observed effect was most likely not due to interaction with the MCH-R1. Topics: Administration, Oral; Animals; Anti-Obesity Agents; Cyclohexylamines; Eating; Humans; Male; Pyrimidines; Quinazolines; Rats; Rats, Sprague-Dawley; Receptors, Somatostatin; Structure-Activity Relationship; Weight Loss | 2009 |