Novel and potent NPY5 receptor antagonists derived from virtual screening and iterative parallel chemistry design.
In the quest for NPY5 receptor antagonists a virtual screening approach yielded a novel and potent hit class from a limited compound selection. The tight and seamless integration between virtual screening and rapid parallel chemistry within the framework of the Roche Lead Generation unit led in only two rounds of iterative chemistry optimisation to a much broader understanding of the factors which influence the potency of the thiazole hit class.
Guba
Wolfgang
W
F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. wolfgang.guba@roche.com
Neidhart
Werner
W
Nettekoven
Matthias
M
D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor