title: Synthesis and SAR of selective small molecule neuropeptide Y Y2 receptor antagonists.
abstract: Highly potent and selective small molecule neuropeptide Y Y2 receptor antagonists are reported. The systematic SAR exploration of a hit molecule N-(4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide, identified from HTS, led to the discovery of highly potent NPY Y2 antagonists 16 (CYM 9484) and 54 (CYM 9552) with IC(50) values of 19 nM and 12 nM respectively.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
authors.forename: Gopi Kumar
authors.initials: GK
authors.lastname: Mittapalli
authors.forename: Danielle
authors.initials: D
authors.lastname: Vellucci
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Marion
authors.initials: M
authors.lastname: Toussaint
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brothers
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.forename: Edward
authors.initials: E
authors.lastname: Roberts
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001681:Biological Assay; D000242:Cyclic AMP / Q000032:analysis; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D010880:Piperidines; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D000242:Cyclic AMP; D013890:Thiourea