title: Structure-activity relationships in a series of NPY Y5 antagonists: 3-amido-9-ethylcarbazoles, core-modified analogues and amide isosteres.
abstract: Beginning with carbazole 1a, the amide and alkyl substituents were optimized to maintain potency while adding solubilizing groups. Efforts to replace the 3-amino-9-ethylcarbazole core, a known carcinogen, used the SAR generated in the carbazole series for guidance and led to the synthesis of a number of core-modified analogues. In addition, an isosteric series, in which the amide was replaced with an imidazole, was prepared. Two potent new series lacking the putative toxicophore were identified from these endeavors.
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA. marlys_hammond@groton.pfizer.com
authors.forename: Marlys
authors.initials: M
authors.lastname: Hammond
authors.forename: Richard L
authors.initials: RL
authors.lastname: Elliott
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Gillaspy
authors.forename: David C
authors.initials: DC
authors.lastname: Hager
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hank
authors.forename: Janet A
authors.initials: JA
authors.lastname: LaFlamme
authors.forename: Robert M
authors.initials: RM
authors.lastname: Oliver
authors.forename: Paul A
authors.initials: PA
authors.lastname: DaSilva-Jardine
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Stevenson
authors.forename: Christine M
authors.initials: CM
authors.lastname: Mack
authors.forename: James V
authors.initials: JV
authors.lastname: Cassella
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000737:chemistry* / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D002227:Carbazoles; D007093:Imidazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; C029899:imidazole; D002118:Calcium