title: Privileged structure based ligands for melanocortin receptors--4,4-disubstituted piperidine derivatives.
abstract: Homologation and cyclization back to the chiral methine of compound 3 yields achiral 4,4-disubstituted piperidine privileged structures (e.g., 8a) useful in the construction of melanocortin 4 receptor (MC4R) ligands. The piperidine nitrogen was replaced with carbon, oxygen, sulfur, and sulfone with minor erosion of binding. The methyl cyclohexane substituent was the most potent while significant affinity was still seen for smaller lipophilic groups such as ethyl.
authors.affiliation: Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46258, USA. Kuklish_steven@lilly.com
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kuklish
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Backer
authors.forename: Karin
authors.initials: K
authors.lastname: Briner
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Doecke
authors.forename: Saba
authors.initials: S
authors.lastname: Husain
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Mullaney
authors.forename: Paul L
authors.initials: PL
authors.lastname: Ornstein
authors.forename: John M
authors.initials: JM
authors.lastname: Zgombick
authors.forename: Thomas P
authors.initials: TP
authors.lastname: O'Brien
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fisher
mesh_terms: D001665:Binding Sites; D002244:Carbon / Q000737:chemistry; D003510:Cyclohexanes / Q000737:chemistry; D008024:Ligands; D010100:Oxygen / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism*; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry
chemical_list: D003510:Cyclohexanes; D008024:Ligands; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4; D013450:Sulfones; D013455:Sulfur; D002244:Carbon; D010100:Oxygen