title: Synthesis and structure-activity relationships of novel dipeptides and reduced dipeptides as ligands for melanocortin subtype-4 receptor.
abstract: A series of benzylic piperazines (e.g., 4 and 5) attached to an 'address element', the dipeptide H-D-Tic-D-p-Cl-Phe-OH, 3 has been identified as ligands for the melanocortin subtype-4 receptor (MC4R). We describe herein the structure-activity relationship (SAR) studies on the N-terminal residue of the 'address element'. Several novel dipeptides and reduced dipeptides with high MC4R binding affinities and selectivity emerged from this SAR study.
authors.affiliation: Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. shi_qing@lilly.com
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
authors.forename: Paul L
authors.initials: PL
authors.lastname: Ornstein
authors.forename: Karin
authors.initials: K
authors.lastname: Briner
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Richardson
authors.forename: Macklin B
authors.initials: MB
authors.lastname: Arnold
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Backer
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Buckmaster
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Canada
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Doecke
authors.forename: Larry W
authors.initials: LW
authors.lastname: Hertel
authors.forename: Nick
authors.initials: N
authors.lastname: Honigschmidt
authors.forename: Hansen M
authors.initials: HM
authors.lastname: Hsiung
authors.forename: Saba
authors.initials: S
authors.lastname: Husain
authors.forename: Steve L
authors.initials: SL
authors.lastname: Kuklish
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Martinelli
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Mullaney
authors.forename: Thomas P
authors.initials: TP
authors.lastname: O'Brien
authors.forename: Matt R
authors.initials: MR
authors.lastname: Reinhard
authors.forename: Roger
authors.initials: R
authors.lastname: Rothhaar
authors.forename: Jikesh
authors.initials: J
authors.lastname: Shah
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Wu
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Xie
authors.forename: John M
authors.initials: JM
authors.lastname: Zgombick
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fisher
mesh_terms: D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4 / Q000737:chemistry / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D008024:Ligands; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4