title: Synthesis of Tic-D-Phe Psi[CH2-CH2] isostere and its use in the development of melanocortin receptor agonists.
abstract: The first synthesis of Tic-D-Phe Psi[CH(2)-CH(2)] isostere is described, which features diastereoselective alkylation of the tricyclic lactam 14. The use of this novel dipeptide isostere in the development of melanocortin agonists has been demonstrated by the synthesis of peptidomimetic 7 and non-peptidic ligand 27. Both compounds displayed significant binding and agonist potency at the MC4R.
authors.affiliation: Health Care Research Center, Procter & Gamble Pharmaceuticals, 8700 Mason Montgomery Road, Mason, OH 45040, USA. tian.x@pg.com
authors.forename: Xinrong
authors.initials: X
authors.lastname: Tian
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.forename: Lixian
authors.initials: L
authors.lastname: Gan
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Hayes
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Switzer
authors.forename: Mark G
authors.initials: MG
authors.lastname: Solinsky
authors.forename: Frank H
authors.initials: FH
authors.lastname: Ebetino
authors.forename: John A
authors.initials: JA
authors.lastname: Wos
authors.forename: Beth B
authors.initials: BB
authors.lastname: Pinney
authors.forename: Julie A
authors.initials: JA
authors.lastname: Farmer
authors.forename: Doreen
authors.initials: D
authors.lastname: Crossdoersen
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Sheldon
mesh_terms: D000478:Alkylation; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007769:Lactams / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D010649:Phenylalanine / Q000737:chemistry*; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D007769:Lactams; D008024:Ligands; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D010649:Phenylalanine