Synthesis and structure-activity relationships of novel dipeptides and reduced dipeptides as ligands for melanocortin subtype-4 receptor

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 9, 2006, Pages 2341-2346

  Shi, Qing ^a   Ornstein, Paul L ^a   Briner, Karin ^a   Richardson, Timothy I ^a   Arnold, Macklin B ^a   Backer, Ryan T ^a   Buckmaster, Jennifer L ^a   Canada, Emily J ^a   Doecke, Christopher W ^a   Hertel, Larry W ^a   Honigschmidt, Nick ^a   Hsiung, Hansen M ^a   Husain, Saba ^a   Kuklish, Steve L ^a   Martinelli, Michael J ^a,b   Mullaney, Jeffrey T ^a   O'Brien, Thomas P ^a   Reinhard, Matt R ^a   Rothhaar, Roger ^a   Shah, Jikesh ^a   Wu, Zhipei ^a   Xie, Chaoyu ^a   Zgombick, John M ^a   Fisher, Matthew J ^a   more..

^a ELI LILLY AND COMPANY   (United States)

^b AMGEN INC   (United States)

Author keywords

MC4R; Melanocortin subtype 4 receptor ligands

Indexed keywords

DIPEPTIDE; LIGAND; MELANOCORTIN 1 RECEPTOR; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN 5 RECEPTOR;

AMINO TERMINAL SEQUENCE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; STRUCTURE ACTIVITY RELATION;

DIPEPTIDES; LIGANDS; MOLECULAR STRUCTURE; PIPERAZINES; PROTEIN BINDING; RECEPTOR, MELANOCORTIN, TYPE 4; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33644981030     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.10.103     Document Type: Article

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18. Compounds 1 and 2 are enantiomerically pure. The chiral chromatographic resolution of the chloro analog 4 (giving 4a and 4b) was accomplished with the same solvent system as reported for fluoro analog 5 in Ref. 10. The order of elution previously reported for 5 was in error with the more active enantiomer 5b being the second eluting isomer, not the first (5a) as reported.
19. i values reported here are an average from two or four runs. Average error of the binding assay is 15%.