Privileged structure based ligands for melanocortin-4 receptors-Aliphatic piperazine derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 13, 2006, Pages 3449-3453

  Briner, Karin ^a   Collado, Iván ^b   Fisher, Matthew J ^a   García Paredes, Cristina ^b   Husain, Saba ^a   Kuklish, Steven L ^a   Mateo, Ana I ^b   O'Brien, Thomas P ^a   Ornstein, Paul L ^a   Zgombick, John ^a   de Frutos, Óscar ^b  

^a ELI LILLY AND COMPANY   (United States)

^b ELI LILLY AND COMPANY   (Spain)

Author keywords

Melanocortin receptors; Privileged structures

Indexed keywords

ALIPHATIC COMPOUND; AROMATIC COMPOUND; BENZYL DERIVATIVE; DIETHYLAMINE; LIGAND; MELANOCORTIN 4 RECEPTOR; PIPERAZINE DERIVATIVE;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; SUBSTITUTION REACTION; SYNTHESIS; CHEMISTRY; DRUG EFFECT; METABOLISM; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION;

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

EID: 33746636462     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.04.002     Document Type: Article

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20. Functional activity was determined by measuring cAMP release with a standard luciferase assay employing HEK 293 cells stably transfected with hMC4 (data not shown). Compounds of this paper were agonists with relative efficacies 60-100% of the maximum response obtained with NDP-α-MSH.
21. Compounds of this report were found to be generally selective for MC4 relative to the related receptors MC1 and MC3. Moderate to good selectivity was observed for MC4 relative to MC5 (data not shown).
22. Each data point represents the average of at least two determinations with an average error of the binding assay being 15%.
23. The numeration of the 2 epimers comes from the order of elution in the chiral separation of intermediate 9b.
24. This same trend was also observed in other less-active derivatives.