Privileged structure based ligands for melanocortin receptors - Substituted benzylic piperazine derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 22, 2005, Pages 4973-4978

  Fisher, Matthew J ^a   Backer, Ryan T ^a   Collado, Iván ^b   De Frutos, Óscar ^b   Husain, Saba ^a   Hsiung, Hansen M ^a   Kuklish, Steve L ^a   Mateo, Ana I ^a   Mullaney, Jeffrey T ^a   Ornstein, Paul L ^a   Paredes, Cristina García ^b   O'Brian, Thomas P ^a   Richardson, Timothy I ^a   Shah, Jikesh ^a   Zgombick, John M ^a   Briner, Karin ^a  

^a ELI LILLY AND COMPANY   (United States)

^b ELI LILLY AND COMPANY   (Spain)

Author keywords

Melanocortin receptors; Priveleged structures

Indexed keywords

MELANOCORTIN 4 RECEPTOR; PIPERAZINE DERIVATIVE;

ARTICLE; ENANTIOMER; RECEPTOR AFFINITY; SUBSTITUTION REACTION;

BENZENE DERIVATIVES; LIGANDS; MOLECULAR STRUCTURE; PIPERAZINES; RECEPTORS, MELANOCORTIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 25844475958     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.08.018     Document Type: Article

References (17)

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14. The details of the binding assay have been recently described. See Ref. 3.
15. Functional activity was determined by measuring cAMP release with a standard luciferase assay employing HEK 293 cells stably transfected with hMC4R. Compounds (both single antipodes and diastereomeric pairs) described in this paper were agonists with relative efficacies 60-100% of the maximum response obtained with NDP-α-MSH. Of the diastereomeric pairs that were separated, we were unable to detect any antagonist activity in the less active diastereomer.
16. Compounds of this report were found to be generally selective for MC4R relative to the related receptors MC1 and MC3. Moderate to good selectivity was observed for MC4R relative to MC5R.
17. Each data point represents the average of at least two determinations with an average error of the binding assay being 15%.