β-Alanine dipeptides as MC4R agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 24, 2003, Pages 4341-4344

  Ruel, Réjean ^a   Herpin, Timothy F ^b   Iben, Lawrence ^b   Luo, Guanglin ^b   Martel, Alain ^a   Mason, Helen ^b   Mattson, Gail ^b   Poirier, Brigitte ^a   Ruediger, Edward H ^a   Shi, Dan ^b   Thibault, Carl ^a   Yu, Guixue ^b   Zimanyi, Ildiko Antal ^b   Poindexter, Graham S ^b   MacOr, John E ^b  

^a BRISTOL MYERS SQUIBB   (United States)

^b Department of Neuroscience ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ALANINE; DIPEPTIDE; MELANOCORTIN 4 RECEPTOR; TETRAHYDROISOQUINOLINE;

AMINO TERMINAL SEQUENCE; ARTICLE; DRUG IDENTIFICATION; DRUG POTENCY; DRUG PROTEIN BINDING; IC 50; LIPOPHILICITY; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION;

EID: 0345358514     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.09.036     Document Type: Article

References (24)

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17. 2. Windows XP ACD Software version 5.0 was used to perform these calculations.
18. Related glycine and 4-aminobutyryl amide derivatives were also studied. This work will be reported in due course.
19. 2) and filtrated over GF/B glass fiber filters that were previously soaked in 1% PEI. Non-specific binding was defined in the presence of 1 μM NDP-α-MSH. Filters were measured by liquid scintillation counting, and the data was analyzed by non-linear regression using the XLfit function of EXCEL.
20. 4 cells/well and incubated overnight. The culture medium was aspirated and changed to the assay medium containing 0.1 mM IBMX, and increasing concentrations of the test compound at final DMSO concentration of 1%. The cells were incubated for 10 min at 37 °C, then the medium was aspirated and replaced with the lysis medium, and cAMP concentration was measured according to the manufacturer's direction. Intrinsic activity was expressed as percent of maximal activity achieved by NDP-α-MSH. Data was analyzed by non-linear regression using the PRIZM program.
21. Hruby V.J., Wilkes B.C., Hadley M.E., Al-Obeidi F., Sawyer T.K., Staples D.J., Devaux A., Dym O., Castrucci A.M., Hintz M.F., Riehm J.P., Rao K.R. J. Med. Chem. 30:1987;2126.
22. 2O: C, 49.69; H, 6.74; N, 13.37. Found: C, 49.96; H, 6.75; N, 12.88.
23. 50 values (nM) for MC1R of selected compounds are provided along with the MC1R/MC4R ratio given in parentheses: 2: 690 (43), 3a: 500 (55), 3b: 110 (12) and 5a: 4400 (367).
24. For a recent disclosure of related compounds with high affinity on MC1 receptor, see: Herpin T.F., Yu G., Carlson K.E., Morton G.C., Wu X., Kang L., Tuerdi H., Khanna H., Tokarski J.S., Lawrence R.M., Macor J.E. J. Med. Chem. 46:2003;1123.