| 17918824 |
Chen C, Jiang W, Tucci F, Tran JA, Fleck BA, Hoare SR, Joppa M, Markison S, Wen J, Sai Y, Johns M, Madan A, Chen T, Chen CW, Marinkovic D, Arellano M, Saunders J, Foster AC: Discovery of 1-[2-[(1S)-(3-dimethylaminopropionyl) amino-2-methylpropyl]-4-methylphenyl] -4-[(2R)-methyl-3-(4-chlorophenyl)-propionyl] piperazine as an orally active antagonist of the melanocortin-4 receptor for the potential treatment of cachexia. J Med Chem. 2007 Nov 1;50(22):5249-52. Epub 2007 Oct 5.
A potent and selective antagonist of the melanocortin-4 receptor, 1-[2-[(1S)-(3-dimethylaminopropionyl) amino-2-methylpropyl]-6-methylphenyl] -4-[(2R)-methyl-3-(4-chlorophenyl) propionyl] piperazine (10d), was identified from a series piperazinebenzylamine attached with a N,N-dimethyl-beta-alanine side chain. This compound possessed high water solubility and exhibited good metabolic profiles. In animals, 10d showed moderate to good oral bioavailability and promoted food intake in tumor-bearing mice after oral administration. |
112(1,2,2,2) |