626220-01-7Relevant academic research and scientific papers
Design, synthesis, in vitro, and in vivo characterization of phenylpiperazines and pyridinylpiperazines as potent and selective antagonists of the melanocortin-4 receptor
Tran, Joe A.,Jiang, Wanlong,Tucci, Fabio C.,Fleck, Beth A.,Wen, Jenny,Sai, Yang,Madan, Ajay,Ta, Kung Chen,Markison, Stacy,Foster, Alan C.,Hoare, Sam R.,Marks, Daniel,Harman, John,Chen, Caroline W.,Arellano, Melissa,Marinkovic, Dragan,Bozigian, Haig,Saunders, John,Chen, Chen
, p. 6356 - 6366 (2008/03/30)
Benzylamine and pyridinemethylamine derivatives were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor (MC4R). These compounds were also profiled in rodents for their pharmacokinetic properties. Two compounds with diversified profiles in chemical structure, pharmacological activities, and pharmacokinetics, 10 and 12b, showed efficacy in an established murine cachexia model. For example, 12b had a Ki value of 3.4 nM at MC4R, was more than 200-fold selective over MC3R, and had a good pharmacokinetic profile in mice, including high brain penetration. Moreover, 12b was able to stimulate food intake in the tumor-bearing mice and reverse their lean body mass loss. Our results provided further evidence that a potent and selective MC4R antagonist with appropriate pharmacokinetic properties might potentially be useful for the treatment of cancer cachexia.
Arylpropionylpiperazines as antagonists of the human melanocortin-4 receptor
Jiang, Wanlong,Tucci, Fabio C.,Chen, Caroline W.,Arellano, Melissa,Tran, Joe A.,White, Nicole S.,Marinkovic, Dragan,Pontillo, Joseph,Fleck, Beth A.,Wen, Jenny,Saunders, John,Madan, Ajay,Foster, Alan C.,Chen, Chen
, p. 4674 - 4678 (2007/10/03)
A series of 3-arylpropionylpiperazines were synthesized as antagonists of the melanocortin-4 receptor. Their potency was found to be increased by replacing the α-methyl substituent of the initial lead 11 with a larger s-Bu or i-Bu group. Further potency enhancement was observed when a glycine or β-alanine was incorporated onto the benzylamine. Some compounds demonstrated good potency, moderate selectivity, and oral bioavailability.
Practical asymmetric synthesis of α-branched 2- piperazinylbenzylamines by 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines
Jiang, Wanlong,Chen, Chen,Marinkovic, Dragan,Tran, Joe A.,Chen, Caroline W.,Arellano, L. Melissa,White, Nicole S.,Tucci, Fabio C.
, p. 8924 - 8931 (2007/10/03)
2-[4-(tert-Butoxycarbonyl)piperazinyl] benzylidene-tert-butanesulfinamides underwent nucleophilic 1,2-addition with different organometallic reagents to give highly diastereomerically enriched adducts. X-ray crystallography of the resulting α-branched N-B
LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO
-
Page/Page column 37, (2010/02/11)
Compounds which function as melanocortin receptor ligands and having utility in the treatment of melanocortin receptor-based disorders. The compounds have the following structure (I): (I) including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R1, R1a, R1b, R2, R3, R4a, R4b, R5a, R5b, X1, X2, X3, X4 and Ar are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.
