Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: In vitro profiling and in vivo evaluation
| Autor: | Bryan A. Kramer, Kevin Whelan, Yoshinori Sekiguchi, Shigeyuki Chaki, Pureza Vallar, Michael Morgan, Graeme Semple, Thuy-Anh Tran, William Thomsen, Dipanjan Sengupta, Juyi Choi, Debbie Hsu, Andrew J. Grottick, Kosuke Kanuma, Erin K. Hauser, Ning Zou, Martin Casper, Sangdon Han |
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| Rok vydání: | 2009 |
| Předmět: |
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Pyrimidine Clinical Biochemistry Administration Oral Pharmaceutical Science Biochemistry Rats Sprague-Dawley Eating Structure-Activity Relationship Pyrimidine analogue chemistry.chemical_compound Pharmacokinetics In vivo Weight Loss Drug Discovery Animals Humans Structure–activity relationship Receptors Somatostatin Molecular Biology PK/PD models Cyclohexylamines Chemistry Organic Chemistry Antagonist In vitro Rats Pyrimidines Quinazolines Molecular Medicine Anti-Obesity Agents |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:6166-6171 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2009.09.003 |
| Popis: | A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body weight in a chronic study. However no clear correlation between the pharmacodynamic effect and the pharmacokinetic data with respect to brain concentration was discernible leading us to conclude that the observed effect was most likely not due to interaction with the MCH-R1. |
| Databáze: | OpenAIRE |
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