848779-69-1Relevant academic research and scientific papers
Identification of 2-(4-benzyloxyphenyl)-N-[1-(2-pyrrolidin-1-yl-ethyl)-1H- indazol-6-yl]acetamide, an orally efficacious melanin-concentrating hormone receptor 1 antagonist for the treatment of obesity
Souers, Andrew J.,Gao, Ju,Brune, Michael,Bush, Eugene,Wodka, Dariusz,Vasudevan, Anil,Judd, Andrew S.,Mulhern, Mathew,Brodjian, Sevan,Dayton, Brian,Shapiro, Robin,Hernandez, Lisa E.,Marsh, Kennan C.,Sham, Hing L.,Collins, Christine A.,Kym, Philip R.
, p. 1318 - 1321 (2005)
Optimization of a high-throughput screening hit against melanin-concentrating hormone receptor 1 (MCHr1) led to the discovery of 2-(4-benzyloxy-phenyl)-N-[1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide (7a). This compound was found to be a high-aff
Screening for cardiovascular safety: A structure-activity approach for guiding lead selection of melanin concentrating hormone receptor 1 antagonists
Kym, Philip R.,Souers, Andrew J.,Campbell, Thomas J.,Lynch, John K.,Judd, Andrew S.,Iyengar, Rajesh,Vasudevan, Anil,Gao, Ju,Freeman, Jennifer C.,Wodka, Dariusz,Mulhern, Mathew,Zhao, Gang,Wagaw, Seble H.,Napier, James J.,Brodjian, Sevan,Dayton, Brian D.,Reilly, Regina M.,Segreti, Jason A.,Fryer, Ryan M.,Preusser, Lee C.,Reinhart, Glenn A.,Hernandez, Lisa,Marsh, Kennan C.,Sham, Hing L.,Collins, Christine A.,Polakowski, James S.
, p. 2339 - 2352 (2007/10/03)
An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor 1 (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (>40 μM) and brain (>20 μg/g) with 15% change in cardiovascular endpoints. As a result of these stringent requirements, lead optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHr1 antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.
Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor
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Page/Page column 26, (2010/02/12)
The present invention relates to the antagonism of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.
Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor
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Page/Page column 27, (2010/02/15)
The present invention relates to the antagonism of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.
