An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine chromone class of MCHr1 antagonists

An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine chromone class of MCHr1 antagonists

The optimization of potent MCHr1 antagonist 1 with respect to improving its in vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety led to the discovery of 19, a compound that showed excellent MCHr1 binding and functional potencies in addition to possessing superior hERG...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2007-02, Vol.17 (4), p.874-878
Hauptverfasser: Iyengar, Rajesh R., Lynch, John K., Mulhern, Mathew M., Judd, Andrew S., Freeman, Jennifer C., Gao, Ju, Souers, Andrew J., Zhao, Gang, Wodka, Dariusz, Doug Falls, H., Brodjian, Sevan, Dayton, Brian D., Reilly, Regina M., Swanson, Sue, Su, Zhi, Martin, Ruth L., Leitza, Sandra T., Houseman, Kathryn A., Diaz, Gilbert, Collins, Christine A., Sham, Hing L., Kym, Philip R.
Format: Artikel
Sprache:eng
Schlagworte:
Alkylation
Animals
Biological and medical sciences
Chemical Phenomena
Chemistry, Physical
Chromones
Cross Reactions
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme Inhibitors
Dose-Response Relationship, Drug
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
ERG1 Potassium Channel
Ether-A-Go-Go Potassium Channels - pharmacology
Heart Rate - drug effects
hERG
Heterocyclic Compounds - chemical synthesis
Heterocyclic Compounds - pharmacology
Hormones. Endocrine system
Humans
MCHR1
Medical sciences
Mice
Obesity
Pharmacology. Drug treatments
Piperidines - chemical synthesis
Piperidines - pharmacology
Piperonyl replacements
Receptors, Somatostatin - antagonists & inhibitors
Structure-Activity Relationship
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Zusammenfassung:The optimization of potent MCHr1 antagonist 1 with respect to improving its in vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety led to the discovery of 19, a compound that showed excellent MCHr1 binding and functional potencies in addition to possessing superior hERG separation, CYP3A4 profile, and receptor cross-reactivity profiles.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.11.065