Discovery and characterization of aminopiperidinecoumarin melanin concentrating hormone receptor 1 antagonists

Journal of Medicinal Chemistry

Volumn 48, Issue 19, 2005, Pages 5888-5891

  Kym, Philip R ^a   Iyengar, Rajesh ^a   Souers, Andrew J ^a   Lynch, John K ^a   Judd, Andrew S ^a   Gao, Ju ^a   Freeman, Jennifer ^a   Mulhern, Mathew ^a   Zhao, Gang ^a   Vasudevan, Anil ^a   Wodka, Dariusz ^a   Blackburn, Christopher ^b   Brown, Jim ^b   Che, Jennifer Lee ^b   Cullis, Courtney ^b   Lai, Su Jen ^b   LaMarche, Matthew J ^b   Marsilje, Tom ^b   Roses, Jon ^b   Sells, Todd ^b   Geddes, Brad ^b   Govek, Elizabeth ^b   Patane, Michael ^b   Fry, Dennis ^a   Dayton, Brian D ^a   Brodjian, Sevan ^a   Falls, Doug ^a   Brune, Michael ^a   Bush, Eugene ^a   Shapiro, Robin ^a   Knourek Segel, Victoria ^a   Fey, Thomas ^a   McDowell, Cathleen ^a   Reinhart, Glenn A ^a   Preusser, Lee C ^a   Marsh, Kennan ^a   Hernandez, Lisa ^a   Sham, Hing L ^a   Collins, Christine A ^a   more..

^a ABBOTT LABORATORIES   (United States)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 BENZO[1,3]DIOXOL 5 YLMETHYPIPERIDIN 4 YLMETHYL) 6 CHLOROCHROMEN 2 ONE; AMINOPIPERIDINECOUMARIN; ANTIOBESITY AGENT; COUMARIN DERIVATIVE; HORMONE RECEPTOR; HORMONE RECEPTOR BLOCKING AGENT; MELANIN CONCENTRATING HORMONE; MELANIN CONCENTRATING HORMONE RECEPTOR; MELANIN CONCENTRATING HORMONE RECEPTOR ANTAGONIST; PIPERIDINE DERIVATIVE; SIBUTRAMINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY WEIGHT; CARDIOVASCULAR EFFECT; CONTROLLED STUDY; DOG; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; HEMODYNAMIC PARAMETERS; LUNG ARTERY PRESSURE; MEAN ARTERIAL PRESSURE; MOUSE; NONHUMAN; OBESITY; STRUCTURE ACTIVITY RELATION; TREATMENT OUTCOME; WEIGHT REDUCTION;

ADMINISTRATION, ORAL; ANIMALS; ANTI-OBESITY AGENTS; BIOLOGICAL AVAILABILITY; BLOOD PRESSURE; BRAIN; CELL LINE, TUMOR; COUMARINS; DOGS; EATING; ENERGY METABOLISM; HUMANS; MALE; MICE; MICE, OBESE; MYOCARDIAL CONTRACTION; PIPERIDINES; RADIOLIGAND ASSAY; RECEPTORS, PITUITARY HORMONE; RECEPTORS, SOMATOSTATIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 24944458852     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050598r     Document Type: Article

References (16)

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10. (b) An orally active small molecule MCHr1 antagonist in an acute feeding model was reported in the following: Takekawa, S.; Asami, A.; Ishihara, Y.; Terauchi, J.; Kato, K.; Shimomura, Y.; Mori, M.; Murakoshi, H.; Kato, K.; Suzuki, N.; Nishimura, O.; Fujino, M. T-226296: A novel, orally active and selective melanin-concentrating hormone receptor antagonist. Eur. J. Pharmacol. 2002, 438 (3), 129-135.
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12. Microsomal stability of 7 (1 mg/mL protein, % parent @ 30 min): mouse, 82% parent; human, 75% parent.
13. Cross-reactivity assays were performed by Novascreen (www. novascreen.com).
14. Functional MCHr2 is not expressed in rodents. For the identification and species characterization of MCHr2, see the following: An, S.; Cutler, G.; Zhao, J. J.; Huang, S.; Tian, H.; Li, W.; Liang, L.; Rich, M.; Bakleh, A.; Du, J.; Chen, J.; Dai, K. Identification and characterization of a melanin-concentrating hormone receptor. Proc. Natl. Acad. Sci. U.S.A. 2001, 98 (13), 7576-7581.
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