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

Journal of Medicinal Chemistry

Volumn 48, Issue 5, 2005, Pages 1318-1321

  Souers, Andrew J ^a   Gao, Ju ^a   Brune, Michael ^a   Bush, Eugene ^a   Wodka, Dariusz ^a   Vasudevan, Anil ^a   Judd, Andrew S ^a   Mulhern, Mathew ^a   Brodjian, Sevan ^a   Dayton, Brian ^a   Shapiro, Robin ^a   Hernandez, Lisa E ^a   Marsh, Kennan C ^a   Sham, Hing L ^a   Collins, Christine A ^a   Kym, Philip R ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (4 BENZYLOXYPHENYL) N [1 (2 PYRROLIDIN 1 YLETHYL) 1H INDAZOL 6 YL]ACETAMIDE; ACETAMIDE DERIVATIVE; DEXFENFLURAMINE; INDAZOLE DERIVATIVE; MELANIN CONCENTRATING HORMONE; MELANIN CONCENTRATING HORMONE RECEPTOR 1 ANTAGONIST; RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CALCIUM TRANSPORT; CONTROLLED STUDY; DISEASE MODEL; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; IC 50; MOUSE; NONHUMAN; OBESITY; PROCESS OPTIMIZATION; RECEPTOR AFFINITY; WEIGHT REDUCTION;

ACETAMIDES; ADMINISTRATION, ORAL; ANIMALS; ANTI-OBESITY AGENTS; BINDING, COMPETITIVE; BRAIN; CALCIUM; CHRONIC DISEASE; INDAZOLES; MICE; OBESITY; PYRROLIDINES; RADIOLIGAND ASSAY; RECEPTORS, SOMATOSTATIN; STRUCTURE-ACTIVITY RELATIONSHIP; TISSUE DISTRIBUTION;

EID: 20144379914     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0490890     Document Type: Article

References (18)

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12. Multiple patents describing small-molecule MCHr1 antagonists have been published recently. For excellent reviews on the subject, see the following: (a) Kowalski, T. J.; McBriar, M. D. Therapeutic potential of melanin-concentrating hormone-1 receptor antagonists for the treatment of obesity. Expert Opin. Invest. Drugs 2004, 13 (9), 1113-1122.
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15. Functional MCHr2 is not expressed in rodents. For the identification and species characterization of MCHr2, respectively, see the following references: (a) 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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17. Cross-reactivity assays were performed by CEREP (www.cerep.com).
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