Identification of aminopiperidine benzamides as MCHr1 antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 14, 2005, Pages 3412-3416

  Vasudevan, Anil ^a   Verzal, Mary K ^a   Wodka, Derek ^a   Souers, Andrew J ^a   Blackburn, Christopher ^b   Che, Jennifer Lee ^b   Lai, Sujen ^b   Brodjian, Sevan ^a   Falls, Doug H ^a   Dayton, Brian D ^a   Govek, Elizabeth ^b   Daniels, Tom ^b   Geddes, Brad ^b   Marsh, Kennan C ^a   Hernandez, Lisa E ^a   Collins, Christine A ^a   Kym, Philip R ^a  

^a ABBOTT LABORATORIES   (United States)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

Benzamides; MCH; Melanin concentrating hormone; Obesity

Indexed keywords

BENZAMIDE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BIOAVAILABILITY; CONTROLLED STUDY; DRUG EFFICACY; IC 50; MOUSE; NONHUMAN; OBESITY; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; ANTI-OBESITY AGENTS; BENZAMIDES; BINDING, COMPETITIVE; DISEASE MODELS, ANIMAL; DOGS; MICE; MOLECULAR STRUCTURE; PIPERIDINES; RECEPTORS, SOMATOSTATIN; STRUCTURE-ACTIVITY RELATIONSHIP; TIME FACTORS;

ANIMALIA;

EID: 20644444795     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.05.023     Document Type: Article

References (14)

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11. PS-DCC was purchased from Argonaut Technologies (www.argotech.com)
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13. Efficacy studies were performed according to the following protocol: C57BL/6J mice were group housed in groups of five under conditions of 12 h lights on, 12 h lights off, with food and water available ad libitum. At the beginning of the study, mice were administered a purified low fat diet (D12450Bi, 10 kcal% fat, 3.8 kcal/g) or a high fat content diet (D12492i, 60 kcal% fat, 5.2 kcal/g) for approximately 16 weeks. Mice were weighed, individually housed, and food consumption monitoring initiated three weeks prior to commencement of drug administration. Pharmacological treatments were administered twice a day at 08:00 h and 15:00 h. Mice were conditioned to oral gavage and daily vehicle administration for one week prior to drug administration. The vehicle used for conditioning and study was 1% Tween 80. All doses were given in 4 ml/kg body weight volume of vehicle. All compound doses are expressed as base equivalent weights per unit body weight. Food intake and body weight were determined on the first day and periodically thereafter for 28 days. Compound 22 was administered po by gavage, at doses of 10 and 30 mg/kg q.d., and sibutramine at a dose of 10 mg/kg po, q.d. At the end of the study (day 28), statistical analyses of body weight, food intake, plasma analyte, DEXA, dual-energy X-ray absorptiometry and tissue weight data were performed by analysis of variance, followed by Dunnett's post hoc test. All comparisons were made at a 0.05 level of significance. Data are presented as means ± SEM.
14. During the course of this work, a poster describing benzamide MCH antagonists was reported. Ma, V. V.; Balan, C.; Tempest, P. A.; Hulme, C.; Bannon, T. Abstract of Papers, 224th National Meeting of the American Chemical Society, Boston, MA; American Chemical Society: Washington, DC, 2002; Abstract MEDI-343