p38 MAP kinase inhibitors: Metabolically stabilized piperidine-substituted quinolinones and naphthyridinones

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 1, 2006, Pages 64-68

  Bao, Jianming ^a   Hunt, Julianne A ^a   Miao, Shouwu ^a   Rupprecht, Kathleen M ^a   Stelmach, John E ^a   Liu, Luping ^a   Ruzek, Rowena D ^a   Sinclair, Peter J ^a   Pivnichny, James V ^a   Hop, Cornelis E C A ^a   Kumar, Sanjeev ^a   Zaller, Dennis M ^a   Shoop, Wesley L ^a   O'Neill, Edward A ^a   O'Keefe, Stephen J ^a   Thompson, Chris M ^a   Cubbon, Rose M ^a   Wang, Ruixiu ^a   Zhang, Wen Xiao ^a   Thompson, James E ^a   Doherty, James B ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Inflammatory disease; Kinase; Naphthyridinone; P38; Quinolinone; Rheumatoid arthritis

Indexed keywords

DEXAMETHASONE; NAPHTHYRIDINE DERIVATIVE; QUINOLONE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTHRITIS; ARTICLE; BLOOD ANALYSIS; CELL ACTIVITY; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; ENZYME INHIBITION; HUMAN; HUMAN CELL; NONHUMAN; SUBSTITUTION REACTION;

ANIMALS; ARTHRITIS, EXPERIMENTAL; COLLAGEN; DEXAMETHASONE; DOGS; ENZYME INHIBITORS; HAPLORHINI; HUMANS; INHIBITORY CONCENTRATION 50; LIPOPOLYSACCHARIDES; MICE; MODELS, CHEMICAL; NAPHTHYRIDINES; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PIPERIDINES; QUINOLONES; RATS; TIME FACTORS; TUMOR NECROSIS FACTOR-ALPHA;

ANIMALIA; MURINAE;

EID: 27744561133     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.09.065     Document Type: Article

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9. Experimental details: Male B10RIII mice approximately 8 weeks of age were injected subcutaneously at the base of the tail with a cold 100 μL emulsion of 100 μg bovine Tyope II collagen (Sigma) and Freund's Complete Adjuvant (BD Biosciences) on day 0. No booster injection was given. Following administration of the emulsion, groups of mice were formed at random and then those groups were assigned at random to the various treatments which started on day 7. Mice were housed individually and given food and water ad lib. Evaluation of inflammation was conducted three times a week for the duration of the trial. At each evaluation, all four paws of each mouse were graded based on the following clinical scale: 0 = no inflammation, 1 = inflammation in at least one digit progressing to the metacarpus or metatarsus, 2 = inflammation progressing to the carpus or tarsus, 3 = inflammation progressing above the carpus or tarsus, 4 = mild to moderate functional ankylosis of the carpus or tarsus, and 5 = severe functional ankylosis (i.e., fusion) of the carpus or tarus. Inflammation in each paw of each mouse was recorded and a summary for each mouse was made by adding the scores of the four paws for each observation period (maximum score for an individual mouse at a given observation was 20). The data are presented as the mean score for each mouse in a treatment group for each observation period.