Tetrahydropyridine derivatives with inhibitory activity on the production of proinflammatory cytokines: Part 3

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 16, 2010, Pages 4774-4778

  Nakao, Akira ^a   Ohkawa, Nobuyuki ^a   Nagasaki, Takayoshi ^a   Kagari, Takashi ^a   Doi, Hiromi ^a   Shimozato, Takaichi ^a   Ushiyama, Shigeru ^a   Aoki, Kazumasa ^a  

^a DAIICHI SANKYO CO   (Japan)

Author keywords

Anti rheumatic drug; p38 MAP kinase; Proinflammatory cytokine; TNF

Indexed keywords

2 (4 FLUOROPHENYL) 4 (1,2,3,5,6,8A HEXAHYDROINDOLIZIN 7 YL) 3 (PYRIDIN 4 YL) 1H PYRROLE; ANTIRHEUMATIC AGENT; BICYCLO COMPOUND; COLLAGEN ANTIBODY; CYTOKINE; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MITOGEN ACTIVATED PROTEIN KINASE 11; MITOGEN ACTIVATED PROTEIN KINASE 12; MITOGEN ACTIVATED PROTEIN KINASE 13; MITOGEN ACTIVATED PROTEIN KINASE 14; PYRIDINE DERIVATIVE; R 132811; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; 2-(4-FLUOROPHENYL)-4-(1,2,3,5,6,8A-HEXAHYDROINDOLIZIN-7-YL)-3-(PYRIDIN-4-YL)-1H-PYRROLE; INDOLIZINE DERIVATIVE; PYRROLE DERIVATIVE;

ADJUVANT ARTHRITIS; ANALGESIC ACTIVITY; ARTICLE; CYTOKINE PRODUCTION; DRUG POTENCY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MOUSE; NONHUMAN; RHEUMATOID ARTHRITIS; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; ARTHRITIS, EXPERIMENTAL; CHEMICALLY INDUCED; CHEMISTRY; METABOLISM; RAT; SYNTHESIS;

ANIMALS; ANTIRHEUMATIC AGENTS; ARTHRITIS, EXPERIMENTAL; CYTOKINES; HUMANS; INDOLIZINES; INTERLEUKIN-1BETA; INTERLEUKIN-6; INTERLEUKIN-8; MICE; PYRIDINES; PYRROLES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR NECROSIS FACTOR-ALPHA;

MUS; RATTUS;

EID: 77955417604     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.06.122     Document Type: Article

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30. Adjuvant arthritis was induced as described above. On day 18, adjuvant arthritis was established in most adjuvant-injected animals and the swelled foot volume almost reached a plateau. We selected animals with prominent swelling of the adjuvant-injected foot (foot volume ≥ 2.75 mL). These animals were divided into groups so that the mean value of the adjuvant-injected foot volume in each group was about the same. The test compounds were suspended in 0.5% CMC aqueous solution at the appropriate concentrations, and orally administered at 5 mL/kg twice a day from day 18 to day 24 (7 days). The volume of both feet was measured on days 18, 20, 23, and 25 (0, 2, 5, and 7 days after the first administration) by a plethysmometer (Ugo Basile) by soaking the hind paw from the toe to the hairline in the bath of the plethysmometer. The swelled foot volume and the ratio of the swelled foot volume were calculated with the equations below, and the % inhibition against control group was obtained. We used the volume of adjuvant-injected foot (right hind foot) for the calculation because the swelling of the adjuvant-injected foot was more prominent and stable than that of the uninjected foot. The swelled foot volume (mL) = right hind foot volume of animals - mean right hind foot volume of normal animals. The ratio of swelled foot volume = {(right hind foot volume of animals on day 25 - mean right hind foot volume of normal animal on day 25)/(right hind foot volume of animals on day 18 - mean right hind foot volume of normal animal on day 18)} × 100
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