The design and synthesis of novel orally active inhibitors of AP-1 and NF-κB mediated transcriptional activation. SAR of in vitro and in vivo studies

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 22, 2003, Pages 4077-4080

  Palanki, Moorthy S S ^a   Erdman, Paul E ^a   Ren, Minghuan ^a   Suto, Mark ^a   Bennett, Brydon L ^a   Manning, Anthony ^a   Ransone, Lynn ^a   Spooner, Cheryl ^a   Desai, Sonal ^a   Ow, Arnie ^a   Totsuka, Ryuichi ^b   Tsao, Peter ^b   Toriumi, Wataru ^b  

^a CELGENE CORPORATION   (United States)

^b MITSUBISHI TANABE PHARMA CORPORATION   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (2 THIENYL)QUINAZOLIN 4 YLAMINO] 3 METHYL 3 PYRROLINE 2,5 DIONE; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN INHIBITOR; QUINAZOLINE DERIVATIVE; TRANSCRIPTION FACTOR AP 1; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTHRITIS; ARTICLE; DRUG DESIGN; DRUG SYNTHESIS; EDEMA; FOOT; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; TRANSCRIPTION INITIATION;

EID: 10744223481     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.08.047     Document Type: Article

References (14)

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11. 50 value is defined as the concentration of compound required to reduce luciferase activity to 50% of control values.
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13. Female Lewis rats, 8 weeks of age, were purchased from Charles River, Japan. After acclimatization, the rats were randomly assigned into 12 groups (n=5 per group) according to treatment received. Rats in 11 groups were induced with arthritis by injecting 100 μg of heat-inactivated Mycobacterium butyricum (Difco, USA) in 100 μL of liquid paraffin in the right hind paw (Day 0), and the rest group was used as a healthy control group. Compound 9, 10, 11 and 20 were suspended in 0.5% carboxymethylcellulose solution containing 0.1% Tween80 and saline for 30 mg/kg, po administration. Dexamethsone 21-phosphate (DEX, a antiinflammatory steroid from Sigma), a positive reference compound, was suspended in 0.5% carboxymethylcellulose solution and administered to rats at a dose level of 0.1 mg/kg, po All compounds and vehicles were administered to arthritic rats once daily for 21 days. The degree of arthritis was determined by measuring hind-paw volume using a plethysmometer (TK-lO5, Unicom, Tokyo) on the Day 0 (immediately before adjuvant injection), 3, 7, 10, 14, 17, and 21.
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