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
| Autor: | Moorthy S. S. Palanki, Lynn J. Ransone, Minghuan Ren, Ryuichi Totsuka, Sonal Desai, Arnie Ow, Paul Erdman, Peter W. Tsao, Cheryl Spooner, Brydon L. Bennett, Mark J. Suto, Wataru Toriumi, Anthony M. Manning |
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| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
Clinical Biochemistry Administration Oral Pharmaceutical Science Arthritis Biochemistry Chemical synthesis Jurkat Cells Structure-Activity Relationship chemistry.chemical_compound In vivo Oral administration Drug Discovery Quinazoline medicine Animals Humans Molecular Biology Bicyclic molecule Organic Chemistry NF-kappa B NF-κB medicine.disease Arthritis Experimental In vitro Rats Transcription Factor AP-1 Disease Models Animal chemistry Drug Design Quinazolines Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 13:4077-4080 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2003.08.047 |
| Popis: | We have developed novel orally active quinazoline analogues as inhibitors of AP-1 and NF-κB mediated transcriptional activation. Among the derivatives prepared, 1-[2-(2-thienyl)quinazolin-4-ylamino]-3-methyl-3-pyrroline-2,5-dione ( 10 ) showed significant activity in an adjuvant-induced arthritis rat model by reducing the swelling by 65% in the non-injected foot. The synthesis, structure–activity relationship, and in vivo activity are described. |
| Databáze: | OpenAIRE |
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