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

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

  • Bioorg Med Chem Lett. 2003 Nov 17;13(22):4077-80. doi: 10.1016/j.bmcl.2003.08.047.
Moorthy S S Palanki 1,  Paul E Erdman,  Minghuan Ren,  Mark Suto,  Brydon L Bennett,  Anthony Manning,  Lynn Ransone,  Cheryl Spooner,  Sonal Desai,  Arnie Ow,  Ryuichi Totsuka,  Peter Tsao,  Wataru Toriumi
Affiliations

Affiliation

  • 1 Celgene, 4550 Towne Centre Court, San Diego, CA 92121, USA. mpalanki@celgene.com
PMID: 14592511 DOI: 10.1016/j.bmcl.2003.08.047
Abstract

We have developed novel orally active quinazoline analogues as inhibitors of AP-1 and NF-kappaB 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.

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