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
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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