New drug candicates!!
...nding selective MMP or TACE inhibitor. Discovery of these molecules should enable more precise studies delineating the biological roles of TACE and other MMP inhibitors in inflammatory, cardiovascular, and oncologic models of human disease and offer new therapeutic agents for the treatment of RA. We have previously reported a novel series of acrylohydroxamic acid derivatives which have showed potent and highly selective TACE inhibitory activity at 222nd ACS National Meeting, Chicago, IL, USA (2001). During our investigation, we found that nature of R1 in the acrylohydroxamic acid influenced the inhibitory activity against MMP-3 and synthesized various R1 derivatives. In this presentation, we describe the synthesis and biological activities of these derivatives. Nonsteroidal anti-inflammatory drugs (NSAIDs) or disease-modifying antirheumatoid drugs (DMARDs) have been widely used for the clinical treatment of rheumatoid arthritis (RA), an inflammatory autoimmune disease. However, because of limited effectiveness and side effects of them, there has been a continued search for improved therapeutic agents. At the present, inhibitors of matrix metalloproteases (MMPs) have been sought as a new class of therapeutic agents for the treatment of RA. MMPs constitute a family ...