202976-34-9Relevant academic research and scientific papers
PHOSPHINATE BASED INHIBITORS OF MATRIX METALLOPROTEASES
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, (2008/06/13)
A compound of the formula wherein R1, R2, R3, R4, R5, R6 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, synergy with cytotoxic anticancer agents, tissue ulceration, macular dege
Phosphinate based inhibitors of matrix metalloproteases
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, (2008/06/13)
A compound of the formula wherein R1, R2, R3, R4, R5, R6 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, synergy with cytotoxic anticancer agents, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, in combination with standard NSAID'S and analgesics and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of TNF. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S) and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinim, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.
Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket
Reiter, Lawrence A.,Rizzi, James P.,Pandit, Jayvardan,Lasut, Michael J.,McGahee, Shunda M.,Parikh, Vinod D.,Blake, James F.,Danley, Dennis E.,Laird, Ellen R.,Lopez-Anaya, Arturo,Lopresti-Morrow, Lori L.,Mansour, Mahmoud N.,Martinelli, Gary J.,Mitchell, Peter G.,Owens, Brian S.,Pauly, Thomas A.,Reeves, Lisa M.,Schulte, Gayle K.,Yocum, Sue A.
, p. 127 - 132 (2007/10/03)
Through the use of empirical and computational methods, phosphinate- based inhibitors of MMP-1 and MMP-13 that bind into the S2 pocket of these enzymes were designed. The synthesis and testing of 2 suggested that binding was occuring as hypothesized. Structure determination of a co-crystal of 2 bound to the catalytic domain of MMP-1 confirmed the binding mode. Substituents binding into S2, S1', S2' and S3', were optimized yielding compounds with low double-digit nM IC50's against these enzymes.
