Inhibitors of lfa-1 binding to icams and uses thereof

Details Inhibitors of lfa-1 binding to icams and uses thereof Inhibitors of lfa-1 binding to icams and uses thereof

C - Chemistry, Metallurgy

07

C

C07C 323/37 (2006.01) A61K 31/04 (2006.01) A61K 31/135 (2006.01) C07C 323/09 (2006.01) C07C 323/32 (2006.01) C07C 323/41 (2006.01) C07C 323/65 (2006.01) C07D 207/416 (2006.01) C07D 213/70 (2006.01) C07D 215/36 (2006.01) C07D 235/06 (2006.01) C07D 277/74 (2006.01) C07D 295/096 (2006.01) C07D 295/12 (2006.01) C07D 295/135 (2006.01) C07D 307/90 (2006.01)

Patent

CA 2369005

The present invention is directed to compounds that bind to a novel regulatory site in the I domain of LFA-1, and thereby inhibit LFA-1 binding to ICAMs that bind LFA-1. The present invention therefore also provides methods to regulate leukocyte adhesion to endothelial cells. Compounds of the ivnention are useful for the treatment of pathologies, such as those associated inflammatory diseases, autoimmune diseases, tumor metastasis, allograft rejection and reperfusion injury. In particular, the present invention is directed to diaryl sulfides of general structural formula (I), a pharmaceutically acceptable salt, or prodrug thereof, and to the use of diaryl sulfides, and particularly compounds of formula (I), to inhibit LFA-1 binding to an ICAM that binds LFA-1 wherein A and B, independently, are aryl groups selected from the group consisting of 5- and 6-membered aromatic rings, including, but not limited to, phenyl, thienyl, furyl, pyrimidinyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrrolyl, and pyridazinyl.

L'invention porte sur de nouveaux composés qui inhibent la liaison de LFA-1 à un partenaire de liaison d'un ligand naturel, ainsi que sur les utilisations de ces composés.

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