Small Molecule Inhibitors of Integrin alpha2-beta1

by: S Choi, G Vilaire, C Marcinkiewicz, JD Winkler, JS Bennett, WF Degrado

J. Med. Chem., Vol. 50, No. 22. (1 November 2007), pp. 5457-5462.

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DOI, American Chem. Soc. Publications

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Abstract

Abstract: Interactions between the integrin, 21, and extracellular matrix (ECM), particularly collagen, play a pivotal role in platelet adhesion and thrombus formation. Platelets interact with collagen in the subendothelial matrix that is exposed by vascular damage. To evaluate the potential of 21 inhibitors for anticancer and antithrombotic applications, we have developed a series of small molecule inhibitors of this integrin based on a prolyl-2,3-diaminopropionic acid (DAP) scaffold using solid-phase parallel synthesis. A benzenesulfonamide substituent at the N-terminus of the dipepetide and a benzyl urea at the DAP side chain resulted in tight and highly selective inhibition of 21-mediated adhesion of human platelets and other cells to collagen.

@article{citeulike:1986421, abstract = {Abstract: Interactions between the integrin, 21, and extracellular matrix (ECM), particularly collagen, play a pivotal role in platelet adhesion and thrombus formation. Platelets interact with collagen in the subendothelial matrix that is exposed by vascular damage. To evaluate the potential of 21 inhibitors for anticancer and antithrombotic applications, we have developed a series of small molecule inhibitors of this integrin based on a prolyl-2,3-diaminopropionic acid (DAP) scaffold using solid-phase parallel synthesis. A benzenesulfonamide substituent at the N-terminus of the dipepetide and a benzyl urea at the DAP side chain resulted in tight and highly selective inhibition of 21-mediated adhesion of human platelets and other cells to collagen.}, address = {Department of Biochemistry and Biophysics, the Department of Chemistry, and the Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Department of Biology, Temple University, Philadelphia, Pennsylvania 19122}, author = {Choi, S. and Vilaire, G. and Marcinkiewicz, C. and Winkler, J. D. and Bennett, J. S. and Degrado, W. F. }, citeulike-article-id = {1986421}, doi = {10.1021/jm070252b}, journal = {J. Med. Chem.}, keywords = {2007, integrins, sm, xf}, month = {November}, number = {22}, pages = {5457--5462}, posted-at = {2007-11-26 13:48:18}, priority = {2}, title = {Small Molecule Inhibitors of Integrin alpha2-beta1}, url = {http://dx.doi.org/10.1021/jm070252b}, volume = {50}, year = {2007} }

RIS record

TY - JOUR ID - citeulike:1986421 L3 - citeulike-article-id:1986421 TI - Small Molecule Inhibitors of Integrin alpha2-beta1 JF - J. Med. Chem. VL - 50 IS - 22 SP - 5457 EP - 5462 AD - Department of Biochemistry and Biophysics, the Department of Chemistry, and the Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Department of Biology, Temple University, Philadelphia, Pennsylvania 19122 N2 - Abstract: Interactions between the integrin, 21, and extracellular matrix (ECM), particularly collagen, play a pivotal role in platelet adhesion and thrombus formation. Platelets interact with collagen in the subendothelial matrix that is exposed by vascular damage. To evaluate the potential of 21 inhibitors for anticancer and antithrombotic applications, we have developed a series of small molecule inhibitors of this integrin based on a prolyl-2,3-diaminopropionic acid (DAP) scaffold using solid-phase parallel synthesis. A benzenesulfonamide substituent at the N-terminus of the dipepetide and a benzyl urea at the DAP side chain resulted in tight and highly selective inhibition of 21-mediated adhesion of human platelets and other cells to collagen. KW - 2007 KW - integrins KW - sm KW - xf AU - Choi, S AU - Vilaire, G AU - Marcinkiewicz, C AU - Winkler, JD AU - Bennett, JS AU - Degrado, WF PY - 2007/11/01/ UR - http://dx.doi.org/10.1021/jm070252b ER -

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