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Exploring N-Arylsulfonyl-l-proline Scaffold as a Platform for Potent and Selective ?v?1 Integrin Inhibitors.

ABSTRACT: One small molecule inhibitor of ?v?1 integrin, c8, shows antifibrotic effects in multiple in vivo mouse models. Here we synthesized c8 analogues and systematically investigate their structure-activity relationships (SAR) in ?v?1 integrin inhibition. N-Phenylsulfonyl-l-homoproline analogues of c8 maintained excellent potency against ?v?1 integrin while retaining good selectivity over other RGD integrins. In addition, 2-aminopyridine or cyclic guanidine analogues were shown to be equally potent to c8. A rigid phenyl linker increased the potency compared to c8, but the selectivity over other RGD integrins diminished. These results can provide further insights on design of ?v?1 integrin inhibitors as antifibrotics.

SUBMITTER: Reed NI

PROVIDER: S-EPMC5066160 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Exploring N-Arylsulfonyl-l-proline Scaffold as a Platform for Potent and Selective αvβ1 Integrin Inhibitors.

Reed Nilgun Isik NI Tang You-Zhi YZ McIntosh Joel J Wu Yibing Y Molnar Kathleen S KS Civitavecchia Annafelicia A Sheppard Dean D DeGrado William F WF Jo Hyunil H

ACS medicinal chemistry letters 20160830 10

One small molecule inhibitor of αvβ1 integrin, c8, shows antifibrotic effects in multiple in vivo mouse models. Here we synthesized c8 analogues and systematically investigate their structure-activity relationships (SAR) in αvβ1 integrin inhibition. N-Phenylsulfonyl-l-homoproline analogues of c8 maintained excellent potency against αvβ1 integrin while retaining good selectivity over other RGD integrins. In addition, 2-aminopyridine or cyclic guanidine analogues were s ...[more]

PMID: 27774126

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