Modification of the N-terminal sulfonyl residue in 3-amidinophenylalanine-based matriptase inhibitors

Replacement of the N-terminal β-alanyl-amide moiety in previously identified matriptase inhibitors by non-charged aryl groups caused a slightly decreased potency and partially reduced selectivity, especially towards thrombin. However, some of these analogues are still potent matriptase inhibitors with Ki-values <10 nM. In contrast, improved activity was observed for newly designed tribasic analogues, especially for compound 21, which inhibits matriptase with an Ki-value of 80 pM.

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