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ID: ALA1130738

Journal: Bioorg Med Chem Lett

Title: Rational design of boropeptide thrombin inhibitors: beta, beta-dialkyl-phenethylglycine P2 analogs of DuP 714 with greater selectivity over complement factor I and an improved safety profile.

Authors: Fevig JM, Buriak J, Cacciola J, Alexander RS, Kettner CA, Knabb RM, Pruitt JR, Weber PC, Wexler RR.

Abstract: The potent boropeptide thrombin inhibitor DuP 714 caused side effects in laboratory animals that appear to be related to its ability to inhibit complement factor I, thereby activating the complement cascade. Using X-ray crystal structure information, we have designed compounds that have greater selectivity for thrombin over factor I and that have reduced tendency to produce these side effects.

CiteXplore: 9871674

DOI: 10.1016/s0960-894x(98)00013-4