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ID: ALA1149210

Journal: Bioorg Med Chem Lett

Title: A novel series of potent and selective small molecule inhibitors of the complement component C1s.

Authors: Subasinghe NL, Ali F, Illig CR, Jonathan Rudolph M, Klein S, Khalil E, Soll RM, Bone RF, Spurlino JC, DesJarlais RL, Crysler CS, Cummings MD, Morris PE, Kilpatrick JM, Sudhakara Babu Y.

Abstract: Activation of the classical pathway of complement has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury and acute transplant rejection. The trypsin-like serine protease C1s represents a pivotal upstream point of control in the classical pathway of complement activation and is therefore likely to be a useful target in the therapeutic intervention of these disease states. A series of thiopheneamidine-based inhibitors of C1s has been optimized to give a 70 nM inhibitor that inhibits the classical pathway of complement activation in vitro.

CiteXplore: 15149641

DOI: 10.1016/j.bmcl.2004.04.034