Potent inhibition of thrombin by the newly synthesized arginine derivative No. 805. The importance of stereo-structure of its hydrophobic carboxamide portion

doi:10.1016/0006-291X(81)91279-1

Biochemical and Biophysical Research Communications

Volume 101, Issue 2, 30 July 1981, Pages 440-446

https://doi.org/10.1016/0006-291X(81)91279-1 Get rights and content

Abstract

Four stereoisomers of 4-methyl-1-[N²-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid were synthesized and examined for the inhibitory effect on thrombin. The inhibitory potency varied largely with the stereo-configuration of the 4-methyl-2-piperidinecarboxylic acid portion. The (2R, 4R)-isomer was the most potent inhibitor with a Ki of 0.019 μM, while the (2R, 4S) and (2S, 4R)-isomers showed the values of Ki 0.24 and 1.9 μM, respectively. The least potent inhibitor, (2S, 4S)-isomer, showed a Ki of 280 μM which is approximately 15,000 times that of (2R, 4R)-isomer.

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Potent inhibition of thrombin by the newly synthesized arginine derivative No. 805. The importance of stereo-structure of its hydrophobic carboxamide portion

Abstract

Thromb. Res

Biochim. Biophys. Acta

J. Med. Chem

J. Med. Chem

Kobe J. Med. Sci