POTENT INHIBITION OF THROMBIN BY THE NEWLY SYNTHESIZED ARGININE DERIVATIVE NO-805 - THE IMPORTANCE OF STEREO-STRUCTURE OF ITS HYDROPHOBIC CARBOXAMIDE PORTION
POTENT INHIBITION OF THROMBIN BY THE NEWLY SYNTHESIZED ARGININE DERIVATIVE NO-805 - THE IMPORTANCE OF STEREO-STRUCTURE OF ITS HYDROPHOBIC CARBOXAMIDE PORTION
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DOI：
10.1016/0006-291x(81)91279-1
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发表时间：
1981-01-01
影响因子：
3.1
通讯作者：
TAMAO, Y
中科院分区：
文献类型：
--
作者：
OKAMOTO, S;HIJIKATA, A;TAMAO, Y
合成了4-甲基-1-[N2-（3-甲基-1，2，3，4-四氢-8-喹啉磺酰基）-L-乙酰基]-2-哌啶羧酸的4个立体异构体，并研究了其对牛凝血酶的抑制作用。抑制效力随4-甲基-2-哌啶羧酸部分的立体构型而变化很大。（2 R，4 R）-异构体是最有效的抑制剂，Ki [抑制常数]为0.019 μ M，而（2 R，4S）和（2S，4 R）-异构体的Ki值分别为0.24和1.9 μ M。最低效力的抑制剂，（2S，4S）-异构体，显示Ki为280 μ M，约为是（2 R，4 R）-异构体的15,000倍。
Four stereoisomers of 4-methyl-l-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid were synthesized and examined for the inhibitory effect on bovine 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 [inhibition constant] of 0.019 .mu.M, while the (2R,4S) and (2S,4R)-isomers showed values of Ki 0.24 and 1.9 .mu.M, respectively. The least potent inhibitor, (2S,4S)-isomer, showed a Ki of 280 .mu.M, which is .apprx. 15,000 times that of (2R,4R)-isomer.