(R)-4-cyano-2-methylbutanoic acid | 206665-56-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-4-cyano-2-methylbutanoic acid
• 英文别名: (2R)-4-cyano-2-methylbutanoic acid
• CAS: 206665-56-7
• 化学式: C₆H₉NO₂
• 分子量: 127.143
• InChiKey: REJFSMLCTZUOJC-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-4-cyano-2-methylbutanoic acid 在 platinum(IV) oxide 、 氢气 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 15.0h， 以94%的产率得到(R)-5-amino-2-methylpentanoic acid hydrochloride
  参考文献：
  名称：

  Conformationally restricted analogs of the direct thrombin inhibitor FM 19

  摘要：

  The serine protease thrombin plays several key roles in the clotting cascade within the hemostatic system, such as in fibrin formation and platelet activation. Thus, development of an inhibitor that binds to the enzyme's active site (a direct thrombin inhibitor) offers an approach for the treatment of thrombus-associated diseases. Previous structure-activity relationship studies originally based on the bradykinin breakdown product Arg-Pro-Pro-Gly-Phe (RPPGF) led to the development of lead compound FM 19 (D-Arg-Oic-Pro-D-Ala-Phe(p-Me)-NH2). The recently determined X-ray structure of FM 19 in the active site of thrombin has revealed sites of modification to potentially improve inhibition. In this study, we report the synthesis and biological characterization of nine peptides that replace only the D-Arg residue of the FM 19 sequence, investigating ways to add conformational restriction, modification of the basic moiety at the end of the side chain, and removal of the charge from the N-terminus. Two of these peptides, 6 and 7 (IC50 values of 0.51 and 0.45 mu M, respectively), show similar potency to the best compounds in the FM 19 series reported thus far. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.045
• 作为产物：
  描述：

  (4R)-5-[(4S)-4-benzyl-2-oxooxazolidin-3-yl]-4-methyl-5-oxopentanenitrile 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以51%的产率得到(R)-4-cyano-2-methylbutanoic acid
  参考文献：
  名称：

  Conformationally restricted analogs of the direct thrombin inhibitor FM 19

  摘要：

  The serine protease thrombin plays several key roles in the clotting cascade within the hemostatic system, such as in fibrin formation and platelet activation. Thus, development of an inhibitor that binds to the enzyme's active site (a direct thrombin inhibitor) offers an approach for the treatment of thrombus-associated diseases. Previous structure-activity relationship studies originally based on the bradykinin breakdown product Arg-Pro-Pro-Gly-Phe (RPPGF) led to the development of lead compound FM 19 (D-Arg-Oic-Pro-D-Ala-Phe(p-Me)-NH2). The recently determined X-ray structure of FM 19 in the active site of thrombin has revealed sites of modification to potentially improve inhibition. In this study, we report the synthesis and biological characterization of nine peptides that replace only the D-Arg residue of the FM 19 sequence, investigating ways to add conformational restriction, modification of the basic moiety at the end of the side chain, and removal of the charge from the N-terminus. Two of these peptides, 6 and 7 (IC50 values of 0.51 and 0.45 mu M, respectively), show similar potency to the best compounds in the FM 19 series reported thus far. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.045

文献信息

• Conformationally restricted analogs of the direct thrombin inhibitor FM 19
  作者：Elizabeth A. Girnys、Vanessa R. Porter、Henry I. Mosberg

  DOI：10.1016/j.bmc.2011.10.045

  日期：2011.12

  The serine protease thrombin plays several key roles in the clotting cascade within the hemostatic system, such as in fibrin formation and platelet activation. Thus, development of an inhibitor that binds to the enzyme's active site (a direct thrombin inhibitor) offers an approach for the treatment of thrombus-associated diseases. Previous structure-activity relationship studies originally based on the bradykinin breakdown product Arg-Pro-Pro-Gly-Phe (RPPGF) led to the development of lead compound FM 19 (D-Arg-Oic-Pro-D-Ala-Phe(p-Me)-NH2). The recently determined X-ray structure of FM 19 in the active site of thrombin has revealed sites of modification to potentially improve inhibition. In this study, we report the synthesis and biological characterization of nine peptides that replace only the D-Arg residue of the FM 19 sequence, investigating ways to add conformational restriction, modification of the basic moiety at the end of the side chain, and removal of the charge from the N-terminus. Two of these peptides, 6 and 7 (IC50 values of 0.51 and 0.45 mu M, respectively), show similar potency to the best compounds in the FM 19 series reported thus far. (C) 2011 Elsevier Ltd. All rights reserved.