selenopropionic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 碳硒酸及其衍生物
• 英文名称: selenopropionic acid
• 英文别名: selenopropionic cid；propaneselenoic Se-acid
• 化学式: C₃H₆OSe
• 分子量: 137.04
• InChiKey: ZZUSRMXUQYWYPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.18
• 重原子数：
  5
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  ethyl 3-{6-[(tert-butoxycarbonyl)amino]pyridin-3-yl}-2-[(propanoylselanyl)methyl]propanoate 、 selenopropionic acid 以 甲苯 为溶剂， 反应 41.0h， 以192.6 mg的产率得到ethyl 3-{6-[(tert-butoxycarbonyl)amino]pyridin-3-yl}-2-[(propanoylselanyl)methyl]propanoate
  参考文献：
  名称：

  Design and Characterization of a Selenium-Containing Inhibitor of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa), a Zinc-Containing Metalloprotease

  摘要：

  Available therapies for thromboembolic disorders include thrombolytics, anticoagulants, and antiplatelets, but these are associated with complications such as bleeding. To develop an alternative drug which is clinically safe, we focused on activated thrombin-activatable fibrinolysis inhibitor (TAFIa) as the target molecule. TAFIa is a zinc-containing carboxypeptidase that significantly inhibits fibrinolysis. Here we designed and synthesized selenium-containing compounds 5-13 to discover novel TAFIa inhibitors having a superior zinc-coordinating group. Compounds 5-13 significantly inhibited TAFIa activity (IC50 2.2 x 10(-12) M - 2.6 x 10(-6) M). We found that selenol is a better functional group than thiol for coordinating to zinc at the active site of TAFIa. Furthermore, compound 12, which has an amino-chloro-pyridine ring, was found to be a potent and selective TAFIa inhibitor that lacks carboxypeptidase N inhibitory activity. Therefore, compound 12 is a promising candidate for the treatment of thromboembolic disorders. This is the first report of a selenium-containing inhibitor for TAFIa.

  DOI：

  10.1021/jm300735t
• 作为产物：
  描述：

  丙酸 在 Woollins 试剂 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以100%的产率得到selenopropionic acid
  参考文献：
  名称：

  New Reactions of Selenocarboxylates

  摘要：

  By treatment with Woollins' reagent in toluene solution, carboxylic acids are converted to selenocarboxylic acids. The latter react in situ to provide new products of acid- or base-promoted substitution, addition, and amidation.

  DOI：

  10.1021/ol047889z

文献信息

• New Reactions of Selenocarboxylates
  作者：Spencer Knapp、Etzer Darout

  DOI：10.1021/ol047889z

  日期：2005.1.1

  By treatment with Woollins' reagent in toluene solution, carboxylic acids are converted to selenocarboxylic acids. The latter react in situ to provide new products of acid- or base-promoted substitution, addition, and amidation.
• Structural basis for the selective inhibition of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) by a selenium-containing inhibitor with chloro-aminopyridine as a basic group
  作者：Toshimasa Itoh、Nobuko Yoshimoto、Yoshinari Hirano、Keiko Yamamoto

  DOI：10.1016/j.bmcl.2018.05.042

  日期：2018.7

  Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) is a target molecule for treating thromboembolic disorders. We previously reported that design and synthesis of compound 1 containing a selenol group and chloloaminopyridine. Compound 1 showed high inhibitory activity towards TAFIa, with a high degree of selectivity for TAFIa over carboxypeptidase N (CPN). Here we report investigation of this selectivity. To obtain co-crystal of 1/pp-CPB (a surrogate of TAFIa), we synthesized protected compound 5 as a stabilized precursor of 1. The X-ray crystal structure and docking study indicated that the Cl substituent is accommodated in the pp-CPB specific pocket whereas CPN has no identical pocket. This is important information for the design of drugs targeting TAFIa with high selectivity.
• Design and Characterization of a Selenium-Containing Inhibitor of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa), a Zinc-Containing Metalloprotease
  作者：Nobuko Yoshimoto、Tomoyuki Sasaki、Katsuyoshi Sugimoto、Hidemi Ishii、Keiko Yamamoto

  DOI：10.1021/jm300735t

  日期：2012.9.13

  Available therapies for thromboembolic disorders include thrombolytics, anticoagulants, and antiplatelets, but these are associated with complications such as bleeding. To develop an alternative drug which is clinically safe, we focused on activated thrombin-activatable fibrinolysis inhibitor (TAFIa) as the target molecule. TAFIa is a zinc-containing carboxypeptidase that significantly inhibits fibrinolysis. Here we designed and synthesized selenium-containing compounds 5-13 to discover novel TAFIa inhibitors having a superior zinc-coordinating group. Compounds 5-13 significantly inhibited TAFIa activity (IC50 2.2 x 10(-12) M - 2.6 x 10(-6) M). We found that selenol is a better functional group than thiol for coordinating to zinc at the active site of TAFIa. Furthermore, compound 12, which has an amino-chloro-pyridine ring, was found to be a potent and selective TAFIa inhibitor that lacks carboxypeptidase N inhibitory activity. Therefore, compound 12 is a promising candidate for the treatment of thromboembolic disorders. This is the first report of a selenium-containing inhibitor for TAFIa.