(1,5-Dioxa-9-thia-spiro[5.5]undec-7-yl)-carbamic acid tert-butyl ester | 189947-46-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1,5-Dioxa-9-thia-spiro[5.5]undec-7-yl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-(1,5-dioxa-9-thiaspiro[5.5]undecan-11-yl)carbamate
• CAS: 189947-46-4
• 化学式: C₁₃H₂₃NO₄S
• 分子量: 289.396
• InChiKey: CTYSFXKMEOVFGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1,5-Dioxa-9-thia-spiro[5.5]undec-7-yl)-carbamic acid tert-butyl ester 在 三异丙基硅烷 、 茴香硫醚 、 水 、 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 7.67h， 生成 N'-(6-aminohexyl)-N'-(1,5-dioxa-9-thiaspiro[5.5]undecan-11-yl)hexane-1,6-diamine
  参考文献：
  名称：

  4-Heterocyclohexanone-Based Inhibitors of the Serine Protease Plasmin

  摘要：

  Three inhibitors that are based upon a 4-heterocyclohexanone nucleus were synthesized and evaluated for activity against the serine protease plasmin. Inhibitors of plasmin have potential as cancer chemotherapeutic agents that act by blocking both angiogenesis and metastasis. Inhibitor 1 has moderate activity against plasmin but shows good selectivity for this enzyme compared to other serine proteases including trypsin, thrombin, and kallikrein. Inhibitor 2 shows both good activity and selectivity for plasmin. Inhibitor 3, which does not incorporate an aminohexyl group that can interact with the S1 subsite, has poor activity. These results, along with previous work, demonstrate that the 4-heterocyclohexanone nucleus can effectively serve as the basis for designing inhibitors of both serine and cyst;eine proteases.

  DOI：

  10.1021/jm990110k
• 作为产物：
  描述：

  methyl 1,5-dioxa-9-thiaspiro[5.5]undecane-7-carboxylate 在 sodium hydroxide 、 二苯基磷酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 苯 为溶剂， 生成 (1,5-Dioxa-9-thia-spiro[5.5]undec-7-yl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Using the Electrostatic Field Effect to Design a New Class of Inhibitors for Cysteine Proteases

  摘要：

  A new class of competitive inhibitors for the cysteine protease papain is described. These inhibitors are based upon a 4-heterocyclohexanone ring and are designed to react with the enzyme active site nucleophile to give a reversibly formed hemithioketal. The electrophilicity of the ketone in these inhibitors is enhanced by ring strain and by through-space electrostatic repulsion with the heteroatom at the 1-position of the ring. Equilibrium constants for addition of water and 3-mercaptopropionic acid to several 4-heterocyclohexanones were measured by H-1 NMR spectroscopy. These reactions model addition of the active site nucleophile to the corresponding inhibitors. The equilibrium constants give a linear correlation with the field substituent constant F for the functional group at the 1-position of the heterocyclohexanone. These equilibrium constants also correlate well with the inhibition constants for the 4-heterocyclohexanone-based inhibitors, which range from 11 to 120 mu M. Thus, the model system can be used to predict the potency of structurally related enzyme inhibitors.

  DOI：

  10.1021/ja9641867

文献信息

• Using the Electrostatic Field Effect to Design a New Class of Inhibitors for Cysteine Proteases
  作者：Jeffrey L. Conroy、Tanya C. Sanders、Christopher T. Seto

  DOI：10.1021/ja9641867

  日期：1997.5.1

  A new class of competitive inhibitors for the cysteine protease papain is described. These inhibitors are based upon a 4-heterocyclohexanone ring and are designed to react with the enzyme active site nucleophile to give a reversibly formed hemithioketal. The electrophilicity of the ketone in these inhibitors is enhanced by ring strain and by through-space electrostatic repulsion with the heteroatom at the 1-position of the ring. Equilibrium constants for addition of water and 3-mercaptopropionic acid to several 4-heterocyclohexanones were measured by H-1 NMR spectroscopy. These reactions model addition of the active site nucleophile to the corresponding inhibitors. The equilibrium constants give a linear correlation with the field substituent constant F for the functional group at the 1-position of the heterocyclohexanone. These equilibrium constants also correlate well with the inhibition constants for the 4-heterocyclohexanone-based inhibitors, which range from 11 to 120 mu M. Thus, the model system can be used to predict the potency of structurally related enzyme inhibitors.
• 4-Heterocyclohexanone-Based Inhibitors of the Serine Protease Plasmin
  作者：Tanya C. Sanders、Christopher T. Seto

  DOI：10.1021/jm990110k

  日期：1999.7.1

  Three inhibitors that are based upon a 4-heterocyclohexanone nucleus were synthesized and evaluated for activity against the serine protease plasmin. Inhibitors of plasmin have potential as cancer chemotherapeutic agents that act by blocking both angiogenesis and metastasis. Inhibitor 1 has moderate activity against plasmin but shows good selectivity for this enzyme compared to other serine proteases including trypsin, thrombin, and kallikrein. Inhibitor 2 shows both good activity and selectivity for plasmin. Inhibitor 3, which does not incorporate an aminohexyl group that can interact with the S1 subsite, has poor activity. These results, along with previous work, demonstrate that the 4-heterocyclohexanone nucleus can effectively serve as the basis for designing inhibitors of both serine and cyst;eine proteases.