benzyl 6-[(tert-butoxycarbonyl)amino]-1,4-dithia-8-azaspiro[4.5]decane-8-carboxylate | 189947-48-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: benzyl 6-[(tert-butoxycarbonyl)amino]-1,4-dithia-8-azaspiro[4.5]decane-8-carboxylate
• 英文别名: Benzyl 6-[(2-methylpropan-2-yl)oxycarbonylamino]-1,4-dithia-8-azaspiro[4.5]decane-8-carboxylate；benzyl 6-[(2-methylpropan-2-yl)oxycarbonylamino]-1,4-dithia-8-azaspiro[4.5]decane-8-carboxylate
• CAS: 189947-48-6
• 化学式: C₂₀H₂₈N₂O₄S₂
• 分子量: 424.585
• InChiKey: FESVRPSCSHHVQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl 6-[(tert-butoxycarbonyl)amino]-1,4-dithia-8-azaspiro[4.5]decane-8-carboxylate 在 1,3-二溴-5,5-二甲基海因 、 pyridine hydrofluoride 作用下， 以 二氯甲烷 为溶剂， 以12.5%的产率得到benzyl 3-[(tert-butoxycarbonyl)amino]-4,4-difluoropiperidine-1-carboxylate
  参考文献：
  名称：

  [EN] 6 SUBSTITUTED 2-HETEROCYCLYLAMINO PYRAZINE COMPOUNDS AS CHK-1 INHIBITORS
  [FR] COMPOSÉS 2-HÉTÉROCYCLYLAMINO PYRAZINES SUBSTITUÉES EN POSITION 6 EN TANT QU'INHIBITEURS DE CHK-1

  摘要：

  本发明涉及式(I)的化合物，及其药用可接受的盐，它们的合成以及它们作为CHK-1抑制剂的用途。

  公开号：

  WO2010016005A1
• 作为产物：
  描述：

  4-氧代-1,3-哌啶二羧酸 3-甲基 1-(苯基甲基)酯 在 sodium hydroxide 、 二苯基磷酸 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 苯 为溶剂， 生成 benzyl 6-[(tert-butoxycarbonyl)amino]-1,4-dithia-8-azaspiro[4.5]decane-8-carboxylate
  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

• 6 SUBSTITUTED 2- HETEROCYCLYLAMINO PYRAZINE COMPOUNDS AS CHK-1 INHIBITORS
  申请人：Braganza John Frederick

  公开号：US20110144084A1

  公开（公告）日：2011-06-16

  The present invention is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, their synthesis, and their use as CHK-1 inhibitors.

  本发明涉及式（I）化合物及其药学上可接受的盐，它们的合成以及它们作为CHK-1抑制剂的用途。
• 6 SUBSTITUTED 2-HETEROCYCLYLAMINO PYRAZINE COMPOUNDS AS CHK-1 INHIBITORS
  申请人：Pfizer Inc.

  公开号：EP2328890A1

  公开（公告）日：2011-06-08
• US8518952B2
  申请人：——

  公开号：US8518952B2

  公开（公告）日：2013-08-27
• [EN] 6 SUBSTITUTED 2-HETEROCYCLYLAMINO PYRAZINE COMPOUNDS AS CHK-1 INHIBITORS<br/>[FR] COMPOSÉS 2-HÉTÉROCYCLYLAMINO PYRAZINES SUBSTITUÉES EN POSITION 6 EN TANT QU'INHIBITEURS DE CHK-1
  申请人：PFIZER

  公开号：WO2010016005A1

  公开（公告）日：2010-02-11

  The present invention is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, their synthesis, and their use as CHK-1 inhibitors.

  本发明涉及式(I)的化合物，及其药用可接受的盐，它们的合成以及它们作为CHK-1抑制剂的用途。
• 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.