1-O-tert-butyl 4-O-ethyl 4-[(4-phenoxyphenyl)sulfanylmethyl]piperidine-1,4-dicarboxylate | 213014-03-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-O-tert-butyl 4-O-ethyl 4-[(4-phenoxyphenyl)sulfanylmethyl]piperidine-1,4-dicarboxylate
• CAS: 213014-03-0
• 化学式: C₂₆H₃₃NO₅S
• 分子量: 471.618
• InChiKey: GCZVGTGXXAPRFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  90.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-O-tert-butyl 4-O-ethyl 4-[(4-phenoxyphenyl)sulfanylmethyl]piperidine-1,4-dicarboxylate 在 盐酸 、 吡啶硼烷 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 74.08h， 生成 Ethyl 4-[(4-phenoxyphenyl)sulfonylmethyl]-1-(2-phenylethyl)piperidine-4-carboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of β- and α-Piperidine Sulfone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy

  摘要：

  alpha-Piperidine-beta-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Tiperidine-alpha-sulfone, hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.

  DOI：

  10.1021/jm0500875
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.75h， 生成 1-O-tert-butyl 4-O-ethyl 4-[(4-phenoxyphenyl)sulfanylmethyl]piperidine-1,4-dicarboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of β- and α-Piperidine Sulfone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy

  摘要：

  alpha-Piperidine-beta-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Tiperidine-alpha-sulfone, hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.

  DOI：

  10.1021/jm0500875

文献信息

• Aromatic sulfonyl alpha-cycloamino hydroxamic acid compounds
  申请人：G.D. Searle & Co.

  公开号：US20040097487A1

  公开（公告）日：2004-05-20

  An aromatic sulfonyl alpha-cycloamino hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated aromatic sulfonyl alpha-cycloamino hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

  本发明揭示了一种芳香基磺酰基α-环氨基羟肟酸化合物，该化合物在抑制基质金属蛋白酶活性方面具有作用。同时，本发明还揭示了一种治疗方法，其包括向患有与病理基质金属蛋白酶活性相关疾病的宿主中，以MMP酶抑制剂有效量的芳香基磺酰基α-环氨基羟肟酸化合物进行治疗。
• AROMATIC SULFONYL ALPHA-CYCLOAMINO HYDROXAMIC ACID COMPOUNDS
  申请人：Monsanto Company

  公开号：EP0983257A1

  公开（公告）日：2000-03-08
• EP0983257A4
  申请人：——

  公开号：EP0983257A4

  公开（公告）日：2001-05-02
• US6638952B1
  申请人：——

  公开号：US6638952B1

  公开（公告）日：2003-10-28
• [EN] AROMATIC SULFONYL ALPHA-CYCLOAMINO HYDROXAMIC ACID COMPOUNDS<br/>[FR] COMPOSES AROMATIQUES D'ACIDE SULFONYL ALPHA-CYCLOAMINO HYDROXAMIQUE
  申请人：——

  公开号：WO1998039315A1

  公开（公告）日：1998-09-11

  [EN] An aromatic sulfonyl alpha-cycloamino hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as is a treatment process that comprises administering a contemplated aromatic sulfonyl alpha-cycloamino hydroxamic acid compound in an MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.
  [FR] La présente invention concerne un composé aromatique d'acide sulfonyl alpha-cycloamino hydroxamique qui inhibe notamment une activité de métalloprotéase matricielle (MMP). La présente invention concerne également un procédé de traitement qui consiste à administrer le composé aromatique d'acide sulfonyl alpha-cycloamino hydroxamique en question, à raison d'une quantité efficace destinée à inhiber l'activité d'un enzyme MMP, à un hôte présentant un état associé à une activité pathologique de métalloprotéase matricielle.