rac-(2-(3-bromophenyl)-1-hydroxymethylethyl)carbamic acid tert-butyl ester | 868274-65-1

• 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: rac-(2-(3-bromophenyl)-1-hydroxymethylethyl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[1-(3-bromophenyl)-3-hydroxypropan-2-yl]carbamate
• CAS: 868274-65-1
• 化学式: C₁₄H₂₀BrNO₃
• 分子量: 330.222
• InChiKey: BHCIXRPUHVBMRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-(2-(3-bromophenyl)-1-hydroxymethylethyl)carbamic acid tert-butyl ester 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以96%的产率得到rac-(2-(3-bromophenyl)-1-formylethyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Hydroxyethylene Sulfones as a New Scaffold To Address Aspartic Proteases:  Design, Synthesis, and Structural Characterization

  摘要：

  Hydroxyethylene sulfones were developed as novel scaffolds against aspartyl proteases. A diastereoselective synthesis has been established to introduce the required side chain decoration with desired stereochemistry. Depending on the substitution of the hydroxyethylene-sulfone core, micro- to submicromolar inhibition of HIV-1 protease is achieved for the S-configuration at P, and R-configuration at the hydroxy-group-bearing backbone atom. This stereochemical preference is consistent with the S,R configuration of amprenavir. The racemic mixture of the most potent derivative (K-i = 80 nM) was separated by chiral HPLC, revealing the S,R,S-enantiomer to be more active (K-i = 45 nM). Docking studies suggested this isomer as the more active one. The subsequently determined crystal structure with HIV-1 protease, cocrystallized from a racemic mixture, exclusively reveals the S,R,S-enantiomer accommodated to the binding pocket. The transition state mimicking hydroxy group of the inhibitor is centered between both catalytic aspartates, while either its carbonyl or sulfonyl group forms H-bonds to the structurally conserved water mediating interactions between ligand and Ile50NH/Ile50NH' of both flaps. Biological testing of the stereoisomeric hydroxyethylene sulfones against cathepsin D and beta-secretase did not reveal significant inhibition. Most likely, the latter proteases require inverted configuration at the hydroxy group.

  DOI：

  10.1021/jm050224y
• 作为产物：
  描述：

  3-溴苄溴 在 盐酸 、 sodium ethanolate 、 碳酸氢钠 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 24.0h， 生成 rac-(2-(3-bromophenyl)-1-hydroxymethylethyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Hydroxyethylene Sulfones as a New Scaffold To Address Aspartic Proteases:  Design, Synthesis, and Structural Characterization

  摘要：

  Hydroxyethylene sulfones were developed as novel scaffolds against aspartyl proteases. A diastereoselective synthesis has been established to introduce the required side chain decoration with desired stereochemistry. Depending on the substitution of the hydroxyethylene-sulfone core, micro- to submicromolar inhibition of HIV-1 protease is achieved for the S-configuration at P, and R-configuration at the hydroxy-group-bearing backbone atom. This stereochemical preference is consistent with the S,R configuration of amprenavir. The racemic mixture of the most potent derivative (K-i = 80 nM) was separated by chiral HPLC, revealing the S,R,S-enantiomer to be more active (K-i = 45 nM). Docking studies suggested this isomer as the more active one. The subsequently determined crystal structure with HIV-1 protease, cocrystallized from a racemic mixture, exclusively reveals the S,R,S-enantiomer accommodated to the binding pocket. The transition state mimicking hydroxy group of the inhibitor is centered between both catalytic aspartates, while either its carbonyl or sulfonyl group forms H-bonds to the structurally conserved water mediating interactions between ligand and Ile50NH/Ile50NH' of both flaps. Biological testing of the stereoisomeric hydroxyethylene sulfones against cathepsin D and beta-secretase did not reveal significant inhibition. Most likely, the latter proteases require inverted configuration at the hydroxy group.

  DOI：

  10.1021/jm050224y

文献信息

• Novel tyrosine kinase inhibitors
  申请人：——

  公开号：US20040044203A1

  公开（公告）日：2004-03-04

  The present invention provides compounds of formula I 1 and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase enzymes thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases which can be treated by inhibiting tyrosine kinase enzymes.

  本发明提供了公式I1的化合物及其药用盐。公式I化合物抑制酪氨酸激酶酶，因此可用作抗癌剂。公式I化合物还可用于治疗其他可以通过抑制酪氨酸激酶酶来治疗的疾病。
• Benzimidazole C-2 heterocycles as kinase inhibitors
  申请人：Beaulieu Francis

  公开号：US20050054655A1

  公开（公告）日：2005-03-10

  Benzimidazole derivatives having the general formula I are provided. These compounds are useful as tyrosine kinase inhibitors, especially for the treatment of cancer.

  提供了具有一般公式的苯并咪唑衍生物。这些化合物可用作酪氨酸激酶抑制剂，特别用于癌症的治疗。
• Imidazole based kinase inhibitors
  申请人：Marinier Anne

  公开号：US20050187218A1

  公开（公告）日：2005-08-25

  The present invention provides compounds having Formula I and their use for the treatment of cancer.

  本发明提供了具有I式的化合物以及它们用于治疗癌症的用途。
• NOVEL TYROSINE KINASE INHIBITORS
  申请人：Beaulieu Francis

  公开号：US20070135443A1

  公开（公告）日：2007-06-14

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase enzymes thereby making them useful as anti-cancer agents.

  本发明提供公式I化合物及其药学上可接受的盐。公式I化合物抑制酪氨酸激酶酶，因此可用作抗癌药物。
• US7081454B2
  申请人：——

  公开号：US7081454B2

  公开（公告）日：2006-07-25