1-((2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl)-2-(4-chloro-2-(hydroxymethyl)phenoxy)ethanone | 478833-49-7

• 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-((2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl)-2-(4-chloro-2-(hydroxymethyl)phenoxy)ethanone
• 英文别名: 2-(4-chloro-2-hydroxymethyl-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone；(2R,5S)-1-((4-chloro-3-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine；2-(4-chloro-2-hydroxymethylphenoxy)-1-[4-(4-ffuorobenzyl)-2R,5S-dimethylpiperazin-1-yl]-ethanone；2-[4-Chloro-2-(hydroxymethyl)phenoxy]-1-{(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl}ethan-1-one；2-[4-chloro-2-(hydroxymethyl)phenoxy]-1-[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]ethanone
• CAS: 478833-49-7
• 化学式: C₂₂H₂₆ClFN₂O₃
• 分子量: 420.911
• InChiKey: ZSEOLRYUWAEEMP-JKSUJKDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-((2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl)-2-(4-chloro-2-(hydroxymethyl)phenoxy)ethanone 在 甲酸 、 thioacetate 、 双氧水 作用下， 以 2-甲基四氢呋喃 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 14.0h， 生成 (2-(2-((2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl)-2-oxoethoxy)-5-chlorophenyl)methanesulfonic acid
  参考文献：
  名称：

  Route Development and Bulk Synthesis of CP-865,569

  摘要：

  The synthesis of zwitterionic CP-865,569 by three different synthetic routes is described. The first two routes differ in the method of introducing the sulfonic acid at the penultimate step: by sulfite displacement of a benzylic chloride and by oxidation of a benzylic thioacetate. The third route is a convergent route to the drug candidate. The synthesis strategy was primarily driven by the need to introduce the sulfonic acid functionality at the final stage of the synthesis due to the high water solubility and low organic solubility of the desired product.

  DOI：

  10.1021/op7000386
• 作为产物：
  描述：

  2,5-dimethyl-piperazine 在 sodium tetrahydroborate 、 四丁基溴化铵 、 potassium carbonate 、 potassium iodide 、 sodium hydroxide 作用下， 以 2-甲基四氢呋喃 、 甲醇 、 环己烷 、 水 为溶剂， 反应 18.42h， 生成 1-((2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl)-2-(4-chloro-2-(hydroxymethyl)phenoxy)ethanone
  参考文献：
  名称：

  Route Development and Bulk Synthesis of CP-865,569

  摘要：

  The synthesis of zwitterionic CP-865,569 by three different synthetic routes is described. The first two routes differ in the method of introducing the sulfonic acid at the penultimate step: by sulfite displacement of a benzylic chloride and by oxidation of a benzylic thioacetate. The third route is a convergent route to the drug candidate. The synthesis strategy was primarily driven by the need to introduce the sulfonic acid functionality at the final stage of the synthesis due to the high water solubility and low organic solubility of the desired product.

  DOI：

  10.1021/op7000386

文献信息

• Novel phosphorus-containing derivatives
  申请人：Pfizer Inc

  公开号：US20040127465A1

  公开（公告）日：2004-07-01

  A compound of the Formula I 1 a prodrug thereof, or the pharmaceutically acceptable salt of the compound or prodrug; wherein X, Y, a, b, c, d, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above and are useful to treat inflammation and other immune disorders. The present invention also relates to pharmaceutical compositions that include compounds of Formula I and a pharmaceutically acceptable carrier. Moreover, the present invention relates to methods of using the above-described compounds and compositions to treat and prevent diseases and conditions.

  一种公式I的化合物，其前体，或该化合物或前体的药用盐；其中X、Y、a、b、c、d、R1、R2、R3、R4、R5、R6和R7如上所定义，并且适用于治疗炎症和其他免疫性疾病。本发明还涉及包括公式I化合物和药用载体的药物组合物。此外，本发明涉及使用上述化合物和组合物治疗和预防疾病和病症的方法。
• Methods of using piperazine derivatives
  申请人：Pfizer Inc

  公开号：US20040092529A1

  公开（公告）日：2004-05-13

  The present invention relates to compounds of the formula I 1 and the pharmaceutically acceptable forms thereof; wherein X, Y, a, b, c, d, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Moreover, the present invention is also directed at pharmaceutical compositions comprising a compound of the formula I and a pharmaceutically acceptable carrier. Furthermore, the present invention is directed at methods of using the herein described compounds and compositions for treating or preventing a disorder or condition that can be treated or prevented by antagonizing the CCR1 receptor in a mammal.

  本发明涉及公式I1的化合物及其药学上可接受的形式；其中X、Y、a、b、c、d、R1、R2、R3、R4和R5如本文所定义。此外，本发明还涉及包含公式I的化合物和药学上可接受的载体的药物组合物。此外，本发明还涉及使用本文所述的化合物和组合物治疗或预防哺乳动物中可通过拮抗CCR1受体治疗或预防的疾病或状况的方法。
• Novel sulfonic acid derivatives
  申请人：——

  公开号：US20030083335A1

  公开（公告）日：2003-05-01

  A compound of the formula 1 or the pharmaceutically acceptable salt thereof; wherein X, Y, a, b, c, d, R 1 , R 2 , R 3 and R 5 are as defined above useful to treat inflammation and other immune disorders.

  该化合物的公式为1或其药学上可接受的盐；其中X、Y、a、b、c、d、R1、R2、R3和R5的定义如上所述，有助于治疗炎症和其他免疫性疾病。
• [EN] AMORPHOUS UND CRYSTAL FORMS OF (5-CHLORO-2-{2-<br/>[FR] FORMES AMORPHES ET CRISTALLINES DE SELS DE L'ACIDE (5-CHLORO-2-{2-[4-(4-FLUORO-BENZYL)-(2R,5S)-2,5-DIMÉTHYL-PIPÉRAZIN-1-YL]-2-OXO-ÉTHOXY}-PHÉNYL)-MÉTHANE SULFONIQUE
  申请人：PFIZER PROD INC

  公开号：WO2004113311A1

  公开（公告）日：2004-12-29

  This invention relates to amorphous and crystal salt forms of (5-chloro-2-2-[4-(4-fluoro­-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy)-phenyl)-methanesulfonic acid, useful in treating or preventing a disorder or condition by antagonizing the CCR1 receptor, and to their methods of preparation and use.

  本发明涉及无定形和晶体盐形式的(5-氯-2-2-[4-(4-氟苯基)- (2R,5S)-2,5-二甲基哌嗪-1-基]-2-氧代乙氧基}-苯基)-甲磺酸，其通过拮抗CCR1受体在治疗或预防疾病或病症中有用，并且涉及其制备和使用方法。
• Methods of using sulfonic acid derivatives
  申请人：Pfizer Inc

  公开号：US20040116441A1

  公开（公告）日：2004-06-17

  The present invention relates to methods of using CCR1 antagonists as immunomodulatory agents. In particular, the methods relate to using compounds of the formula 1 or the pharmaceutically acceptable salt thereof; wherein X, Y, a, b, c, d, R 1 , R 2 , R 3 and R 5 are as defined herein.

  本发明涉及使用CCR1拮抗剂作为免疫调节剂的方法。特别地，所述方法涉及使用式1的化合物或其药学上可接受的盐；其中X、Y、a、b、c、d、R1、R2、R3和R5的定义如本文所述。