(S)-1-((R)-2-甲氧基-1-(4-(三氟甲基)苯基)乙基)-2-甲基哌嗪 | 612494-07-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-1-((R)-2-甲氧基-1-(4-(三氟甲基)苯基)乙基)-2-甲基哌嗪
• 英文名称: (S)-1-((R)-2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-2-methylpiperazine
• 英文别名: (2S)-1-[(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl]-2-methylpiperazine
• CAS: 612494-07-2
• 化学式: C₁₅H₂₁F₃N₂O
• 分子量: 302.34
• InChiKey: URQFAVGDNQPJAB-FZMZJTMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  (S)-1-((R)-2-甲氧基-1-(4-(三氟甲基)苯基)乙基)-2-甲基哌嗪 在 titanium(IV) isopropylate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 94.0h， 生成 (S)-1-((R)-2-甲氧基-1-(4-(三氟甲基)苯基)乙基)-2-甲基-4-(4-甲基哌啶-4-基)哌嗪
  参考文献：
  名称：

  Piperazine-Based CCR5 Antagonists as HIV-1 Inhibitors. IV. Discovery of 1-[(4,6-Dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-{2-methoxy-1(R)-4-(trifluoromethyl)phenyl}ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a Potent, Highly Selective, and Orally Bioavailable CCR5 Antagonist

  摘要：

  The nature and the size of the benzylic substituent are shown to be the key to controlling receptor selectivity (CCR5 vs M1, M2) and potency in the title compounds. Optimization of the lead benzylic methyl compound 3 led to the methoxymethyl analogue 30, which had excellent receptor selectivity and oral bioavailability in rats and monkeys. Compound 30 (Sch-417690/Sch-D), a potent inhibitor of HIV-1 entry into target cells, is currently in clinical trials.

  DOI：

  10.1021/jm0304515
• 作为产物：
  描述：

  2-甲氧基-1-(4’-三氟甲基)苯乙酮 在 dimethyl sulfide borane 、 potassium carbonate 、 三乙胺 、 三氟乙酸 、 (S)-2-甲基-CBS-恶唑硼烷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 76.5h， 生成 (S)-1-((R)-2-甲氧基-1-(4-(三氟甲基)苯基)乙基)-2-甲基哌嗪
  参考文献：
  名称：

  Piperazine-Based CCR5 Antagonists as HIV-1 Inhibitors. IV. Discovery of 1-[(4,6-Dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-{2-methoxy-1(R)-4-(trifluoromethyl)phenyl}ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a Potent, Highly Selective, and Orally Bioavailable CCR5 Antagonist

  摘要：

  The nature and the size of the benzylic substituent are shown to be the key to controlling receptor selectivity (CCR5 vs M1, M2) and potency in the title compounds. Optimization of the lead benzylic methyl compound 3 led to the methoxymethyl analogue 30, which had excellent receptor selectivity and oral bioavailability in rats and monkeys. Compound 30 (Sch-417690/Sch-D), a potent inhibitor of HIV-1 entry into target cells, is currently in clinical trials.

  DOI：

  10.1021/jm0304515

文献信息

• Piperazine derivatives useful as CCR5 antagonists
  申请人：Schering Corporation

  公开号：US06391865B1

  公开（公告）日：2002-05-21

  The use of CCR5 antagonists of the formula or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R1 is hydrogen or alkyl; R2 is substituted phenyl, substituted heteroaryl, naphthyl, fluorenyl, diphenylmethyl or optionally substituted phenyl- or heteroaryl-alkyl; R3 is hydrogen, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, or optionally substituted phenyl, phenylalkyl, naphthyl, naphthylalkyl, heteroaryl or heteroarylalkyl; R4, R5 and R7 are hydrogen or alkyl; R6 is hydrogen, alkyl or alkenyl; for the treatment of HIV, solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis is disclosed, as well as novel compounds, pharmaceutical compositions comprising them, and the combination of CCR5 antagonists of the invention in combination with antiviral agents useful in the treatment of HIV or agents useful in the treatment of inflammatory diseases.

  公开了使用CCR5拮抗剂的公式，其中 R是可选择的取代苯基，吡啶基，噻吩基或萘基; R1是氢或烷基; R2是取代苯基，取代杂环基，萘基，芴基，二苯甲基或可选择的取代苯基或杂环基烷基; R3是氢，烷基，烷氧基烷基，环烷基，环烷基烷基，或可选择的取代苯基，苯基烷基，萘基，萘基烷基，杂环基或杂环基烷基; R4，R5和R7是氢或烷基; R6是氢，烷基或烯基; 用于治疗HIV，固体器官移植排斥，移植物宿主病，关节炎，类风湿关节炎，炎症性肠病，特应性皮炎，牛皮癣，哮喘，过敏或多发性硬化症的方法，以及包含它们的新化合物，包含它们的药物组合物，以及CCR5拮抗剂与抗HIV治疗中有用的抗病毒剂或与治疗炎症性疾病中有用的药物的组合。
• Stereoselective alkylation of chiral 2-methyl-4-protected piperazines
  申请人：Schering Corporation

  公开号：US20030208074A1

  公开（公告）日：2003-11-06

  In an illustrative embodiment, the present invention describes the synthesis of the following compound and similar compounds, in high stereochemical purity by a novel stereoselective alkylation process: 1

  在一个说明性实施例中，本发明描述了通过一种新颖的立体选择性烷基化过程，在高立体化纯度下合成以下化合物及类似化合物：1
• Synthesis of³H,²H₄and¹⁴C-SCH 417690 (Vicriviroc)
  作者：D. Hesk、S. Borges、S. Hendershot、D. Koharski、P. McNamara、S. Ren、S. Saluja、V. Truong、K. Voronin

  DOI：10.1002/jlcr.3387

  日期：2016.5.15

  Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. CCR5 receptor antagonists have the potential for the treatment of HIV infections. Four distinct isotopically labelled forms of SCH 417690 were synthesized. Low specific activity [(3) H]SCH 417690 was prepared for a preliminary absorption, distribution, metabolism and excretion evaluation of the compound and [(14) C]SCH

  Vicriviroc 或 SCH 417690 是 CCR5 受体的有效选择性拮抗剂。CCR5 受体拮抗剂具有治疗 HIV 感染的潜力。合成了四种不同的同位素标记形式的 SCH 417690。低比活性 [(3) H]SCH 417690 用于化合物的初步吸收、分布、代谢和排泄评估，[(14) C]SCH 417690 用于更明确的吸收、分布、代谢和排泄工作，包括人体吸收、代谢和排泄研究。此外，为 CCR5 受体结合工作制备了高比活性 [(3) H]SCH 417690，并制备了 [(2) H4 ]SCH 417690 作为液相色谱-质谱生物分析方法的内标。
• Stereoselective alkylation of chiral 2-methyl-4 protected piperazines
  申请人：Schering Corporation

  公开号：EP2141143A2

  公开（公告）日：2010-01-06

  The invention relates to a process for preparing 4-trifluoromethyl methoxyacetophenone comprising: (a) reacting the compound of Formula XIII with the compound of formula XIX to form the product of formula XX: and (b) hydrolyzing the compound of formula XX to 4-trifluoromethyl methoxyacetophenone:

  本发明涉及一种制备 4-三氟甲基甲氧基苯乙酮的工艺，包括 (a) 式 XIII 的化合物与式 XIX 的化合物反应生成式 XX 的产物： 和 (b) 将式 XX 的化合物水解为 4-三氟甲基甲氧基苯乙酮：
• Evaluation of a 4-aminopiperidine replacement in several series of CCR5 antagonists
  作者：Rémy C. Lemoine、Ann C. Petersen、Lina Setti、Lijing Chen、Jutta Wanner、Andreas Jekle、Gabrielle Heilek、André deRosier、Changhua Ji、David M. Rotstein

  DOI：10.1016/j.bmcl.2010.02.004

  日期：2010.3

  The bicyclic 5-amino-3-azabicyclo[3.3.0]octanes were shown to be effective replacements for the conformationally restricted 4-aminopiperidine ring found in several series of CCR5 antagonists. (C) 2010 Elsevier Ltd. All rights reserved.