(R)-α-methyl-3,5-bis(trifluoromethyl)benzeneacetic acid | 374794-63-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (R)-α-methyl-3,5-bis(trifluoromethyl)benzeneacetic acid
• 英文别名: (R)-alpha-methyl-3,5-bis(trifluoromethyl)benzeneacetic acid；(2R)-2-[3,5-bis(trifluoromethyl)phenyl]propanoic acid
• CAS: 374794-63-5
• 化学式: C₁₁H₈F₆O₂
• 分子量: 286.174
• InChiKey: SFSCZXRNLPFPTP-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R)-α-methyl-3,5-bis(trifluoromethyl)benzeneacetic acid 、 3-甲氧基-4-(2-甲基吡啶-4-基)苯胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (2R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(3-methoxy-4-(2-methyl-4-pyridinyl)-phenyl)propanamide
  参考文献：
  名称：

  Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer’s disease

  摘要：

  gamma-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer's disease. They selectively lower pathogenic A beta 42 levels by shifting the enzyme cleavage sites without inhibiting gamma-secretase activity, possibly avoiding known adverse effects observed with complete inhibition of the enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM lead. Lead optimization studies identified compound 25 with improved cell potency, PKDM properties, and it lowered A beta 42 levels in the cerebrospinal fluid ( CSF) of Sprague-Dawley rats following oral administration. Further optimization of 25 to improve cellular potency is described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.041

文献信息

• Cyclohexane derivatives and their use as therapeutic agents
  申请人：——

  公开号：US20030236250A1

  公开（公告）日：2003-12-25

  The present invention relates compounds of formula (I), wherein ring A is a phenyl or pyridyl ring; X represents a linker selected from the group consisting of formulae: (a), (b), (c), (d), and (e); and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 21a and R 21b are as defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia. 1

  本发明涉及式(I)的化合物，其中环A是苯环或吡啶环；X代表从以下式组成的选择性连接物：(a)、(b)、(c)、(d)和(e)；以及R1、R2、R3、R4、R5、R6、R7、R13、R14、R15、R16、R17、R21a和R21b如本文所定义。这些化合物特别适用于治疗或预防抑郁症、焦虑、疼痛、炎症、偏头痛、呕吐或带状疱疹后神经痛。
• [EN] CYCLOHEXANE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS<br/>[FR] DERIVES DE CYCLOHEXYLE ET LEUR UTILISATION COMME AGENTS THERAPEUTIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2001087838A1

  公开（公告）日：2001-11-22

  The present invention relates compounds of formula (I), wherein ring A is a phenyl or pyridyl ring; X represents a linker selected from the group consisting of formulae: (a), (b), (c), (d), and (e); and R?1, R2, R3, R4, R5, R6, R7, R13, R14, R15, R16, R17, R21a and R21b¿ are as defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia.

  本发明涉及公式（I）的化合物，其中环A是苯环或吡啶环；X代表从公式（a）、（b）、（c）、（d）和（e）组成的链连接物；R?1、R2、R3、R4、R5、R6、R7、R13、R14、R15、R16、R17、R21a和R21b¿如本文所定义。该化合物特别适用于治疗或预防抑郁症、焦虑症、疼痛、炎症、偏头痛、呕吐或带状疱疹后神经痛。
• CYCLOHEXANE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1286967B1

  公开（公告）日：2006-09-27
• US7105507B2
  申请人：——

  公开号：US7105507B2

  公开（公告）日：2006-09-12
• Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer’s disease
  作者：Jian Jeffrey Chen、Wenyuan Qian、Kaustav Biswas、Chester Yuan、Albert Amegadzie、Qingyian Liu、Thomas Nixey、Joe Zhu、Mqhele Ncube、Robert M. Rzasa、Frank Chavez、Ning Chen、Frenel DeMorin、Shannon Rumfelt、Christopher M. Tegley、Jennifer R. Allen、Stephen Hitchcock、Randy Hungate、Michael D. Bartberger、Leeanne Zalameda、Yichin Liu、John D. McCarter、Jianhua Zhang、Li Zhu、Safura Babu-Khan、Yi Luo、Jodi Bradley、Paul H. Wen、Darren L. Reid、Frank Koegler、Charles Dean、Dean Hickman、Tiffany L. Correll、Toni Williamson、Stephen Wood

  DOI：10.1016/j.bmcl.2013.09.041

  日期：2013.12

  gamma-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer's disease. They selectively lower pathogenic A beta 42 levels by shifting the enzyme cleavage sites without inhibiting gamma-secretase activity, possibly avoiding known adverse effects observed with complete inhibition of the enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM lead. Lead optimization studies identified compound 25 with improved cell potency, PKDM properties, and it lowered A beta 42 levels in the cerebrospinal fluid ( CSF) of Sprague-Dawley rats following oral administration. Further optimization of 25 to improve cellular potency is described. (C) 2013 Elsevier Ltd. All rights reserved.