3-([(tert-butoxycarbonyl)(methyl)amino]methyl)-5-(trifluoromethyl)benzoic acid | 1237535-85-1

• 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: 3-([(tert-butoxycarbonyl)(methyl)amino]methyl)-5-(trifluoromethyl)benzoic acid
• 英文别名: 3-[[Methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]-5-(trifluoromethyl)benzoic acid
• CAS: 1237535-85-1
• 化学式: C₁₅H₁₈F₃NO₄
• 分子量: 333.307
• InChiKey: MRUHYGWLFIMRCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-([(tert-butoxycarbonyl)(methyl)amino]methyl)-5-(trifluoromethyl)benzoic acid 、 5-([-(7R)-7-amino-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.08h， 生成 3-[(methylamino)methyl]-N-((2R)-7-[(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalen-2-yl)-5-(trifluoromethyl)benzamide hydrochloride
  参考文献：
  名称：

  Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors

  摘要：

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

  DOI：

  10.1021/jm101479y
• 作为产物：
  描述：

  tert-butyl 3-formyl-5-(trifluoromethyl)benzoate 在 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 3.75h， 生成 3-([(tert-butoxycarbonyl)(methyl)amino]methyl)-5-(trifluoromethyl)benzoic acid
  参考文献：
  名称：

  Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors

  摘要：

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

  DOI：

  10.1021/jm101479y

文献信息

• PREPARATION OF AMINOTETRALIN COMPOUNDS
  申请人：Gould Alexandra E.

  公开号：US20100197924A1

  公开（公告）日：2010-08-05

  The present invention relates to synthetic processes for preparation of aminotetralin compounds with kinase inhibitory activity. The invention also provides synthetic intermediates useful in the processes of the invention.

  本发明涉及用于制备具有激酶抑制活性的氨基四氢吡啶化合物的合成过程。该发明还提供了在本发明的过程中有用的合成中间体。
• US20140256947A1
  申请人：——

  公开号：US20140256947A1

  公开（公告）日：2014-09-11
• Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors
  作者：Alexandra E. Gould、Ruth Adams、Sharmila Adhikari、Kathleen Aertgeerts、Roushan Afroze、Christopher Blackburn、Emily F. Calderwood、Ryan Chau、Jouhara Chouitar、Matthew O. Duffey、Dylan B. England、Cheryl Farrer、Nancy Forsyth、Khristofer Garcia、Jeffery Gaulin、Paul D. Greenspan、Ribo Guo、Sean J. Harrison、Shih-Chung Huang、Natalia Iartchouk、Dave Janowick、Mi-Sook Kim、Bheemashankar Kulkarni、Steven P. Langston、Jane X. Liu、Li-Ting Ma、Saurabh Menon、Hirotake Mizutani、Erin Paske、Christelle C. Renou、Mansoureh Rezaei、R. Scott Rowland、Michael D. Sintchak、Michael D. Smith、Stephen G. Stroud、Ming Tregay、Yuan Tian、Ole P. Veiby、Tricia J. Vos、Stepan Vyskocil、Juliet Williams、Tianlin Xu、Johnny J. Yang、Jason Yano、Hongbo Zeng、Dong Mei Zhang、Qin Zhang、Katherine M. Galvin

  DOI：10.1021/jm101479y

  日期：2011.3.24

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.