ethyl 4-(bromomethyl)-5-(4-(trifluoromethyl)phenyl)isoxazole-3-carboxylate | 1237714-73-6

• 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: ethyl 4-(bromomethyl)-5-(4-(trifluoromethyl)phenyl)isoxazole-3-carboxylate
• 英文别名: ethyl 4-(bromomethyl)-5-[4-(trifluoromethyl)phenyl]-1,2-oxazole-3-carboxylate
• CAS: 1237714-73-6
• 化学式: C₁₄H₁₁BrF₃NO₃
• 分子量: 378.145
• InChiKey: WZXRUQLGJPWZCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 4-(bromomethyl)-5-(4-(trifluoromethyl)phenyl)isoxazole-3-carboxylate 在 碳酸氢钠 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N-cyclopentyl-4-((isopropylamino)methyl)-5-(4-(trifluoromethyl)-phenyl)isoxazole-3-carboxamide
  参考文献：
  名称：

  Discovery of potent, soluble and orally active TRPV1 antagonists. Structure–activity relationships of a series of isoxazoles

  摘要：

  Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.051
• 作为产物：
  描述：

  4-methyl-5-(4-trifluoromethyl phenyl)-isoxazole-3-carboxylic acid ethyl ester 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氯化碳 为溶剂， 反应 2.0h， 生成 ethyl 4-(bromomethyl)-5-(4-(trifluoromethyl)phenyl)isoxazole-3-carboxylate
  参考文献：
  名称：

  [EN] ISOXAZOLE-3-CARBOXAMIDE DERIVATIVES
  [FR] DÉRIVÉS D'ISOXAZOLE-3-CARBOXAMIDE

  摘要：

  本发明涉及具有一般式I的异噁唑-3-羧酰胺衍生物或其药学上可接受的盐，以及包含相同的药物组合物，以及用于治疗TRPV1介导的疾病的异噁唑-3-羧酰胺衍生物，如急性和慢性疼痛疾病、急性和慢性神经痛、急性和慢性炎症性疼痛、呼吸系统疾病和下尿路疾病的用途。

  公开号：

  WO2010091009A1

文献信息

• [EN] ISOXAZOLE-3-CARBOXAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS D'ISOXAZOLE-3-CARBOXAMIDE
  申请人：ORGANON NV

  公开号：WO2010091009A1

  公开（公告）日：2010-08-12

  The present invention relates to isoxazole-3-carboxamide derivative having the general Formula I or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of said isoxazole-3-carboxamide derivatives for the treatment of TRPV1 mediated disorders, such as acute and chronic pain disorders, acute and chronic neuropathic pain, acute and chronic inflammatory pain, respiratory diseases, and lower urinary tract disorders.

  本发明涉及具有一般式I的异噁唑-3-羧酰胺衍生物或其药学上可接受的盐，以及包含相同的药物组合物，以及用于治疗TRPV1介导的疾病的异噁唑-3-羧酰胺衍生物，如急性和慢性疼痛疾病、急性和慢性神经痛、急性和慢性炎症性疼痛、呼吸系统疾病和下尿路疾病的用途。
• ISOXAZOLE-5-CARBOXAMIDE DERIVATIVES
  申请人：Palin Ronald

  公开号：US20120071481A1

  公开（公告）日：2012-03-22

  The present invention relates to isoxazole-3-carboxamide derivative having the general Formula I or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of said isoxazole-3-carboxamide derivatives for the treatment of TRPV1 mediated disorders, such as acute and chronic pain disorders, acute and chronic neuropathic pain, acute and chronic inflammatory pain, respiratory diseases, and lower urinary tract disorders.

  本发明涉及一种具有一般式I或其药学上可接受的盐的异噁唑-3-羧酰胺衍生物，以及包含该衍生物的制药组合物，以及利用该异噁唑-3-羧酰胺衍生物治疗TRPV1介导的疾病，如急性和慢性疼痛疾病、急性和慢性神经病性疼痛、急性和慢性炎症性疼痛、呼吸系统疾病和下尿路疾病的用途。
• ISOXAZOLE-3-CARBOXAMIDE DERIVATIVES
  申请人：N.V. Organon

  公开号：EP2393789A1

  公开（公告）日：2011-12-14
• Discovery of potent, soluble and orally active TRPV1 antagonists. Structure–activity relationships of a series of isoxazoles
  作者：Paul Ratcliffe、Lynn Abernethy、Nasrin Ansari、Ken Cameron、Tom Clarkson、Maureen Dempster、David Dunn、Anna-Marie Easson、Darren Edwards、Katy Everett、Helen Feilden、Koc-Kan Ho、Steve Kultgen、Peter Littlewood、John Maclean、Duncan McArthur、Deborah McGregor、Hazel McLuskey、Irina Neagu、Olaf Nimz、Lesley-Anne Nisbet、Michael Ohlmeyer、Ronnie Palin、Quynhchi Pham、Yajing Rong、Andrew Roughton、Melanie Sammons、Robert Swanson、Heather Tracey、Glenn Walker

  DOI：10.1016/j.bmcl.2011.01.051

  日期：2011.8

  Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration. (C) 2011 Elsevier Ltd. All rights reserved.
• Identification of potent, soluble, and orally active TRPV1 antagonists
  作者：Paul Ratcliffe、John Maclean、Lynn Abernethy、Tom Clarkson、Maureen Dempster、Anna-Marie Easson、Darren Edwards、Katy Everett、Helen Feilden、Peter Littlewood、Duncan McArthur、Deborah McGregor、Hazel McLuskey、Olaf Nimz、Lesley-Anne Nisbet、Ronnie Palin、Heather Tracey、Glenn Walker

  DOI：10.1016/j.bmcl.2011.01.112

  日期：2011.4

  Optimization of a water soluble, moderately potent lead series of isoxazole-3-carboxamides was conducted, affording a compound with the requisite balance of potency, solubility and physicochemical properties for in vivo use. Compound 8e was demonstrated to be efficacious in a rat model of inflammatory pain, following oral administration. (C) 2011 Published by Elsevier Ltd.