4-chloro-3-(4-fluorophenyl)isoxazole-5-carboxylic acid | 1239576-23-8

• 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: 4-chloro-3-(4-fluorophenyl)isoxazole-5-carboxylic acid
• 英文别名: 4-Chloro-3-(4-fluorophenyl)-1,2-oxazole-5-carboxylic acid
• CAS: 1239576-23-8
• 化学式: C₁₀H₅ClFNO₃
• 分子量: 241.606
• InChiKey: WAWCGDCEHWAFDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-chloro-3-(4-fluorophenyl)isoxazole-5-carboxylic acid 、 (1S,3R)-3-氨基环己醇 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-chloro-3-(4-fluorophenyl)-N-((1R,3S)-3-hydroxycyclohexyl)isoxazole-5-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：

  [3-(4-氟苯基)异噁唑-5-基]甲醇 在 甲醇 、 sodium hypochlorite 、 sodium chlorite 、 sodium dihydrogenphosphate 、 N-氯代丁二酰亚胺 、 2,2,6,6-四甲基哌啶氧化物 、 硫酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 生成 4-chloro-3-(4-fluorophenyl)isoxazole-5-carboxylic acid
  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

文献信息

• [EN] ISOXAZOLE-5-CARBOXAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS D'ISOXAZOLE-5-CARBOXAMIDE
  申请人：ORGANON NV

  公开号：WO2010089297A1

  公开（公告）日：2010-08-12

  The present invention relates to isoxazole-5-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-5-carboxamide derivatives for the treatment of TRPV1 mediated disorders, such as acute and chronic pain disorders, acute and chronic neuropathic pain, acute and chronic inflammatorypain, respiratorydiseases, and lower urinary tract disorders.

  本发明涉及具有一般式（I）的异噁唑-5-羧酰胺衍生物或其药学上可接受的盐，包括含有它们的制药组合物，以及使用该异噁唑-5-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-5-CARBOXAMIDE DERIVATIVES
  申请人：Ratcliffe Paul David

  公开号：US20120095002A1

  公开（公告）日：2012-04-19

  The present invention relates to isoxazole-5-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-5-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）的异恶唑-5-羧酰胺衍生物或其药学上可接受的盐，以及包含它们的制药组合物，以及所述异恶唑-5-羧酰胺衍生物在TRPV1介导的疾病治疗中的应用，例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，呼吸系统疾病和下泌尿道疾病。
• 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.