N-[(1R,3S)-3-hydroxycyclohexyl]-4-[[[(2R)-1-hydroxy-3-methylbutan-2-yl]amino]methyl]-5-[4-(trifluoromethyl)phenyl]-1,2-oxazole-3-carboxamide | 1237714-95-2

• 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: N-[(1R,3S)-3-hydroxycyclohexyl]-4-[[[(2R)-1-hydroxy-3-methylbutan-2-yl]amino]methyl]-5-[4-(trifluoromethyl)phenyl]-1,2-oxazole-3-carboxamide
• CAS: 1237714-95-2
• 化学式: C₂₃H₃₀F₃N₃O₄
• 分子量: 469.504
• InChiKey: BJXXTUUHHKNKSP-AOIWGVFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(chloromethyl)-5-(4-(trifluoromethyl)phenyl)isoxazole-3-carbonyl chloride 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.25h， 生成 N-[(1R,3S)-3-hydroxycyclohexyl]-4-[[[(2R)-1-hydroxy-3-methylbutan-2-yl]amino]methyl]-5-[4-(trifluoromethyl)phenyl]-1,2-oxazole-3-carboxamide
  参考文献：
  名称：

  Identification of potent, soluble, and orally active TRPV1 antagonists

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2011.01.112

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
• 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.