(4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one | 1198174-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: (4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one
• 英文别名: (4R)-4-[3-(3-methoxypropoxy)phenyl]-2-sulfanylidene-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5-one
• CAS: 1198174-47-8
• 化学式: C₂₁H₂₀N₂O₃S
• 分子量: 380.467
• InChiKey: DTVXBNDIMDRBBV-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  间羟基苯甲醛 在 盐酸 、 potassium carbonate 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 40.0~110.0 ℃ 、10.0 MPa 条件下， 反应 1.09h， 生成 (4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one 、 (4S)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one
  参考文献：
  名称：

  [EN] 3,4-DIHYDROPYRIMIDINE TRPA1 ANTAGONISTS
  [FR] ANTAGONISTES DES TRPA1 CONSTITUÉS PAR DES 3,4-DIHYDROPYRIMIDINES

  摘要：

  本发明涉及具有TRPA1受体拮抗性质的新型3,4-二氢嘧啶化合物（I）的药物组合物，包括这些化合物的化学制备过程以及它们在治疗与动物中TRPA1受体调节相关的疾病，特别是人类中的用途。

  公开号：

  WO2009147079A1

文献信息

• Development of novel azabenzofuran TRPA1 antagonists as in vivo tools
  作者：Katrina W. Copeland、Alessandro A. Boezio、Eugene Cheung、Josie Lee、Philip Olivieri、Laurie B. Schenkel、Qian Wan、Weiya Wang、Mary C. Wells、Beth Youngblood、Narender R. Gavva、Sonya G. Lehto、Stephanie Geuns-Meyer

  DOI：10.1016/j.bmcl.2014.05.069

  日期：2014.8

  transient receptor potential ankyrin 1 (TRPA1) channel is activated by noxious stimuli including chemical irritants and endogenous inflammatory mediators. Antagonists of this channel are currently being investigated for use as therapeutic agents for treating pain, airway disorders, and itch. A novel azabenzofuran series was developed that demonstrated in vitro inhibition of allyl isothiocyanate (AITC)-induced

  瞬时受体电位锚蛋白1（TRPA1）通道被有害刺激物激活，包括化学刺激物和内源性炎症介质。目前正在研究该通道的拮抗剂用作治疗疼痛，气道疾病和瘙痒的治疗剂。开发了一种新型的氮杂苯并呋喃系列，该系列证明了对异硫氰酸烯丙基异氰酸酯（AITC）诱导的45 Ca 2+吸收具有纳摩尔浓度的抗人和大鼠TRPA1的体外抑制作用。从该系列中，化合物10在AITC诱导的大鼠退缩模型中表现出体内靶标覆盖率，同时提供的未结合血浆浓度比TRPA1大鼠IC 50高16倍。
• Tricyclic 3,4-dihydropyrimidine-2-thione derivatives as potent TRPA1 antagonists
  作者：Harrie J.M. Gijsen、Didier Berthelot、Michel A.J. De Cleyn、Ivo Geuens、Bert Brône、Marc Mercken

  DOI：10.1016/j.bmcl.2011.12.068

  日期：2012.1

  The transient receptor potential A1 (TRPA1) channel has been implicated in a number of inflammatory and nociceptive processes, and antagonists of the TRPA1 receptor could offer a potential treatment for conditions such as inflammatory or neuropathic pain, airway disorders, and itch. In a high throughput screen aimed at the identification of TRPA1 antagonists, 4-phenyl-2-thioxo-1,2,3,4-tetrahydroindeno[1,2-d]pyrimidin-5-one (1) was identified as a potent TRPA1 receptor antagonist. A series of analogous tricyclic 3,4-dihydropyrimidine-2-thiones has been prepared via the multi-component Biginelli reaction and subsequent derivatization. This has led to TRPA1 antagonists with potencies around 10 nM for both rat and human derived TRPA1 receptors. The activity was shown to reside exclusively in the 4R-enantiomers. (C) 2011 Elsevier Ltd. All rights reserved.
• 3,4-DIHYDROPYRIMIDINE TRPA1 ANTAGONISTS
  申请人：Gijsen Henricus Jacobus Maria

  公开号：US20110124666A1

  公开（公告）日：2011-05-26

  The present invention is related to novel 3,4-dihydropyrimidine compounds of formula (I) having TRPA1 receptor antagonistic properties, pharmaceutical compositions comprising these compounds, chemical processes for preparing these compounds and their use in the treatment of diseases linked to the modulation of the TRPA1 receptors in animals, in particular humans.
• USE OF NEUROKININ-1 ANTAGONISTS AS ANTITUSSIVES
  申请人：Menlo Therapeutics Inc.

  公开号：US20180235931A1

  公开（公告）日：2018-08-23

  The disclosure relates to the use of neurokinin-1 (NK-1) antagonists, such as serlopitant, MK-0303 or MK-8478, in alleviating or suppressing cough (including acute, subacute and chronic cough) and urge to cough. The cough can have an unknown cause (idiopathic cough) or can be associated with any type of medical condition, such as a respiratory disorder. The NK-1 antagonist can be delivered by oral inhalation for more rapid peripheral and central antitussive action. Another antitussive agent in addition to the NK-1 antagonist can optionally be administered for the treatment of the cough or urge to cough, or the cough-associated medical condition.
• USE OF NEUROKININ-1 ANTAGONISTS TO TREAT A VARIETY OF PRURITIC CONDITIONS
  申请人：MENLO THERAPEUTICS INC.

  公开号：US20190216779A1

  公开（公告）日：2019-07-18

  The disclosure relates to the use of neurokinin-1 (NK-1) antagonists, such as serlopitant, in treating acute or chronic pruritus associated with a variety of medical conditions, including dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma, epidermolysis bullosa, bums and hepato-biliary diseases, or/and treating the medical conditions themselves. One or more additional antipruritic or therapeutic agents can optionally be used in combination with an NK-1 antagonist to treat acute or chronic pruritus associated with a medical condition or/and the medical condition itself.