2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrrolo[3,2-d ]pyrimidin-5-yl)-N-[4-(4-fluoro-3-trifluoromethyl-phenyl)-thiazol-2-yl]-acetamide | 1246275-16-0

• 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: 2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrrolo[3,2-d ]pyrimidin-5-yl)-N-[4-(4-fluoro-3-trifluoromethyl-phenyl)-thiazol-2-yl]-acetamide
• 英文别名: 2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)-N-{4-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}acetamide；2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)-N-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide
• CAS: 1246275-16-0
• 化学式: C₂₀H₁₅F₄N₅O₃S
• 分子量: 481.43
• InChiKey: DTXASEKLDRHEQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1,3,4-三甲基尿嘧啶 在 硫酸 、 硝酸 、 potassium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 、 锌 作用下， 以 甲醇 、 DCE 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.42h， 生成 2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrrolo[3,2-d ]pyrimidin-5-yl)-N-[4-(4-fluoro-3-trifluoromethyl-phenyl)-thiazol-2-yl]-acetamide
  参考文献：
  名称：

  7-Substituted-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives as antagonists of the transient receptor potential ankyrin 1 (TRPA1) channel: A promising approach for treating pain and inflammation

  摘要：

  The transient receptor potential ankyrin 1 (TRPA1) channel is activated by a series of by-products of oxidative/nitrative stress, produced under inflammatory conditions or in the case of tissue damage, thus generating inflammatory and neuropathic pain and neurogenic inflammatory responses. These findings have identified TRPA1 as an emerging opportunity for the design and synthesis of selective inhibitors as potential analgesic and antiinflammatory agents. Herein we present the synthesis and functional evaluation of a new series of 7-substituted-1,3-dimethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives designed as TRPA1 antagonists. A small library of compounds has been built by the introduction of differently substituted N-7-phenylacetamide or N-7-[4-(substituted-phenyl)-thiazol-2-yl]acetamide chains. All the synthesized compounds were assayed to evaluate their ability to block acrolein-mediated activation of native human and rat TRPA1 channels employing a fluorometric calcium imaging assay. Our study led us to the identification of compound 3h which showed considerably improved potency (IC50 = 400 nM) against human TRPA1 with regard to some of the most representative antagonists previously reported and integrated in our screening program as reference compounds. In addition, 3h proved to maintain its efficacy toward rTRPA1, which designates it as a possible candidate for future evaluation of in vivo efficacy in rodent animal model of inflammatory and neuropathic pain. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.020

文献信息

• FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPAI MODULATORS
  申请人：Chaudhari Sachin Sundarlal

  公开号：US20120041004A1

  公开（公告）日：2012-02-16

  The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1.

  本发明涉及化合物公式(I)的新型融合嘧啶二酮衍生物，其为TRPA（瞬时受体电位亚家族A）调节剂。特别地，本发明所描述的化合物可用于治疗或预防由TRPA1（瞬时受体电位亚家族A，成员1）调节的疾病、状况和/或障碍。本发明还提供了制备所述化合物的方法、用于其合成的中间体、其制药组合物以及用于治疗或预防由TRPA1调节的疾病、状况和/或障碍的方法。
• Fused pyrimidine-dione derivatives as TRPA1 modulators
  申请人：Glenmark Pharmaceuticals, S.A.

  公开号：US09000159B2

  公开（公告）日：2015-04-07

  The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1.

  本发明涉及式（I）的新型融合嘧啶二酮衍生物，其为TRPA（瞬时受体电位亚家族A）调节剂。特别地，本文所描述的化合物可用于治疗或预防由TRPA1（瞬时受体电位亚家族A，成员1）调节的疾病、症状和/或障碍。本发明还提供了制备所述化合物的方法、用于其合成的中间体、其制药组合物以及用于治疗或预防由TRPA1调节的疾病、症状和/或障碍的方法。
• FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPA1 MODULATORS
  申请人：Glenmark Pharmaceuticals, S.A.

  公开号：US20140128603A1

  公开（公告）日：2014-05-08

  The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1.

  本发明涉及式（I）的新型融合嘧啶二酮衍生物，其为TRPA（瞬时受体电位亚家族A）调节剂。特别地，本发明所描述的化合物可用于治疗或预防由TRPA1（瞬时受体电位亚家族A，成员1）调节的疾病、状况和/或紊乱。本发明还提供了制备所述化合物的方法、用于其合成的中间体、其药物组成物以及用于治疗或预防由TRPA1调节的疾病、状况和/或紊乱的方法。
• Process for preparing fused pyrimidine-dione derivatives, useful as as TRPA1 modulators
  申请人：Glenmark Pharmaceuticals S.A.

  公开号：EP2708538A1

  公开（公告）日：2014-03-19

  The present invention relates to a process for preparing a compound of formula (Id-1) or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of formula (35) with amine compound of formula (18) wherein, R1 and R2, which may be same or different, are independently selected from hydrogen and substituted or unsubstituted alkyl; U is substituted or unsubstituted heterocycles selected from thiazole and isoxazole; and V is substituted or unsubstituted aryl.

  本发明涉及一种制备式（Id-1）化合物的工艺 或其药学上可接受的盐的工艺，该工艺包括 使式（35）化合物与式（18）胺化合物反应 其中 R1 和 R2（可以相同或不同）独立地选自氢和取代或未取代的烷基； U 是取代或未取代的杂环，选自噻唑和异噁唑；以及 V 是取代或未取代的芳基。
• US8623880B2
  申请人：——

  公开号：US8623880B2

  公开（公告）日：2014-01-07