1,3-二甲基-1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮 | 46155-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 中文名称: 1,3-二甲基-1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮
• 英文名称: 1,3-dimethylpyrrolo<3,2-d>pyrimidine-2,4-dione
• 英文别名: 1,3-dimethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione；1,3-dimethylpyrrolo[3,2-d]pyrimidine-2,4(1H,3H)-dione；9-deazaxanthine；theophylline；1,3-dimethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione；1,3-dimethyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione；1,3-dimethyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-dione
• CAS: 46155-89-9
• 化学式: C₈H₉N₃O₂
• mdl: MFCD00457572
• 分子量: 179.178
• InChiKey: XLSXPKZIKMPZHK-UHFFFAOYSA-N

物化性质

• 熔点：
  210-212 °C(Solv: benzene (71-43-2))
• 沸点：
  369.6±34.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  存放于室温环境，保持干燥并密封。

反应信息

• 作为反应物：
  描述：

  1,3-二甲基-1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮 在 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.17h， 生成 2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrrolo[3,2-d]pyrimidin-5-yl)-N-(4-trifluoromethoxy-phenyl)-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
• 作为产物：
  描述：

  1,3,4-三甲基尿嘧啶 在 硫酸 、 硝酸 、 溶剂黄146 、 锌 作用下， 反应 5.25h， 生成 1,3-二甲基-1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮
  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

• [EN] FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPA1 MODULATORS<br/>[FR] DÉRIVÉS DE PYRIMIDINEDIONES FUSIONNÉS UTILISÉS COMME MODULATEURS DES RÉCEPTEURS TRPA1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2010109287A1

  公开（公告）日：2010-09-30

  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 TRPAl (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 TRPAl. Formula (I)

  本发明描述的是一类新颖的杂合吡啶二酮衍生物，其化学公式为（I），这些衍生物是TRPA（瞬时受体电位亚家族A）的调节剂。特别是，本文所述的化合物对于治疗或预防由TRPA1（瞬时受体电位亚家族A成员1）调控的疾病、状况和/或失调是有用的。本发明还提供了制备所述化合物、它们合成中使用的中间体、药物组合物以及治疗或预防由TRPA1调控的疾病、状况和/或失调的方法。公式（I）
• Nitro derivatives of pyrrolo[3,2-d]pyrimidine-2,4-diones: Synthesis of amines and new polynuclear heterocycles based thereon
  作者：Yu. N. Tkachenko、L. D. Popov、A. F. Pozharskii、S. A. Borodkin、S. I. Levchenkov

  DOI：10.1134/s1070428017100128

  日期：2017.10

  4-diones under different conditions led to the formation of their 6(7)-mono- and 6,7-dinitro derivatives which were reduced to the corresponding amines. The latter reacted with α- and β-dicarbonyl compounds, as well as with ortho-quinones to give a number of new polycyclic heteroaromatic systems.

  1,3-二甲基吡咯并[3,2- d ]嘧啶-2,4-二酮在不同条件下的硝化导致它们的6（7）-单-和6,7-二硝基衍生物的形成，还原为相应的胺。后者与α-和β-二羰基化合物以及邻醌反应生成许多新的多环杂芳族体系。
• Heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05753664A1

  公开（公告）日：1998-05-19

  A novel compound of the formula: A--Z--Ar.sup.1 1'CO--Ar.sup.2 wherein A is a condensed pyrimidinone or condensed pyridazinone ring; Ar.sup.1 and Ar.sup.2 are independently a ring; Z is a divalent group, or a salt thereof which have an excellent antitumor activity.

  一种新的化合物，其化学式为：A--Z--Ar.sup.1 1'CO--Ar.sup.2，其中A是一个紧凑的嘧啶酮或紧凑的吡啶并酮环；Ar.sup.1和Ar.sup.2分别是一个环；Z是一个二价基团，或其盐，具有出色的抗肿瘤活性。
• 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：Chaudhari Sachin Sundarlal

  公开号：US08623880B2

  公开（公告）日：2014-01-07

  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、病症和/或障碍。本发明还提供了制备所述化合物的工艺、用于其合成的中间体、其药物组成物以及治疗或预防由TRPA1调节的疾病、病症和/或障碍的方法。