2-chloro-4-(3,4-dimethoxyphenyl)pyrimidine | 954234-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-4-(3,4-dimethoxyphenyl)pyrimidine
• CAS: 954234-18-5
• 化学式: C₁₂H₁₁ClN₂O₂
• 分子量: 250.685
• InChiKey: HOHBBEPVHSIWQZ-UHFFFAOYSA-N

物化性质

• 沸点：
  410.3±35.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(3,4-dimethoxyphenyl)pyrimidine 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.67h， 生成 2-[4-(3,4-Dimethoxyphenyl)pyrimidin-2-yl]acetonitrile
  参考文献：
  名称：

  PHARMACEUTICALLY ACTIVE COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING PENDRIN

  摘要：

  The present invention relates to a novel compound as pendrin corrector represented by the following Chemical formula 1 and a composition for preventing or treating pendred syndrome and the related disease thereof comprising the same as an active ingredient:(I)

  公开号：

  WO2024144371A1
• 作为产物：
  描述：

  邻苯二甲醚 在 2,2'-联吡啶 、 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 正庚烷 、 水 为溶剂， 反应 20.0h， 生成 2-chloro-4-(3,4-dimethoxyphenyl)pyrimidine
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIMIDINE COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS DE PYRIMIDINE SUBSTITUÉE ET LEURS UTILISATIONS

  摘要：

  本发明涉及嘧啶化合物（式1的化合物），其所有立体异构体和互变异构体形式及其在所有比例上的混合物；以及它们的药学上可接受的盐、溶剂合物、前药和多型体以及其N-氧化物。本发明还涉及制备嘧啶化合物的方法以及含有它们的药物组合物。本发明还涉及式1化合物在治疗由一个或多个激酶介导的疾病或紊乱中的用途，特别是增殖性疾病或紊乱，如癌症。这些化合物还可用于治疗由一个或多个促炎细胞因子（如肿瘤坏死因子-α（TNF-α）或白细胞介素（IL-1β、IL-2、IL-6和/或IL-8））介导的紊乱。

  公开号：

  WO2013175415A1

文献信息

• AROMATIC NITROGEN-CONTAINING 6-MEMBERED RING COMPOUNDS AND THEIR USE
  申请人：Morimoto Hiroshi

  公开号：US20110166135A1

  公开（公告）日：2011-07-07

  The present invention provides aromatic nitrogen-containing 6-membered ring compounds having excellent PDE10 inhibitory activity. The present invention relates to an aromatic nitrogen-containing 6-membered ring compound represented by the following formula [I 0 ] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compounds for PDE10 inhibitors, and a pharmaceutical composition comprising said compounds as an active ingredient: Formula [I 0 ] wherein: X 1 , X 2 and X 3 each independently are N or CH, and at least two of X 1 , X 2 and X 3 are N; A is *—CH═CH—, *—C(Alk)=CH—, *—CH 2 —CH 2 — or *—O—CH 2 — (* is a bond with R 1 ); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R 1 is an optionally substituted nitrogen-containing heterocyclic group, a nitrogen-containing heterocyclic moiety of which is a moiety selected from the group consisting of quinoxalinyl, quinolyl, isoquinolyl, quinazolinyl, pyrazinyl, pyrimidinyl and a moiety thereof fused with a 5 to 6-membered aliphatic ring thereto; Y 0 is a group selected from the group consisting of the following (1) to (5): (1) an optionally substituted phenyl or an optionally substituted aromatic monocyclic 5 to 6-membered heterocyclic group; (2) an optionally substituted aminocarbonyl; (3) an optionally substituted amino lower alkyl; (4) —O—R 2 wherein R 2 is hydrogen, an optionally substituted lower alkyl, lower cycloalkyl, aliphatic monocyclic 5 to 6-membered heterocyclic group, or Formula [AA]; (5) mono- or di-substituted amino; provided that, when Y 0 is mono- or di-substituted amino, the nitrogen-containing heterocyclic moiety of R 1 is not quinoxalinyl or quinolyl.

  本发明提供了具有优异的PDE10抑制活性的芳香族含氮6元环化合物。本发明涉及以下式[I0]或其药学上可接受的盐，其为一种芳香族含氮6元环化合物，以及其制备方法，用于PDE10抑制剂的化合物和包含该化合物作为活性成分的药物组合物：式[I0]其中：X1、X2和X3各自独立地为N或CH，且至少两个X1、X2和X3为N；A为*—CH═CH—、*—C(Alk)=CH—、*—CH2—CH2—或*—O—CH2—（*为R1的键）；Alk为低碳基；环B为可选取代的含氮脂肪族杂环基；R1为可选取代的含氮杂环基，其中含氮杂环基是从喹啉基、喹啉基、异喹啉基、喹唑啉基、吡嗪基、嘧啶基和它们与5至6元脂环环融合的基中选择的基；Y0为从以下组合中选择的基（1）到（5）：（1）可选取代的苯基或可选取代的芳香单环5至6元杂环基；（2）可选取代的氨基甲酰基；（3）可选取代的氨基低碳基；（4）—O—R2，其中R2为氢、可选取代的低碳基、低环烷基、脂肪单环5至6元杂环基或式[AA]；（5）单取代或双取代的氨基；但当Y0为单取代或双取代的氨基时，R1的含氮杂环基不是喹啉基或喹啉基。
• Discovery of the 2,4-disubstituted quinazoline derivative as a novel neddylation inhibitor for tumor therapy
  作者：Jingtian Su、Mengyu Li、Yuanyuan Chang、Meiqi Jia、Mei Zhao、Sumeng Guan、Jinbo Niu、Saiyang Zhang、Hua Yang、Moran Sun

  DOI：10.1016/j.bioorg.2024.107237

  日期：2024.4

  Overactivation of neddylation has been found in a number of common human tumor-related diseases. In recent years, targeting the neddylation pathway has become an appealing anti-cancer strategy, and it is critical to find neddylation inhibitors with novel structures and higher efficacy. Here, we present the discovery of novel inhibitors of the NEDD8-activating enzyme (NAE) and their antitumor activity

  在许多常见的人类肿瘤相关疾病中发现了neddylation的过度激活。近年来，针对neddylation途径已成为一种颇具吸引力的抗癌策略，寻找结构新颖、疗效更高的neddylation抑制剂至关重要。在这里，我们介绍了 NEDD8 激活酶 (NAE) 新型抑制剂的发现及其抗肿瘤活性。评估所有合成的 1,4-二取代哌啶化合物对 MGC-803、MCF-7、A549 和 KYSE-30 细胞的抗增殖活性。在五个代表性化合物中，带有喹唑啉基序的 III-26 被确定为主要化合物，因为它显着阻碍了 Cullin1 的 neddylation。细胞机制阐明，III-26 抑制 UBC12 过表达的 MGC-803 细胞系的增殖、迁移和侵袭，并诱导细胞凋亡并将细胞周期阻滞在 G2/M 期。重要的是，III-26 降低了 NAE 活性，从而选择性地防止 Cullin3 和 Cullin1 相对于其他 Cullin
• Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors
  作者：Isabelle Paquin、Stéphane Raeppel、Silvana Leit、Frédéric Gaudette、Nancy Zhou、Oscar Moradei、Oscar Saavedra、Naomy Bernstein、Franck Raeppel、Giliane Bouchain、Sylvie Fréchette、Soon H. Woo、Arkadii Vaisburg、Marielle Fournel、Ann Kalita、Marie-France Robert、Aihua Lu、Marie-Claude Trachy-Bourget、Pu Theresa Yan、Jianhong Liu、Jubrail Rahil、A. Robert MacLeod、Jeffrey M. Besterman、Zuomei Li、Daniel Delorme

  DOI：10.1016/j.bmcl.2007.12.009

  日期：2008.2

  Inhibition of histone deacetylases (HDAC) is emerging as a new strategy in human cancer therapy. The synthesis and biological evaluation of a variety of 4-(heteroaryl aminomethyl)-N-(2-aminophenyl)-benzamides is presented herein. From the different series bearing a six-membered heteroaromatic ring studied, the s-triazine series showed the best HDAC1 enzyme and in vitro anti-proliferative activities with IC50 values below micromolar range. Some of these compounds can also significantly reduce tumor growth in human tumor xenograft models in mice. (C) 2007 Elsevier Ltd. All rights reserved.
• [EN] SUBSTITUTED PYRIMIDINE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE PYRIMIDINE SUBSTITUÉE ET LEURS UTILISATIONS
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2013175415A1

  公开（公告）日：2013-11-28

  The present invention relates to pyrimidine compounds, (the compounds of formula 1), in all its stereoisomeric and tautomeric forms and mixtures thereof in all ratios; and their pharmaceutically acceptable salts, solvates, prodrugs and polymorphs and N-oxides thereof. The invention also relates to processes for the manufacture of the pyrimidine compounds and to pharmaceutical compositions containing them. The invention also relates to use of the compounds of formula 1 in the treatment of diseases or disorders mediated by one or more kinases, particularly proliferative diseases or disorders such as cancer. These compounds can also be used in the treatment of disorders mediated by one or more pro-inflammatory cytokines selected from Tumor Necrosis Factor-alpha (TNF-α) or interleukins (IL-1β, IL-2, IL-6, and/or IL- 8).

  本发明涉及嘧啶化合物（式1的化合物），其所有立体异构体和互变异构体形式及其在所有比例上的混合物；以及它们的药学上可接受的盐、溶剂合物、前药和多型体以及其N-氧化物。本发明还涉及制备嘧啶化合物的方法以及含有它们的药物组合物。本发明还涉及式1化合物在治疗由一个或多个激酶介导的疾病或紊乱中的用途，特别是增殖性疾病或紊乱，如癌症。这些化合物还可用于治疗由一个或多个促炎细胞因子（如肿瘤坏死因子-α（TNF-α）或白细胞介素（IL-1β、IL-2、IL-6和/或IL-8））介导的紊乱。
• PHARMACEUTICALLY ACTIVE COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING PENDRIN
  申请人：[en]ARBORMED CO., LTD.

  公开号：WO2024144371A1

  公开（公告）日：2024-07-04

  The present invention relates to a novel compound as pendrin corrector represented by the following Chemical formula 1 and a composition for preventing or treating pendred syndrome and the related disease thereof comprising the same as an active ingredient:(I)