N-(4-(chloromethyl)benzyl)acetamide | 223512-41-2

• 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-(4-(chloromethyl)benzyl)acetamide
• 英文别名: N-(4-chloromethylphenylmethyl)acetamide；N-[[4-(chloromethyl)phenyl]methyl]acetamide
• CAS: 223512-41-2
• 化学式: C₁₀H₁₂ClNO
• 分子量: 197.664
• InChiKey: UADHOMUWKSPYAI-UHFFFAOYSA-N

物化性质

• 沸点：
  399.6±30.0 °C(Predicted)
• 密度：
  1.146±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(4-(chloromethyl)benzyl)acetamide 在 亚硝酸特丁酯 、 sodium methylate 、 copper dichloride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 30.5h， 生成 2-(6-(4-(acetamidomethyl)benzylthio)-3,5-dicyano-4-ethylpyridin-2-ylthio)-2-phenylacetamide
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
  [FR] PYRIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE DNMT1

  摘要：

  该发明涉及取代吡啶衍生物。具体而言，该发明涉及符合以下式（Iar）的化合物：（Iar）其中Yar、X1ar、X2ar、R1ar、R2ar、R3ar、R4ar和R5ar如本文所定义；或其药学上可接受的盐或前药。该发明的化合物是DNMT1的选择性抑制剂，可用于治疗癌症、癌前综合征、β血红蛋白病、镰状细胞病、镰状细胞贫血、β地中海贫血以及与DNMT1抑制相关的疾病。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制DNMT1活性和治疗相关疾病的方法。

  公开号：

  WO2017216726A1
• 作为产物：
  描述：

  4-氨甲基苯甲酸 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 氯化亚砜 、 硫酸 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 生成 N-(4-(chloromethyl)benzyl)acetamide
  参考文献：
  名称：

  Novel phenylpiperazine derivatives as dual cytokine regulators with TNF-α suppressing and IL-10 augmenting activity

  摘要：

  Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice, suggesting that 5k would be a promising drug candidate for the treatment of TNF-alpha associated diseases including septic shock. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00128-1

文献信息

• Piperazine compounds and medicinal use thereof
  申请人：Mitsubishi Pharma Corporation

  公开号：US06455528B1

  公开（公告）日：2002-09-24

  The present invention relates to a piperazine compound of the formula wherein R1 and R2 are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4 and R5 are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6 and R7 are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8 and R9 are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-&agr; production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-&agr; production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-&agr; production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-&agr; mediated diseases.

  本发明涉及一种哌嗪化合物，其化学式为 其中R1和R2分别为氢、卤素、低烷基、低烷氧基、氨基、取代氨基、硝基、羟基或氰基，R3、R4和R5分别为氢、卤素、低烷基、低烷氧基、硝基、氨基、取代氨基或羟基，R6和R7分别为氢、低烷基、受卤素取代的低烷基、芳基烷基、酰基或受卤素取代的低酰基，R8和R9分别为氢或低烷基，Y为低烷基烯基等，环A为苯基、嘧啶基、噻唑基、吡啶基、吡啉基或咪唑基，其药学上可接受的盐及含有这些化合物的药物制剂。本发明的化合物具有优越的TNF-α产生抑制作用和/或IL-10产生促进作用，由于它不含或仅显示对中枢神经系统有显著减少的作用，该化合物可用作高度安全和优越的TNF-α产生抑制剂和/或IL-10产生促进剂，并可用作预防或治疗由异常TNF-α产生引起的各种疾病的药剂，例如可用于治疗可通过IL-10治愈的慢性炎症性疾病、急性炎症性疾病、感染引起的炎症性疾病、自身免疫疾病、过敏性疾病和TNF-α介导的疾病。
• Imidazole derivatives
  申请人：Welfide Corporation

  公开号：US06288061B1

  公开（公告）日：2001-09-11

  The present invention relates to the imidazole derivative of the following formula (I) wherein R1 is hydrogen, optionally substituted alkyl and the like, R2 is hydrogen, optionally substituted alkyl and the like, R3is optionally substituted heteroaryl, R4 is optionally substituted cycloalkyl, optionally substituted phenyl and the like, provided that when R1 is hydrogen, and R2 and R4 are the same or different and each is phenyl or phenyl substituted by halogen atom, lower alkyl or lower alkoxy, R3 is benzothiazolyl or thiazolyl substituted by phenyl, the imidazole derivative of the following formula (XII) wherein R6 is optionally substituted phenyl or optionally substituted heteroaryl and R7 is substituted phenyl, and pharmaceutically acceptable salts thereof. The compounds of the formulas (I) and (XII) and pharmaceutically acceptable salts thereof of the present invention inhibit IL-4 and IL-5 production by Th2 cells and are effective for the prophylaxis and treatment of allergic diseases such as atopic dermatitis, bronchial asthma, allergic rhinitis and the like.

  本发明涉及以下式（I）的咪唑衍生物 其中R1是氢，可选择地取代的烷基等，R2是氢，可选择地取代的烷基等，R3是可选择地取代的杂芳基，R4是可选择地取代的环烷基，可选择地取代的苯基等，但当R1是氢，且R2和R4相同或不同，且每个是苯基或被卤原子、较低烷基或较低烷氧基取代的苯基时，R3是苯并噻唑基或被苯基取代的噻唑基，以下式（XII）的咪唑衍生物 其中R6是可选择地取代的苯基或可选择地取代的杂芳基，R7是被取代的苯基，以及其药学上可接受的盐。本发明的式（I）和（XII）的化合物及其药学上可接受的盐通过抑制Th2细胞产生IL-4和IL-5，在预防和治疗特应性皮炎、支气管哮喘、过敏性鼻炎等过敏性疾病方面具有有效性。
• [EN] THERAPEUTIC INHIBITORY COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS THÉRAPEUTIQUES
  申请人：LIFESCI PHARMACEUTICALS INC

  公开号：WO2015103317A1

  公开（公告）日：2015-07-09

  The invention provides compounds of Formula I and Formula II: A-B-C-D-E-F-G-J (I) C-D-E-F-G-J (II) wherein A, B, C, D, E, F, G, and J have any of the values defined in the specification, and salts thereof. The compounds are useful for inhibiting plasma kallikrein, and for treating a disease or condition in an animal where inhibition of plasma kallikrein is indicated.

  该发明提供了Formula I和Formula II的化合物：A-B-C-D-E-F-G-J (I)和C-D-E-F-G-J (II)，其中A、B、C、D、E、F、G和J具有规范中定义的任何值，以及它们的盐。这些化合物对抑制血浆激肽酶和治疗动物中需要抑制血浆激肽酶的疾病或症状是有用的。
• PIPERAZINE COMPOUNDS AND MEDICINAL USE THEREOF
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP1029851A1

  公开（公告）日：2000-08-23

  Piperazine compounds represented by the following general formula (I) or pharmaceutically acceptable salts thereof and drugs comprising these compounds, wherein R1 and R2 represent each hydrogen, halogeno, lower alkyl, lower alkoxy, optionally substituted amino, nitro, hydroxy or cyano; R3, R4 and R5 represent each hydrogen, halogeno, lower alkyl, lower alkoxy, nitro, optionally substituted amino or hydroxy; R6 and R7 represent each hydrogen, optionally halogenated lower alkyl, aralkyl, acyl or halogenated lower acyl; R8 and R9 represent each hydrogen or lower alkyl; Y represents lower alkylene, etc.; and the ring A represents phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl. Because of having excellent TNF-α production inhibitory effect and/or IL-10 production promoting effect, these compounds are useful as TNF-α production inhibitors and/or IL-10 production promoters with high safety. They are useful as preventives or remedies for, e.g., chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases caused by infection, autoimmune diseases, allergic diseases and other TNF-α-mediated diseases.

  由以下通式(I)代表的哌嗪化合物或其药学上可接受的盐以及包含这些化合物的药物，其中 R1 和 R2 分别代表氢、卤素、低级烷基、低级烷氧基、任选取代的氨基、硝基、羟基或氰基；R3、R4 和 R5 分别代表氢、卤素、低级烷基、低级烷氧基、硝基、任选取代的氨基或羟基； R6 和 R7 分别代表氢、任选卤代低级烷基、芳基、酰基或卤代低级酰基； R8 和 R9 分别代表氢或低级烷基； Y 代表低级亚烷基等。环 A 代表苯基、嘧啶基、噻唑基、吡啶基、吡嗪基或咪唑基。由于这些化合物具有优异的 TNF-α 生成抑制作用和/或 IL-10 生成促进作用，因此可用作 TNF-α 生成抑制剂和/或 IL-10 生成促进剂，安全性高。它们可用于预防或治疗慢性炎症性疾病、急性炎症性疾病、感染引起的炎症性疾病、自身免疫性疾病、过敏性疾病和其他TNF-α介导的疾病。
• Substituted pyridines as inhibitors of DNMT1
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10975056B2

  公开（公告）日：2021-04-13

  The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代的吡啶衍生物。具体地说，本发明是针对符合式（Iar）的化合物： 其中 Yar、X1ar、X2ar、R1ar、R2ar、R3ar、R4ar 和 R5ar 如本文所定义；或其药学上可接受的盐或原药。 本发明的化合物是 DNMT1 的选择性抑制剂，可用于治疗癌症、癌前综合征、β 血红蛋白病疾病、镰状细胞病、镰状细胞性贫血和β 地中海贫血以及与 DNMT1 抑制相关的疾病。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物抑制 DNMT1 活性和治疗与之相关疾病的方法。