N-methyl-4-(methylsulfinyl)aniline | 1586823-53-1

• 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-methyl-4-(methylsulfinyl)aniline
• 英文别名: 4-methylaminophenyl methyl sulfoxide；N-methyl-4-methylsulfinylaniline
• CAS: 1586823-53-1
• 化学式: C₈H₁₁NOS
• 分子量: 169.247
• InChiKey: IBDFJQCEIACADI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methyl-4-(methylsulfinyl)aniline 在 间氯过氧苯甲酸 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以59%的产率得到N-甲基-4-(甲基磺酰基)苯胺盐酸盐
  参考文献：
  名称：

  基于结构的药物设计和体外代谢研究：发现N-（4-甲硫基苯基）-N，2-二甲基-环戊[d]嘧啶作为有效的微管靶向剂。

  摘要：

  我们报告了一系列的微管蛋白靶向剂，其中一些表现出有效的抗增殖活性。这些类似物的设计旨在通过改变4'-位的杂原子取代基，4-位氨基部分的碱性和构象限制条件来优化1的抗增殖活性。还合成了活性化合物的潜在代谢产物。一些化合物在MDA-MB-435黑色素瘤细胞中显示出抗增殖作用的一位数纳摩尔IC50值。特别是，在MDA-MB-435细胞中，S-甲基类似物3比1更有效（IC50 = 4.6 nM）。与人肝微粒体一起孵育3，表明3的S-甲基部分的主要代谢产物是甲基亚磺酰基，与类似物5一样。该代谢产物在MDA-MB-435细胞中与先导化合物1等价（IC50 = 7。9 nM）。确定分子模型和静电表面积以解释类似物的活性。大多数有效的化合物克服了多种耐药性机制，化合物3作为进一步SAR和临床前开发的先导化合物而出现。

  DOI：

  10.1016/j.bmc.2018.04.010
• 作为产物：
  描述：

  N-methyl-4-(methylthio)aniline 在 间氯过氧苯甲酸 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以67%的产率得到N-methyl-4-(methylsulfinyl)aniline
  参考文献：
  名称：

  基于结构的药物设计和体外代谢研究：发现N-（4-甲硫基苯基）-N，2-二甲基-环戊[d]嘧啶作为有效的微管靶向剂。

  摘要：

  我们报告了一系列的微管蛋白靶向剂，其中一些表现出有效的抗增殖活性。这些类似物的设计旨在通过改变4'-位的杂原子取代基，4-位氨基部分的碱性和构象限制条件来优化1的抗增殖活性。还合成了活性化合物的潜在代谢产物。一些化合物在MDA-MB-435黑色素瘤细胞中显示出抗增殖作用的一位数纳摩尔IC50值。特别是，在MDA-MB-435细胞中，S-甲基类似物3比1更有效（IC50 = 4.6 nM）。与人肝微粒体一起孵育3，表明3的S-甲基部分的主要代谢产物是甲基亚磺酰基，与类似物5一样。该代谢产物在MDA-MB-435细胞中与先导化合物1等价（IC50 = 7。9 nM）。确定分子模型和静电表面积以解释类似物的活性。大多数有效的化合物克服了多种耐药性机制，化合物3作为进一步SAR和临床前开发的先导化合物而出现。

  DOI：

  10.1016/j.bmc.2018.04.010

文献信息

• [EN] BENZAMIDE COMPOUNDS AND RELATED METHODS OF USE<br/>[FR] COMPOSÉS BENZAMIDE ET LEURS PROCÉDÉS D'UTILISATION CONNEXES
  申请人：UNIV NORTHWESTERN

  公开号：WO2014100833A1

  公开（公告）日：2014-06-26

  Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease.

  苯甲酰胺化合物及其衍生物，可用于选择性抑制SIRT2酶和/或在亨廷顿病的治疗中用于治疗用途。
• Benzamide Compounds and Related Methods of Use
  申请人：Northwestern University

  公开号：US20150025235A1

  公开（公告）日：2015-01-22

  Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease.

  苯甲酰胺化合物及其衍生物可用于选择性抑制SIRT2酶和/或治疗亨廷顿病。
• Cyclopenta[d]pyrimidines and substituted cyclopenta[d]pyrimidines as antitubulin and microtubule targeting agents, monocyclic pyrimidines as tubulin inhibitors, and pyrrolopyrimidines as targeted antifolates and tubulin and multiple receptor tyrosine kinase inhibition and antitumor agents
  申请人：Duquesne University of the Holy Spirit

  公开号：US10239880B2

  公开（公告）日：2019-03-26

  The present invention provides a compound of Formula I, and salts thereof, and a pharmaceutical composition comprising a compound of Formula I: wherein R1 is selected from the group consisting of and R2 is an alkyl group having from one to ten carbon atoms, or wherein R2 is selected from the group consisting of R1 is an alkyl group having from one to ten carbon atoms; and R is H, or an alkyl group having from one to ten carbon atoms, and R3 is H, an alkyl group having from one to ten carbon atoms, or a halogen. Preferably the compound of Formula V includes wherein R3 is a halogen, and most preferably wherein the halogen is chlorine. Methods of treating a patient with cancer with these compounds are also provided.

  本发明提供了一种式 I 的化合物及其盐类，以及一种包含式 I 化合物的药物组合物： 其中 R1 选自以下组成的组 和 R2 是具有 1 至 10 个碳原子的烷基，或 其中 R2 选自以下组成的组 R1 是具有一至十个碳原子的烷基；R 是 H 或具有一至十个碳原子的烷基，R3 是 H、具有一至十个碳原子的烷基或卤素。其中 R3 是卤素，最优选的是卤素是氯。还提供了用这些化合物治疗癌症患者的方法。
• Cyclopenta[d]pyrimidines and substituted cyclopenta[d]pyrimidines as antitubulin and microtubule targeting agents, monocyclic pyrimidines as tubulin inhibitors, and pyrrolopyrimidines as targeted antifolates and tubulin and multiple receptor tyrosine kinase inhibitor and antitumor agents
  申请人：Duquesne University of the Holy Spirit

  公开号：US11124520B2

  公开（公告）日：2021-09-21

  The present invention provides a compound of Formula III, and salts thereof, and a pharmaceutical composition comprising a compound of Formula III: wherein R1 is selected from the group consisting of: wherein R2 is H or an alkyl group having from one to ten carbon atoms; R3 is H or an alkyl group having from one to ten carbon atoms; and R4 is H or an alkyl group having from one to ten carbon atoms. Methods of treating a patient with cancer with these compounds are also provided.

  本发明提供了一种式 III 的化合物及其盐类，以及一种包含式 III 化合物的药物组合物： 其中 R1 选自以下组成的组 在其中 R2 是 H 或具有一至十个碳原子的烷基； R3 是 H 或具有一至十个碳原子的烷基；以及 R4 是 H 或具有一至十个碳原子的烷基。还提供了用这些化合物治疗癌症患者的方法。
• Development and characterization of 3-(benzylsulfonamido)benzamides as potent and selective SIRT2 inhibitors
  作者：Mohammad A. Khanfar、Luisa Quinti、Hua Wang、Soo Hyuk Choi、Aleksey G. Kazantsev、Richard B. Silverman

  DOI：10.1016/j.ejmech.2014.02.003

  日期：2014.4

  Inhibitors of sirtuin-2 deacetylase (SIRT2) have been shown to be protective in various models of Huntington's disease (HD) by decreasing polyglutamine aggregation, a hallmark of HD pathology. The present study was directed at optimizing the potency of SIRT2 inhibitors containing the neuroprotective sulfobenzoic acid scaffold and improving their pharmacology. To achieve that goal, 176 analogues were designed, synthesized, and tested in deacetylation assays against the activities of major human sirtuins SIRT1-3. This screen yielded 15 compounds with enhanced potency for SIRT2 inhibition and 11 compounds having SIRT2 inhibition equal to reference compound AK-1. The newly synthesized compounds also demonstrated higher SIRT2 selectivity over SIRT1 and SIRT3. These candidates were subjected to a dose-response bioactivity assay, measuring an increase in alpha-tubulin K40 acetylation in two neuronal cell lines, which yielded five compounds bioactive in both cell lines and eight compounds bioactive in at least one of the cell lines tested. These bioactive compounds were subsequently tested in a tertiary polyglutamine aggregation assay, which identified five inhibitors. ADME properties of the bioactive SIRT2 inhibitors were assessed, which revealed a significant improvement of the pharmacological properties of the new entities, reaching closer to the goal of a clinically-viable candidate. (C) 2014 Elsevier Masson SAS. All rights reserved.