(3-amino-4-methylphenyl)(morpholino)methanone | 21447-53-0

• 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: (3-amino-4-methylphenyl)(morpholino)methanone
• 英文别名: 2-Methyl-5-(morpholine-4-carbonyl)aniline；(3-amino-4-methylphenyl)-morpholin-4-ylmethanone
• CAS: 21447-53-0
• 化学式: C₁₂H₁₆N₂O₂
• mdl: MFCD09043756
• 分子量: 220.271
• InChiKey: KAUCCBZBIGZLFO-UHFFFAOYSA-N

物化性质

• 沸点：
  448.4±45.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-amino-4-methylphenyl)(morpholino)methanone 在 tris-(dibenzylideneacetone)dipalladium(0) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 、 potassium carbonate 、 三氟乙酸 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 水 、 叔丁醇 为溶剂， 反应 9.0h， 生成 (4-methyl-3-((6-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)amino)phenyl)(morpholino)methanone
  参考文献：
  名称：

  Discovery and Identification of Small Molecules as Methuosis Inducers with in Vivo Antitumor Activities

  摘要：

  Methuosis is a novel nonapoptotic mode of cell death characterized by vacuole accumulation in the cytoplasm. In this article, we describe a series of azaindole-based compounds that cause vacuolization in MDA-MB-231 cells. The most potent vacuole inducer, compound 13 (compound 13), displayed differential cytotoxicities against a broad panel of cancer cell lines, such as MDA-MB-231, A375, HCT116, and MCF-7, but it did not inhibit the growth of the nontumorigenic epithelial cell line MCF-10A. A mechanism study confirmed that the cell death was caused by inducing methuosis. Furthermore, compound 13 exhibited substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects, which makes this compound the first example of a methuosis inducer with potent in vivo efficacy. These results demonstrate that methuosis inducers might serve as novel therapeutics for the treatment of cancer.

  DOI：

  10.1021/acs.jmedchem.8b00753
• 作为产物：
  描述：

  4-甲基-3-硝基苯甲酸 在 铁粉 、 氯化铵 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (3-amino-4-methylphenyl)(morpholino)methanone
  参考文献：
  名称：

  基于片段的茶碱衍生物在 BT-549 细胞中作为 ATAD2 抑制剂的设计、合成和生物学评价

  摘要：

  摘要 ATP酶家族AAA结构域蛋白2（ATAD2）因其致癌表观遗传修饰与癌细胞增殖、凋亡、迁移和耐药性密切相关，已成为热门的抗癌药物靶点。在本研究中，我们通过基于片段的筛选和支架生长策略设计了一系列茶碱衍生物作为新型ATAD2抑制剂。我们发现了一种新型有效的 ATAD2 抑制剂（化合物19f） ，其针对 ATAD2的 IC 50值为 0.27 μM，采用经典和非典型结合模式的组合。此外，化合物19f可以阻碍 ATAD2 活性和 c-Myc 激活，诱导显着的细胞凋亡，并在 BT-549 细胞中显示出抗迁移作用。总的来说，这些结果为开发用于三阴性乳腺癌（TNBC）治疗的新型有效 ATAD2 抑制剂提供了新的启示。

  DOI：

  10.1080/14756366.2023.2242601

文献信息

• Benzene derivatives and pharmaceutical composition
  申请人：Kureha Chemical Industry Co., Ltd.

  公开号：US05696118A1

  公开（公告）日：1997-12-09

  A benzene derivative of the formula (I): ##STR1## wherein R.sup.1 is hydrogen, C.sub.1-6 -alkyl, C.sub.1-6 -haloalkyl, --NH.sub.2, --NHR.sup.21 ; R.sup.2 is hydroxyl, --OR.sup.22, three- to seven-membered saturated cycloaliphatic amino optionally interrupted by one or more nitrogen, oxygen or sulfur atoms, --NHR.sup.23, --N(R.sup.24).sub.2, --NH.sub.2 ; R.sup.4 is hydrogen, C.sub.1-6 -alkyl, or --C(.dbd.O)R.sup.25 ; R.sup.7 is --CO--, --SO.sub.2 --; R.sup.8 is --CO--, single bond; R.sup.12 is --R.sup.11 --R.sup.5 ; R.sup.11 is --N(R.sup.5)--, --NH--, --O--, --N(R.sup.26)--, --N(C(.dbd.O)R.sup.27)--, --N(C(.dbd.O)NH.sub.2)--, --N(C(.dbd.O)NHR.sup.28)--; R.sup.13 is hydrogen, C.sub.1-6 -alkyl, C.sub.1-6 -haloalkyl, --NHC(.dbd.O)(CH.sub.2).sub.m C.sub.6 H.sub.5, --NHC(.dbd.O)R.sup.29, --NHC(.dbd.O)CH(C.sub.6 H.sub.5).sub.2, --NH.sub.2, --NHR.sup.30, --(CH.sub.2).sub.n C.sub.6 H.sub.5 ; Z is C, CH, N; A is CH, N; R.sup.5 is hydrogen, --CH.sub.2 C.sub.6 H.sub.4 COOH, --CH.sub.2 C.sub.6 H.sub.4 COOR.sup.31, --CH.sub.2 C.sub.6 H.sub.4 OH, --CH.sub.2 C.sub.6 H.sub.4 OR.sup.32, --CH.sub.2 C.sub.6 H.sub.4 NH.sub.2, --CH.sub.2 C.sub.6 H.sub.4 N(R.sup.33).sub.2, --CH.sub.2 C.sub.6 H.sub.4 -azole, --CH.sub.2 C.sub.6 H.sub.4 NHR.sup.34, --CH.sub.2 C.sub.6 H.sub.4 C.sub.6 H.sub.4 R.sup.14 ; R.sup.14 is azole, --COOH; R.sup.21 to R.sup.34 are independently C.sub.1-6 -alkyl or C.sub.1-6 -haloalkyl; m is 0 to 6; n is 0 to 6; t is 0 or 1, with the proviso that when Z is N, R.sup.5 is hydrogen, --CH.sub.2 C.sub.6 H.sub.4 COOH, --CH.sub.2 C.sub.6 H.sub.4 COOR.sup.31, --CH.sub.2 C.sub.6 H.sub.4 OH, --CH.sub.2 C.sub.6 H.sub.4 OR.sup.32, --CH.sub.2 C.sub.6 H.sub.4 NH.sub.2, --CH.sub.2 C.sub.6 H.sub.4 N(R.sup.33).sub.2, --CH.sub.2 C.sub.6 H.sub.4 -azole, or --CH.sub.2 C.sub.6 H.sub.4 NHR.sup.34, or a salt thereof, and a pharmaceutical composition comprising said benzene derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier are disclosed.

  一种化学式为(I)的苯衍生物：其中R.sup.1是氢，C.sub.1-6-烷基，C.sub.1-6-卤代烷基，-NH.sub.2，-NHR.sup.21；R.sup.2是羟基，-OR.sup.22，三至七元饱和环脂肪族氨基，可选地由一个或多个氮、氧或硫原子中断，-NHR.sup.23，-N(R.sup.24).sub.2，-NH.sub.2；R.sup.4是氢，C.sub.1-6-烷基，或-C(.dbd.O)R.sup.25；R.sup.7是-CO-，-SO.sub.2-；R.sup.8是-CO-，单键；R.sup.12是-R.sup.11-R.sup.5；R.sup.11是-N(R.sup.5)-，-NH-，-O-，-N(R.sup.26)-，-N(C(.dbd.O)R.sup.27)-，-N(C(.dbd.O)NH.sub.2)-，-N(C(.dbd.O)NHR.sup.28)-；R.sup.13是氢，C.sub.1-6-烷基，C.sub.1-6-卤代烷基，-NHC(.dbd.O)(CH.sub.2).sub.mC.sub.6H.sub.5，-NHC(.dbd.O)R.sup.29，-NHC(.dbd.O)CH(C.sub.6H.sub.5).sub.2，-NH.sub.2，-NHR.sup.30，-(CH.sub.2).sub.nC.sub.6H.sub.5；Z是C，CH，N；A是CH，N；R.sup.5是氢，-CH.sub.2C.sub.6H.sub.4COOH，-CH.sub.2C.sub.6H.sub.4COOR.sup.31，-CH.sub.2C.sub.6H.sub.4OH，-CH.sub.2C.sub.6H.sub.4OR.sup.32，-CH.sub.2C.sub.6H.sub.4NH.sub.2，-CH.sub.2C.sub.6H.sub.4N(R.sup.33).sub.2，-CH.sub.2C.sub.6H.sub.4-唑，-CH.sub.2C.sub.6H.sub.4NHR.sup.34，-CH.sub.2C.sub.6H.sub.4C.sub.6H.sub.4R.sup.14；R.sup.14是唑，-COOH；R.sup.21到R.sup.34独立地是C.sub.1-6-烷基或C.sub.1-6-卤代烷基；m为0至6；n为0至6；t为0或1，但当Z为N时，R.sup.5是氢，-CH.sub.2C.sub.6H.sub.4COOH，-CH.sub.2C.sub.6H.sub.4COOR.sup.31，-CH.sub.2C.sub.6H.sub.4OH，-CH.sub.2C.sub.6H.sub.4OR.sup.32，-CH.sub.2C.sub.6H.sub.4NH.sub.2，-CH.sub.2C.sub.6H.sub.4N(R.sup.33).sub.2，-CH.sub.2C.sub.6H.sub.4-唑，或-CH.sub.2C.sub.6H.sub.4NHR.sup.34，或其盐，以及包括所述苯衍生物或其药学上可接受的盐的药物组合物和药学上可接受的载体。
• SUBSTITUTED PENTA-FUSED HEXA-HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR, DRUG COMBINATION AND USE THEREOF
  申请人：Xiamen University

  公开号：US20200165246A1

  公开（公告）日：2020-05-28

  A type of substituted penta-fused hexa-heterocyclic compounds having selective inhibition for PIKfyve kinase, a pharmaceutically acceptable salt and pharmaceutically acceptable solvate thereof, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with PIKfyve in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

  一种替代的五重融合六元杂环化合物，具有对PIKfyve激酶的选择性抑制作用，其药学上可接受的盐及其药学上可接受的溶剂，其制备方法，包括这些化合物的药物组合物，以及在制备用于预防或治疗与PIKfyve相关疾病的药物中使用这些化合物，特别是在制备用于预防或治疗肿瘤生长和转移的药物中。
• PYRIMIDINE DERIVATIVES AS PI3K INHIBITOR AND USE THEREOF
  申请人：Shimma Nobuo

  公开号：US20100069629A1

  公开（公告）日：2010-03-18

  A drug is provided that is useful as a preventive or therapeutic for cancer as a result of having superior PI3K inhibitory effects as well as superior stability in the body and water-solubility. A compound, or pharmaceutically acceptable salt thereof, represented by formula (I): [wherein, X represents a single bond, etc.; Y represents a single bond, etc. (provided that X and Y are not simultaneously single bonds); Z represents a hydrogen atom, etc.; m represents an integer of 1 or 2; and R 1 represents a cyclic substituent].

  提供了一种药物，由于具有优越的PI3K抑制作用以及在体内具有优越的稳定性和水溶性，因此可用作预防或治疗癌症。化合物或其药学上可接受的盐的表示式（I）：[其中，X表示单键等；Y表示单键等（前提是X和Y不同时为单键）；Z表示氢原子等；m表示1或2的整数；R1表示环状取代基]。
• SUBSTITUTED PENTA- AND HEXA-HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR, DRUG COMBINATION AND USE THEREOF
  申请人：Xiamen University

  公开号：EP3663293A1

  公开（公告）日：2020-06-10

  A type of substituted penta- fused hexa-heterocyclic compounds having selective inhibition for PIKfyve kinase, a pharmaceutically acceptable salt and pharmaceutically acceptable solvate thereof, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with PIKfyve in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

  一种对PIKfyve激酶具有选择性抑制作用的取代五融合六杂环化合物、其药学上可接受的盐和药学上可接受的溶液、其制备方法、包含这些化合物的药物组合物，以及这些化合物在制造预防或治疗体内PIKfyve相关疾病的药物中的用途，特别是在制造预防或治疗肿瘤生长和转移的药物中的用途。
• Substituted penta-fused hexa-heterocyclic compounds, preparation method therefor, drug combination and use thereof
  申请人：Xiamen University

  公开号：US11352354B2

  公开（公告）日：2022-06-07

  A type of substituted penta-fused hexa-heterocyclic compounds having selective inhibition for PIKfyve kinase, a pharmaceutically acceptable salt and pharmaceutically acceptable solvate thereof, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with PIKfyve in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

  一种对PIKfyve激酶具有选择性抑制作用的取代五融合六六环化合物、其药学上可接受的盐和药学上可接受的溶液、其制备方法、包含这些化合物的药物组合物，以及这些化合物在制造预防或治疗体内PIKfyve相关疾病的药物中的用途，特别是在制造预防或治疗肿瘤生长和转移的药物中的用途。