1-methyl-4-(4-nitro-phenyl)-[1,4]-diazepane | 223786-22-9

• 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: 1-methyl-4-(4-nitro-phenyl)-[1,4]-diazepane
• 英文别名: 1-Methyl-4-(4-nitrophenyl)-1,4-diazepane
• CAS: 223786-22-9
• 化学式: C₁₂H₁₇N₃O₂
• mdl: MFCD01604428
• 分子量: 235.286
• InChiKey: XNADLAKKHYPORF-UHFFFAOYSA-N

物化性质

• 沸点：
  383.8±37.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)
• 溶解度：
  >35.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-methyl-4-(4-nitro-phenyl)-[1,4]-diazepane 在 palladium on activated charcoal 吡啶 、 盐酸 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 64.0h， 生成 ethyl ({((2E)-3-{3-[amino(imino)methyl]phenyl}prop-2-en-1-yl)[4-(4-methyl-1,4-diazepan-1-yl)phenyl]amino}sulfonyl)acetate
  参考文献：
  名称：

  Orally active factor Xa inhibitor: synthesis and biological activity of masked amidines as prodrugs of novel 1,4-diazepane derivatives

  摘要：

  Factor Xa (fXa) is a serine protease, which plays a pivotal role in the coagulation cascade. To improve the oral anticoagulant activity of fXa inhibitors containing a 1,4-diazepane moiety as the P4 part, a prodrug strategy was examined. Among the compounds evaluated in this study, amidoxime prodrugs bearing an ester moiety, Such as compounds 21 and 30, showed effective oral anticoagulant activity in mice. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.046
• 作为产物：
  描述：

  高哌嗪 在 sodium hydride 、 potassium carbonate 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 1-methyl-4-(4-nitro-phenyl)-[1,4]-diazepane
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x

文献信息

• Design and Synthesis of 4-(Heterocyclic Substituted Amino)-1H-Pyrazole-3-Carboxamide Derivatives and Their Potent Activity against Acute Myeloid Leukemia (AML)
  作者：Yanle Zhi、Zhijie Wang、Chao Yao、Baoquan Li、Hao Heng、Jiongheng Cai、Li Xiang、Yue Wang、Tao Lu、Shuai Lu

  DOI：10.3390/ijms20225739

  日期：——

  Fms-like receptor tyrosine kinase 3 (FLT3) has been emerging as an attractive target for the treatment of acute myeloid leukemia (AML). By modifying the structure of FN-1501, a potent FLT3 inhibitor, 24 novel 1H-pyrazole-3-carboxamide derivatives were designed and synthesized. Compound 8t showed strong activity against FLT3 (IC50: 0.089 nM) and CDK2/4 (IC50: 0.719/0.770 nM), which is more efficient than FN-1501(FLT3, IC50: 2.33 nM; CDK2/4, IC50: 1.02/0.39 nM). Compound 8t also showed excellent inhibitory activity against a variety of FLT3 mutants (IC50 < 5 nM), and potent anti-proliferative effect within the nanomolar range on acute myeloid leukemia (MV4-11, IC50: 1.22 nM). In addition, compound 8t significantly inhibited the proliferation of most human cell lines of NCI60 (GI50 < 1 μM for most cell lines). Taken together, these results demonstrated the potential of 8t as a novel compound for further development into a kinase inhibitor applied in cancer therapeutics.

  Fms-like受体酪氨酸激酶3（FLT3）已经成为治疗急性髓系白血病（AML）的一个吸引人的靶点。通过修改FN-1501的结构，设计并合成了24个新的1H-吡唑-3-羧酰胺衍生物。化合物8t对FLT3（IC50：0.089 nM）和CDK2/4（IC50：0.719/0.770 nM）表现出强大的活性，比FN-1501（FLT3，IC50：2.33 nM；CDK2/4，IC50：1.02/0.39 nM）更有效。化合物8t还对多种FLT3突变体显示出优秀的抑制活性（IC50 < 5 nM），并在纳摩尔级范围内对急性髓系白血病（MV4-11，IC50：1.22 nM）显示出强效的抗增殖作用。此外，化合物8t显著抑制了NCI60中大多数人类细胞系的增殖（对大多数细胞系的GI50 < 1 μM）。综合这些结果表明，8t具有潜力作为一种新型化合物，进一步开发成为应用于癌症治疗的激酶抑制剂。
• Substituted isoquinoline-1,3(2H,4H)-diones, 1-thioxo-1,4-dihydro-2H-isoquinoline-3-ones and 1,4-dihydro-3 (2H)-isoquinolones and methods of use thereof
  申请人：Tsou Hwei-Ru

  公开号：US20080085890A1

  公开（公告）日：2008-04-10

  This invention provides compounds of Formula (I), having the structure where G 1 , G 2 , G 3 , G 4 , A 1 , A 2 , Y 1 , Y 2 , L 1 , Z, e and f are defined herein, or a pharmaceutically acceptable salt thereof, which are useful for treating or preventing cancer.

  这项发明提供了具有结构的化合物（I），其中G1、G2、G3、G4、A1、A2、Y1、Y2、L1、Z、e和f在此处定义，或其药用可接受盐，用于治疗或预防癌症。
• MACROCYCLIC COMPOUND SERVING AS WEE1 INHIBITOR AND APPLICATIONS THEREOF
  申请人：SHIJIAZHUANG SAGACITY NEW DRUG DEVELOPMENT CO., LTD.

  公开号：US20200325145A1

  公开（公告）日：2020-10-15

  Disclosed in the present invention are a macrocyclic compound serving as a Weel inhibitor, and applications thereof in the preparation of drugs for treating Weel-related diseases. The present invention specifically relates to a compound represented by formula (II), an isomer thereof, and a pharmaceutically acceptable salt thereof.

  本发明揭示了一种作为Weel抑制剂的大环化合物，以及在制备用于治疗与Weel相关疾病的药物中的应用。本发明具体涉及一种由式（II）表示的化合物，其异构体和其药用可接受的盐。
• [EN] PYRROLO [2, 3-B] PYRIDINES OR PYRROLO [2, 3-B] PYRAZINES AS HPK1 INHIBITOR AND THE USE THEREOF<br/>[FR] PYRROLO [2, 3-B] PYRIDINES OU PYRROLO [2, 3-B] PYRAZINES COMME INHIBITEUR DE HPK1 ET LEUR UTILISATION
  申请人：BEIGENE LTD

  公开号：WO2019238067A1

  公开（公告）日：2019-12-19

  Disclosed herein is a compound of Formula (AIII) or (III), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.

  本文披露了一种公式（AIII）或（III）的化合物，或其立体异构体，或其药用可接受的盐，以及包含该化合物的药物组合物。还披露了一种利用本文披露的化合物治疗HPK1相关疾病或疾病的方法。
• Inhibitors of factor Xa
  申请人：——

  公开号：US20020091116A1

  公开（公告）日：2002-07-11

  Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.

  揭示了针对哺乳动物因子Xa具有活性的新化合物、它们的盐和相关组合物。这些化合物在体外或体内用于预防或治疗凝血障碍。