4-amino-N-(3-morpholinopropyl)benzamide

• 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: 4-amino-N-(3-morpholinopropyl)benzamide
• 英文别名: 4-amino-N-(3-morpholin-4-ylpropyl)benzamide
• 化学式: C₁₄H₂₁N₃O₂
• 分子量: 263.34
• InChiKey: LTHBSUQRHMHMEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-N-(3-morpholinopropyl)benzamide 在 吡啶 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.5h， 生成
  参考文献：
  名称：

  Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model

  摘要：

  FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV411 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.021
• 作为产物：
  描述：

  N-(3-morpholinopropyl)-4-nitrobenzamide 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 生成 4-amino-N-(3-morpholinopropyl)benzamide
  参考文献：
  名称：

  鉴定新型 2,4,5-三取代嘧啶作为具有体外抗血期寄生虫活性的血浆 PfGSK3/PfPK6 的强效双重抑制剂

  摘要：

  必需的疟原虫激酶Pf GSK3 和Pf PK6 被认为是新的药物靶点，可对抗对传统抗疟治疗不断上升的耐药性。在此，我们报告了IKK16作为Pf GSK3/ Pf PK6 双重抑制剂的发现，对血液阶段Pf 3D7 寄生虫具有活性。为了建立Pf PK6 和Pf GSK3 的构效关系，合成了 52 种类似物并评估了对Pf GSK3 和Pf PK6 的抑制作用，并进一步评估了强效抑制剂对血液和肝脏阶段寄生虫的活性。这最终导致发现了双Pf GSK3/Pf PK6 抑制剂23d ( Pf GSK3/ Pf PK6 IC 50 = 172/11 nM) 和23e ( Pf GSK3/ Pf PK6 IC 50 = 97/8 nM) 具有抗疟原虫活性 ( 23d Pf 3D7 EC 50 = 552 ± 37 nM 和23e Pf 3D7 EC 50 = 1400 ± 13 nM)。然而，当在一组人类激酶

  DOI：

  10.1021/acs.jmedchem.2c00996

文献信息

• FUSED HETEROCYCLIC DERIVATIVES, THEIR PREPARATION METHODS THEREOF AND MEDICAL USES THEREOF
  申请人：Beijing Innocare Pharma Tech Co., Ltd.

  公开号：US20190185472A1

  公开（公告）日：2019-06-20

  The present invention relates to fused heterocyclic derivatives, processes for their preparation and their use in medicine. Specifically, the present invention relates to a novel derivative represented by the formula (I′), or its pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the derivative or its pharmaceutically acceptable salt thereof, and the method for preparing the derivative and its pharmaceutically acceptable salt thereof. The present invention also relates to the use of the derivative and its pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the derivative and its pharmaceutically acceptable salt thereof in the preparation of medicines, in particularly as IDO inhibitor medicines, for treating and/or preventing cancers. Wherein each substituent of the formula (I′) is the same as defined in the specification.

  本发明涉及融合的杂环衍生物，其制备方法以及在医学上的应用。具体而言，本发明涉及一种由式(I′)表示的新型衍生物，或其药学上可接受的盐，含有该衍生物或其药学上可接受的盐的药物组合物，以及制备该衍生物及其药学上可接受的盐的方法。本发明还涉及利用该衍生物及其药学上可接受的盐，或含有该衍生物及其药学上可接受的盐的药物组合物，在制备药物中的应用，特别是作为IDO抑制剂药物，用于治疗和/或预防癌症。其中，式(I′)的每个取代基与规范中定义的相同。
• DRUG FRAGMENT IMAGING AGENT CONJUGATES
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20200390909A1

  公开（公告）日：2020-12-17

  Functional dyes and methods of use are provided. The dyes are useful in a variety of medical applications including, but not limited to, diagnostic imaging and therapy, endoscopic applications for the detection of tumors and other abnormalities, particularly with oral administration of the dyes.

  本发明提供功能染料及其使用方法。这些染料可用于各种医学应用，包括但不限于诊断成像和治疗，内窥镜应用以检测肿瘤和其他异常情况，特别是通过口服染料。
• Design, Synthesis, and Biological Evaluation of 2-Substituted Aniline Pyrimidine Derivatives as Potent Dual Mer/c-Met Inhibitors
  作者：Daowei Huang、Ying Chen、Jixia Yang、Bingyang Zhao、Shouying Wang、Tingting Chai、Jie Cui、Xiaolei Zhou、Zhenhua Shang

  DOI：10.3390/molecules29020475

  日期：——

  which are commonly overexpressed in various tumors, are ideal targets for the development of antitumor drugs. This study focuses on the design, synthesis, and evaluation of several 2-substituted aniline pyrimidine derivatives as highly potent dual inhibitors of Mer and c-Met kinases for effective tumor treatment. Compound 18c emerged as a standout candidate, demonstrating robust inhibitory activity

  Mer 和 c-Met 激酶通常在各种肿瘤中过表达，是抗肿瘤药物开发的理想靶点。本研究的重点是设计、合成和评估几种 2-取代苯胺嘧啶衍生物作为 Mer 和 c-Met 激酶的高效双重抑制剂，用于有效治疗肿瘤。化合物 18c 成为一种出色的候选化合物，对 Mer 和 c-Met 激酶具有强大的抑制活性，IC50 值分别为 18.5 ± 2.3 nM 和 33.6 ± 4.3 nM。此外，化合物 18c 对 HepG2 、 MDA-MB-231 和 HCT116 癌细胞具有良好的抗增殖活性，并且在 hERG 检测中具有良好的安全性。值得注意的是，它在体外表现出优异的肝脏微粒体稳定性，在人肝微粒体中的半衰期为 53.1 分钟。化合物 18c 还表现出剂量依赖性细胞毒性和 HCT116 癌细胞迁移受阻，如细胞凋亡和迁移测定所示。这些发现共同表明，化合物 18c 有望作为癌症治疗的双重 Mer/c-Met
• PI3-Kinase Inhibitoren
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2343303A1

  公开（公告）日：2011-07-13

  Es werden neue Verbindungen der Formel 1 bereitgestellt, die aufgrund ihrer pharmazeutischen Wirksamkeit als PI3-Kinase Modulator zur Anwendung auf therapeutischem Gebiet zur Behandlung von entzündlichen oder allergischen Erkrankungen gelangen können. Beispielhaft seien hier entzündliche und allergische Atemwegserkrankungen, entzündliche Erkrankungen des Magen-Darm-Traktes und des Bewegungsapparates, entzündliche und allergische Hauterkrankungen, entzündliche Augenerkrankungen, Erkrankungen der Nasenschleimhaut, entzündliche oder allergische Krankheitszustände, bei denen Autoimmun-Reaktionen beteiligt sind oder Nierenentzündungen genannt.

  本发明提供了式 1 的新化合物，由于其作为 PI3 激酶调节剂的药效，可用于治疗炎症或过敏性疾病。 例如，炎症性和过敏性呼吸系统疾病、胃肠道和肌肉骨骼系统的炎症性疾病、炎症性和过敏性皮肤病、炎症性眼病、鼻粘膜疾病、涉及自身免疫反应或肾脏炎症的炎症性或过敏性疾病状态。
• FUSED HETEROCYCLIC DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF
  申请人：Beijing InnoCare Pharma Tech Co., Ltd.

  公开号：EP3505517A1

  公开（公告）日：2019-07-03

  The present invention relates to fused heterocyclic derivatives, processes for their preparation and their use in medicine. Specifically, the present invention relates to a novel derivative represented by the formula (I'), or its pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the derivative or its pharmaceutically acceptable salt thereof, and the method for preparing the derivative and its pharmaceutically acceptable salt thereof. The present invention also relates to the use of the derivative and its pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the derivative and its pharmaceutically acceptable salt thereof in the preparation of medicines, in particularly as IDO inhibitor medicines, for treating and/or preventing cancers. Wherein each substituent of the formula (I') is the same as defined in the specification.

  本发明涉及融合杂环衍生物、其制备工艺及其在医药中的用途。具体而言，本发明涉及一种由式（I'）表示的新型衍生物或其药学上可接受的盐、一种含有该衍生物或其药学上可接受的盐的药物组合物，以及制备该衍生物及其药学上可接受的盐的方法。本发明还涉及该衍生物及其药学上可接受的盐，或含有该衍生物及其药学上可接受的盐的药物组合物在制备治疗和/或预防癌症的药物（尤其是 IDO 抑制剂药物）中的用途。其中，式（I'）的各取代基与说明书中定义的相同。