1-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dichlorophenyl)urea | 32539-39-2

• 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: 1-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dichlorophenyl)urea
• 英文别名: 1-(3,4-dichloro-phenyl)-3-(2-indol-3-yl-ethyl)-urea；1-(3,4-dichlorophenyl)-3-[2-(1H-indol-3-yl)ethyl]urea
• CAS: 32539-39-2
• 化学式: C₁₇H₁₅Cl₂N₃O
• mdl: MFCD00397149
• 分子量: 348.232
• InChiKey: JAWNRLZTUAFYAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  56.9
• 氢给体数：
  3
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  色胺 、 3,4-二氯苯异氰酸酯 以 四氢呋喃 为溶剂， 反应 3.0h， 以78%的产率得到1-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dichlorophenyl)urea
  参考文献：
  名称：

  第二代色胺胺衍生物会有效地使抗科氏素的细菌对科氏素敏感。

  摘要：

  自21世纪初以来，抗生素耐药性已显着提高。当前，多粘菌毒素粘菌素通常被视为治疗多药耐药的革兰氏阴性细菌感染的最后手段。但是，增加粘菌素的使用导致抗粘菌素的细菌分离株变得更加普遍。质粒携带的大肠菌素抗性基因（mcr 1-8）最近在人病原体库中的传播进一步威胁到大肠菌素疗法无效。需要对抗抗生素抗性病原体的新方法。在本文中，描述了有效抵抗大肠粘菌素抗性细菌的大粘菌素-佐剂组合的用途。在5μM时，仅对细菌无毒的铅佐剂，将大肠杆菌素对含有mcr-1基因的细菌的功效提高32倍，并使大肠杆菌素对具有染色体编码的大肠杆菌素抗性决定簇的细菌的功效提高1024倍；这些组合可将粘菌素最低抑菌浓度（MIC）降低至或低于临床断点水平（≤2μg/ mL）。

  DOI：

  10.1021/acsmedchemlett.9b00135

文献信息

• [EN] ADJUVANT-ANTIBIOTIC COMBINATION AGAINST GRAM-NEGATIVE BACTERIA<br/>[FR] COMBINAISON ADJUVANT-ANTIBIOTIQUE CONTRE DES BACTÉRIES À GRAM NÉGATIF
  申请人：UNIV NOTRE DAME DU LAC

  公开号：WO2021211123A1

  公开（公告）日：2021-10-21

  Tryptamine ureas and derivatives function as adjuvants to sensitize gram-negative bacteria to the effects of polymyxin antibiotics (e.g., colistin). Combination therapy of polymyxin antibiotics and the adjuvants has utility in the treatment of gram-negative bacterial infection, including treatment of drug-resistant strains.

  Tryptamine尿素及其衍生物作为佐剂，可以增强革兰氏阴性细菌对多粘菌素类抗生素（如可利霉素）的敏感性。多粘菌素类抗生素和佐剂的联合治疗在治疗革兰氏阴性细菌感染，包括治疗耐药菌株方面具有实用价值。
• Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma
  作者：Justin Anglin、Reza Beheshti Zavareh、Philipp N. Sander、Daniel Haldar、Edouard Mullarky、Lewis C. Cantley、Alec C. Kimmelman、Costas A. Lyssiotis、Luke L. Lairson

  DOI：10.1016/j.bmcl.2018.04.061

  日期：2018.9

  Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is extremely refractory to the therapeutic approaches that have been evaluated to date. Recently, it has been demonstrated that PDAC tumors are dependent upon a metabolic pathway involving aspartate aminotransferase 1, also known as glutamate-oxaloacetate transaminase 1 (GOT1), for the maintenance of redox homeostasis and sustained proliferation. As such, small molecule inhibitors targeting this metabolic pathway may provide a novel therapeutic approach for the treatment of this devastating disease. To this end, from a high throughput screen of similar to 800,000 molecules, 4-(1H-indol-4-yl)-N-phenylpiperazine-1-carboxamide was identified as an inhibitor of GOT1. Mouse pharmacokinetic studies revealed that potency, rather than inherent metabolic instability, would limit immediate cell- and rodent xenograft-based experiments aimed at validating this potential cancer metabolism-related target. Medicinal chemistry-based optimization resulted in the identification of multiple derivatives with >10-fold improvements in potency, as well as the identification of a tryptamine-based series of GOT1 inhibitors. (C) 2018 Elsevier Ltd. All rights reserved.