2-chloro-5-isocyanatobenzonitrile | 1261672-37-0

• 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: 2-chloro-5-isocyanatobenzonitrile
• 英文别名: 2-chloro-5-isocyanatobenznitrile
• CAS: 1261672-37-0
• 化学式: C₈H₃ClN₂O
• 分子量: 178.578
• InChiKey: CRFHRZUTHFEELM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲胍 、 2-chloro-5-isocyanatobenzonitrile 生成 1-(4-chloro-3-cyanophenyl)-3-(N'-methylcarbamimidoyl)urea
  参考文献：
  名称：

  Douglas; Diamond; Studt, Arzneimittel-Forschung/Drug Research, 1978, vol. 28, # 8 A, p. 1435 - 1441

  摘要：

  DOI：

文献信息

• Design, synthesis, and evaluation of 4(1H)-quinolinone and urea derivatives as KRASG12C inhibitors with potent antitumor activity against KRAS-mutant non-small cell lung cancer
  作者：Rongjie Cheng、Xiashi Lv、Huagang Bu、Qiaoliang Xu、Jianzhuang Wu、Kexin Xie、Jiaqi Tang、Lei Wang、Jian Zhuang、Yihua Zhang、Yaliang Zhang、Chao Yan、Yisheng Lai

  DOI：10.1016/j.ejmech.2022.114808

  日期：2022.12

  KRASG12C is the most prevalent KRAS mutation in non-small cell lung cancer (NSCLC) and has emerged as a promising therapeutic target. Herein, two series of novel 4(1H)-quinolinone and urea compounds were designed based on the reported KRASG12C inhibitor SH-9. Many compounds showed significantly growth inhibitory activity against human NSCLC cells with KRASG12C mutation in cell viability assays. Compound

  KRAS G12C是非小细胞肺癌 (NSCLC) 中最普遍的 KRAS 突变，已成为一个有前途的治疗靶点。在此，基于已报道的 KRAS G12C抑制剂 SH-9 ，设计了两个系列的新型 4(1 H )-喹啉酮和尿素化合物。许多化合物在细胞活力测定中显示出对具有 KRAS G12C突变的人 NSCLC 细胞的显着生长抑制活性。化合物20a在 KRAS G12C突变体 NCI–H358 细胞中表现出 0.5 μM 的 IC 50值，选择性是 KRAS WT NCI–H2228 细胞的 21 倍。LC-MS 分析表明化合物14c、14h和20a共价结合 KRAS G12C而不是 KRAS WT。此外，这些化合物可以通过阻断 SOS1 介导的 GDP/GTP 交换，显着捕获处于非活性状态的 KRAS G12C。此外，用20a剂量依赖性地处理 NCI–H358 而不是 NCI–H2228 细胞会降低
• UREA DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP3524240A1

  公开（公告）日：2019-08-14

  An object of the present invention is to find a novel pharmaceutical that has an excellent tryptophanase inhibitory effect, and suppresses worsening of renal function to preserve the kidney by reducing production of indoxyl sulfate in the blood. The present invention provides a pharmaceutical composition containing, as an active ingredient, a compound represented by the following formula, or a pharmacologically acceptable salt thereof: wherein R1 and R2 are the same or different, and represent a C1-C6 alkyl group or the like, and Ar represents an optionally substituted phenyl group or an optionally substituted thienyl group.

  本发明的目的是找到一种新型药物，它具有极佳的色氨酸酶抑制作用，并通过减少血液中吲哚硫酸酯的产生来抑制肾功能恶化，从而保护肾脏。本发明提供了一种药物组合物，其活性成分含有下式所代表的化合物或其药理学上可接受的盐： 其中 R1 和 R2 相同或不同，代表 C1-C6 烷基或类似物，Ar 代表任选取代的苯基或任选取代的噻吩基。
• Urea derivative
  申请人：Daiichi Sankyo Company, Limited

  公开号：US10968169B2

  公开（公告）日：2021-04-06

  An object of the present invention is to find a novel pharmaceutical that has an excellent tryptophanase inhibitory effect, and suppresses worsening of renal function to preserve the kidney by reducing production of indoxyl sulfate in the blood. The present invention provides a pharmaceutical composition containing, as an active ingredient, a compound represented by the following formula, or a pharmacologically acceptable salt thereof: wherein R1 and R2 are the same or different, and represent a C1-C6 alkyl group or the like, and Ar represents an optionally substituted phenyl group or an optionally substituted thienyl group.

  本发明的目的是找到一种新型药物，它具有极佳的色氨酸酶抑制作用，并通过减少血液中吲哚硫酸酯的产生来抑制肾功能恶化，从而保护肾脏。本发明提供了一种药物组合物，其活性成分含有下式所代表的化合物或其药理学上可接受的盐： 其中 R1 和 R2 相同或不同，代表 C1-C6 烷基或类似基团，Ar 代表任选取代的苯基或任选取代的噻吩基。
• Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase
  作者：Andrew S. Rosenthal、Thomas S. Dexheimer、Opher Gileadi、Giang H. Nguyen、Wai Kit Chu、Ian D. Hickson、Ajit Jadhav、Anton Simeonov、David J. Maloney

  DOI：10.1016/j.bmcl.2013.08.025

  日期：2013.10

  Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating that a selective BLM inhibitor could be useful in potentiating the anticancer activity of these agents. In this work, we describe the medicinal chemistry optimization of the hit molecule following a quantitative high-throughput screen of >355,000 compounds. These efforts lead to the identification of ML216 and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome. Published by Elsevier Ltd.
• Douglas; Diamond; Studt, Arzneimittel-Forschung/Drug Research, 1978, vol. 28, # 8 A, p. 1435 - 1441
  作者：Douglas、Diamond、Studt、Mir、Alioto、Auyang、Burns、Cias、Darkes、Dodson、O'Connor、Santora、Tsuei、Zalipsky、Zimmerman

  DOI：——

  日期：——