(9ci)-1-异氰酰基-2-甲氧基-3-甲苯 | 324008-66-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (9ci)-1-异氰酰基-2-甲氧基-3-甲苯
• 英文名称: 1-Isocyanato-2-methoxy-3-methyl-benzene
• 英文别名: 1-Isocyanato-2-methoxy-3-methylbenzene
• CAS: 324008-66-4
• 化学式: C₉H₉NO₂
• 分子量: 163.176
• InChiKey: KOMWTBYKWFLQDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (9ci)-1-异氰酰基-2-甲氧基-3-甲苯 、 4-(1-哌嗪基)-1H-吲哚 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 4-(1H-indol-4-yl)-N-(2-methoxy-3-methylphenyl)piperazine-1-carboxamide
  参考文献：
  名称：

  Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2018.04.061

文献信息

• Synthesis of 2-aryl-2H-indazoles by base catalysed reaction of 2-nitrobenzyl triphenylphosphonium bromide and aryl isocyanates
  作者：Abutariq Taher、Sweta Ladwa、Srinath Thirumalai Rajan、George W Weaver

  DOI：10.1016/s0040-4039(00)01757-3

  日期：2000.12

  The synthesis of a series of 2-aryl-2H-indazoles is reported. These compounds are obtained in moderate to good yield by reaction of 2-nitrobenzyl triphenylphosphonium bromide with aryl isocyanates, catalysed by sodium hydride or DBU.

  一系列的2-芳基2的合成ħ -indazoles报道。通过使2-硝基苄基三苯基溴化with与氢化钠或DBU催化的异氰酸芳基酯反应，可以以中等至良好的产率获得这些化合物。
• Aminopyrrolidines as chemokine receptor antagonists
  申请人：George Dawn M.

  公开号：US20080176883A1

  公开（公告）日：2008-07-24

  The present invention is directed to novel aminopyrrolidines of formula I pharmaceutically acceptable salts thereof, metabolites thereof, isomers thereof, stereoisomers thereof or pro-drugs thereof, wherein the variables are as defined herein. The compounds of formula (I) are useful as chemokine receptor antagonists and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

  本发明涉及公式I的新型氨基吡咯烷及其药学上可接受的盐、代谢物、异构体、立体异构体或前药。其中变量的定义如本文所述。公式（I）化合物可用作趋化因子受体拮抗剂，因此可用于治疗某些疾病和病症，特别是炎症性疾病和病症以及增生性疾病和病症，例如癌症。
• US4437919A
  申请人：——

  公开号：US4437919A

  公开（公告）日：1984-03-20
• US8754107B2
  申请人：——

  公开号：US8754107B2

  公开（公告）日：2014-06-17
• 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.