2-溴-3,4-二氯-6-硝基苯胺 | 172215-93-9

• 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: 2-溴-3,4-二氯-6-硝基苯胺
• 英文名称: 2-bromo-3,4-dichloro-6-nitroaniline
• CAS: 172215-93-9
• 化学式: C₆H₃BrCl₂N₂O₂
• 分子量: 285.912
• InChiKey: PMLIETDTBZGKBM-UHFFFAOYSA-N

物化性质

• 沸点：
  370.8±37.0 °C(Predicted)
• 密度：
  1.990±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-溴-3,4-二氯-6-硝基苯胺 在 吡啶 、 盐酸 、 三氟甲磺酸三甲基硅酯 、 1-环已基-2-吗啉乙基碳二亚胺对甲苯磺酸盐 、 铁粉 、 sodium carbonate 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 18.5h， 生成 4-bromo-5,6-dichloro-2-isopropylamino-1-(β-D-erythrofuranosyl)benzimidazole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Halogenated β-d- and -l-Erythrofuranosylbenzimidazoles

  摘要：

  A series of 2-substituted benzimidazole D- and L-erythrofuranosyl nucleosides were synthesized and tested for activity against herpesviruses and for cytotoxicity. The D-nucleosides 2,5,6-trichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8a) and 2-bromo-5,6-dichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8b) were prepared by coupling 1,2,3,-tri-O-acetyl-beta-D-erythrofuranose (D-6) with the appropriate benzimidazole, followed by removal of the acetyl protecting groups. The 2-isopropylamino (9), 2-cyclopropylamino (10), and 2-mercaptobenzyl (11) derivatives were synthesized by nucleophilic displacements of the C-2 chlorine in the benzimidazole moiety of 8a. The D-nucleoside 4-bromo-5,6-dichloro-2-isopropylamino-1-(beta-D-erythrofuranosyl)benzimidazole (17) was prepared by coupling D-6 with the appropriate benzimidazole. The L-erythrofuranosyl derivatives, 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a), its 2-cyclopropylamine analogue (21b), and the 2-isopropylamino analogue (4c). In comparison, 8a was 15-fold more active against HCMV than 4a, and 8b was 4-fold more active against HCMV than 4b. The 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a) was less active than 4c, which is now in clinical trials for HCMV infection. Both 8a,b had comparable HCMV activity to 4c. Mode of action studies with the D-erythrose analogues established that 8b acted by inhibition of viral DNA processing whereas 9 and 10 may act via a different mechanism. The lack of a 5'-hydroxymethyl group in all members of this series established that antiviral activity occurred without 5'-phosphorylation, a feature required for the activity of most nucleoside analogues.

  DOI：

  10.1021/jm990195p
• 作为产物：
  描述：

  4,5-二氯-2-硝基苯胺 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-溴-3,4-二氯-6-硝基苯胺
  参考文献：
  名称：

  L-benzimidazole nucleosides

  摘要：

  本发明涉及苯并咪唑衍生物及其在医学疗法中的应用，特别是用于治疗或预防病毒感染，如由疱疹病毒引起的感染。该发明还涉及苯并咪唑衍生物的制备以及含有它们的药物配方。

  公开号：

  US06204249B1

文献信息

• [EN] HETEROARYL RHEB INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE RHEB À BASE D'HÉTÉROARYLE ET LEURS UTILISATIONS
  申请人：NAVITOR PHARM INC

  公开号：WO2018191146A1

  公开（公告）日：2018-10-18

  The present invention provides compounds, compositions thereof, and methods of using the same. Compositions comprising a compound of this invention or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of the compound in compositions of this invention is such that it is effective to measurably inhibit Rheb, in a biological sample or in a patient.

  本发明提供了化合物、其组合物以及使用方法。包括本发明的化合物或其药学上可接受的衍生物与药学上可接受的载体、辅料或载体组成的组合物。本发明组合物中的化合物的量使其能够在生物样本或患者中明显抑制Rheb。
• Synthesis and Structure-Activity Relationships of Substituted 1,4-Dihydroquinoxaline-2,3-diones: Antagonists of N-Methyl-D-aspartate (NMDA) Receptor Glycine Sites and Non-NMDA Glutamate Receptors
  作者：John F. W. Keana、Sunil M. Kher、Sui Xiong Cai、Christian M. Dinsmore、Anne G. Glenn、J. Guastella、Jin-Cheng Huang、Victor Ilyin、Yixin Lu

  DOI：10.1021/jm00022a003

  日期：1995.10

  and 7 positions, displayed high potency (Kb approximately 6-8 nM) at the glycine site, moderate potency at non-NMDA receptors (Kb = 0.9-1.5 microM), and the highest (120-250-fold) selectivity in favor of glycine site antagonism over non-NMDA receptors. Tetrasubstituted QXs 17d,e were more than 100-fold weaker glycine site antagonists than the corresponding trisubstituted QXs with F being better tolerated

  合成了一系列的单，二，三和四取代的1,4-二氢喹喔啉-2,3-二酮（QXs），并在N-甲基-D-天冬氨酸（NMDA）/甘氨酸位点和α位作为拮抗剂进行了评估-氨基-3-羟基-5-甲基异恶唑-4-丙酸优先的非NMDA受体。通过电测定在表达大鼠全脑poly（A）+ RNA的非洲爪蟾卵母细胞中测量拮抗剂的效力。三取代QX 17a（ACEA 1021），17b（ACEA 1031），24a和27，在5位含硝基，在6和7位含卤素，在甘氨酸上显示出高效价（Kb约为6-8 nM）位点，对非NMDA受体的药效中等（Kb = 0.9-1.5 microM），与非NMDA受体相比，甘氨酸位点拮抗作用的选择性最高（120-250倍）。四取代的QX 17d e是比相应的三取代QX弱100倍的弱甘氨酸位点拮抗剂，在8位上F作为取代基比Cl具有更好的耐受性。与三取代类似物相比，二取代和单取代的QX显示出越来越弱的拮抗作
• Therapeutic compounds
  申请人：——

  公开号：US06617315B1

  公开（公告）日：2003-09-09

  The present invention relates to benzimidazole derivatives and their use in medical therapy particularly for the treatment or prophylaxis of restenosis.

  本发明涉及苯并咪唑衍生物及其在医学治疗中的应用，特别是用于治疗或预防再狭窄。
• Heteroaryl Rheb inhibitors and uses thereof
  申请人：Navitor Pharmaceuticals, Inc.

  公开号：US11339144B2

  公开（公告）日：2022-05-24

  The present invention provides compounds of general Formula I and I′: compositions thereof, and methods of using same to treat Rheb-mediated disorders.

  本发明提供通式I和I′的化合物： 其组合物，以及用其治疗 Rheb 介导的疾病的方法。
• Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema
  作者：Mark A. Hilfiker、Tram H. Hoang、Johan Cornil、Hilary S. Eidam、Daniel S. Matasic、Theresa J. Roethke、Michael Klein、Kevin S. Thorneloe、Mui Cheung

  DOI：10.1021/ml300449k

  日期：2013.2.14

  High-throughput screening and subsequent hit optimization identified 1-piperidinyl-benzimidazoles, exemplified by compound 1, as TRPV4 inhibitors. Lead optimization identified potent TRPV4 blocker 19, which has good target activity and pharmacokinetic properties. Inhibitor 19 was then profiled in an in vivo rat model, demonstrating its ability to inhibit TRPV4-mediated pulmonary edema.