2-bromo-6-methoxy-p-toluidine | 147699-87-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-bromo-6-methoxy-p-toluidine
• 英文别名: 2-Bromo-6-methoxy-4-methylaniline
• CAS: 147699-87-4
• 化学式: C₈H₁₀BrNO
• 分子量: 216.077
• InChiKey: UOJKOUMHFJQDEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-6-methoxy-p-toluidine 在 盐酸 、 异丙基氯化镁 、 sodium nitrite 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 反应 4.41h， 生成 2-bromo-6-methoxy-4-methylbenzaldehyde
  参考文献：
  名称：

  Picomolar Inhibitors of HIV Reverse Transcriptase Featuring Bicyclic Replacement of a Cyanovinylphenyl Group

  摘要：

  Members of the catechol diether class are highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). The most active compounds yield EC50 values below 0.5 nM in assays using human T-cells infected by wild-type HIV-1. However, these compounds such as rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group. This is an uncommon substructure in drugs that gives reactivity concerns. In the present work, computer simulations were used to design bicyclic replacements for the CVP group. The predicted viability of a 2-cyanoindolizinyl alternative was confirmed experimentally and provided compounds with 0.4 nM activity against the wild-type virus. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. Indolyl and benzofuranyl analogues were also investigated; the most potent compounds in these cases have EC50 values toward wild-type HIV-1 near 10 nM and high-nanomolar activities toward the double-variant. The structural expectations from the modeling were much enhanced by obtaining an X-ray crystal structure at 2.88 Å resolution for the complex of the parent 2-cyanoindolizine 10b and HIV-1 RT. The aqueous solubilities of the most potent indolizine analogues were also measured to be ~40 μg/mL, which is similar to that for the approved drug efavirenz and ~1000-fold greater than for rilpivirine.

  DOI：

  10.1021/ja408917n
• 作为产物：
  描述：

  乙烷,三氯氟- 、 alkaline earth salt of/the/ methylsulfuric acid 在 copper(l) iodide 、 sodium 、 溴-1,4-二氧六环复合物 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-bromo-6-methoxy-p-toluidine
  参考文献：
  名称：

  3-甲氧基-5-甲基邻氨基苯甲酸的合成：从链霉菌菌株中分离出的抗球虫和抗肿瘤抗生素合成的关键中间体

  摘要：

  摘要 描述了 3-甲氧基-5-甲基邻氨基苯甲酸的有效合成，该酸是通过催化羰基化途径合成从链霉菌菌株中分离的抗球虫和抗肿瘤抗生素的关键中间体。

  DOI：

  10.1080/00397919308009806

文献信息

• Synthesis of 3-Methoxy-5-methyl Anthranilic Acid: A Key Intermediate in the Synthesis of Anticoccidial and Antitumour Antibiotics Isolated from the Strains of Streptomyces
  作者：A. Rama Devi、D. Sarangapani Iyengar、M. Pardhasaradhi

  DOI：10.1080/00397919308009806

  日期：1993.2

  Abstract An efficient synthesis of 3-methoxy-5-methyl anthranilic acid, a key intermediate in the synthesis of anticoccidial and anti-tumour antibiotics isolated from the strains of streptomyces by catalytic carbonylation route is described.

  摘要 描述了 3-甲氧基-5-甲基邻氨基苯甲酸的有效合成，该酸是通过催化羰基化途径合成从链霉菌菌株中分离的抗球虫和抗肿瘤抗生素的关键中间体。
• [EN] AZAINDOLE DERIVATIVE AND USE THEREOF AS FGFR AND C-MET INHIBITOR<br/>[FR] DÉRIVÉ D'AZAINDOLE ET SON UTILISATION EN TANT QU'INHIBITEUR DE FGFR ET DE C-MET<br/>[ZH] 氮杂吲哚衍生物及其作为FGFR和C-Met抑制剂的应用
  申请人：MEDSHINE DISCOVERY INC

  公开号：WO2020015744A1

  公开（公告）日：2020-01-23

  一系列吡唑并嘧啶衍生物，及其在制备治疗与FGFR和c-Met相关疾病的药物中的应用，所述吡唑并嘧啶衍生物为式(I)所示化合物、其互变异构体或其药学上可接受的盐。 (I)
• US8791267B2
  申请人：——

  公开号：US8791267B2

  公开（公告）日：2014-07-29
• Picomolar Inhibitors of HIV Reverse Transcriptase Featuring Bicyclic Replacement of a Cyanovinylphenyl Group
  作者：Won-Gil Lee、Ricardo Gallardo-Macias、Kathleen M. Frey、Krasimir A. Spasov、Mariela Bollini、Karen S. Anderson、William L. Jorgensen

  DOI：10.1021/ja408917n

  日期：2013.11.6

  Members of the catechol diether class are highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). The most active compounds yield EC50 values below 0.5 nM in assays using human T-cells infected by wild-type HIV-1. However, these compounds such as rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group. This is an uncommon substructure in drugs that gives reactivity concerns. In the present work, computer simulations were used to design bicyclic replacements for the CVP group. The predicted viability of a 2-cyanoindolizinyl alternative was confirmed experimentally and provided compounds with 0.4 nM activity against the wild-type virus. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. Indolyl and benzofuranyl analogues were also investigated; the most potent compounds in these cases have EC50 values toward wild-type HIV-1 near 10 nM and high-nanomolar activities toward the double-variant. The structural expectations from the modeling were much enhanced by obtaining an X-ray crystal structure at 2.88 Å resolution for the complex of the parent 2-cyanoindolizine 10b and HIV-1 RT. The aqueous solubilities of the most potent indolizine analogues were also measured to be ~40 μg/mL, which is similar to that for the approved drug efavirenz and ~1000-fold greater than for rilpivirine.
• A new convergent synthesis of WS-5995-B, an anticoccidial antibiotic from Streptomyces auranticolor
  作者：Devi A. Rama、D.S. Iyengar、M. Pardhasaradhi

  DOI：10.1016/s0040-4020(01)86970-2

  日期：1994.2