3-溴-5-(三氟甲基)-1H-吲唑 | 1086378-32-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 3-溴-5-(三氟甲基)-1H-吲唑
• 英文名称: 3-bromo-5-(trifluoromethyl)-1H-indazole
• 英文别名: 3-bromo-5-(trifluoromethyl)-2H-indazole
• CAS: 1086378-32-6
• 化学式: C₈H₄BrF₃N₂
• 分子量: 265.032
• InChiKey: NJWMXXMBNBUURG-UHFFFAOYSA-N

物化性质

• 沸点：
  328.2±37.0 °C(Predicted)
• 密度：
  1.830±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-溴-5-(三氟甲基)-1H-吲唑 在 盐酸 、 (R)-1-[(S_P)-2-(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine 、 palladium diacetate 、 caesium carbonate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙酸乙酯 为溶剂， 生成 N-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)-1H-indazol-3-amine
  参考文献：
  名称：

  Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model

  摘要：

  Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50=3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.026
• 作为产物：
  描述：

  5-三氟甲基-1H-吲唑 在 N-溴代丁二酰亚胺(NBS) 、 rose bengal 作用下， 以 乙腈 为溶剂， 以96 %的产率得到3-溴-5-(三氟甲基)-1H-吲唑
  参考文献：
  名称：

  有机染料、可见光光氧化还原催化增强吲唑的溴化

  摘要：

  在可见光激活条件下，使用 N-溴代琥珀酰亚胺 (NBS) 可以以中等至优异的产率对各种官能化吲唑进行溴化。对有机染料催化剂的筛选结果表明，玫瑰红是与 NBS 一起使用以生成吲唑的最有效催化剂。根据机理研究，推测该反应是通过NBS 的单电子氧化进行的，该氧化放大了溴原子的亲电性，从而增强了作为溴化试剂的反应性。根据吲唑取代基的电子性质，已经观察到不同的中间体吲唑种类。含吲唑的药物使用优化的反应条件作为溴化方法的示范，以良好的产率对苯甲胺进行溴化。

  DOI：

  10.1016/j.tet.2023.133523

文献信息

• 10.3390/molecules29133114
  作者：Gowda, Krishne、Raza, Asif、Vangala, Venugopal、Lone, Nazir Ahmad、Lin, Jyh Ming、Singh, Jaikee Kumar、Srivastava, Sandeep Kumar、Schell, Todd D.、Robertson, Gavin P.、Amin, Shantu、Sharma, Arun K.

  DOI：10.3390/molecules29133114

  日期：——

  isoform inhibitors based on the isatin and indazole pharmacophore. Molecular docking studies and enzymatic tests revealed that among all of the synthesized analogs, compound 3 is the most potent inhibitor of ALDH1A1, ALDH3A1, and ALDH1A3, exhibiting 51.32%, 51.87%, and 36.65% inhibition, respectively. The ALDEFLUOR assay further revealed that compound 3 acts as an ALDH broad spectrum inhibitor at 500

  醛脱氢酶 (ALDH) 是有助于解毒的酶家族，在多种不同的恶性肿瘤中过度表达。 ALDH 表达增加与不良预后、干性和对多种药物的耐药性之间存在相关性。由于 ALDH 在癌症干细胞中发挥的关键作用，已经产生了多种 ALDH 抑制剂。然而，所有这些抑制剂要么无效，要么毒性很大，要么尚未对其有效性进行严格的测试。尽管文献中已经报道了多种针对 ALDH 的药物样化合物，但尚未在肿瘤临床中常规使用。因此，仍然需要新的有效、无毒、生物可利用且治疗有效的 ALDH 抑制剂。在本研究中，我们基于靛红和吲唑药效团设计并合成了有效的多 ALDH 亚型抑制剂。分子对接研究和酶学测试表明，在所有合成的类似物中，化合物3是ALDH1A1、ALDH3A1和ALDH1A3最有效的抑制剂，抑制率分别为51.32%、51.87%和36.65%。 ALDEFLUOR 测定进一步表明，化合物 3 在 500 nM 时可充当 ALDH
• Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
  作者：Maud Bollenbach、Claire Lugnier、Mélanie Kremer、Eric Salvat、Salim Megat、Frédéric Bihel、Jean-Jacques Bourguignon、Michel Barrot、Martine Schmitt

  DOI：10.1016/j.ejmech.2019.05.026

  日期：2019.9

  Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50=3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.