N-(3-chloro-4-methoxyphenyl)-1H-indazole-5-carboxamide | 1619884-57-9

• 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: N-(3-chloro-4-methoxyphenyl)-1H-indazole-5-carboxamide
• CAS: 1619884-57-9
• 化学式: C₁₅H₁₂ClN₃O₂
• 分子量: 301.732
• InChiKey: CLFVNPBLZVZJOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  吲唑-5-甲酸盐酸盐 、 3-氯-4-甲氧基苯胺 以11%的产率得到N-(3-chloro-4-methoxyphenyl)-1H-indazole-5-carboxamide
  参考文献：
  名称：

  [EN] SUBSTITUTED INDAZOLE OR INDOLE DERIVATIVES AS IN VITRO MAO-B INHIBITORS
  [FR] DÉRIVÉS D'INDAZOLE OU D'INDOLE SUBSTITUÉS EN TANT QU'INHIBITEURS DE MAO-B IN VITRO

  摘要：

  I式中取代的吲唑或咪唑衍生物可作为体外选择性和可逆的MAO-B抑制剂，并用于预防和治疗神经退行性疾病，如帕金森病、阿尔茨海默病和痴呆症。

  公开号：

  WO2014107771A1

文献信息

• [EN] SUBSTITUTED INDAZOLE OR INDOLE DERIVATIVES AS IN VITRO MAO-B INHIBITORS<br/>[FR] DÉRIVÉS D'INDAZOLE OU D'INDOLE SUBSTITUÉS EN TANT QU'INHIBITEURS DE MAO-B IN VITRO
  申请人：NTZ LAB LTD

  公开号：WO2014107771A1

  公开（公告）日：2014-07-17

  Substituted indazole or imidazole derivatives of formula I as in vitro selective and reversible MAO-B inhibitors and for use in the prevention and treatment of meurodegenerative disorders such as Parkinson's disease, Alzheimer's disase and dementia

  I式中取代的吲唑或咪唑衍生物可作为体外选择性和可逆的MAO-B抑制剂，并用于预防和治疗神经退行性疾病，如帕金森病、阿尔茨海默病和痴呆症。
• SUBSTITUTED INDAZOLE DERIVATIVES AS IN VITRO MAO-B INHIBITORS
  申请人："NTZ LAB" LTD.

  公开号：US20150353504A1

  公开（公告）日：2015-12-10

  Substituted indazole or imidazole derivatives of formula I as in vitro selective and reversible MAO-B inhibitors and for use in the prevention and treatment of meurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and dementia

  公式I中的替代吲唑或咪唑衍生物可作为体外选择性和可逆的MAO-B抑制剂，并用于预防和治疗神经退行性疾病，如帕金森病、阿尔茨海默病和痴呆症。
• SUBSTITUTED INDAZOLE OR INDOLE DERIVATIVES AS IN VITRO MAO-B INHIBITORS
  申请人："NTZ Lab" Ltd.

  公开号：EP2964219B1

  公开（公告）日：2017-05-03
• US9643930B2
  申请人：——

  公开号：US9643930B2

  公开（公告）日：2017-05-09
• Indazole- and Indole-5-carboxamides: Selective and Reversible Monoamine Oxidase B Inhibitors with Subnanomolar Potency
  作者：Nikolay T. Tzvetkov、Sonja Hinz、Petra Küppers、Marcus Gastreich、Christa E. Müller

  DOI：10.1021/jm500729a

  日期：2014.8.14

  Indazole- and indole-carboxamides were discovered as highly potent, selective, competitive, and reversible inhibitors of monoamine oxidase B (MAO-B). The compounds are easily accessible by standard synthetic procedures with high overall yields. The most potent derivatives were N-(3,4-dichlorophenyl)-1-methyl-1H-indazole-5-carboxamide (38a, PSB-1491, IC50 human MAO-B 0.386 nM, >25000-fold selective versus MAO-A) and N-(3,4-dichlorophenyl)-1H-indole-5-carboxamide (53, PSB-1410, IC50 human MAO-B 0.227 nM, >5700-fold selective versus MAO-A). Replacement of the carboxamide linker with a methanimine spacer leading to (E)-N-(3,4-dichlorophenyl)-1-(1H-indazol-5-yl)methanimine (58) represents a further novel class of highly potent and selective MAO-B inhibitors (IC50 human MAO-B 0.612 nM, >16000-fold selective versus MAO-A). In N-(3,4-difluorophenyl-1H-indazole-5-carboxamide (30, PSB-1434, IC50 human MAO-B 1.59 nM, selectivity versus MAO-A>6000-fold), high potency and selectivity are optimally combined with superior physicochemical properties. Computational docking studies provided insights into the inhibitors' interaction with the enzyme binding site and a rationale for their high potency despite their small molecular size.