N-(5,6-dichloropyridin-3-yl)-1H-indazole-5-carboxamide | 1619884-66-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: N-(5,6-dichloropyridin-3-yl)-1H-indazole-5-carboxamide
• CAS: 1619884-66-0
• 化学式: C₁₃H₈Cl₂N₄O
• 分子量: 307.139
• InChiKey: JLABGNSHSHVIHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-氨基-2,3-二氯吡啶 、 吲唑-5-甲酸盐酸盐 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 为溶剂， 以93%的产率得到N-(5,6-dichloropyridin-3-yl)-1H-indazole-5-carboxamide
  参考文献：
  名称：

  甲酰胺与甲胺的关系：（吲唑-5-基）甲胺作为单胺氧化酶B和乙酰胆碱酯酶抑制剂的晶体结构，结合相互作用，光物理研究和生物学评估

  摘要：

  首次进行了一项综合研究，比较了两种与结构相关的物质类别，即吲唑-5-甲酰胺（11 – 16）和（吲唑-5-基）甲亚胺（17 – 22）。这两种化学实体都是有效的，选择性的和可逆的MAO-B抑制剂，因此，可作为开发针对帕金森氏病（PD）和其他神经系统疾病的候选药物的有前途的先导结构。化合物15（K i  = 170 pM，SI = 25907）和17（K i = 270 pM，SI = 16340）是这两个系列中最有效和最具选择性的MAO-B抑制剂。为了研究多靶标抑制活性，进一步筛选了所有化合物对人AChE和BuChE酶的效力。发现化合物15是所有系列中最有效和最具选择性的AChE抑制剂（h AChE IC 50  = 78.3±1.7μM）。而且，如初步细胞毒性筛选所确定的，化合物11和17没有药物引起的肝毒性的风险，并且具有更宽的安全范围。由HYDE分析支持的对人MAO-B酶结合位点的分

  DOI：

  10.1016/j.ejmech.2019.06.041

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。
• 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.
• 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