methyl 5-chloro-1-methyl-1H-indazole-3-carboxylate | 1620412-40-9

• 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: methyl 5-chloro-1-methyl-1H-indazole-3-carboxylate
• 英文别名: 1H-Indazole-3-carboxylic acid, 5-chloro-1-methyl-, methyl ester；methyl 5-chloro-1-methylindazole-3-carboxylate
• CAS: 1620412-40-9
• 化学式: C₁₀H₉ClN₂O₂
• 分子量: 224.647
• InChiKey: OWOZKXUUWJEJDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 5-chloro-1-methyl-1H-indazole-3-carboxylate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 3.0h， 生成 5-chloro-1-methyl-1H-indazole-3-carboxylic acid
  参考文献：
  名称：

  Discovery and Pharmacological Profile of New 1H-Indazole-3-carboxamide and 2H-Pyrrolo[3,4-c]quinoline Derivatives as Selective Serotonin 4 Receptor Ligands

  摘要：

  Since the discovery of the serotonin 4 receptor (5-HT4R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4- piperidinyl)methyl]-1H-indazole-3-carboxamide and 4-[(4-piperidinyl)methoxy]-2H-pyrrolo[3,4-c]quinoline derivatives as new 5-HT4R ligands endowed with high selectivity over the serotonin 2A receptor and human ether-a-go-go-related gene potassium ion channel. Within these series, two molecules (11ab and 12g) were identified as potent and selective 5-HT4R antagonists with good in vitro pharmacokinetic properties. These compounds were evaluated for their antinociceptive action in two analgesia animal models. 12g showed a significant antinociceptive effect in both models and is proposed as an interesting lead compound as a 5-HT4R antagonist with analgesic action.

  DOI：

  10.1021/jm300573d
• 作为产物：
  描述：

  5-氯-3-吲唑甲酸 在 硫酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.33h， 生成 methyl 5-chloro-1-methyl-1H-indazole-3-carboxylate
  参考文献：
  名称：

  [EN] NOVEL SUBSTITUTED PYRIDO-PIPERAZINONE DERIVATIVES AS GAMMA SECRETASE MODULATORS
  [FR] DÉRIVÉS SUBSTITUÉS DE PYRIDO-PIPÉRAZINONE D'UN NOUVEAU TYPE EN TANT QUE MODULATEURS DE LA GAMMA-SÉCRÉTASE

  摘要：

  本发明涉及新颖的Formula (I)中R1、R2、R3、R4、R5、L、Z和X所定义含义的取代吡啶哌唑酮衍生物。根据本发明的化合物可用作γ-分泌酶调节剂。本发明还涉及制备这种新型化合物的方法，包含该化合物作为活性成分的药物组合物，以及将该化合物用作药物的用途。

  公开号：

  WO2014111457A1

文献信息

• NOVEL SUBSTITUTED PYRIDO-PIPERAZINONE DERIVATIVES AS GAMMA SECRETASE MODULATORS
  申请人：Janssen Pharmaceutica NV

  公开号：US20180319797A1

  公开（公告）日：2018-11-08

  The present invention is concerned with novel substituted pyrido-piperazinone derivatives of Formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , L, Z and X have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及新颖的Formula (I)中的取代吡啶哌唑酮衍生物，其中R1、R2、R3、R4、R5、L、Z和X的含义如权利要求中所定义。根据本发明的化合物可用作γ-分泌酶调节剂。本发明还涉及制备这种新型化合物的方法，包含上述化合物作为活性成分的药物组合物，以及将这些化合物用作药物的用途。
• Substituted 3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-diones as gamma secretase modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US10246454B2

  公开（公告）日：2019-04-02

  The present invention is concerned with novel substituted pyrido-piperazinone derivatives of Formula (I) wherein R1, R2, R3, R4, R5, L, Z and X have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及式 (I) 的新型取代吡啶-哌嗪酮衍生物 其中 R1、R2、R3、R4、R5、L、Z 和 X 具有权利要求中定义的含义。根据本发明的化合物可用作γ 分泌酶调节剂。本发明进一步涉及制备这种新型化合物的工艺、包含所述化合物作为活性成分的药物组合物以及所述化合物作为药物的用途。
• [EN] NOVEL SUBSTITUTED PYRIDO-PIPERAZINONE DERIVATIVES AS GAMMA SECRETASE MODULATORS<br/>[FR] DÉRIVÉS SUBSTITUÉS DE PYRIDO-PIPÉRAZINONE D'UN NOUVEAU TYPE EN TANT QUE MODULATEURS DE LA GAMMA-SÉCRÉTASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014111457A1

  公开（公告）日：2014-07-24

  The present invention is concerned with novel substituted pyrido-piperazinone derivatives of Formula (I) wherein R1, R2, R3, R4, R5, L, Z and X have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及新颖的Formula (I)中R1、R2、R3、R4、R5、L、Z和X所定义含义的取代吡啶哌唑酮衍生物。根据本发明的化合物可用作γ-分泌酶调节剂。本发明还涉及制备这种新型化合物的方法，包含该化合物作为活性成分的药物组合物，以及将该化合物用作药物的用途。
• Discovery and Pharmacological Profile of New 1<i>H</i>-Indazole-3-carboxamide and 2<i>H</i>-Pyrrolo[3,4-<i>c</i>]quinoline Derivatives as Selective Serotonin 4 Receptor Ligands
  作者：Guido Furlotti、Maria Alessandra Alisi、Claudia Apicella、Alessandra Capezzone de Joannon、Nicola Cazzolla、Roberta Costi、Giuliana Cuzzucoli Crucitti、Beatrice Garrone、Alberto Iacovo、Gabriele Magarò、Giorgina Mangano、Gaetano Miele、Rosella Ombrato、Luca Pescatori、Lorenzo Polenzani、Federica Rosi、Marco Vitiello、Roberto Di Santo

  DOI：10.1021/jm300573d

  日期：2012.11.26

  Since the discovery of the serotonin 4 receptor (5-HT4R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4- piperidinyl)methyl]-1H-indazole-3-carboxamide and 4-[(4-piperidinyl)methoxy]-2H-pyrrolo[3,4-c]quinoline derivatives as new 5-HT4R ligands endowed with high selectivity over the serotonin 2A receptor and human ether-a-go-go-related gene potassium ion channel. Within these series, two molecules (11ab and 12g) were identified as potent and selective 5-HT4R antagonists with good in vitro pharmacokinetic properties. These compounds were evaluated for their antinociceptive action in two analgesia animal models. 12g showed a significant antinociceptive effect in both models and is proposed as an interesting lead compound as a 5-HT4R antagonist with analgesic action.