Ethyl 5-((4-methoxy-2-methylphenyl)amino)-3-methyl-1H-pyrazole-4-carboxylate | 1355959-27-1

• 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: Ethyl 5-((4-methoxy-2-methylphenyl)amino)-3-methyl-1H-pyrazole-4-carboxylate
• 英文别名: ethyl 3-(4-methoxy-2-methylanilino)-5-methyl-1H-pyrazole-4-carboxylate
• CAS: 1355959-27-1
• 化学式: C₁₅H₁₉N₃O₃
• 分子量: 289.334
• InChiKey: IZVAWVAABMAKMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 5-((4-methoxy-2-methylphenyl)amino)-3-methyl-1H-pyrazole-4-carboxylate 在 水 、 potassium hydroxide 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 4-Chloro-6-methoxy-3,8-dimethyl-1H-pyrazolo[3,4-B]quinoline
  参考文献：
  名称：

  发现口服活性吡唑并喹啉作为有效的PDE10抑制剂可用于精神分裂症的治疗

  摘要：

  已合成了一系列吡唑并喹啉类似物，并显示出与PDE10的高亲和力结合。通过SAR研究和我们的前导优化工作，发现化合物16和27在MK-801诱导的多动症大鼠模型中具有有效的口服抗精神病活性。

  DOI：

  10.1016/j.bmcl.2011.11.023
• 作为产物：
  描述：

  2-甲基-4-甲氧基苯胺 在 ammonium hydroxide 、 sodium monochloroacetic acid 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 生成 Ethyl 5-((4-methoxy-2-methylphenyl)amino)-3-methyl-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  Pyrazoloquinolines as PDE10A inhibitors: Discovery of a tool compound

  摘要：

  A series of pyrazoloquinolines, possessing (hetero)arylhydroxymethyl substituents at the quinoline C-4 position were evaluated as PDE10A inhibitors. Among these, methylpyrimidyl analogue 15 was identified as having good rodent and monkey exposure, and a MED of 10 mg/kg in an in vivo model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.080

文献信息

• [EN] SUBSTITUTED PYRAZOLOQUINOLINES AND DERIVATIVES THEREOF<br/>[FR] PYRAZOLOQUINOLÉINES SUBSTITUÉES ET LEURS DÉRIVÉS
  申请人：SCHERING CORP

  公开号：WO2010062559A1

  公开（公告）日：2010-06-03

  The present invention relates to substituted pyrazoloquinolines of formula I and derivatives thereof, the use of the compounds as phosphodiesterase 10 (PDElO) inhibitors for the treatment of PDElO -modulated disorders, to pharmaceutical compositions comprising the compounds, and to the use of additional substituted pyrazoloquinolines and derivatives thereof for the treatment of PDElO -modulated disorders.

  本发明涉及式I的取代吡唑喹啉及其衍生物，将这些化合物用作磷酸二酯酶10（PDE10）抑制剂，用于治疗PDE10调控的疾病，以及包含这些化合物的药物组合物，以及用于治疗PDE10调控的疾病的其他取代吡唑喹啉及其衍生物的使用。
• Pyrazoloquinolines as PDE10A inhibitors: Discovery of a tool compound
  作者：William T. McElroy、Zheng Tan、Kallol Basu、Shu-Wei Yang、Jennifer Smotryski、Ginny D. Ho、Deen Tulshian、William J. Greenlee、Deborra Mullins、Mario Guzzi、Xiaoping Zhang、Carina Bleickardt、Robert Hodgson

  DOI：10.1016/j.bmcl.2011.12.080

  日期：2012.2

  A series of pyrazoloquinolines, possessing (hetero)arylhydroxymethyl substituents at the quinoline C-4 position were evaluated as PDE10A inhibitors. Among these, methylpyrimidyl analogue 15 was identified as having good rodent and monkey exposure, and a MED of 10 mg/kg in an in vivo model. (C) 2011 Elsevier Ltd. All rights reserved.
• CN115677586
  申请人：——

  公开号：——

  公开（公告）日：——
• The discovery of potent, selective, and orally active pyrazoloquinolines as PDE10A inhibitors for the treatment of Schizophrenia
  作者：Ginny D. Ho、Shu-Wei Yang、Jennifer Smotryski、Ana Bercovici、Terry Nechuta、Elizabeth M. Smith、William McElroy、Zheng Tan、Deen Tulshian、Brian McKittrick、William J. Greenlee、Alan Hruza、Li Xiao、Diane Rindgen、Deborra Mullins、Mario Guzzi、Xiaoping Zhang、Carina Bleickardt、Robert Hodgson

  DOI：10.1016/j.bmcl.2011.11.127

  日期：2012.1

  High-throughput screening identified a series of pyrazoloquinolines as PDE10A inhibitors. The SAR development led to the discovery of compound 27 as a potent, selective, and orally active PDE10A inhibitor. Compound 27 inhibits MK-801 induced hyperactivity at 3 mg/kg with an ED50 of 4 mg/kg and displays a similar to 6-fold separation between the ED50 for inhibition of MK-801 induced hyperactivity and hypolocomotion in rats. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia
  作者：Shu-Wei Yang、Jennifer Smotryski、William T. McElroy、Zheng Tan、Ginny Ho、Deen Tulshian、William J. Greenlee、Mario Guzzi、Xiaoping Zhang、Deborra Mullins、Li Xiao、Alan Hruza、Tze-Ming Chan、Diane Rindgen、Carina Bleickardt、Robert Hodgson

  DOI：10.1016/j.bmcl.2011.11.023

  日期：2012.1

  A series of pyrazoloquinoline analogs have been synthesized and shown to bind to PDE10 with high affinity. From the SAR study and our lead optimization efforts, compounds 16 and 27 were found to possess potent oral antipsychotic activity in the MK-801 induced hyperactive rat model.

  已合成了一系列吡唑并喹啉类似物，并显示出与PDE10的高亲和力结合。通过SAR研究和我们的前导优化工作，发现化合物16和27在MK-801诱导的多动症大鼠模型中具有有效的口服抗精神病活性。