ethyl 3-(4-chloro-2-methylanilino)-5-methyl-1H-pyrazole-4-carboxylate | 122813-96-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-(4-chloro-2-methylanilino)-5-methyl-1H-pyrazole-4-carboxylate
• CAS: 122813-96-1；1359979-46-6
• 化学式: C₁₄H₁₆ClN₃O₂
• 分子量: 293.753
• InChiKey: SDDDPTIXUSIDHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-chloro-2-methylanilino)-5-methyl-1H-pyrazole-4-carboxylate 在 盐酸 、 potassium hydroxide 、 三氯氧磷 、 三溴氧磷 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-bromo-6-chloro-3,8-dimethyl-1H-pyrazolo[3,4-b]quinoline
  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
• 作为产物：
  描述：

  4-氯-2-甲基苯胺 在 ammonium hydroxide 、 sodium monochloroacetic acid 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 生成 ethyl 3-(4-chloro-2-methylanilino)-5-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

• 3-amino-5-methyl-1H-pyrazole-4-carboxylic acids and esters thereof as
  申请人：A. H. Robins Company, Incorporated

  公开号：US04826866A1

  公开（公告）日：1989-05-02

  A novel method of controlling epilepsy, muscle tension, muscular spasticity, and anxiety in living animal bodies by administering compounds of the formula: ##STR1## wherein: R.sup.1 is hydrogen, loweralkyl or a pharmaceutically acceptable cation; R.sup.2 and R.sup.3, same or different, are hydrogen, loweralkyl, aryl, cycloalkyl, loweralkenyl, 1-adamantyl, heterocyclicaminoalkyl, diloweralkylaminoloweralkyl, or R.sup.2 with R.sup.3 and adjacent nitrogen may form a heterocyclic ring structure; and the pharmaceutical acceptable acid salts, and tautomeric isomers thereof; and novel pharmaceutical compositions therefor are disclosed.

  一种通过给予以下式化合物来控制癫痫、肌肉紧张、肌肉痉挛和焦虑的新方法，其中：##STR1## 其中：R.sup.1 为氢、较低的烷基或药学上可接受的阳离子；R.sup.2 和 R.sup.3，相同或不同，为氢、较低的烷基、芳基、环烷基、较低的烯基、1-金刚烷基、杂环氨基烷基、二较低烷基氨基较低烷基，或 R.sup.2 与 R.sup.3 和相邻的氮原子可能形成杂环环结构；以及其药学上可接受的酸盐和互变异构体；以及相关的新型药物组合物。
• 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。
• 3-amino-5-methyl-1H-pyrazole-4-carboxylic acids and esters thereof as anticonvulsants, muscle relaxants and anxiolytics
  申请人：A.H. ROBINS COMPANY, INCORPORATED

  公开号：EP0315433A2

  公开（公告）日：1989-05-10

  Pharmaceutical compositions which comprise a compound represented by the formula where R¹ represents a hydrogen atom, a lower alkyl group or a pharmaceutically acceptable cation; R² and R³ independently represent a hydrogen atom, a lower alkyl group, an aryl group, a cycloalkyl group, a lower alkenyl group, a 1-adamantyl group, a hetero­cyclicaminoalkyl group, a diloweralkylaminoloweralkyl group, or R² together with R³ and the adjacent nitrogen atom may form a heterocyclic ring structure; and/or a pharmaceutically acceptable acid salt thereof; the use of such compounds in medicine; and the use of such compounds in the preparation of anticonvul­sant agents, muscle relaxants and anxiolytic agents, are disclosed.

  药物组合物，其中包含由式表示的化合物 其中 R¹ 代表氢原子、低级烷基或药学上可接受的阳离子； R²和R³各自代表氢原子、低级烷基、芳基、环烷基、低级烯基、1-金刚烷基、杂环氨基烷基、稀释烷基氨基低级烷基，或R²与R³及相邻氮原子可形成杂环环结构； 和/或其药学上可接受的酸盐；公开了此类化合物在医药中的用途；以及此类化合物在制备抗惊厥剂、肌肉松弛剂和抗焦虑剂中的用途。
• US4826866A
  申请人：——

  公开号：US4826866A

  公开（公告）日：1989-05-02
• 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.