2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)pyridine | 1223597-19-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)pyridine
• 英文别名: 2-(4-Benzyl-3-ethoxy-5-methylpyrazol-1-yl)pyridine；2-(4-benzyl-3-ethoxy-5-methylpyrazol-1-yl)pyridine
• CAS: 1223597-19-0
• 化学式: C₁₈H₁₉N₃O
• 分子量: 293.368
• InChiKey: AJQVHXAMGSHKPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)pyridine 在 三溴化硼 、 水 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 48.0h， 以88%的产率得到4-benzyl-5-methyl-1-(pyridin-2-yl)-1H-pyrazol-3(2H)-one
  参考文献：
  名称：

  N-arylation of 3-alkoxypyrazoles, the case of the pyridines

  摘要：

  In the course of a research program focused on the preparation of libraries of new chemical entities derived from 3-alkoxypyrazoles, we studied their N-pyridylation using 2, 3 or 4-bromopyridines This was achieved using Cristau and Taillefer copper-catalyzed arylation method and mostly led to the 3-alkoxy-1H-pyrazol-1-yl pyridine isomer along with lesser amount of the alternative 5-alkoxy-1H-pyrazol-1-yl pyridine The structures of these isomers were often established via their chemical tansformations and sometimes recourse to unambiguous synthetic routes for comparison purposes The alternative use of 2-fluoropyridine-based arylation was also investigated and lifted some of the limitations encountered in the course of this study (C) 2010 Elsevier Ltd All rights reserved

  DOI：

  10.1016/j.tet.2010.02.032
• 作为产物：
  描述：

  2-溴吡啶 、 4-benzyl-3-ethoxy-5-methyl-1H-pyrazole 在 [N,N′-bis((2′-pyridine)-methylene)]-1,2-diaminocyclohexane 、 caesium carbonate 、 copper(II) oxide 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以66%的产率得到2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)pyridine
  参考文献：
  名称：

  Original 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH)

  摘要：

  Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. As in out previous report, the structure activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biological evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine. Inhibition of DHODH by this compound was confirmed in an array of in vitro assays, including enzymatic tests and cell-based assays for viral replication and cellular growth. This molecule was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its Use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other Series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH.

  DOI：

  10.1021/acs.jmedchem.5b00606

文献信息

• Pyrazole derivatives as dihydroorotate dehydrogenase (DHODH) inhibitors
  申请人：INSTITUT PASTEUR

  公开号：EP2929883A1

  公开（公告）日：2015-10-14

  The present invention relates to compounds of formula (I) for their use in the treatment and/or prevention of auto-immune or auto-immune related diseases, cancer, viral infections, and central nervous system diseases and disorders, by inhibiting human dehydroorate dehydrogenase (DHODH): Wherein R1, R2, R3, R4 and Ar are as defined in claim 1.

  本发明涉及式（I）化合物，通过抑制人脱氢脱氢酶（DHODH），用于治疗和/或预防自身免疫或自身免疫相关疾病、癌症、病毒感染以及中枢神经系统疾病和失调： 其中 R1、R2、R3、R4 和 Ar 如权利要求 1 所定义。
• MALONATE SALT OF VARLITINIB
  申请人：Aslan Pharmaceuticals PTE LTD

  公开号：US20210379070A1

  公开（公告）日：2021-12-09

  The present disclosure relates to a pharmaceutically acceptable salt of compounds (I), i.e. varlitinib, a method of producing the salt, a purer form of the free base obtainable from the salt, and a pharmaceutical composition comprising any one of the same. Also provided is a salt, free base or composition thereof for use in treatment, in particular the treatment of cancer, including as part of a combination therapy, for example in combination with a chemotherapeutic agent. The disclosure also extends to compositions comprising the same and use of any one of the same in treatment, in particular treatment of cancer.
• Original 2-(3-Alkoxy-1<i>H</i>-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH)
  作者：Marianne Lucas-Hourani、Hélène Munier-Lehmann、Farah El Mazouni、Nicholas A. Malmquist、Jane Harpon、Eloi P. Coutant、Sandrine Guillou、Olivier Helynck、Anne Noel、Artur Scherf、Margaret A. Phillips、Frédéric Tangy、Pierre-Olivier Vidalain、Yves L. Janin

  DOI：10.1021/acs.jmedchem.5b00606

  日期：2015.7.23

  Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. As in out previous report, the structure activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biological evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine. Inhibition of DHODH by this compound was confirmed in an array of in vitro assays, including enzymatic tests and cell-based assays for viral replication and cellular growth. This molecule was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its Use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other Series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH.
• N-arylation of 3-alkoxypyrazoles, the case of the pyridines
  作者：Sandrine Guillou、Frédéric J. Bonhomme、Di Betina Chahine、Olivier Nesme、Yves L. Janin

  DOI：10.1016/j.tet.2010.02.032

  日期：2010.4

  In the course of a research program focused on the preparation of libraries of new chemical entities derived from 3-alkoxypyrazoles, we studied their N-pyridylation using 2, 3 or 4-bromopyridines This was achieved using Cristau and Taillefer copper-catalyzed arylation method and mostly led to the 3-alkoxy-1H-pyrazol-1-yl pyridine isomer along with lesser amount of the alternative 5-alkoxy-1H-pyrazol-1-yl pyridine The structures of these isomers were often established via their chemical tansformations and sometimes recourse to unambiguous synthetic routes for comparison purposes The alternative use of 2-fluoropyridine-based arylation was also investigated and lifted some of the limitations encountered in the course of this study (C) 2010 Elsevier Ltd All rights reserved