2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-isopropylpyridine

• 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)-5-isopropylpyridine
• 英文别名: 2-(4-Benzyl-3-ethoxy-5-methylpyrazol-1-yl)-5-propan-2-ylpyridine；2-(4-benzyl-3-ethoxy-5-methylpyrazol-1-yl)-5-propan-2-ylpyridine
• 化学式: C₂₁H₂₅N₃O
• 分子量: 335.449
• InChiKey: BJRRCWUNFBTJML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氟-5-溴吡啶 在 正丁基锂 、 17-甲睾酮 、 三异丙基硅基三氟甲磺酸酯 、 caesium carbonate 、 三氟乙酸 作用下， 以 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 0.75h， 生成 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-isopropylpyridine
  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
• 作为试剂：
  描述：

  2-(6-fluoropyridin-3-yl)propan-2-ol 、 4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazole 在 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-isopropylpyridine 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以68%的产率得到2-(6-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyridin-3-yl)propan-2-ol
  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。
• WO2015/155680
  申请人：——

  公开号：——

  公开（公告）日：——