3-ethoxy-4-bromo-5-methyl-1H-pyrazole | 13246-95-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-ethoxy-4-bromo-5-methyl-1H-pyrazole
• 英文别名: 4-bromo-3-ethoxy-5-methyl-1(2)H-pyrazole；3(5)-Methyl-4-brom-5(3)-ethoxy-pyrazol；4-bromo-3-ethoxy-5-methyl-1H-pyrazole
• CAS: 13246-95-2
• 化学式: C₆H₉BrN₂O
• 分子量: 205.054
• InChiKey: JGEFVMSUMVPALJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-ethoxy-4-bromo-5-methyl-1H-pyrazole 在 palladium diacetate 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 28.0h， 生成 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-cyclopropylpyridine
  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
• 作为产物：
  描述：

  3-乙氧基-5-甲基-1H-吡唑 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 以91%的产率得到3-ethoxy-4-bromo-5-methyl-1H-pyrazole
  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

• Chemical Compounds
  申请人：Chai Deping

  公开号：US20130225524A1

  公开（公告）日：2013-08-29

  The invention is directed to substituted quinoline derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R 1 , R 2 , R 3 , R 4 , and R 5 are defined herein. The compounds of the invention are inhibitors of lactate dehydrogenase A and can be useful in the treatment of cancer and diseases associated with tumor cell metabolism, such as cancer, and more specifically cancers of the breast, colon, prostate and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting lactate dehydrogenase A activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代喹啉衍生物。具体而言，本发明涉及公式I的化合物：其中R1，R2，R3，R4和R5在此定义。本发明的化合物是乳酸脱氢酶A的抑制剂，可用于治疗癌症和与肿瘤细胞代谢相关的疾病，例如乳腺癌、结肠癌、前列腺癌和肺癌。因此，本发明进一步涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物来抑制乳酸脱氢酶A活性和治疗与之相关的疾病的方法。
• 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：——
• BOGUNETS N. P., BECTH. XARKOV. POLITEXN. IN-TA, 1975, HO 104, 67-69
  作者：BOGUNETS N. P.

  DOI：——

  日期：——
• CHEMICAL COMPOUNDS
  申请人：Glaxosmithkline Intellectual Property (No. 2) Limited

  公开号：EP2635279A2

  公开（公告）日：2013-09-11