5-氨基-1-（2-氟苯基）-1H-吡唑-4-羧酸乙酯 | 618070-65-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-氨基-1-（2-氟苯基）-1H-吡唑-4-羧酸乙酯
• 中文别名: 5-氨基-1-（2-氟苯基）吡唑-4-羧酸乙酯；5-氨基-1-(2-氟苯基)-1h吡唑-4-羧酸乙酯
• 英文名称: ethyl-5-amino-1-(2-fluorophenyl)-pyrazole-4-carboxylate
• 英文别名: ethyl 5-amino-1-(2-fluorophenyl)-1H-pyrazole-4-carboxylate；ethyl 5-amino-1-(2-fluorophenyl)pyrazole-4-carboxylate
• CAS: 618070-65-8
• 化学式: C₁₂H₁₂FN₃O₂
• mdl: MFCD03407403
• 分子量: 249.245
• InChiKey: NYHXOVWRDYMNGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933199090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  5-氨基-1-（2-氟苯基）-1H-吡唑-4-羧酸乙酯 在 磷酸 、 potassium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 36.5h， 生成 ethyl 4-(4-(3-cyanopyridin-2-yl)piperazin-1-yl)-1-(2-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
  参考文献：
  名称：

  Deciphering the robustness of pyrazolo-pyridine carboxylate core structure-based compounds for inhibiting α-synuclein in transgenic C. elegans model of Synucleinopathy

  摘要：

  Parkinson's disease (PD), a calamitous neurodegenerative disorder with no cure till date, is closely allied with the misfolding and aggregation of alpha-Synuclein (alpha-Syn). Inhibition of alpha-Syn aggregation is one of the optimistic approaches for the treatment for PD. Here, we carried out hypothesis-driven studies towards synthesising a series of pyrazolo-pyridine carboxylate containing compounds (7a-7m) targeted at reducing deleterious alpha-Syn aggregation. The target compounds were synthesized through multi-step organic synthesis reactions. From docking studies, compounds 7b, 7g and 7i displayed better interaction with the key residues of alpha-Syn with values: -6.8, -8.9 and -7.2 Kcal/mol, respectively. In vivo transgenic C. elegans model of Synucleinopathy was used to evaluate the ability of the designed and synthesized compounds to inhibit alpha-Syn aggregation. These lead compounds 7b, 7g and 7i displayed 1.7, 2.4 and 1.5-fold inhibition of alpha-Syn with respect to the control. Further, the strategy of employing pyrazolo-pyridine-based compounds worked with success and these scaffolds could be further modified and validated for betterment of endpoints associated with PD.

  DOI：

  10.1016/j.bmc.2020.115640
• 作为产物：
  描述：

  2-氟苯胺 在 盐酸 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.5h， 生成 5-氨基-1-（2-氟苯基）-1H-吡唑-4-羧酸乙酯
  参考文献：
  名称：

  Deciphering the robustness of pyrazolo-pyridine carboxylate core structure-based compounds for inhibiting α-synuclein in transgenic C. elegans model of Synucleinopathy

  摘要：

  Parkinson's disease (PD), a calamitous neurodegenerative disorder with no cure till date, is closely allied with the misfolding and aggregation of alpha-Synuclein (alpha-Syn). Inhibition of alpha-Syn aggregation is one of the optimistic approaches for the treatment for PD. Here, we carried out hypothesis-driven studies towards synthesising a series of pyrazolo-pyridine carboxylate containing compounds (7a-7m) targeted at reducing deleterious alpha-Syn aggregation. The target compounds were synthesized through multi-step organic synthesis reactions. From docking studies, compounds 7b, 7g and 7i displayed better interaction with the key residues of alpha-Syn with values: -6.8, -8.9 and -7.2 Kcal/mol, respectively. In vivo transgenic C. elegans model of Synucleinopathy was used to evaluate the ability of the designed and synthesized compounds to inhibit alpha-Syn aggregation. These lead compounds 7b, 7g and 7i displayed 1.7, 2.4 and 1.5-fold inhibition of alpha-Syn with respect to the control. Further, the strategy of employing pyrazolo-pyridine-based compounds worked with success and these scaffolds could be further modified and validated for betterment of endpoints associated with PD.

  DOI：

  10.1016/j.bmc.2020.115640

文献信息

• Aryl-substituted pyrazole-amide compounds useful as kinase inhibitors
  申请人：Dyckman J. Alaric

  公开号：US20050159424A1

  公开（公告）日：2005-07-21

  The present invention relates to compounds having the formula, and pharmaceutically-acceptable salts, prodrugs, solvates, isomers, and/or hydrates thereof, wherein Q is an optionally-substituted phenyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl ring; R 2 is alkyl or an amino group as defined herein; and Z is optionally-substituted oxadiazolyl or —C(═O)NR 6 , wherein R 6 is lower alkyl or cyclopropyl. The compounds are surprisingly advantageous in preparing pharmaceutical compositions for treating p38 kinase related conditions and/or in methods of treating conditions associated with the activity of p38 kinase in a patient.

  本发明涉及具有下列式的化合物，以及其药学上可接受的盐、前药、溶剂化合物、异构体和/或水合物，其中Q是可选择取代的苯基、吡啶基、吡嗪基、嘧啶基或吡嗪啉基环；R2是如下所定义的烷基或氨基；Z是可选择取代的噁二唑基或—C(═O)NR6，其中R6是低烷基或环丙基。这些化合物在制备用于治疗与p38激酶相关的病症的药物组合物方面具有惊人的优势，或者在治疗患者p38激酶活性相关病症的方法中具有惊人的优势。
• ARYL-SUBSTITUTED PYRAZOLE-AMIDE COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Dyckman Alaric J.

  公开号：US20100016320A1

  公开（公告）日：2010-01-21

  The present invention relates to compounds having the formula, and pharmaceutically-acceptable salts, prodrugs, solvates, isomers, and/or hydrates thereof, wherein Q is an optionally-substituted phenyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl ring; R 2 is alkyl or an amino group as defined herein; and Z is optionally-substituted oxadiazolyl or —C(═O)NR 6 , wherein R 6 is lower alkyl or cyclopropyl. The compounds are surprisingly advantageous in preparing pharmaceutical compositions for treating p38 kinase related conditions and/or in methods of treating conditions associated with the activity of p38 kinase in a patient.

  本发明涉及具有以下式的化合物，以及其药学上可接受的盐、前药、溶剂化物、异构体和/或水合物，其中Q为可选择取代的苯基、吡啶基、吡嗪基、嘧啶基或吡嗪啉基环；R2为定义如下的烷基或氨基基团；Z为可选择取代的噁二唑基或—C(═O)NR6，其中R6为低烷基或环丙基。这些化合物在制备用于治疗与p38激酶相关的疾病的药物组合物和/或治疗患者与p38激酶活性相关的疾病的方法中具有惊人的优势。
• 5-Amino-pyrazoles as potent and selective p38α inhibitors
  作者：Jagabandhu Das、Robert V. Moquin、Alaric J. Dyckman、Tianle Li、Sidney Pitt、Rosemary Zhang、Ding Ren Shen、Kim W. McIntyre、Kathleen Gillooly、Arthur M. Doweyko、John A. Newitt、John S. Sack、Hongjian Zhang、Susan E. Kiefer、Kevin Kish、Murray McKinnon、Joel C. Barrish、John H. Dodd、Gary L. Schieven、Katerina Leftheris

  DOI：10.1016/j.bmcl.2010.10.034

  日期：2010.12

  The synthesis and structure-activity relationships (SAR) of p38 alpha MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38 alpha MAP kinase with excellent cellular potency toward the inhibition of TNF alpha production. Compound 2j was highly efficacious in vivo in inhibiting TNF alpha production in an acute murine model of TNF alpha production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38 alpha is also disclosed. (C) 2010 Elsevier Ltd. All rights reserved.
• ARYL-SUBSTITUTED PYRAZOLE-AMIDE COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1618092B1

  公开（公告）日：2010-09-22
• PYRAZOLE-AMINE COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Dyckman J. Alaric

  公开号：US20080108626A1

  公开（公告）日：2008-05-08

  The present invention provides pyrazole derived compounds of formula (I) useful for treating p38 kinase-associated conditions, where G, X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and m are as defined herein. The invention further pertains to pharmaceutical compositions containing at least one compound according to the invention useful for treating p38 kinase-associated conditions, and methods of inhibiting the activity of p38 kinase in a mammal.