4-fluoro-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester | 681034-80-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-fluoro-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: ethyl 4-fluoro-5-methyl-1H-pyrazole-3-carboxylate
• CAS: 681034-80-0
• 化学式: C₇H₉FN₂O₂
• mdl: MFCD16619994
• 分子量: 172.159
• InChiKey: IORLZUSUXYOBTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-fluoro-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester 在 氨 作用下， 以 甲醇 为溶剂， 以87%的产率得到4-fluoro-5-methyl-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a

  摘要：

  A series of 5-alkyl pyrazole-3-carboxylic acids were prepared and found to act as potent and selective agonists of the human GPCR, GPR109a, the high affinity nicotinic acid receptor. No activity was observed at the highly homologous low affinity niacin receptor, GPR109b. A further series of 4-fluoro-5-alkyl pyrazole-3-carboxylic acids were shown to display similar potency. One example from the series was shown to have improved properties in vivo compared to niacin. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.101
• 作为产物：
  描述：

  3-甲基吡唑-5-甲酸乙酯 在 Selectfluor 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以29%的产率得到4-fluoro-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  [EN] 5-SUBSTITUTED 2H-PYRAZONE-3-CARBOXYLIC ACID DERIVATIVES AS ANTILIPOLYTIC AGENTS FOR THE TREATMENT OF METABOLIC-RELATED DISORDERS SUCH AS DYSLIPIDEMIA
  [FR] DERIVES D'ACIDE 2H-PYRAZOLE-3-CARBOXYLIQUE SUBSTITUE EN 5 UTILISES EN TANT QU'AGENTS ANTILIPOTYQUES POUR LE TRAITEMENT DE TROUBLES METABOLIQUES, TELS QUE LA DYSLIPIDEMIE

  摘要：

  本发明涉及具有化学式（Ia）的某些吡唑羧酸衍生物及其药学上可接受的盐，作为抗脂解作用剂和针对受体RUP25的药物，在该化合物中：R2为H、卤素、C1-12烷基或C1-12卤代烷基；R3为C3-6环烷基、C1-12烷基、C1-12卤代烷基、C3-6环烷基-C1-4-烷基、芳基-C1-4-烷基或杂环芳基-C1-4-烷基，其中所述的芳基-C1-4-烷基和杂环芳基-C1-4-烷基可以选择性地取代1至5个选自权利要求中所列取代基的取代基。本发明还提供了含有该化合物的药物组合物，以及在治疗代谢相关疾病，包括脂质代谢紊乱、动脉粥样硬化、冠心病、胰岛素抵抗、2型糖尿病、综合征X等方面使用该化合物和组合物的方法。此外，本发明还提供了与其他活性剂结合的药物组合物，例如，属于α-葡萄糖苷酶抑制剂、醛糖还原酶抑制剂、双胍类、HMG-CoA还原酶抑制剂、角鲨烯合成抑制剂、贝特类药物、LDL降解增强剂、血管紧张素转化酶（ACE）抑制剂、胰岛素分泌增强剂、噻唑烷二酮类药物等类别的药物。

  公开号：

  WO2004032928A1

文献信息

• [EN] 6,7-DIHYDRO-PYRAZOLO[1,5-A]PYRAZIN-4-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)<br/>[FR] DÉRIVÉS DE 6,7-DIHYDRO-PYRAZOLO[1,5-A]PYRAZIN-4-YLAMINE UTILES EN TANT QU'INHIBITEURS DE BÊTA-SÉCRÉTASE (BACE)
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2012117027A1

  公开（公告）日：2012-09-07

  The present invention relates to novel 6,7-dihydro-pyrazolo[1,5-a]pyrazin-4-yl-amine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACEl, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.

  本发明涉及作为β-分泌酶抑制剂的新型6,7-二氢吡唑并[1,5-a]吡嗪-4-基胺衍生物，该酶也称为β-位点淀粉样蛋白裂解酶、BACE、BACEl、Asp2或memapsin2。该发明还涉及包含这些化合物的药物组合物，制备这些化合物和组合物的方法，以及利用这些化合物和组合物预防和治疗涉及β-分泌酶的疾病的用途，如阿尔茨海默病（AD）、轻度认知障碍、老年痴呆、带有Lewy小体的痴呆、唐氏综合征、与中风相关的痴呆、与帕金森病相关的痴呆或与β-淀粉样蛋白相关的痴呆。
• [EN] 5-SUBSTITUTED 2H-PYRAZONE-3-CARBOXYLIC ACID DERIVATIVES AS ANTILIPOLYTIC AGENTS FOR THE TREATMENT OF METABOLIC-RELATED DISORDERS SUCH AS DYSLIPIDEMIA<br/>[FR] DERIVES D'ACIDE 2H-PYRAZOLE-3-CARBOXYLIQUE SUBSTITUE EN 5 UTILISES EN TANT QU'AGENTS ANTILIPOTYQUES POUR LE TRAITEMENT DE TROUBLES METABOLIQUES, TELS QUE LA DYSLIPIDEMIE
  申请人：ARENA PHARM INC

  公开号：WO2004032928A1

  公开（公告）日：2004-04-22

  The present invention relates to certain pyrazole carboxylic acid derivatives of Formula (Ia), and pharmaceutically acceptable salts thereof, as antilipolytic agents and against for the receptor RUP25, wherein: R2 is H, halogen, C1-12 alkyl or C1-12 haloalkyl; and R3 is C3-6 cycloalkyl, C1-12 alkyl, C1-12 haloalkyl, C3-6 cycloalkyl-C1-4-alkylene, aryl-C1-4-alkylene or heteroaryl-C1-4-alkylene, wherein said aryl-C1-4-alkylene and heteroaryl-C1-4-alkylene can be optionally substituted 1 to 5 substituents selected from the substituents listed in the claims. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for pharmaceutical compositions in combination with other active agents, for example, those agents belonging to the class of α-glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers, thiazolidinedione and the like.

  本发明涉及具有化学式（Ia）的某些吡唑羧酸衍生物及其药学上可接受的盐，作为抗脂解作用剂和针对受体RUP25的药物，在该化合物中：R2为H、卤素、C1-12烷基或C1-12卤代烷基；R3为C3-6环烷基、C1-12烷基、C1-12卤代烷基、C3-6环烷基-C1-4-烷基、芳基-C1-4-烷基或杂环芳基-C1-4-烷基，其中所述的芳基-C1-4-烷基和杂环芳基-C1-4-烷基可以选择性地取代1至5个选自权利要求中所列取代基的取代基。本发明还提供了含有该化合物的药物组合物，以及在治疗代谢相关疾病，包括脂质代谢紊乱、动脉粥样硬化、冠心病、胰岛素抵抗、2型糖尿病、综合征X等方面使用该化合物和组合物的方法。此外，本发明还提供了与其他活性剂结合的药物组合物，例如，属于α-葡萄糖苷酶抑制剂、醛糖还原酶抑制剂、双胍类、HMG-CoA还原酶抑制剂、角鲨烯合成抑制剂、贝特类药物、LDL降解增强剂、血管紧张素转化酶（ACE）抑制剂、胰岛素分泌增强剂、噻唑烷二酮类药物等类别的药物。
• 5-substituted 2h-pyrazone-3-carbixylic acid derivatives as antilipolytic agents for the treatment of metabolic-related disorders such as dyslipidemia
  申请人：Semple Graeme

  公开号：US20060167270A1

  公开（公告）日：2006-07-27

  The present invention relates to certain pyrazole carboxylic acid derivatives of Formula (Ia), and pharmaceutically acceptable salts thereof, as antilipolytic agents and against for the receptor RUP25, wherein: R 2 is H, halogen, C 1-12 alkyl or C 1-12 haloalkyl; and R 3 is C 3-6 cycloalkyl, C 1-12 alkyl, C 1-12 haloalkyl, C 3-6 cycloalkyl-C 1-4 -alkylene, aryl-C 1-4 -alkylene or heteroaryl-C 1-4 -alkylene, wherein said aryl-C 1-4 -alkylene and heteroaryl-C 1-4 -alkylene can be optionally substituted 1 to 5 substituents selected from the substituents listed in the claims. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for pharmaceutical compositions in combination with other active agents, for example, those agents belonging to the class of α-glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers, thiazolidinedione and the like.

  本发明涉及公式（Ia）的某些吡唑羧酸衍生物及其药学上可接受的盐，作为抗脂解作用剂和对RUP25受体的作用剂，其中：R2为H、卤素、C1-12烷基或C1-12卤代烷基；R3为C3-6环烷基、C1-12烷基、C1-12卤代烷基、C3-6环烷基-C1-4-烷基、芳基-C1-4-烷基或杂环芳基-C1-4-烷基，其中所述的芳基-C1-4-烷基和杂环芳基-C1-4-烷基可以选择性地被1至5个在权利要求书中列出的取代基所取代。本发明还提供了含有该化合物的药物组合物，并且提供了使用该化合物和该组合物治疗代谢相关疾病的方法，包括血脂异常、动脉粥样硬化、冠心病、胰岛素抵抗、2型糖尿病、X综合症等。此外，本发明还提供了与其他活性剂组合的药物组合物，例如属于α-葡萄糖苷酶抑制剂、醛还原酶抑制剂、双胍类、HMG-CoA还原酶抑制剂、角鲨烷合成抑制剂、纤维酸类、LDL降解增强剂、血管紧张素转换酶（ACE）抑制剂、胰岛素分泌增强剂、噻唑烷二酮等类别的活性剂。
• 6,7-DIHYDRO-PYRAZOLO[1,5-a]PYRAZIN-4-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)
  申请人：Trabanco-Suárez Andrés Avelino

  公开号：US20140005200A1

  公开（公告）日：2014-01-02

  The present invention relates to novel 6,7-dihydro-pyrazolo[1,5-a]pyrazin-4-yl-amine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.

  本发明涉及一种新型的6,7-二氢-吡唑并[1,5-a]吡嗪-4-基胺衍生物，作为β-分泌酶抑制剂，也被称为β-淀粉样蛋白裂解酶、BACE、BACE1、Asp2或memapsin2。本发明还涉及包含这些化合物的制药组合物，制备这些化合物和组合物的方法，以及使用这些化合物和组合物预防和治疗β-分泌酶参与的疾病，如阿尔茨海默病（AD）、轻度认知障碍、老年痴呆、帕金森病相关痴呆、Lewy小体痴呆、唐氏综合症、中风相关痴呆或β-淀粉样蛋白相关的痴呆。
• Compounds, compositions and methods
  申请人：Denali Therapeutics Inc.

  公开号：US10131676B2

  公开（公告）日：2018-11-20

  The present disclosure relates generally to compounds and compositions, and their use as kinase inhibitors.

  本公开总体上涉及化合物和组合物，以及它们作为激酶抑制剂的用途。