Ethyl 1-(2,2-difluoroethyl)pyrazole-3-carboxylate | 1309951-83-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Ethyl 1-(2,2-difluoroethyl)pyrazole-3-carboxylate
• CAS: 1309951-83-4
• 化学式: C₈H₁₀F₂N₂O₂
• 分子量: 204.176
• InChiKey: MJBLJXAWAQTENU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 1-(2,2-difluoroethyl)pyrazole-3-carboxylate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Discovery of Hepatitis C Virus NS3-4A Protease Inhibitors with Improved Barrier to Resistance and Favorable Liver Distribution

  摘要：

  Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly Unproved potency against the key resistant variants and with increased liver partitioning.

  DOI：

  10.1021/jm400121t
• 作为产物：
  描述：

  3-吡唑甲酸乙酯 以 甲醇 为溶剂， 生成 Ethyl 1-(2,2-difluoroethyl)pyrazole-3-carboxylate
  参考文献：
  名称：

  2-硫代-2,3-二氢嘧啶-4-酮衍生物、药物组合物及其制备方法和应用

  摘要：

  本发明提供了一种式I所示的2‑硫代‑2,3‑二氢嘧啶‑4‑酮类衍生物、药物组合物及其制备方法和应用。该化合物具有良好的MPO抑制作用，可用于治疗或预防与髓过氧化物酶有关的病症和疾病，以及制备用于此类病症和疾病的药物。

  公开号：

  CN115403584A

文献信息

• [EN] HEPATITIS C INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE L'HÉPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011063501A1

  公开（公告）日：2011-06-03

  Compounds of the invention, which are macrocyclic peptide analogs containing an acylsulfonamide moiety, maintain good activity against NS3 proteases containing clinically relevant resistance mutations for this class as represented by genotype 1 a R155K, genotype 1 b D168V and genotype 1 a D168V resistance mutations. The compounds of the invention are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  本发明的化合物是含有酰磺酰胺基团的大环肽类似物，对包含临床相关耐药突变的NS3蛋白酶保持良好的活性，这些耐药突变由基因型1a的R155K、基因型1b的D168V和基因型1a的D168V耐药突变代表。本发明的化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• [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。
• HEPATITIS C INHIBITOR COMPOUNDS
  申请人：Llinas-Brunet Montse

  公开号：US20120077737A1

  公开（公告）日：2012-03-29

  Compounds of the invention, which are macrocyclic peptide analogs containing an acylsulfonamide moiety, maintain good activity against NS3 proteases containing clinically relevant resistance mutations for this class as represented by genotype 1a R155K, genotype 1b D168V and genotype 1a D168V resistance mutations. The compounds of the invention are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  本发明的化合物是含有酰基磺酰胺基团的大环肽类似物，在对于该类别的NS3蛋白酶含有临床相关的耐药突变，如基因型1a R155K、基因型1b D168V和基因型1a D168V耐药突变时，仍然保持良好的活性。本发明的化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• 5-SUBSTITUTED 2H-PYRAZONE-3-CARBOXYLIC ACID DERIVATIVES AS ANTILIPOLYTIC AGENTS FOR THE TREATMENT OF METABOLIC-RELATED DISORDERS SUCH AS DYSLIPIDEMIA
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP1551403A1

  公开（公告）日：2005-07-13
• Discovery of Hepatitis C Virus NS3-4A Protease Inhibitors with Improved Barrier to Resistance and Favorable Liver Distribution
  作者：Benoît Moreau、Jeff A. O’Meara、Josée Bordeleau、Michel Garneau、Cedrickx Godbout、Vida Gorys、Mélissa Leblanc、Elisia Villemure、Peter W. White、Montse Llinàs-Brunet

  DOI：10.1021/jm400121t

  日期：2014.3.13

  Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly Unproved potency against the key resistant variants and with increased liver partitioning.