1-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid | 187999-20-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid
• 英文别名: 1-(2,4-difluorophenyl)-5-methylpyrazole-4-carboxylic acid
• CAS: 187999-20-8
• 化学式: C₁₁H₈F₂N₂O₂
• mdl: MFCD09046309
• 分子量: 238.194
• InChiKey: RJBXTZNSOMPKAC-UHFFFAOYSA-N

物化性质

• 沸点：
  370.4±42.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid 在 氯化亚砜 作用下， 以 吡啶 、 1,2-二氯乙烷 为溶剂， 反应 1.5h， 生成 N-{3-cyano-4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl}-1-(2,4-difluorophenyl)-5-methylpyrazole-4-carboxamide
  参考文献：
  名称：

  AMIDE COMPOUNDS AND MEDICINAL USE THEREOF

  摘要：

  公开号：

  EP1176140B1
• 作为产物：
  描述：

  1-(2,4-二氟苯基)-5-甲基-1H-吡唑-4-羧酸乙酯 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 1-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation

  摘要：

  Dysregulation of the Wnt/beta-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of beta-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.

  DOI：

  10.1021/acs.jmedchem.9b01252

文献信息

• AMIDE DERIVATIVE AND USE THEREOF
  申请人：Ushio Hiroyuki

  公开号：US20130211075A1

  公开（公告）日：2013-08-15

  The present invention relates to a novel amide derivative. More specifically, the present invention provides a medicinal agent useful as a prophylactic or therapeutic agent for diseases, which relies on the production of cytokines from T cells, and which comprises an amide derivative or a pharmacologically acceptable salt thereof or a solvate of the derivative or the pharmacologically acceptable salt as an active ingredient. Provided is an amide derivative represented by general formula (I) [wherein each symbol is as defined in the description] or a pharmacologically acceptable salt thereof, or a solvate of the derivative or the pharmacologically acceptable salt.

  本发明涉及一种新型酰胺衍生物。更具体地说，本发明提供了一种药用剂，可用作依赖于T细胞产生细胞因子的疾病的预防或治疗剂，该药用剂包括酰胺衍生物或其药理学上可接受的盐或该衍生物或药理学上可接受的盐的溶剂的溶剂作为活性成分。提供的是由通式(I)所表示的酰胺衍生物[其中每个符号如描述中所定义]或其药理学上可接受的盐，或该衍生物或药理学上可接受的盐的溶剂。
• N-[(substituted five-membered di-or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia
  申请人：Pfizer Inc.

  公开号：US20030149043A1

  公开（公告）日：2003-08-07

  NHE-1 inhibitors, methods of using such NHE-1 inhibitors and pharmaceutical compositions containing such NHE-1 inhibitors. The NHE-1 inhibitors are useful for the reduction of tissue damage resulting from tissue ischemia.

  NHE-1抑制剂，使用这种NHE-1抑制剂的方法以及含有这种NHE-1抑制剂的制药组合物。NHE-1抑制剂对于减少组织缺血引起的组织损伤是有用的。
• Amide compounds and medicinal use thereof
  申请人：Mitsubishi Pharma Corporation

  公开号：US07015218B1

  公开（公告）日：2006-03-21

  The present invention relates to a compound of the formula wherein R1 is substituted aryl, heteroaryl and the like, R2 and R3 are hydrogen, alkyl, halogen, hydroxyl group and the like, Q is N, CH and the like, W is hydrogen, alkyl, hydroxycarbonylalkyl and the like, X is halogen, cyano, nitro, amino and the like, X′ is hydrogen, halogen, cyano, nitro, and Y is alkyl, hydroxyl group, alkoxy, mercapto and the like and a salt thereof, and a medicine containing the said compound. The compound of the present invention shows a superior inhibitory effect on activated lymphocytes proliferation and is useful as an agent for the prophylaxis or treatment of various autoimmune diseases.

  本发明涉及一种化合物，其化学式为其中R1为取代芳基，杂环芳基等，R2和R3为氢，烷基，卤素，羟基等，Q为N，CH等，W为氢，烷基，羟基羧基烷基等，X为卤素，氰基，硝基，氨基等，X'为氢，卤素，氰基，硝基，Y为烷基，羟基，烷氧基，巯基等及其盐，以及包含所述化合物的药物。本发明的化合物显示出对活化淋巴细胞增殖的优越抑制作用，并可用作各种自身免疫性疾病的预防或治疗剂。
• Wnt signaling pathway inhibitors for treatments of disease
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE

  公开号：US10882841B2

  公开（公告）日：2021-01-05

  Compounds and compositions are provided as inhibitors of the Wnt/β-catenin pathway for the treatment of diseases that implicate the same.

  提供了作为 Wnt/β-catenin 通路抑制剂的化合物和组合物，用于治疗涉及 Wnt/β-catenin 通路的疾病。
• New Azole Antifungals. 2. Synthesis and Antifungal Activity of Heterocyclecarboxamide Derivatives of 3-Amino-2-aryl-1-azolyl-2-butanol
  作者：Javier Bartroli、Enric Turmo、Mònica Algueró、Eulàlia Boncompte、Maria L. Vericat、Lourdes Conte、Joaquim Ramis、Manuel Merlos、Julián García-Rafanell、Javier Forn

  DOI：10.1021/jm970726e

  日期：1998.5.1

  A series of 92 azole antifungals containing an amido alcohol unit was synthesized. The nature and substitution of the amide portion was systematically modified in search of improved antifungal activity, especially against filamentous fungi. The compounds were tested in vitro against a variety of clinically important pathogens and in vivo (po) in a murine candidosis model. Thiazole and thiophene carboxamides carrying both a substituted phenyl ring and a small alkyl. group were best suited for activity against filamentous fungi. In a subset of these compounds, the amide portion was conformationally locked by means of a pyrimidone ring and it was proven that only an orthogonal orientation of the phenyl ring yields bioactive products. A tendency to display long plasma elimination half-lives was observed in both series. Two compounds, 74 and 107, representative of the open and cyclic amides, respectively, were chosen for further studies, based on their excellent activity in in vivo murine models of candidosis and aspergillosis. This work describes the SARs found within this series. The next paper displays the results obtained in a related series of compounds, the quinazolinones.