5-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid | 187998-46-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid
• 英文别名: 1-(4-trifluoromethylphenyl)-5-(trifluoromethyl)-4-pyrazolecarboxylic acid；5-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-1pyrazole-4-carboxylic acid；5-(trifluoromethyl)-1-[4-(trifluoromethyl)phenyl]pyrazole-4-carboxylic Acid
• CAS: 187998-46-5
• 化学式: C₁₂H₆F₆N₂O₂
• 分子量: 324.182
• InChiKey: ALMFCZMUUGHOGY-UHFFFAOYSA-N

物化性质

• 沸点：
  365.0±42.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R,3R)-3-amino-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol 、 5-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazole-4-carboxylic acid [(1R,2R)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]-amide
  参考文献：
  名称：

  New Azole Antifungals. 2. Synthesis and Antifungal Activity of Heterocyclecarboxamide Derivatives of 3-Amino-2-aryl-1-azolyl-2-butanol

  摘要：

  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.

  DOI：

  10.1021/jm970726e
• 作为产物：
  描述：

  ethyl 5-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以96%的产率得到5-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  Discovery of Novel Inhibitors of Uridine Diphosphate-N-Acetylenolpyruvylglucosamine Reductase (MurB) from Pseudomonas aeruginosa, an Opportunistic Infectious Agent Causing Death in Cystic Fibrosis Patients

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c01684

文献信息

• [EN] SPHINGOSINE-1-PHOSPHATE RECEPTOR AGONISTS<br/>[FR] AGONISTES DES RÉCEPTEURS SPHINGOSINE-1-PHOSPHATE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011017578A1

  公开（公告）日：2011-02-10

  Disclosed are compounds of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein: A is formula (II) Q is a substituted 5-membered monocyclic heteroaryl group; W is CH2, O, or NH; and R1, R2, R3, R4, R5, R6, m, n, t, and x are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

  揭示了Formula (I)的化合物，或其立体异构体或药用可接受的盐，其中：A为Formula (II)，Q为取代的5-成员单环杂芳基团；W为CH2、O或NH；而R1、R2、R3、R4、R5、R6、m、n、t和x在此处有定义。还揭示了将这些化合物用作G蛋白偶联受体S1P1的选择性激动剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或紊乱方面具有用处，如自身免疫疾病和血管疾病。
• HETEROCYCLIC COMPOUNDS
  申请人：Gilmore John L.

  公开号：US20110190255A1

  公开（公告）日：2011-08-04

  Disclosed are compounds of Formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein: A is Q is a substituted 5-membered monocyclic heteroaryl group; W is CH 2 , O, or NH; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , m, n, t, and x are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P 1 , and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

  本发明涉及化合物I式或其立体异构体或其药学上可接受的盐，其中：A为Q为取代的5-成员单环杂芳基；W为CH2、O或NH；R1、R2、R3、R4、R5、R6、m、n、t和x在此定义。本发明还涉及使用这些化合物作为选择性G蛋白偶联受体S1P1的激动剂的方法，以及包含这些化合物的制药组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或疾病的进展方面是有用的，如自身免疫性疾病和血管疾病。
• Discovery of Novel Piperidinylthiazole Derivatives As Broad-Spectrum Fungicidal Candidates
  作者：Qifan Wu、Bin Zhao、Zhijin Fan、Xiaofeng Guo、Dongyan Yang、Nailou Zhang、Bin Yu、Shuang Zhou、Jiabao Zhao、Fan Chen

  DOI：10.1021/acs.jafc.8b06054

  日期：2019.2.6

  Oxathiapiprolin is one of the best active fungicides discovered for oomycetes control. To develop a fungicide candidate with a broad spectrum of activity, 22 new piperidinylthiazole derivatives were designed and synthesized. Compound 51 showed the best activity against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo with 100% and 80% of inhibition, respectively, at 1 mg/L, and 72.87% of field efficacy against P. cubensis at 1 g ai/667 m(2) validated these results. Compound 5i exhibited a broad spectrum of excellent activity against Sclerotinia sclerotiorum with EC50 = 0.30 mg/ L (>10 times more active than oxathiapiprolin and azoxystrobin in vitro), good activity against Botrytis cinerea, Cercospora arachidicola, and Gibberella zeae with EC50 of 14.54, 5.57, and 14.03 mg/L in vitro and against P. cubensis and P. infestans with 60% and 30% inhibition rates, respectively, at 1 mg/L in vivo. Mode of action studies by RNA sequencing analysis discovered oxysterol-binding protein (OSBP), chitin synthase (CHS1), and (1,3)-beta-glucan synthase (FKS2) as the potent target of 5i against S. sclerotiorum. Quenching studies validated that OSBP was the same target of both 5i and oxathiapiprolin; it was quenched by both of them. Our studies discovered isothiazole-containing piperidinylthiazole as an OSBP target-based novel lead for fungicide development.
• NEW CARBOXAMIDES WITH ANTIFUNGAL ACTIVITY
  申请人：J. URIACH & CIA. S.A.

  公开号：EP0783502A1

  公开（公告）日：1997-07-16
• PYRAZOLE-AMIDES FOR USE IN THE TREATMENT OF PAIN
  申请人：Icagen, Inc.

  公开号：EP1451160B1

  公开（公告）日：2010-01-13