1-(3-cyano-4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic Acid | 209960-58-7

• 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-(3-cyano-4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic Acid
• 英文别名: 1-(4'-fluoro-3'-cyanophenyl)-3-trifluoromethyl-1H-pyrazole-5-carboxylic acid；1-(4-fluoro-3-cyanophenyl)-3-trifluoromethyl-5-pyrazolecarboxylic acid；1-(3-cyano-4-fluorophenyl)-3-trifluoromethyl-5-hydroxycarbonyl pyrazole；1-(4-fluoro-3-cyano)phenyl-3-trifluoromethylpyrazole-5-carboxylic acid；1-(4-fluoro-3-cyanophenyl)-3-trifluoromethyl-5-hydroxycarbonylpyrazole；1-(3-Cyano-4-fluorophenyl)-3-trifluoromethyl-5-hydroxycarbonylpyrazole；2-(3-cyano-4-fluorophenyl)-5-(trifluoromethyl)pyrazole-3-carboxylic acid
• CAS: 209960-58-7
• 化学式: C₁₂H₅F₄N₃O₂
• 分子量: 299.184
• InChiKey: JJNADBOHSHJDJK-UHFFFAOYSA-N

物化性质

• 沸点：
  425.1±45.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(3-cyano-4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic Acid 在 四(三苯基膦)钯 、 氯化亚砜 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-(3-Cyano-4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (3-fluoro-2'-formyl-biphenyl-4-yl)-amide
  参考文献：
  名称：

  Aminobenzisoxazoles with biaryl P4 moieties as potent, selective, and orally bioavailable factor Xa inhibitors

  摘要：

  We have previously reported on a series of aminobenzisoxazoles as potent, selective, and orally bioavailable factor Xa inhibitors. which culminated in the discovery of razaxaban. Herein, we describe another approach to improve factor Xa inhibitory potency and pharmacokinetic profile by incorporating basic and water soluble functionalities on the terminal ring of the P4 biaryl group found ill our earlier Xa inhibitors. This approach resulted in a series of potent, selective, and orally bioavailable factor Xa inhibitors. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.010
• 作为产物：
  描述：

  5-氨基-2-氟苯腈 在 盐酸 、 ruthenium trichloride 、 sodium periodate 、 sodium nitrite 作用下， 以 四氯化碳 、 乙腈 为溶剂， 反应 36.5h， 生成 1-(3-cyano-4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic Acid
  参考文献：
  名称：

  Discovery of 1-(3‘-Aminobenzisoxazol-5‘-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2‘-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide Hydrochloride (Razaxaban), a Highly Potent, Selective, and Orally Bioavailable Factor Xa Inhibitor

  摘要：

  Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P(1) ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P(4) moiety led to compounds with enhanced permeability and reduced protein binding. The SAR and pharmacokinetic profile of this series of compounds is described herein. These efforts culminated in 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide (11d), a potent, selective, and orally bioavailable inhibitor of factor Xa. On the basis of its excellent in vitro potency and selectivity profile, high free fraction in human plasma, good oral bioavailability, and in vivo efficacy in antithrombotic models, the HCl salt of this compound was selected for clinical development as razaxaban (DPC 906, BMS-561389).

  DOI：

  10.1021/jm0497949

文献信息

• Substituted amino methyl factor Xa inhibitors
  申请人：——

  公开号：US20030212054A1

  公开（公告）日：2003-11-13

  The present application describes substituted-aminomethyl substituted compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了替代氨甲基取代化合物及其衍生物，或其药用盐形式，这些化合物可用作因子Xa的抑制剂。
• [EN] HUMAN PLASMA KALLIKREIN INHIBITORS<br/>[FR] INHIBITEURS DE LA KALLICRÉINE PLASMATIQUE HUMAINE
  申请人：BIOCRYST PHARM INC

  公开号：WO2015134998A1

  公开（公告）日：2015-09-11

  Disclosed are compounds of formula (I), as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.

  本文披露的是公式（I）的化合物及其药用盐。这些化合物是血浆激肽酶的抑制剂。还提供了包含本发明化合物的药物组合物，以及涉及使用这些化合物和组合物治疗和预防由不需要的血浆激肽酶活性特征的疾病和症状的方法。
• Guanidine mimics as factor Xa inhibitors
  申请人：DuPont Pharmaceuticals Company

  公开号：US06339099B1

  公开（公告）日：2002-01-15

  The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula I: or pharmaceutically acceptable salt forms thereof, wherein rings D—E represent guanidine mimics, which are useful as inhibitors of factor Xa.

  本申请描述了含氮杂环化合物及其衍生物的化学式I：或其药用可接受的盐形式，其中环D—E代表胍嘧啶模拟物，这些化合物可作为凝血因子Xa的抑制剂。
• Lactam-containing compounds and derivatives thereof as factor Xa inhibitors
  申请人：——

  公开号：US20030191115A1

  公开（公告）日：2003-10-09

  The present application describes lactam-containing compounds and derivatives thereof of Formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了具有Formula I的内酰胺含有化合物及其衍生物，或其药用可接受的盐形式，其中环P（如存在）是一个5-7成员碳环或杂环，环M是一个5-7成员碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa。
• LACTAM-CONTAINING COMPOUNDS AND DERIVATIVES THEREOF AS FACTOR XA INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：US20170050964A1

  公开（公告）日：2017-02-23

  The present application describes lactam-containing compounds and derivatives thereof of Formula I: P 4 —P-M-M 4 I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了公式I中含有内酰胺的化合物及其衍生物：P4—P-M-M4I或其药用盐形式，其中环P（如果存在）是一个5-7成员的碳环或杂环，环M是一个5-7成员的碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa。