1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-5-(2'-furanyl)pyrazole | 218301-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-5-(2'-furanyl)pyrazole
• 英文别名: 5-(5-(furan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzonitrile；1-(3-cyano-4-fluoro-phenyl)-3-trifluoromethyl-5-(furan-2-yl)-pyrazole；1-(4-fluoro-3-cyanophenyl)-3-trifluoromethyl-5-(furan-2-yl)-pyrazole；1-(4-fluoro-3-cyanophenyl)-3-trifluoromethyl-5-(2-furyl) pyrazole；1-(3-cyano-4-fluoro-phenyl)-3-trifluoromethyl-5-(2-furyl) pyrazole；1-(4-Fluoro-3-cyanophenyl)-3-trifluoromethyl-5-(2-furyl)pyrazole；2-fluoro-5-[5-(furan-2-yl)-3-(trifluoromethyl)pyrazol-1-yl]benzonitrile
• CAS: 218301-47-4
• 化学式: C₁₅H₇F₄N₃O
• 分子量: 321.234
• InChiKey: HVYCCVDJGAJOBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  54.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-5-(2'-furanyl)pyrazole 在 ruthenium trichloride 、 sodium periodate 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氯化碳 、 二氯甲烷 、 乙腈 为溶剂， 反应 13.5h， 生成 methyl 1-(4'-fluoro-3'-cyanophenyl)-3-trifluoromethyl-5-pyrazolecarboxylic acid ester
  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
• 作为产物：
  描述：

  2-氟-5-硝基苯腈 在 盐酸 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 乙酸乙酯 为溶剂， 反应 28.0h， 生成 1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-5-(2'-furanyl)pyrazole
  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

• [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。
• Palladium-catalyzed cyanation reactions of aryl chlorides
  作者：Fuqiang Jin、Pat N Confalone

  DOI：10.1016/s0040-4039(00)00384-1

  日期：2000.4

  discovered an efficient cyanation of aryl chlorides which employs Pd2(dba)3, dppf and Zn as the catalyst and Zn(CN)2 as the cyanide source. Both electron-deficient and electron-rich aryl chlorides are effectively cyanated under these conditions. This discovery represents the first successful palladium-catalyzed cyanation of both electron-deficient and electron-rich aryl chlorides.

  我们发现使用Pd 2（dba）3，dppf和Zn作为催化剂和Zn（CN）2作为氰化物源的芳基氯化物的有效氰化。在这些条件下，缺电子的和富电子的芳基氯化物均被有效地氰化。这一发现代表了贫电子和富电子的芳基氯化物首次成功的钯催化氰化反应。
• Novel N-[4- (1H-imidazol-1-yl) -2-fluorophenyl ] -3- (trifluoromethyl) -1H-pyrazole-5-carboxamides as factor Xa inhibitors
  申请人：——

  公开号：US20030144287A1

  公开（公告）日：2003-07-31

  The present application describes N-[4-(1H-imidazol-1-yl)-2-fluorophenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides and derivatives thereof of, which are useful as inhibitors of factor Xa.

  本申请描述了N-[4-(1H-咪唑-1-基)-2-氟苯基]-3-(三氟甲基)-1H-吡唑-5-甲酰胺及其衍生物，这些化合物可作为因子Xa的抑制剂。
• [EN] NOVEL GUANIDINE MIMICS AS FACTOR Xa INHIBITORS<br/>[FR] NOUVEAUX IMITATEURS DE GUANIDINE UTILISES EN TANT QU'INHIBITEURS DU FACTEUR Xa
  申请人：DU PONT PHARMACEUTICALS COMPANY

  公开号：WO1998057951A1

  公开（公告）日：1998-12-23

  (EN) 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.(FR) Cette invention concerne des composés hétéroaromatiques contenant de l'azote et des dérivés de ces derniers de formule (I) ou des formes de sel pharmaceutiquement acceptables de ces derniers. Dans la formule les cycles D-E représentent des imitateurs de guanidine qui sont utiles en tant qu'inhibiteurs du facteur Xa.

  本申请描述了含氮杂环和其衍生物的化合物，其化学式为（I）或其药学上可接受的盐形式，其中环D-E代表胍基模拟物，可用作因子Xa的抑制剂。