1-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one | 630382-44-4

• 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-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one
• 英文别名: 1-(4-methoxyphenyl)-3-trifluoromethyl-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one；1-(4-methoxyphenyl)-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one；1-(4-Methoxy-phenyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one；1-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-4H-pyrazolo[3,4-c]pyridin-7-one
• CAS: 630382-44-4
• 化学式: C₁₄H₁₂F₃N₃O₂
• 分子量: 311.263
• InChiKey: ZTMREVJGRDWWBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one 在 sodium tetrahydroborate 、 copper(l) iodide 、 1,10-菲罗啉 、 sodium acetate 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 pyridinium chlorochromate 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 10.66h， 生成 1-(4-methoxyphenyl)-6-(4-(1-(2-(pyrrolidin-1-yl)ethyl)cyclopropyl)phenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one
  参考文献：
  名称：

  Highly efficacious factor Xa inhibitors containing α-substituted phenylcycloalkyl P4 moieties

  摘要：

  We previously disclosed a series of highly potent FXa inhibitors bearing alpha-substituted ((CH2NRR2)-R-1) phenylcyclopropyl P4 moieties in the pyrazolodihydropyridone core system. Herein, we describe our continuous SAR efforts in this series. Effects of the C-3 substitution of the pyrazolodihydropyridone core and the alpha-substitution (R group) of the cyclopropyl ring on FXa binding affinity (FXa K-i), human plasma anticoagulant activity (PT EC2x) and permeability are discussed. A set of compounds obtained from optimization of the R group and the C-3 substituent were orally bioavailable in dogs. Furthermore, representative compounds were highly efficacious in the rabbit arterio-venous shunt thrombosis model (EC(50)s = 29-81 nM). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.049
• 作为产物：
  描述：

  5,6-二氢-3-(4-吗啉基)-2(1H)-吡啶酮 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 18.0h， 生成 1-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one
  参考文献：
  名称：

  HYDRAZINE COMPOUND AS BLOOD COAGULATION FACTOR XA INHIBITOR

  摘要：

  公开号：

  EP3147283B1

文献信息

• [EN] 1,1-DISUBSTITUTED CYCLOALKYL DERIVATIVES AS FACTOR XA INHIBITORS<br/>[FR] DERIVES CYCLOALKYLES 1,1-DISUBSTITUES UTILISES EN TANT QU'INHIBITEURS DU FACTEUR XA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2003099276A1

  公开（公告）日：2003-12-04

  The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了1,1-二取代环烷基化合物及其衍生物，或其药用可接受的盐形式，这些化合物对于Xa因子的抑制剂具有用处。
• Linear chain substituted monocyclic and bicyclic derivatives as factor Xa inhibitors
  申请人：——

  公开号：US20040214808A1

  公开（公告）日：2004-10-28

  The present application describes linear chain substituted monocyclic and bicyclic compounds and derivatives thereof of Formula I: P 4 -P-M-M 4 I or pharmaceutically acceptable salt forms thereof, P-M are rings substituted by a linear group. 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：P4-P-M-M4I的线性链取代的单环和双环化合物及其衍生物，或其药学上可接受的盐形式，其中P-M是由线性基团取代的环。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的抑制剂。
• 1,1-Disubstituted cycloalkyl derivatives as factor Xa inhibitors
  申请人：——

  公开号：US20040254158A1

  公开（公告）日：2004-12-16

  The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了1,1-二取代环烷基化合物及其衍生物，或其药学上可接受的盐形式，这些化合物可用作因子Xa的抑制剂。
• 1, 1-disubstituted cycloalkyl derivatives as factor Xa inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US07312214B2

  公开（公告）日：2007-12-25

  The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了1,1-二取代环烷基化合物及其衍生物或其药学上可接受的盐形式，它们可用作凝血因子Xa的抑制剂。
• HYDRAZINE COMPOUND AS BLOOD COAGULATION FACTOR Xa INHIBITOR
  申请人：North China Pharmaceutical Company., Ltd.

  公开号：EP3147283A1

  公开（公告）日：2017-03-29

  Provided is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein X is selected from a 3-9 membered carbon ring or its phenyl ring, and a 4-10 membered heterocyclic ring or its benzo ring; Y and Z are independently selected from 4-9 membered saturated heterocyclic rings respectively; RI-3 are independently selected from H, F, Cl, Br, I, CN, OH, SH,NH2, CHO, COOH respectively, or selected from C1-10 alkyls or heteroalkyls optionally substituted by R01, C3-10 alkyls ring hydrocarbon groups or heterocyclic hydrocarbon groups, C1-10 alkyls or heteroalkyls substituted by C3-10 ring hydrocarbon groups or heterocyclic hydrocarbon group. The compound can be used as an anticoagulant for treating and preventing thrombotic disorders, and can meet the real needs of selectivity and a potent inhibitor for coagulation Xa.

  提供的是式(I)化合物或其药学上可接受的盐，其中X选自3-9个成员的碳环或其苯基环，以及4-10个成员的杂环或其苯环；Y和Z分别独立地选自4-9个成员的饱和杂环；RI-3 分别独立地选自 H、F、Cl、Br、I、CN、OH、SH、NH2、CHO、COOH，或选自任选被 R01 取代的 C1-10 烷基或杂烷基、C3-10 烷基环烃基团或杂环烃基团、被 C3-10 环烃基团或杂环烃基团取代的 C1-10 烷基或杂烷基。该化合物可用作治疗和预防血栓性疾病的抗凝剂，能满足对凝血 Xa 的选择性和强效抑制剂的实际需要。