1-(4-methoxyphenyl)-3-(methylsulfonyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one | 630383-13-0

• 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-(methylsulfonyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one
• 英文别名: 1-(4-methoxyphenyl)-3-(methylsulfonyl) 1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one；1-(4-methoxyphenyl)-3-methylsulfonyl-5,6-dihydro-4H-pyrazolo[3,4-c]pyridin-7-one
• CAS: 630383-13-0
• 化学式: C₁₄H₁₅N₃O₄S
• 分子量: 321.357
• InChiKey: QUGQBLJFETZNDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-3-(methylsulfonyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one 在 copper(l) iodide 、 1,10-菲罗啉 、 硼烷 、 水 、 sodium acetate 、 sodium cyanoborohydride 、 potassium carbonate 、 pyridinium chlorochromate 、 zinc(II) chloride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 6-{4-[1,1-dimethyl-2-(4-morpholinyl)ethyl]phenyl}-1-(4-methoxyphenyl)-3-(methylsulfonyl)-1,4,5,7-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one
  参考文献：
  名称：

  Orally bioavailable factor Xa inhibitors containing alpha-substituted gem-dimethyl P4 moieties

  摘要：

  In an effort to identify a potential back-up to apixaban (Eliquie (R)), we explored a series of diversified P4 moieties. Several analogs with substituted gem-dimethyl moieties replacing the terminal lactam of apixaban were identified which demonstrated potent FXa binding affinity (FXa K-i), good human plasma anticoagulant activity (PT EC2x), cell permeability, and oral bioavailability. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.101
• 作为产物：
  描述：

  (Z)-N'-(4-methoxyphenyl)-1-(methylsulfonyl)methanehydrazonoyl chloride 、 3-氯-5,6-二氢-2(1h)-吡啶酮 以 甲苯 为溶剂， 以31%的产率得到1-(4-methoxyphenyl)-3-(methylsulfonyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one
  参考文献：
  名称：

  [EN] 1,1-DISUBSTITUTED CYCLOALKYL DERIVATIVES AS FACTOR XA INHIBITORS
  [FR] DERIVES CYCLOALKYLES 1,1-DISUBSTITUES UTILISES EN TANT QU'INHIBITEURS DU FACTEUR XA

  摘要：

  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。

  公开号：

  WO2003099276A1

文献信息

• 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。
• Highly efficacious factor Xa inhibitors containing α-substituted phenylcycloalkyl P4 moieties
  作者：Jennifer X. Qiao、Sarah R. King、Kan He、Pancras C. Wong、Alan R. Rendina、Joseph M. Luettgen、Baomin Xin、Robert M. Knabb、Ruth R. Wexler、Patrick Y.S. Lam

  DOI：10.1016/j.bmcl.2008.11.049

  日期：2009.1

  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.
• EP1505966A4
  申请人：——

  公开号：EP1505966A4

  公开（公告）日：2006-08-30
• 1,1-DISUBSTITUTED CYCLOALKYL DERIVATIVES AS FACTOR XA INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1505966A1

  公开（公告）日：2005-02-16