(1S, 2R)-3-chloro-1H-indole-6-carboxylic acid {1-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-indan-2-yl}-amide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (1S, 2R)-3-chloro-1H-indole-6-carboxylic acid {1-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-indan-2-yl}-amide
• 英文别名: 3-chloro-N-((1S,2R)-1-(4-(2-oxopyridin-1(2H)-yl)benzamido)-2,3-dihydro-1H-inden-2-yl)-1H-indole-6-carboxamide；3-chloro-N-[(1S,2R)-1-[[4-(2-oxopyridin-1-yl)benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]-1H-indole-6-carboxamide
• 化学式: C₃₀H₂₃ClN₄O₃
• 分子量: 522.991
• InChiKey: ADBZQJUYCOQPFF-IAPPQJPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  94.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1S,2R)-2-aminoindanol 在 palladium on activated charcoal N-甲基吗啉 、 sodium azide 、 氢气 、 sodium methylate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (1S, 2R)-3-chloro-1H-indole-6-carboxylic acid {1-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-indan-2-yl}-amide
  参考文献：
  名称：

  Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications

  摘要：

  We previously reported a series of enantiopure cis-(1 R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa K; of 0.50 nM, PT EC2x of 2.1 mu M in human plasma, bioavailability of 25% and t z of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.020

文献信息

• US7205318B2
  申请人：——

  公开号：US7205318B2

  公开（公告）日：2007-04-17
• Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications
  作者：Jennifer X. Qiao、Tammy C. Wang、Gren Z. Wang、Daniel L. Cheney、Kan He、Alan R. Rendina、Baomin Xin、Joseph M. Luettgen、Robert M. Knabb、Ruth R. Wexler、Patrick Y.S. Lam

  DOI：10.1016/j.bmcl.2007.07.020

  日期：2007.9

  We previously reported a series of enantiopure cis-(1 R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa K; of 0.50 nM, PT EC2x of 2.1 mu M in human plasma, bioavailability of 25% and t z of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented. (c) 2007 Elsevier Ltd. All rights reserved.