(S)-2-(9-fluoro-2-(4-(morpholine-4-carbonyl)phenyl)-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid | 1620483-76-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (S)-2-(9-fluoro-2-(4-(morpholine-4-carbonyl)phenyl)-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid
• 英文别名: 2-[(5S)-9-fluoro-2-[4-(morpholine-4-carbonyl)phenyl]-5H-chromeno[2,3-b]pyridin-5-yl]-2-methylpropanoic acid
• CAS: 1620483-76-2
• 化学式: C₂₇H₂₅FN₂O₅
• 分子量: 476.504
• InChiKey: AFUROCXMWYAWBE-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-2-(9-fluoro-2-(4-(morpholine-4-carbonyl)phenyl)-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid 在 sodium hexamethyldisilazane 、 氯化铵 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-acetyl-2-[(5S)-9-fluoro-2-[4-(morpholine-4-carbonyl)phenyl]-5H-chromeno[2,3-b]pyridin-5-yl]-2-methylpropanamide
  参考文献：
  名称：

  Discovery of acylurea isosteres of 2-acylaminothiadiazole in the azaxanthene series of glucocorticoid receptor agonists

  摘要：

  Acylureas and acyclic imides are found to be excellent isosteres for 2-acylamino-1,3,4-thiadiazole in the azaxanthene-based series of glucocorticoid receptor (GR) agonists. The results reported herein show that primary acylureas maintain high affinity and selectivity for GR while providing improved CYP450 inhibition and pharmacokinetic profile over 2-acylamino-1,3,4-thiadiazoles. General methods for synthesis of a variety of acylureas and acyclic imides from a carboxylic acid were utilized and are described. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.010
• 作为产物：
  描述：

  4-羧基苯硼酸频那醇酯 在 potassium phosphate monohydrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.25h， 生成 (S)-2-(9-fluoro-2-(4-(morpholine-4-carbonyl)phenyl)-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid
  参考文献：
  名称：

  [EN] IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR
  [FR] DÉRIVÉS IMIDE ET ACYLURÉE UTILISÉS COMME MODULATEURS DU RÉCEPTEUR DE GLUCOCORTICOÏDES

  摘要：

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-KB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、二对映体或互变异构体，或其药用可接受盐，其中变量如规范中所定义。

  公开号：

  WO2015027021A1

文献信息

• [EN] IMIDAZOLE-DERIVED MODULATORS OF THE GLUCOCORTICOID RECEPTOR<br/>[FR] MODULATEURS DU RÉCEPTEUR GLUCOCORTICOÏDE DÉRIVÉS DE L'IMIDAZOLE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015027015A1

  公开（公告）日：2015-02-26

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-kB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-kB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、二对映体或互变异构体，或其前药酯，或其药用可接受盐，其中变量如规范中所定义。
• IMIDAZOLE-DERIVED MODULATORS OF THE GLUCOCORTICOID RECEPTOR
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160200728A1

  公开（公告）日：2016-07-14

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-kB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

  提供了一些新型非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-kB活性调节相关的疾病或疾病，包括代谢性、炎症和免疫性疾病或疾病，其结构为公式（I）：其对映体，二对映异构体或互变异构体，或其前药酯，或其药学上可接受的盐，其中变量如规范中所定义。
• Improving the Pharmacokinetic and CYP Inhibition Profiles of Azaxanthene-Based Glucocorticoid Receptor Modulators—Identification of (<i>S</i>)-5-(2-(9-Fluoro-2-(4-(2-hydroxypropan-2-yl)phenyl)-5<i>H</i>-chromeno[2,3-<i>b</i>]pyridin-5-yl)-2-methylpropanamido)-<i>N</i>-(tetrahydro-2<i>H</i>-pyran-4-yl)-1,3,4-thiadiazole-2-carboxamide (BMS-341)
  作者：Michael G. Yang、T. G. Murali Dhar、Zili Xiao、Hai-Yun Xiao、James J.-W. Duan、Bin Jiang、Michael A. Galella、Mark Cunningham、Jinhong Wang、Sium Habte、David Shuster、Kim W. McIntyre、Julie Carman、Deborah A. Holloway、John E. Somerville、Steven G. Nadler、Luisa Salter-Cid、Joel C. Barrish、David S. Weinstein

  DOI：10.1021/acs.jmedchem.5b00257

  日期：2015.5.28

  An empirical approach to improve the microsomal stability and CYP inhibition profile of lead compounds 1a and 1b led to the identification of 5 (BMS-341) as a dissociated glucocorticoid receptor modulator. Compound 5 showed significant improvements in pharmacokinetic properties and, unlike compounds 1a-b, displayed a linear, dose-dependent pharmacokinetic profile in rats. When tested in a chronic model of adjuvant-induced arthritis in rat, the ED50 of 5 (0.9 mg/kg) was superior to that of both 1a and 1b (8 and 17 mg/kg, respectively).
• IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160185776A1

  公开（公告）日：2016-06-30

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF- K B activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.
• US9593113B2
  申请人：——

  公开号：US9593113B2

  公开（公告）日：2017-03-14