(R)-1-(7-trifluoromethoxy-2,2-dimethylchroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea | 1221443-90-8

• 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: (R)-1-(7-trifluoromethoxy-2,2-dimethylchroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea
• 英文别名: N-[(4R)-2,2-dimethyl-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-N'-(3-methylisoquinolin-5-yl)urea；1-[(4R)-2,2-dimethyl-7-(trifluoromethoxy)-3,4-dihydrochromen-4-yl]-3-(3-methylisoquinolin-5-yl)urea
• CAS: 1221443-90-8
• 化学式: C₂₃H₂₂F₃N₃O₃
• 分子量: 445.441
• InChiKey: YJLGMMODESAVMW-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氨基-3-甲基异喹啉 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 (R)-1-(7-trifluoromethoxy-2,2-dimethylchroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea
  参考文献：
  名称：

  Discovery of (R)-1-(7-Chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): A Temperature-Neutral Transient Receptor Potential Vanilloid-1 (TRPV1) Antagonist with Analgesic Efficacy

  摘要：

  The synthesis and characterization of a series of selective, orally bioavailable 1-(chroman-4-yl)urea TRPV1 antagonists is described. Whereas first-generation antagonists that inhibit all modes of TRPV1 activation can elicit hyperthermia, the compounds disclosed herein do not elevate core body temperature in preclinical models and only partially block acid activation of TRPV1. Advancing the SAR of this series led to the eventual identification of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442, 52), an analogue that possesses excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents.

  DOI：

  10.1021/jm500916t

文献信息

• [EN] TRPV1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE TRPV1
  申请人：ABBOTT LAB

  公开号：WO2010045402A1

  公开（公告）日：2010-04-22

  Disclosed herein are compounds of formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文披露了式（I）的化合物，或其药用可接受的盐、溶剂化合物、前药、前药的盐或它们的组合，其中R1、R2、R3、R4和m在规范中有定义。还披露了包含这种化合物的组合物以及使用这种化合物和组合物治疗疾病和疾病的方法。
• TRPV1 ANTAGONISTS
  申请人：Gomtsyan Arthur R.

  公开号：US20100120846A1

  公开（公告）日：2010-05-13

  Disclosed herein are compounds of formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R 1 , R 2 , R 3 , R 4 , and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文揭示了式(I)的化合物，或其药学上可接受的盐、溶剂、前药盐、前药的盐或其组合物，其中R1、R2、R3、R4和m在规范中被定义。还揭示了包含这些化合物的组合物以及使用这些化合物和组合物治疗疾病和病症的方法。
• US8604053B2
  申请人：——

  公开号：US8604053B2

  公开（公告）日：2013-12-10
• US8609692B2
  申请人：——

  公开号：US8609692B2

  公开（公告）日：2013-12-17
• Discovery of (<i>R</i>)-1-(7-Chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): A Temperature-Neutral Transient Receptor Potential Vanilloid-1 (TRPV1) Antagonist with Analgesic Efficacy
  作者：Eric A. Voight、Arthur R. Gomtsyan、Jerome F. Daanen、Richard J. Perner、Robert G. Schmidt、Erol K. Bayburt、Stanley DiDomenico、Heath A. McDonald、Pamela S. Puttfarcken、Jun Chen、Torben R. Neelands、Bruce R. Bianchi、Ping Han、Regina M. Reilly、Pamela H. Franklin、Jason A. Segreti、Richard A. Nelson、Zhi Su、Andrew J. King、James S. Polakowski、Scott J. Baker、Donna M. Gauvin、LaGeisha R. Lewis、Joseph P. Mikusa、Shailen K. Joshi、Connie R. Faltynek、Philip R. Kym、Michael E. Kort

  DOI：10.1021/jm500916t

  日期：2014.9.11

  The synthesis and characterization of a series of selective, orally bioavailable 1-(chroman-4-yl)urea TRPV1 antagonists is described. Whereas first-generation antagonists that inhibit all modes of TRPV1 activation can elicit hyperthermia, the compounds disclosed herein do not elevate core body temperature in preclinical models and only partially block acid activation of TRPV1. Advancing the SAR of this series led to the eventual identification of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442, 52), an analogue that possesses excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents.