(R)-1-(7-chloro-2,2-bis(fluoromethyl)-chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea | 1221443-94-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (R)-1-(7-chloro-2,2-bis(fluoromethyl)-chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea
• 英文别名: (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea；A-1165442；N-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-N'-(3-methylisoquinolin-5-yl)urea；1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydrochromen-4-yl]-3-(3-methylisoquinolin-5-yl)urea
• CAS: 1221443-94-2
• 化学式: C₂₂H₂₀ClF₂N₃O₂
• 分子量: 431.87
• InChiKey: VJJGAJAUECQWSZ-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  63.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-甲基-5-硝基异喹啉 在 吡啶 、 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~25.0 ℃ 、308.18 kPa 条件下， 反应 23.0h， 生成 (R)-1-(7-chloro-2,2-bis(fluoromethyl)-chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea
  参考文献：
  名称：

  色胺酮通过叔丁烷亚磺酰胺定向还原胺的不对称合成TRPV1拮抗剂。

  摘要：

  已经开发了权宜的TRPV1拮抗剂1的不对称合成物，并已在多千克规模上得到证明。到1的实现途径在此进行了详细说明，其特征在于以下关键转换：安装苯并二氢吡喃酮的羟醛-环脱水序列和辅助介导的非对映选择性还原胺化反应。

  DOI：

  10.1021/op400184f

文献信息

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

  公开号：WO2010045401A1

  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。
• 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.
• NOVEL TREATMENT FOR HOT FLUSHES
  申请人：Dignity Health

  公开号：US20200147014A1

  公开（公告）日：2020-05-14

  Disclosed herein are methods for treating hot flushes in a subject. In one embodiment, treating hot flushes includes administering to a subject in need of such treatment, a therapeutically effective amount of a transient receptor potential channel (TRP channel) blocker or a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for amelioration, alleviation, or prevention of the thermal discomfort in hot flushes, comprising: selecting a subject in need of treatment for hot flushes, administering to the subject a therapeutically effective amount of a TRP channel blocker, such as a TRPV1 blocker, or a pharmaceutically acceptable salt thereof.
• CAPSAICIN AND TRPV1 MODULATOR COMBINATIONS AND METHODS OF USE THEREOF
  申请人：Pano Therapeutics, Inc.

  公开号：US20220098143A1

  公开（公告）日：2022-03-31

  Provided herein are combinations of capsaicin and TrpV1 modulators that are useful for treating capsaicin-responsive diseases or disorders.