(4R)-8-chloro-7-fluoro-2,2-dimethylchroman-4-amine | 1221444-70-7

• 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: (4R)-8-chloro-7-fluoro-2,2-dimethylchroman-4-amine
• 英文别名: (R)-8-chloro-7-fluoro-2,2-dimethyl-chroman-4-ylamine；(R)-8-chloro-7-fluoro-2,2-dimethylchroman-4-amine；(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-amine
• CAS: 1221444-70-7
• 化学式: C₁₁H₁₃ClFNO
• 分子量: 229.682
• InChiKey: CGTPNUOWDUWKMW-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,2-二氟-苯并[1,3]二氧代l-5-基)-环丙烷羧酸 、 (4R)-8-chloro-7-fluoro-2,2-dimethylchroman-4-amine 在 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 N,N-二甲基乙酰胺 为溶剂， 以19%的产率得到N-[(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxamide
  参考文献：
  名称：

  Discovery of 4-[(2R,4R)-4-({[1-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-7-(difluoromethoxy)-3,4-dihydro-2H-chromen-2-yl]benzoic Acid (ABBV/GLPG-2222), a Potent Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Corrector for the Treatment of Cystic Fibrosis

  摘要：

  Cystic fibrosis (CF) is a multiorgan disease of the lungs, sinuses, pancreas, and gastrointestinal tract that is caused by a dysfunction or deficiency of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an epithelial anion channel that regulates salt and water balance in the tissues in which it is expressed. To effectively treat the most prevalent patient population (F508del mutation), two biomolecular modulators are required: correctors to increase CFTR levels at the cell surface, and potentiators to allow the effective opening of the CFTR channel. Despite approved potentiator and potentiator/corrector combination therapies, there remains a high need to develop more potent and efficacious correctors. Herein, we disclose the discovery of a highly potent series of CFTR correctors and the structureactivity relationship (SAR) studies that guided the discovery of ABBV/GLPG-2222 (22), which is currently in clinical trials in patients harboring the F508del CFTR mutation on at least one allele.

  DOI：

  10.1021/acs.jmedchem.7b01339
• 作为产物：
  描述：

  (R)-tert-butyl 8-chloro-7-fluoro-2,2-dimethylchroman-4-ylcarbamate 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 生成 (4R)-8-chloro-7-fluoro-2,2-dimethylchroman-4-amine
  参考文献：
  名称：

  [EN] TRPV1 ANTAGONISTS
  [FR] ANTAGONISTES DE TRPV1

  摘要：

  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。

  公开号：

  WO2010045402A1

文献信息

• TRPV1 Antagonists
  申请人：AbbVie Inc.

  公开号：US20130158067A1

  公开（公告）日：2013-06-20

  Disclosed herein are compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein X 1 , L, R x , R y , R z , A, m, n, p, q, s, and positions a and b are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  披露于此的是公式（I）的化合物： 或其药用可接受的盐，其中X 1 ，L，R x ，R y ，R z ，A，m，n，p，q，s，以及位置a和b如说明书所述定义。还披露了包含此类化合物的组合物以及使用此类化合物和组合物治疗状况和失调的方法。
• TRPV1 ANTAGONISTS
  申请人：AbbVie Inc.

  公开号：US20130345255A1

  公开（公告）日：2013-12-26

  Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, prodrugs, or combinations thereof, wherein X 1 , L, R x , R y , R z , R 1 , R 2 , A, m, n, p, q, and r are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文披露了具有以下结构的化合物（I）或药用盐、前药或其组合物，其中X1、L、Rx、Ry、Rz、R1、R2、A、m、n、p、q和r在规范中有定义。还披露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疾病的方法。
• TRPV1 antagonists
  申请人：AbbVie Inc.

  公开号：US08859584B2

  公开（公告）日：2014-10-14

  Disclosed herein are compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein X1, L, Rx, Ry, Rz, A, m, n, p, q, s, and positions a and b are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文揭示了以下式子(I)的化合物，或其药学上可接受的盐，其中X1，L，Rx，Ry，Rz，A，m，n，p，q，s和位置a和b如规范中定义。本文还揭示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。
• SUBSTITUTED CHROMANES AND METHOD OF USE
  申请人：AbbVie Inc.

  公开号：US20160120841A1

  公开（公告）日：2016-05-05

  The invention provides for compounds of formula (I) wherein R 1 , X, Y, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , m, and R″ have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjögren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

  本发明提供了以下式子(I)的化合物，其中R1、X、Y、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、m和R″的任何一个取值均符合规范要求，并且其药学上可接受的盐，在治疗由CFTR介导和调节的疾病和病状中具有作用，包括囊性纤维化、Sjögren综合征、胰腺功能不全、慢性阻塞性肺病和慢性阻塞性气道疾病。还提供了由一个或多个式(I)化合物组成的制药组合物。
• Substituted Chromanes and Method of Use
  申请人：AbbVie S.à.r.l.

  公开号：US20190127356A1

  公开（公告）日：2019-05-02

  The invention provides for compounds of formula (I) wherein R 1 , X, Y, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , m, and R″ have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjögren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).