2,4-dichloro-6-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]-1,3,5-triazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2,4-dichloro-6-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]-1,3,5-triazine
• 英文别名: 2,4-Dichloro-6-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)-1,3,5-triazine；2,4-dichloro-6-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)-1,3,5-triazine
• 化学式: C₆HCl₂F₆N₃O
• mdl: MFCD32264533
• 分子量: 315.99
• InChiKey: RLUITKZEDAVPDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-6-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]-1,3,5-triazine 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 N,N-diethyl-N'-(3-fluorophenyl)-6-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]-1,3,5-triazine-2,4-diamine
  参考文献：
  名称：

  Nanomolar-Potency Aminophenyl-1,3,5-triazine Activators of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel for Prosecretory Therapy of Dry Eye Diseases

  摘要：

  Dry eye disorders are a significant health problem for which limited therapeutic options are available. CFTR is a major prosecretory chloride channel at the ocular surface. We previously identified, by high-throughput screening, aminophenyl-1,3,5-triazine CFTRact-K089 (1) that activated CFTR with EC50 approximate to 250 nM, which when delivered topically increased tear fluid secretion in mice and showed efficacy in an experimental dry eye model. Here, functional analysis of aminophenyl-1,3,5-triazine analogs elucidated structure-activity relationships for CFTR activation and identified substantially more potent analogs than 1. The most potent compound, 12, fully activated CFTR chloride conductance with EC50 approximate to 30 nM, without causing cAMP or calcium elevation. 12 was rapidly metabolized by hepatic microsomes, which supports its topical use. Single topical administration of 25 pmol of 12 increased tear volume in wild-type mice with sustained action for 8 h and was without effect in CFTR-deficient mice. Topically delivered 12 may be efficacious in human dry eye diseases.

  DOI：

  10.1021/acs.jmedchem.6b01792
• 作为产物：
  描述：

  三聚氯氰 、 六氟异丙醇 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以62%的产率得到2,4-dichloro-6-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]-1,3,5-triazine
  参考文献：
  名称：

  [EN] CFTR REGULATORS AND METHODS OF USE THEREOF
  [FR] RÉGULATEURS CFTR ET LEURS MÉTHODES D'UTILISATION

  摘要：

  本文提供了激活CFTR的化合物以及治疗便秘、干眼症和其他疾病和障碍的方法。

  公开号：

  WO2017112951A1

文献信息

• METHOD FOR PRODUCING LACTAM COMPOUND
  申请人：Shibamoto Akihiro

  公开号：US20100029931A1

  公开（公告）日：2010-02-04

  Disclosed is a method for industrially efficiently producing a lactam compound having 8 to 15 carbon atoms at low cost by allowing a rearrangement reaction of a cyclic oxime compound to proceed without causing large amounts of by-products such as ammonium sulfate. [Solving Means] Disclosed is a method for producing a lactam compound, which includes the step of rearranging a cyclic oxime compound in a nonpolar solvent B in the presence of an aromatic compound A to give the lactam compound, in which the aromatic compound A has a leaving group bonded to a carbon atom constituting its aromatic ring and contains, as an atom constituting the aromatic ring, a heteroatom, or a carbon atom bonded with an electron-withdrawing group, the cyclic oxime compound is represented by following Formula (1): wherein “m” denotes an integer of 7 to 14, and the lactam compound is represented by following Formula (2): wherein “m” is as defined above.

  揭示了一种工业高效地以低成本生产具有8至15个碳原子的内酰胺化合物的方法，通过使环氧肟化合物的重排反应在不产生大量副产物如硫酸铵的情况下进行。 【解决手段】揭示了一种生产内酰胺化合物的方法，包括在非极性溶剂B中在芳香化合物A存在下重排环氧肟化合物的步骤，以得到内酰胺化合物，其中芳香化合物A具有与构成其芳香环的碳原子结合的离去基团，并且包含作为构成芳香环的原子，一个杂原子，或者与带有电子吸引基团的碳原子结合，环氧肟化合物由以下式（1）表示：其中“m”表示一个整数，范围为7至14，内酰胺化合物由以下式（2）表示：其中“m”如上所定义。
• [EN] CFTR REGULATORS AND METHODS OF USE THEREOF<br/>[FR] RÉGULATEURS CFTR ET LEURS MÉTHODES D'UTILISATION
  申请人：UNIV CALIFORNIA

  公开号：WO2017112951A1

  公开（公告）日：2017-06-29

  Provided herein are compounds that activate CFTR and methods for treating constipation, dry eye disorders, and other diseases and disorders.

  本文提供了激活CFTR的化合物以及治疗便秘、干眼症和其他疾病和障碍的方法。
• PROCESS FOR PRODUCTION OF AMIDES OR LACTAMS
  申请人：Daicel Chemical Industries, Ltd.

  公开号：EP2006283A9

  公开（公告）日：2009-07-15

  An amide or lactam is produced by conducting a rearrangement of a corresponding oxime compound in the presence of a cyclic compound containing a structure represented by following Formula (1) as a ring constituent and a fluorinated alcohol: wherein Z represents a halogen atom or an -OR group, where R represents an organic group. Z is preferably chlorine atom. Exemplary fluorinated alcohols include fluorine-containing branched-chain aliphatic alcohols represented by following Formula (3): wherein Rf1 and Rf2 may be the same as or different from each other and each represent a perfluoroalkyl group having one to eight carbon atoms; and "n" denotes an integer of 0 to 8. According to this process, amides or lactams can be simply produced in high yields without causing large amounts of by-products.

  通过在含有以下式（1）所代表的结构的环组分和氟化醇的存在下对相应的肟化合物进行重排，可以产生酰胺或内酰胺：其中Z代表卤素原子或-OR基团，其中R代表有机基团。Z最好是氯原子。示例氟化醇包括以下式（3）所代表的含氟支链脂肪醇：其中Rf1和Rf2可以相同也可以不同，每个代表具有一至八个碳原子的全氟烷基基团；“n”表示0至8的整数。根据这个过程，可以简单地高产率地生产酰胺或内酰胺，而不产生大量副产物。
• PROCESS FOR PRODUCING AMIDE OR LACTAM
  申请人：Daicel Chemical Industries, Ltd.

  公开号：EP2301918A1

  公开（公告）日：2011-03-30

  A process produces an amide or lactam by subjecting an oxime compound to rearrangement in a solvent in the presence of: at least one catalyst selected from the group consisting of an aromatic compound (A1) containing a leaving group bound to a carbon atom constituting the aromatic ring, the aromatic ring including, as a constitutive atom thereof, a heteroatom or including, as a constitutive atom thereof, a carbon atom bound to an electron-withdrawing group, and a compound (A2) containing a structure of Formula (1): -G-LA (1) wherein G represents P, N, S, B or Si atom; and LA represents a leaving group, wherein G is bound to one or more atoms or groups in addition to LA; and a co-catalyst including a halogen-containing organic acid, to give the corresponding amide or lactam, wherein, when the aromatic compound (A1) alone is used as the catalyst, the solvent is at least one solvent selected typically from hydrocarbon solvents. The production process can yield amides or lactams simply in high yields without causing large amounts of by-products such as ammonium sulfate.

  一种生产酰胺或内酰胺的工艺，其方法是使肟化合物在以下物质存在下在溶剂中进行重排：至少一种催化剂，该催化剂选自由以下组成的组芳香化合物(A1)，该芳香化合物含有与构成芳香环的碳原子结合的离去基团，芳香环包括作为其构成原子的杂原子或包括作为其构成原子的与抽电子基团结合的碳原子，以及含有式(1)结构的化合物(A2)：-G-LA(1)，其中 G 代表 P、N、S、B 或 Si 原子；LA 代表离去基团，其中 G 除 LA 外还与一个或多个原子或基团结合；以及助催化剂，包括含卤素的有机酸，以得到相应的酰胺或内酰胺，其中，当单独使用芳香族化合物（A1）作为催化剂时，溶剂为通常选自烃溶剂的至少一种溶剂。该生产工艺可简单高产地得到酰胺或内酰胺，而不会产生大量副产物，如硫酸铵。
• CFTR regulators and methods of use thereof
  申请人：The Regents of the University of California

  公开号：US10604492B2

  公开（公告）日：2020-03-31

  Provided herein are compounds that activate CFTR and methods for treating constipation, dry eye disorders, and other diseases and disorders.

  本文提供了激活 CFTR 的化合物和治疗便秘、干眼症及其他疾病和失调的方法。