2-(3,5-二氯-4-吡啶基)-1-(2-羟基-3,4-二甲氧基苯基)乙酮 | 1035571-27-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(3,5-二氯-4-吡啶基)-1-(2-羟基-3,4-二甲氧基苯基)乙酮
• 英文名称: 2-(3,5-dichloro-4-pyridinyl)-1-(2-hydroxy-3,4-dimethoxyphenyl)ethanone
• 英文别名: 2-(3,5-dichloropyridin-4-yl)-1-(2-hydroxy-3,4-dimethoxyphenyl)ethanone；2-(3,5-Dichloro-pyridin-4-yl)-1-(2-hydroxy-3,4-dimethoxy-phenyl)-ethanone
• CAS: 1035571-27-7
• 化学式: C₁₅H₁₃Cl₂NO₄
• 分子量: 342.179
• InChiKey: IRKBYACLGSSVDO-UHFFFAOYSA-N

物化性质

• 沸点：
  478.9±40.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3,5-二氯-4-吡啶基)-1-(2-羟基-3,4-二甲氧基苯基)乙酮 在 potassium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 2-{6-[2-(3,5-dichloropyridin-4-yl)acetyl]-2,3-dimethoxyphenoxy}-N-propylacetamide
  参考文献：
  名称：

  Discovery and Early Clinical Development of 2-{6-[2-(3,5-Dichloro-4-pyridyl)acetyl]-2,3-dimethoxyphenoxy}-N-propylacetamide (LEO 29102), a Soft-Drug Inhibitor of Phosphodiesterase 4 for Topical Treatment of Atopic Dermatitis

  摘要：

  Development of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been going on for decades. However, only roflumilast has received FDA approval. One key challenge has been the low therapeutic window observed in the dinic for PDE4 inhibitors, primarily due to PDE4 mediated side effects. Here we describe our approach to circumvent this issue by applying a soft-drug concept in the design of a topically acting PDE4 inhibitor for treatment of dermatological diseases. We used a fast follower approach, starting from piclamilast. In particular, simultaneous introduction of 2'-alkoxy substituents and changing an amide to a keto linker proved to be beneficial when designing potential soft-drug candidates. This effort culminated in identification of LEO 29102 (20), a potent, selective, and soft-drug PDE4 inhibitor with properties suitable for patient-friendly formulations giving efficient drug delivery to the skin. Compound 20 has reached phase 2 and demonstrated clinically relevant efficacy in the treatment of atopic dermatitis.

  DOI：

  10.1021/jm500378a
• 作为产物：
  描述：

  3,4,5-三氯吡啶 在 三氯化硼 、 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-(3,5-二氯-4-吡啶基)-1-(2-羟基-3,4-二甲氧基苯基)乙酮
  参考文献：
  名称：

  [EN] METHODS FOR THE PREPARATION OF SUBSTITUTED ACETOPHENONES
  [FR] PROCÉDÉS DE PRÉPARATION D'ACÉTOPHÉNONES SUBSTITUÉES

  摘要：

  本申请披露了一种制备吡啶-4-基取代苯乙酮的新方法，特别是2-{6-[2-(3,5-二氯吡啶-4-基)-乙酰基]-2,3-二甲氧基苯氧基}-N-丙基乙酰胺。该申请还披露了2-{6-[2-(3,5-二氯吡啶-4-基)-乙酰基]-2,3-二甲氧基苯氧基}-N-丙基乙酰胺的新稳定结晶形式。

  公开号：

  WO2014096018A1

文献信息

• SUBSTITUTED ACETOPHENONES USEFUL AS PDE4 INHIBITORS
  申请人：Felding Jakob

  公开号：US20100035908A1

  公开（公告）日：2010-02-11

  The present invention relates to a compound according to formula: (I); wherein X 1 , X 2 , X 3 , X 4 and X 5 independently of each other represent —CH— or N; or X 3 , X 4 and X 5 independently of each other represent —CH— or N, and Xi and X 2 independently of each other represent C and form part of an additional 6-membered aromatic ring; R 1 represents hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, or alkylcarbonyl, all of which are optionally substituted; R 2 and R 3 independently represent hydrogen, —CH 2 —C(O)NR—R′, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, haloalkyl, hydroxyalkyl, heterocycloalkenyl, alkylaryl, alkylalkoxycarbonyl, alkylcarbonyloxy, or alkoxyalkyl, all of which are optionally substituted; R 11 represents hydrogen, halogen, cyano, amino, alkoxy or alkylamino, X 1 -X 5 represent —CH— or N, including N-oxides, enantiomers and diastereomers; and pharmaceutically acceptable salts, hydrates, or solvates thereof. The invention relates further to processes for the preparation of said compounds, to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases, e.g. dermal diseases, with said compounds, and to the use of said compounds in the manufacture of medicaments.

  本发明涉及一种化合物，其化学式为（I）; 其中X1，X2，X3，X4和X5相互独立地表示—CH—或N; 或者X3，X4和X5相互独立地表示—CH—或N，Xi和X2相互独立地表示C，并形成额外的6元芳香环的一部分; R1表示氢，烷基，烯基，炔基，卤代烷基，羟基烷基或烷基羰基，所有这些都可以被取代; R2和R3相互独立地表示氢，—CH2—C（O）NR—R′，烷基，环烷基，烯基，环烯基，炔基，卤代烷基，羟基烷基，杂环烯基，烷基芳基，烷基烷氧羰基，烷基羰氧基或烷氧基烷基，所有这些都可以被取代; R11表示氢，卤素，氰基，氨基，烷氧基或烷基氨基，X1-X5表示—CH—或N，包括N-氧化物，对映体和非对映体;以及其药学上可接受的盐，水合物或溶剂化物。本发明还涉及制备该化合物的方法，使用该化合物进行治疗的方法，包括该化合物的制药组合物，治疗疾病的方法，例如皮肤疾病，并且涉及使用该化合物制造药物的用途。
• Substituted acetophenones useful as PDE4 inhibitors
  申请人：Leo Pharma A/S

  公开号：US08148537B2

  公开（公告）日：2012-04-03

  The present invention relates to a compound according to formula: (I); wherein X1, X2, X3, X4 and X5 independently of each other represent —CH— or N; or X3, X4 and X5 independently of each other represent —CH— or N, and Xi and X2 independently of each other represent C and form part of an additional 6-membered aromatic ring; R1 represents hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, or alkylcarbonyl, all of which are optionally substituted; R2 and R3 independently represent hydrogen, —CH2—C(O)NR—R′, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, haloalkyl, hydroxyalkyl, heterocycloalkenyl, alkylaryl, alkylalkoxycarbonyl, alkylcarbonyloxy, or alkoxyalkyl, all of which are optionally substituted; R11 represents hydrogen, halogen, cyano, amino, alkoxy or alkylamino, X1-X5 represent —CH— or N, including N-oxides, enantiomers and diastereomers; and pharmaceutically acceptable salts, hydrates, or solvates thereof. The invention relates further to processes for the preparation of said compounds, to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases, e.g. dermal diseases, with said compounds, and to the use of said compounds in the manufacture of medicaments.

  本发明涉及一种化合物，其化学式为：（I）；其中X1、X2、X3、X4和X5分别独立地表示—CH—或N；或X3、X4和X5分别独立地表示—CH—或N，而Xi和X2分别独立地表示C并构成一个额外的6元芳香环；R1表示氢、烷基、烯基、炔基、卤代烷基、羟基烷基或烷基羰基，所有这些均可选择性地被取代；R2和R3独立地表示氢、—CH2—C（O）NR—R′、烷基、环烷基、烯基、环烯基、炔基、卤代烷基、羟基烷基、杂环烯基、烷基芳基、烷基烷氧羰基、烷基羰氧基或烷氧基烷基，所有这些均可选择性地被取代；R11表示氢、卤素、氰基、氨基、烷氧基或烷基氨基，X1-X5表示—CH—或N，包括N-氧化物、对映体和非对映异构体；以及其药学上可接受的盐、水合物或溶剂化物。本发明还涉及制备这些化合物的方法，以及将这些化合物用于治疗、包括皮肤疾病等疾病的药物组成物，以及将这些化合物用于制造药物的用途。
• WO2008/77404
  申请人：——

  公开号：——

  公开（公告）日：——
• J. Med. Chem. 2014, 57, 5893-5903
  作者：

  DOI：——

  日期：——
• US8148537B2
  申请人：——

  公开号：US8148537B2

  公开（公告）日：2012-04-03