2-(3,5-二氯吡啶-4-基)-1-(3,4-二甲氧基苯基)乙酮 | 1001909-95-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(3,5-二氯吡啶-4-基)-1-(3,4-二甲氧基苯基)乙酮
• 英文名称: 2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethanone
• 英文别名: 2-(3,5-dichloro-pyridin-4-yl)-1-(3,4-dimethoxy-phenyl)-ethanone
• CAS: 1001909-95-0
• 化学式: C₁₅H₁₃Cl₂NO₃
• 分子量: 326.179
• InChiKey: CMTBUHVOEWKSIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 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：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3,5-二氯吡啶-4-基)-1-(3,4-二甲氧基苯基)乙酮 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以50%的产率得到(R,S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethanol
  参考文献：
  名称：

  "Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors"

  摘要：

  这项发明涉及磷酸二酯酶4（PDE4）酶的抑制剂。更具体地说，这项发明涉及1-苯基-2-吡啶基烷基醇衍生物化合物，制备这些化合物的方法，含有它们的组合物以及它们的治疗用途。

  公开号：

  EP2022783A1
• 作为产物：
  描述：

  3,4-二甲氧基苯甲酰氯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 以52%的产率得到2-(3,5-二氯吡啶-4-基)-1-(3,4-二甲氧基苯基)乙酮
  参考文献：
  名称：

  Derivatives of 1-phenyl-2-pyridynyl alkylene alcohols as phosphodiesterase inhibitors

  摘要：

  该发明涉及磷酸二酯酶4（PDE4）酶的抑制剂。更具体地，该发明涉及1-苯基-2-吡啶基烷基醇衍生物化合物，制备这种化合物的方法，含有它们的组合物以及它们的治疗用途。

  公开号：

  US20080015226A1

文献信息

• DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
  申请人：Delcanale Maurizio

  公开号：US20090048220A1

  公开（公告）日：2009-02-19

  Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme.

  1-苯基-2-吡啶基烷基醇的衍生物可用作磷酸二酯酶4（PDE4）酶的抑制剂。
• Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors
  申请人：Chiesi Farmaceutici S.p.A.

  公开号：US08203000B2

  公开（公告）日：2012-06-19

  Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme.

  1-苯基-2-吡啶基烷基醇的衍生物可用作磷酸二酯酶4（PDE4）酶的抑制剂。
• Discovery and Early Clinical Development of 2-{6-[2-(3,5-Dichloro-4-pyridyl)acetyl]-2,3-dimethoxyphenoxy}-<i>N</i>-propylacetamide (LEO 29102), a Soft-Drug Inhibitor of Phosphodiesterase 4 for Topical Treatment of Atopic Dermatitis
  作者：Jakob Felding、Morten D. Sørensen、Tina D. Poulsen、Jens Larsen、Christina Andersson、Pia Refer、Karen Engell、Lotte G. Ladefoged、Thorsten Thormann、Anne Marie Vinggaard、Pontus Hegardt、Anders Søhoel、Simon Feldbæk Nielsen

  DOI：10.1021/jm500378a

  日期：2014.7.24

  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.
• DERIVATIVES OF 1-PHENYL-2-PYRIDYNYL ALKYLENE ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：EP2044023B1

  公开（公告）日：2011-01-19
• US7671066B2
  申请人：——

  公开号：US7671066B2

  公开（公告）日：2010-03-02