1,2-diamino-3-methoxypyridinium 2,4,6-trimethylbenzenesulfonate | 1232335-82-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,2-diamino-3-methoxypyridinium 2,4,6-trimethylbenzenesulfonate
• 英文别名: 3-Methoxypyridin-1-ium-1,2-diamine;2,4,6-trimethylbenzenesulfonate；3-methoxypyridin-1-ium-1,2-diamine;2,4,6-trimethylbenzenesulfonate
• CAS: 1232335-82-8
• 化学式: C₆H₁₀N₃O*C₉H₁₁O₃S
• 分子量: 339.415
• InChiKey: UQFOGGRJJHJKSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.79
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropanecarbaldehyde 、 1,2-diamino-3-methoxypyridinium 2,4,6-trimethylbenzenesulfonate 在 potassium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 以47%的产率得到2-(1-((tert-butyldiphenylsilyloxy)methyl)cyclopropyl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
  参考文献：
  名称：

  [EN] TRIAZOLOPYRIDINES AS PHOSPHODIESTERASE INHIBITORS FOR TREATMENT OF DERMAL DISEASES
  [FR] TRIAZOLOPYRIDINES EN TANT QU'INHIBITEURS DE PHOSPHODIESTÉRASE POUR LE TRAITEMENT DE MALADIES DU DERME

  摘要：

  本发明涉及一种符合式I的化合物，其中R1、R2和A如本文所定义，具有PDE4抑制活性，可用于治疗炎症性疾病或自身免疫性疾病，特别是炎症性或增生性皮肤疾病。

  公开号：

  WO2010069322A1
• 作为产物：
  描述：

  3-甲氧基-2-硝基吡啶 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、303.99 kPa 条件下， 生成 1,2-diamino-3-methoxypyridinium 2,4,6-trimethylbenzenesulfonate
  参考文献：
  名称：

  Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel “Dual-Soft” PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis

  摘要：

  We describe the design of a novel PDE4 scaffold and the exploration of the dual-soft concept to reduce systemic side effects via rapid elimination: introducing ester functionalities that can be inactivated in blood as well as by the liver (dual-soft) while being stable in human skin. Compound 40 was selected as a clinical candidate as it was potent and rapidly degraded by blood and liver to inactive metabolites and because in preclinical studies it showed high exposure at the target organ: the skin. Preclinical and clinical data are presented confirming the value of the dual-soft concept in reducing systemic exposure.

  DOI：

  10.1021/acs.jmedchem.0c00797

文献信息

• TRIAZOLOPYRIDINES AS PHOSPHODIESTERASE INHIBITORS FOR TREATMENT OF DERMAL DISEASES
  申请人：Nielsen Simon Feldbaek

  公开号：US20120028974A1

  公开（公告）日：2012-02-02

  The present invention relates to a compound according to formula I, wherein R 1 , R 2 and A are as defined herein, which exhibit PDE4 inhibitory activity and may be used in the treatment of inflammatory diseases or autoimmune diseases, in particular inflammatory or proliferative dermal diseases.

  本发明涉及一种化合物，其符合I式，其中R1、R2和A如此定义，该化合物表现出PDE4抑制活性，可用于治疗炎症性疾病或自身免疫性疾病，特别是炎症性或增生性皮肤疾病的治疗。
• US8952162B2
  申请人：——

  公开号：US8952162B2

  公开（公告）日：2015-02-10
• Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3<i>H</i>-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-<i>a</i>]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel “Dual-Soft” PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis
  作者：Jens Larsen、Maja Lambert、Henrik Pettersson、Thomas Vifian、Mogens Larsen、Anna Ollerstam、Pontus Hegardt、Cecilia Eskilsson、Steen Laursen、Anders Soehoel、Tine Skak-Nielsen、Lene M. Hansen、Nina Ø. Knudsen、Stefan Eirefelt、Morten D. Sørensen、Tatiana G. Stilou、Simon F. Nielsen

  DOI：10.1021/acs.jmedchem.0c00797

  日期：2020.12.10

  We describe the design of a novel PDE4 scaffold and the exploration of the dual-soft concept to reduce systemic side effects via rapid elimination: introducing ester functionalities that can be inactivated in blood as well as by the liver (dual-soft) while being stable in human skin. Compound 40 was selected as a clinical candidate as it was potent and rapidly degraded by blood and liver to inactive metabolites and because in preclinical studies it showed high exposure at the target organ: the skin. Preclinical and clinical data are presented confirming the value of the dual-soft concept in reducing systemic exposure.
• [EN] TRIAZOLOPYRIDINES AS PHOSPHODIESTERASE INHIBITORS FOR TREATMENT OF DERMAL DISEASES<br/>[FR] TRIAZOLOPYRIDINES EN TANT QU'INHIBITEURS DE PHOSPHODIESTÉRASE POUR LE TRAITEMENT DE MALADIES DU DERME
  申请人：LEO PHARMA AS

  公开号：WO2010069322A1

  公开（公告）日：2010-06-24

  The present invention relates to a compound according to formula I, wherein R1, R2 and A are as defined herein, which exhibit PDE4 inhibitory activity and may be used in the treatment of inflammatory diseases or autoimmune diseases, in particular inflammatory or proliferative dermal diseases.

  本发明涉及一种符合式I的化合物，其中R1、R2和A如本文所定义，具有PDE4抑制活性，可用于治疗炎症性疾病或自身免疫性疾病，特别是炎症性或增生性皮肤疾病。