(1S)-1-(3-methoxyphenyl)propan-1-amine hydrochloride | 2103395-83-9

• 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: (1S)-1-(3-methoxyphenyl)propan-1-amine hydrochloride
• 英文别名: (S)-1-(3-Methoxyphenyl)propan-1-amine hydrochloride；(1S)-1-(3-methoxyphenyl)propan-1-amine;hydrochloride
• CAS: 2103395-83-9
• 化学式: C₁₀H₁₅NO*ClH
• 分子量: 201.696
• InChiKey: MRMOMOWBZZIRBU-PPHPATTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.53
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.2
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (1S)-1-(3-methoxyphenyl)propan-1-amine hydrochloride 、 (5R)-3-(4-cyanophenyl)-2-oxo-oxazolidine-5-carboxylic acid 在 盐酸羟胺 、 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 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 (5R)-3-(4-carbamimidoylphenyl)-N-[(1S)-1-(3-methoxyphenyl)propyl]-2-oxo-oxazolidine-5-carboxamide
  参考文献：
  名称：

  Synthesis and Structure‐Activity Relationships of N ‐(4‐Benzamidino)‐Oxazolidinones: Potent and Selective Inhibitors of Kallikrein‐Related Peptidase 6

  摘要：

  AbstractKallikrein‐related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression of KLK6 has been found in different cancers and neurodegenerative diseases, and KLK6 is currently studied as a potential target in these pathologies. We report a novel series of KLK6 inhibitors discovered in a high‐throughput screen within the European Lead Factory program. Structure‐guided design based on docking studies enabled rapid progression of a hit cluster to inhibitors with improved potency, selectivity and pharmacokinetic properties. In particular, inhibitors 32 ((5R)‐3‐(4‐carbamimidoylphenyl)‐N‐((S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) and 34 ((5R)‐3‐(6‐carbamimidoylpyridin‐3‐yl)‐N‐((1S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) have single‐digit nanomolar potency against KLK6, with over 25‐fold and 100‐fold selectivities against the closely related enzyme trypsin, respectively. The most potent compound, 32, effectively reduces KLK6‐dependent invasion of HCT116 cells. The high potency in combination with good solubility and low clearance of 32 make it a good chemical probe for KLK6 target validation in vitro and potentially in vivo.

  DOI：

  10.1002/cmdc.201900536
• 作为产物：
  描述：

  3-甲氧基苯甲醛 在 盐酸 、 一水合硫酸镁 、 4-甲基苯磺酸吡啶 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 70.5h， 生成 (1S)-1-(3-methoxyphenyl)propan-1-amine hydrochloride
  参考文献：
  名称：

  Synthesis and Structure‐Activity Relationships of N ‐(4‐Benzamidino)‐Oxazolidinones: Potent and Selective Inhibitors of Kallikrein‐Related Peptidase 6

  摘要：

  AbstractKallikrein‐related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression of KLK6 has been found in different cancers and neurodegenerative diseases, and KLK6 is currently studied as a potential target in these pathologies. We report a novel series of KLK6 inhibitors discovered in a high‐throughput screen within the European Lead Factory program. Structure‐guided design based on docking studies enabled rapid progression of a hit cluster to inhibitors with improved potency, selectivity and pharmacokinetic properties. In particular, inhibitors 32 ((5R)‐3‐(4‐carbamimidoylphenyl)‐N‐((S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) and 34 ((5R)‐3‐(6‐carbamimidoylpyridin‐3‐yl)‐N‐((1S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) have single‐digit nanomolar potency against KLK6, with over 25‐fold and 100‐fold selectivities against the closely related enzyme trypsin, respectively. The most potent compound, 32, effectively reduces KLK6‐dependent invasion of HCT116 cells. The high potency in combination with good solubility and low clearance of 32 make it a good chemical probe for KLK6 target validation in vitro and potentially in vivo.

  DOI：

  10.1002/cmdc.201900536

文献信息

• [EN] N3-SUBSTITUTED IMINOPYRIMIDINONES AS RENIN INHIBITORS, COMPOSITIONS, AND THEIR USE<br/>[FR] IMINOPYRIMIDINONES SUBSTITUÉES EN N3 EN TANT QU'INHIBITEURS DE LA RÉNINE, COMPOSITIONS ET LEUR UTILISATION
  申请人：MERCK SHARP & DOHME

  公开号：WO2013142396A1

  公开（公告）日：2013-09-26

  In its many embodiments, the present invention provides provides certain N3-substituted iminopyrimidinones of Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of the variables shown in the formula are as defined herein. The novel compounds of the invention are useful as renin inhibitors and/or for the treatment and prevention of various pathologies related thereto, including cardiovascular events, hypertension, and renal insufficiency. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, are also disclosed.

  在其多种实施方式中，本发明提供了以下式（I）的某些N3-取代的咪唑嘧啶酮化合物及其互变异构体和立体异构体，以及所述化合物的药学上可接受的盐，所述互变异构体和所述立体异构体，其中所示的各变量如本文所定义。本发明的新化合物可用作肾素抑制剂和/或用于治疗和预防与之相关的各种病理，包括心血管事件、高血压和肾功能不全。还公开了包括一种或多种这样的化合物（单独和与一种或多种其他活性剂的组合）的药物组合物，以及其制备和使用方法。