(R)-N-(2-(3-(dimethylamino)-3-oxopropylthio)-4-(1H-pyrazol-4-yl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide | 1161832-84-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (R)-N-(2-(3-(dimethylamino)-3-oxopropylthio)-4-(1H-pyrazol-4-yl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
• 英文别名: (3R)-N-[2-[3-(dimethylamino)-3-oxopropyl]sulfanyl-4-(1H-pyrazol-4-yl)phenyl]-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
• CAS: 1161832-84-3
• 化学式: C₂₅H₂₉N₅O₃S
• 分子量: 479.603
• InChiKey: SKSMFVZCCJUUTA-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl (3R)-3-[[2-[3-(dimethylamino)-3-oxopropyl]sulfanyl-4-(1H-pyrazol-4-yl)phenyl]carbamoyl]-6-methoxy-3,4-dihydro-1H-isoquinoline-2-carboxylate 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (R)-N-(2-(3-(dimethylamino)-3-oxopropylthio)-4-(1H-pyrazol-4-yl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Tetrahydroisoquinoline Derivatives As Highly Selective and Potent Rho Kinase Inhibitors

  摘要：

  Rho kinase (ROCK) is a promising drug target for the treatment of many diseases including hypertension, multiple sclerosis, cancer, and glaucoma. The structure-activity relationships (SAR) around a series of tetrahydroisoquinolines were evaluated utilizing biochemical and cell-based assays to measure ROCK inhibition. These novel ROCK inhibitors possess high potency, high selectivity, and appropriate pharmacokinetic properties for glaucoma applications. The lead compound, 35, had subnanomolar potency in enzyme ROCK-II assays as well as excellent cell-based potency (IC(50) = 51 nM). In a kinase panel profiling, 35 had an off-target hit rate of only 1.6% against 442 kinases. Pharmacology studies showed that compound 35 was efficacious in reducing intraocular pressure (IOP) in rats with reasonably long duration of action. These results suggest that compound 35 may serve as a promising agent for further development in the treatment of glaucoma.

  DOI：

  10.1021/jm100579r

文献信息

• ANILIDES AND ANALOGS AS RHO KINASE INHIBITORS
  申请人：Feng Yangbo

  公开号：US20110038835A1

  公开（公告）日：2011-02-17

  Compounds useful as Rho kinase inhibitors of formula (I): wherein variable are as defined herein are provided. Methods of treatment of malconditions mediated by Rho kinase, and methods of preparation of the compounds, are also provided.

  提供了公式（I）中变量如定义所述的作为Rho激酶抑制剂有用的化合物。还提供了治疗由Rho激酶介导的恶性疾病的方法，以及制备这些化合物的方法。
• [EN] ANILIDES AND ANALOGS AS RHO KINASE INHIBITORS<br/>[FR] ANILIDES ET ANALOGUES UTILISÉS COMME INHIBITEURS DE LA RHO KINASE
  申请人：FENG YANGBO

  公开号：WO2009079009A1

  公开（公告）日：2009-06-25

  Compounds useful as Rho kinase inhibitors of formula (I): wherein variable are as defined herein are provided. Methods of treatment of malconditions mediated by Rho kinase, and methods of preparation of the compounds, are also provided.