3-(4-bromophenyl)-1-(2-hydroxyethyl)-1-(3-methoxybenzyl)urea | 1219729-13-1

• 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: 3-(4-bromophenyl)-1-(2-hydroxyethyl)-1-(3-methoxybenzyl)urea
• 英文别名: 3-(4-Bromophenyl)-1-(2-hydroxyethyl)-1-[(3-methoxyphenyl)methyl]urea；3-(4-bromophenyl)-1-(2-hydroxyethyl)-1-[(3-methoxyphenyl)methyl]urea
• CAS: 1219729-13-1
• 化学式: C₁₇H₁₉BrN₂O₃
• 分子量: 379.253
• InChiKey: NWULOXOACUMUGG-UHFFFAOYSA-N

物化性质

• 沸点：
  582.0±50.0 °C(Predicted)
• 密度：
  1.452±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-bromophenyl)-1-(2-hydroxyethyl)-1-(3-methoxybenzyl)urea 在 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 [(2S)-1-[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-1-[4-[4-[[2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-acetyloxypropanoyl]oxypropanoyl]oxypropanoyl]oxypropanoyl]oxypropanoyl]oxypropanoyl]oxyethyl-[(3-methoxyphenyl)methyl]carbamoyl]amino]phenyl]pyrazol-1-yl]-1-oxopropan-2-yl]oxy-1-oxopropan-2-yl]oxy-1-oxopropan-2-yl]oxy-1-oxopropan-2-yl]oxy-1-oxopropan-2-yl] (2S)-2-acetyloxypropanoate
  参考文献：
  名称：

  [EN] DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS
  [FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE TROUBLES OCULAIRES

  摘要：

  本发明提供了治疗活性化合物的新前药，包括寡聚前药，以及用于治疗医学疾病的组合物，例如青光眼，一种与眼压增高有关的疾病或异常，需要神经保护的疾病，年龄相关性黄斑变性，或糖尿病性视网膜病变。

  公开号：

  WO2018175922A1
• 作为产物：
  描述：

  2-{[(3-methoxyphenyl)methylene]amino}ethanol 在 sodium tetrahydroborate 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 3-(4-bromophenyl)-1-(2-hydroxyethyl)-1-(3-methoxybenzyl)urea
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

  摘要：

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.

  DOI：

  10.1021/jm400062r

文献信息

• DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS
  申请人：Graybug Vision, Inc.

  公开号：EP3600324A1

  公开（公告）日：2020-02-05
• [EN] DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE TROUBLES OCULAIRES
  申请人：GRAYBUG VISION INC

  公开号：WO2018175922A1

  公开（公告）日：2018-09-27

  The present invention provides new prodrugs of therapeutically active compounds, including oligomeric prodrugs, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.

  本发明提供了治疗活性化合物的新前药，包括寡聚前药，以及用于治疗医学疾病的组合物，例如青光眼，一种与眼压增高有关的疾病或异常，需要神经保护的疾病，年龄相关性黄斑变性，或糖尿病性视网膜病变。
• Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors
  作者：Yan Yin、Li Lin、Claudia Ruiz、Susan Khan、Michael D. Cameron、Wayne Grant、Jennifer Pocas、Nibal Eid、HaJeung Park、Thomas Schröter、Philip V. LoGrasso、Yangbo Feng

  DOI：10.1021/jm400062r

  日期：2013.5.9

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.