(tert-butyl-dimethyl-[(1R)-1-methyl-2-(6-prop-2-ynoxyindazol-1-yl)ethoxy]silane) | 478132-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: (tert-butyl-dimethyl-[(1R)-1-methyl-2-(6-prop-2-ynoxyindazol-1-yl)ethoxy]silane)
• 英文别名: 1-[2-(R)-(tert-butyl-dimethyl-silanyloxy)-propyl]-6-prop-2-ynyloxy-1H-indazole；tert-butyl-dimethyl-[(2R)-1-(6-prop-2-ynoxyindazol-1-yl)propan-2-yl]oxysilane
• CAS: 478132-45-5
• 化学式: C₁₉H₂₈N₂O₂Si
• 分子量: 344.529
• InChiKey: FOTGFVRQOSASEP-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.46
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (tert-butyl-dimethyl-[(1R)-1-methyl-2-(6-prop-2-ynoxyindazol-1-yl)ethoxy]silane) 在 9-borabicyclo[3.3.1]nonane dimer 、 四丁基氟化铵 、 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 、 均三甲苯 为溶剂， 反应 25.0h， 生成 ((2R)-1-[(8R)-8-(1-ethoxyethoxy)-8,9-dihydro-7Hpyrano[2,3-g]indazol-1-yl]propan-2-ol)
  参考文献：
  名称：

  Ocular Hypotensive Response in Nonhuman Primates of (8R)-1-[(2S)-2-Aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol a Selective 5-HT₂ Receptor Agonist

  摘要：

  Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicochemical and permeability profile, subsequently identified cardiovascular side effects in multiple species precluded further clinical evaluation of this compound. Herein, we report selected structural modifications that resulted in the identification of (8R)-1-[(2S)-2-aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol (13), which displayed an acceptable profile to support advancement for further preclinical evaluation as a candidate for proof-of-concept studies in humans.

  DOI：

  10.1021/acs.jmedchem.5b00857
• 作为产物：
  描述：

  (R)-1-(6-benzyloxy-indazol-1-yl)-propan-2-ol 在 咪唑 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 86.0h， 生成 (tert-butyl-dimethyl-[(1R)-1-methyl-2-(6-prop-2-ynoxyindazol-1-yl)ethoxy]silane)
  参考文献：
  名称：

  Ocular Hypotensive Response in Nonhuman Primates of (8R)-1-[(2S)-2-Aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol a Selective 5-HT₂ Receptor Agonist

  摘要：

  Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicochemical and permeability profile, subsequently identified cardiovascular side effects in multiple species precluded further clinical evaluation of this compound. Herein, we report selected structural modifications that resulted in the identification of (8R)-1-[(2S)-2-aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol (13), which displayed an acceptable profile to support advancement for further preclinical evaluation as a candidate for proof-of-concept studies in humans.

  DOI：

  10.1021/acs.jmedchem.5b00857

文献信息

• Pyranoindazoles and their use for the treatment of glaucoma
  申请人：——

  公开号：US20030171418A1

  公开（公告）日：2003-09-11

  Pyranoindazoles are disclosed. Also disclosed are methods for the lowering and controlling of normal or elevated intraocular pressure as well as a method for the treatment of glaucoma using compositions containing one or more of the compounds of the present invention.

  吡啶并吡唑类化合物已被披露。还公开了降低和控制正常或升高眼内压力的方法，以及使用含有本发明化合物之一或多个的组合物治疗青光眼的方法。
• [EN] PYRANOINDAZOLES AND THEIR USE FOR THE TREATMENT OF GLAUCOMA<br/>[FR] PYRANOINDAZOLES ET LEUR UTILISATION POUR LE TRAITEMENT DU GLAUCOME
  申请人：——

  公开号：WO2003101379A3

  公开（公告）日：2004-03-04
• Ocular Hypotensive Response in Nonhuman Primates of (8<i>R</i>)-1-[(2<i>S</i>)-2-Aminopropyl]-8,9-dihydro-7<i>H</i>-pyrano[2,3-<i>g</i>]indazol-8-ol a Selective 5-HT₂ Receptor Agonist
  作者：Jesse A. May、Najam A. Sharif、Marsha A. McLaughlin、Hwang-Hsing Chen、Bryon S. Severns、Curtis R. Kelly、William F. Holt、Richard Young、Richard A. Glennon、Mark R. Hellberg、Thomas R. Dean

  DOI：10.1021/acs.jmedchem.5b00857

  日期：2015.11.25

  Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicochemical and permeability profile, subsequently identified cardiovascular side effects in multiple species precluded further clinical evaluation of this compound. Herein, we report selected structural modifications that resulted in the identification of (8R)-1-[(2S)-2-aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol (13), which displayed an acceptable profile to support advancement for further preclinical evaluation as a candidate for proof-of-concept studies in humans.