(8R)-1-[(2R)-2-[tert-butyl(dimethyl)silyl]oxypropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol | 478132-47-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (8R)-1-[(2R)-2-[tert-butyl(dimethyl)silyl]oxypropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol
• 英文别名: (R)-1-[(R)-2-(tert-butyl-dimethyl-silanyloxy)-propyl]-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol
• CAS: 478132-47-7
• 化学式: C₁₉H₃₀N₂O₃Si
• 分子量: 362.544
• InChiKey: XDKJEOVVPVARIU-UKRRQHHQSA-N

物化性质

• 沸点：
  462.1±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  56.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (8R)-1-[(2R)-2-[tert-butyl(dimethyl)silyl]oxypropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol 在 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 为溶剂， 反应 3.0h， 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：

  (1-[(2R)-2-[tert-butyl(dimethyl)silyl]oxypropyl]indazol-6-ol) 在 potassium carbonate 、 9-硼双环[3.3.1]壬烷 作用下， 以 四氢呋喃 、 丙酮 、 均三甲苯 为溶剂， 反应 42.5h， 生成 (8R)-1-[(2R)-2-[tert-butyl(dimethyl)silyl]oxypropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol
  参考文献：
  名称：

  [EN] PYRANOINDAZOLES AND THEIR USE FOR THE TREATMENT OF GLAUCOMA
  [FR] PYRANOINDAZOLES ET LEUR UTILISATION POUR LE TRAITEMENT DU GLAUCOME

  摘要：

  公开号：

  WO2003101379A3

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。
• PYRANOINDAZOLE CYCLIC CARBONATES AND METHODS OF USE
  申请人：DELGADO Pete

  公开号：US20080058533A1

  公开（公告）日：2008-03-06

  Described are methods of making pyranoindazole compounds comprising converting a pyranoindazole diol mixture to form a diastereomeric mixture of cyclic pyranoindazole carbonates, separating the mixture of cyclic pyranoindazole carbonates, and converting at least one of the separated diastereoisomeric cyclic pyranoindazole carbonates by hydrogenolysis. Also disclosed are intermediates useful for such and additional methods.

  本文描述了制备吡喃吲唑化合物的方法，包括将吡喃吲唑二醇混合物转化为环状吡喃吲唑碳酸酯的对映体混合物，分离环状吡喃吲唑碳酸酯混合物，并通过氢解反应转化至少一种分离的对映体环状吡喃吲唑碳酸酯。此外还公开了用于这种和其他方法的中间体。
• [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.