(((3S,4R)-6-cyano-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)chroman-3-yl)oxy)methyl (tert-butoxycarbonyl)glycyl-L-leucinate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (((3S,4R)-6-cyano-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)chroman-3-yl)oxy)methyl (tert-butoxycarbonyl)glycyl-L-leucinate
• 英文别名: [(3S,4R)-6-cyano-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydrochromen-3-yl]oxymethyl (2S)-4-methyl-2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]pentanoate
• 化学式: C₃₀H₄₂N₄O₈
• 分子量: 586.685
• InChiKey: FVSJIWMGNVNJLR-BYXVTNLJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (((3S,4R)-6-cyano-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)chroman-3-yl)oxy)methyl (tert-butoxycarbonyl)glycyl-L-leucinate 在 盐酸 作用下， 以 水 为溶剂， 反应 0.5h， 以23%的产率得到(((3S,4R)-6-cyano-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)chroman-3-yl)oxy)methyl glycyl-L-leucinate
  参考文献：
  名称：

  具有体内眼部降压活性的ATP敏感性钾（K ATP）通道开放剂克罗卡林的类似物

  摘要：

  ATP敏感性钾（K ATP）通道开放剂已成为治疗青光眼，降低动物模型和培养的人前眼节的眼内压（IOP）的潜在疗法。我们已经制备了K ATP的水溶性磷酸酯和二肽衍生物开沟剂cromakalim并评估了它们在体内降低IOP的能力。通常，在血压正常的小鼠模型中，每天给药一次，磷酸盐衍生物在降低IOP方面具有更强的化学稳定性和有效性。在正常血压的兔子模型中进一步评估了其中的两种磷酸盐衍生物，观察到活性存在显着差异。用最有效的化合物（3 S，4 R）-2处理后，未观察到对房水流出通道的细胞结构或形态变化有毒害作用，表明它是发展为眼压降压药的强力候选者。 。

  DOI：

  10.1021/acs.jmedchem.6b00406
• 作为产物：
  描述：

  左色满卡林 在 磺酰氯 、 乙酸酐 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 反应 28.5h， 生成 (((3S,4R)-6-cyano-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)chroman-3-yl)oxy)methyl (tert-butoxycarbonyl)glycyl-L-leucinate
  参考文献：
  名称：

  具有体内眼部降压活性的ATP敏感性钾（K ATP）通道开放剂克罗卡林的类似物

  摘要：

  ATP敏感性钾（K ATP）通道开放剂已成为治疗青光眼，降低动物模型和培养的人前眼节的眼内压（IOP）的潜在疗法。我们已经制备了K ATP的水溶性磷酸酯和二肽衍生物开沟剂cromakalim并评估了它们在体内降低IOP的能力。通常，在血压正常的小鼠模型中，每天给药一次，磷酸盐衍生物在降低IOP方面具有更强的化学稳定性和有效性。在正常血压的兔子模型中进一步评估了其中的两种磷酸盐衍生物，观察到活性存在显着差异。用最有效的化合物（3 S，4 R）-2处理后，未观察到对房水流出通道的细胞结构或形态变化有毒害作用，表明它是发展为眼压降压药的强力候选者。 。

  DOI：

  10.1021/acs.jmedchem.6b00406

文献信息

• Therapeutics for the treatment of glaucoma
  申请人：MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH

  公开号：US10981951B2

  公开（公告）日：2021-04-20

  The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a KATP channel to reduce an intraocular pressure.

  本发明提供苯并噻二嗪和色苷衍生物，特别是用于治疗青光眼、视网膜病变、治疗年龄相关性黄斑变性、治疗、稳定和/或抑制血液和淋巴血管生成，并通过向眼睛内给予药学有效量的前药，其中前药特异性调节KATP通道以降低眼内压力。
• NOVEL THERAPEUTICS FOR THE TREATMENT OF GLAUCOMA
  申请人：MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH

  公开号：US20170002040A1

  公开（公告）日：2017-01-05

  The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a KATP channel to reduce an intraocular pressure.
• THERAPEUTICS FOR THE TREATMENT OF GLAUCOMA
  申请人：Mayo Foundation for Medical Education and Research

  公开号：US20210040148A1

  公开（公告）日：2021-02-11

  The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a K ATP channel to reduce an intraocular pressure.
• [EN] NOVEL THERAPEUTICS FOR THE TREATMENT OF GLAUCOMA<br/>[FR] NOUVEAUX AGENTS THÉRAPEUTIQUES POUR LE TRAITEMENT DU GLAUCOME
  申请人：MAYO FOUNDATION

  公开号：WO2015117024A1

  公开（公告）日：2015-08-06

  The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a KATP channel to reduce an intraocular pressure.