N'-(((4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxido-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-yl)sulfonyl)-N,N-dimethylformimidamide | 1034583-83-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: N'-(((4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxido-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-yl)sulfonyl)-N,N-dimethylformimidamide
• 英文别名: N'-[(4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7λ⁶-thieno[2,3-b]thiopyran-2-sulfonyl]-N,N-dimethylmethanimidamide
• CAS: 1034583-83-9
• 化学式: C₁₃H₂₁N₃O₄S₃
• 分子量: 379.525
• InChiKey: YHRCEUGGTUPDAV-ONGXEEELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.24
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  95.91
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N'-(((4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxido-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-yl)sulfonyl)-N,N-dimethylformimidamide 、 氯甲酸烯丙酯 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以33%的产率得到allyl ((4S,6S)-2-(N-((dimethylamino)methylene)sulfamoyl)-6-methyl-7,7-dioxido-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-yl)(ethyl)carbamate
  参考文献：
  名称：

  Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma

  摘要：

  Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.036
• 作为产物：
  描述：

  盐酸多佐胺 、 N,N-二甲基甲酰胺二乙基缩醛 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N'-(((4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxido-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-yl)sulfonyl)-N,N-dimethylformimidamide
  参考文献：
  名称：

  Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma

  摘要：

  Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.036

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS FOR OCULAR DELIVERY<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR ADMINISTRATION OCULAIRE
  申请人：GRAYBUG VISION INC

  公开号：WO2020069353A1

  公开（公告）日：2020-04-02

  The present invention provides new prodrags of Sunitinib, Brinzolamide, and Dorzolamide and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (TOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.

  本发明提供了新的Sunitinib、Brinzolamide和Dorzolamide的前药，以及用于治疗医学疾病的组合物，例如青光眼、与眼内压增高有关的疾病或异常（TOP）、需要神经保护的疾病、年龄相关性黄斑变性或糖尿病视网膜病变。
• COMPOUNDS AND COMPOSITIONS FOR OCULAR DELIVERY
  申请人：Graybug Vision, Inc.

  公开号：US20210214374A1

  公开（公告）日：2021-07-15

  The present invention provides new prodrugs of Sunitinib, Brinzolamide, and Dorzolamide 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.
• AGGREGATED MICROPARTICLES
  申请人：Graybug Vision, Inc.

  公开号：US20210275456A1

  公开（公告）日：2021-09-09

  Compositions and methods are provided that include aggregating microparticles which include an active agent that exhibit an increased hardness and/or durability of the resulting aggregated microparticles in vivo, which can lead to more stable, long-term ocular therapy.