SUAM-14541

• 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: SUAM-14541
• 英文别名: Cbz-leu-phe-CHO；N-benzyloxycarbonyl-L-leucyl-L-phenylalaninal；MDL28170；gamma-Secretase Inhibitor V；benzyl N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]carbamate
• 化学式: C₂₃H₂₈N₂O₄
• 分子量: 396.486
• InChiKey: CSKGFHNQMOIAFM-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  SUAM-14541 在 4-氧-2,2,6,6-四甲基哌啶-1-氧自由基 、 臭氧 、 iron(II) bromide 作用下， 以 二氯甲烷 、 乙腈 、 正戊烷 为溶剂， 反应 0.08h， 生成 4-噁高金刚烷-5-酮
  参考文献：
  名称：

  Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity

  摘要：

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.

  DOI：

  10.1021/jm1009567
• 作为产物：
  描述：

  benzyl ((S)-1-(((S)-1-hydroxy-3-phenylpropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以60%的产率得到SUAM-14541
  参考文献：
  名称：

  Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity

  摘要：

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.

  DOI：

  10.1021/jm1009567

文献信息

• CELL CULTURE
  申请人：ViaCyte, Inc

  公开号：EP3521418A1

  公开（公告）日：2019-08-07

  An in vitro cell culture comprising human cells. At least 10% of the human cells are unipotent immature beta cells that co-express INS and NKX6.1 and do not substantially express NGN3.

  由人体细胞组成的体外细胞培养物。其中至少 10%的人体细胞是单能未成熟β细胞，它们共同表达 INS 和 NKX6.1，但基本上不表达 NGN3。
• Methods for producing hormone secreting cells in a subject
  申请人：ViaCyte, Inc.

  公开号：US10376545B2

  公开（公告）日：2019-08-13

  A human immature endocrine cell population and methods for making an immature endocrine cell population are provided. Specifically, immature beta cells and methods for production of immature beta cells are described. Immature beta cells co-express INS and NKX6.1 and are uni-potent and thereby develop into mature beta cells when implanted in vivo. The mature beta cells in vivo are capable of producing insulin in response to glucose stimulation.

  本文提供了一种人类未成熟内分泌细胞群和制造未成熟内分泌细胞群的方法。具体地说，描述了未成熟β细胞和生产未成熟β细胞的方法。未成熟β细胞共同表达 INS 和 NKX6.1，具有单能性，因此植入体内后可发育成成熟的β细胞。体内的成熟β细胞能够在葡萄糖刺激下产生胰岛素。
• Human airway stem cells in lung epithelial engineering
  申请人：The General Hospital Corporation

  公开号：US10624992B2

  公开（公告）日：2020-04-21

  Methods of using human airway stem cells in lung epithelial engineering, optionally wherein the cells are contacted with a gamma secretase inhibitor, bioartificial airway organs produced thereby, and the use thereof, e.g., for transplantation. Also methods of treating a bio-artificial matrix with Tenascin-C and/or fibrillin 2.

  在肺上皮工程中使用人气道干细胞的方法，其中细胞可选择与γ分泌酶抑制剂接触，由此产生的生物人工气道器官及其用途，例如用于移植。还包括用Tenascin-C和/或纤维蛋白2处理生物人工基质的方法。
• Treating hearing loss
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US10898492B2

  公开（公告）日：2021-01-26

  This invention relates to methods for treating hearing loss associated with loss of cochlear hair cells, e.g., caused by noise exposure, using certain gamma secretase inhibitors, in post-neonatal animals, e.g., adolescents and adults.

  本发明涉及使用某些γ分泌酶抑制剂治疗与耳蜗毛细胞缺失有关的听力损失的方法，例如，在新生后动物（如青少年和成年人）中使用这些抑制剂治疗由噪声暴露引起的耳蜗毛细胞缺失。
• Treatment of hearing loss by inhibition of casein kinase 1
  申请人：Massachusetts Eye & Ear Infirmary

  公开号：US11185536B2

  公开（公告）日：2021-11-30

  Methods for treating hearing loss that include administering an inhibitor, e.g., a small molecule inhibitor, of casein kinase 1, preferably in combination with a treatment that stimulates Atoh1 gene expression, e.g., a gamma-secretase inhibitor, an Atoh1 stimulatory compound, or a GSK-3-beta inhibitor.

  治疗听力损失的方法，包括施用酪蛋白激酶1的抑制剂，如小分子抑制剂，最好与刺激Atoh1基因表达的治疗剂，如γ-分泌酶抑制剂、Atoh1刺激化合物或GSK-3-beta抑制剂联合使用。