N-benzyloxycarbonyl-leucyl-leucyl-norleucinal | 133407-83-7

• 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: N-benzyloxycarbonyl-leucyl-leucyl-norleucinal
• 英文别名: gamma-Secretase Inhibitor I；benzyl N-[4-methyl-1-[[4-methyl-1-oxo-1-(1-oxohexan-2-ylamino)pentan-2-yl]amino]-1-oxopentan-2-yl]carbamate
• CAS: 133407-83-7
• 化学式: C₂₆H₄₁N₃O₅
• 分子量: 475.629
• InChiKey: RNPDUXVFGTULLP-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  34
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• WGK Germany：
  3

文献信息

• Prophylactic and therapeutic agent for bone diseases comprising di- or tripeptide derivative as active ingredient
  申请人：SUNTORY LIMITED

  公开号：EP0504938A2

  公开（公告）日：1992-09-23

  Use of a compound represented by the following general formula (I): wherein R¹ represents a straight or branched acyl group having 2 to 10 carbon atoms, a branched cyclic or bridged cyclic alkyloxycarbonyl group having 4 to 15 carbon atoms, a substituted or unsubstituted benzyloxycarbonyl group, a 2,2,2-trichloroethyloxycarbonyl group, a 2-(trimethylsilyl)-ethyloxycarbonyl group, a p-toluenesulfonyl group, an o-nitrophenylsulfenyl group, a diphenylphosphonothioyl group, a triphenylmethyl group, a 2-benzoyl-1-methylvinyl group or a 4-phenylbutanoyl group; R² represents a hydrogen atom or forms a phthaloyl group together with R¹; R³ represents an isobutyl group, an n-butyl group or an isopropyl group; R⁴ represents an n-butyl group or an isobutyl group; X represents a direct bond, a methionine residue, a leucine residue or a norleucine residue; and H at the C-terminal means that the carboxyl group is reduced in the form of the aldehyde; as an active ingredient for the preparation of a pharmaceutical composition useful in preventing or treating malignant hypercalcemia, bone Paget's disease or osteoporosis.

  使用以下通式 (I) 所代表的化合物： 其中 R¹ 代表具有 2 至 10 个碳原子的直链或支链酰基、具有 4 至 15 个碳原子的支链环状或桥接环状烷氧基羰基、取代或未取代的苄氧基羰基、2,2、2-三氯乙基氧羰基、2-（三甲基硅基）乙基氧羰基、对甲苯磺酰基、邻硝基苯磺酰基、二苯基膦酰基、三苯基甲基、2-苯甲酰基-1-甲基乙烯基或 4-苯基丁酰基； R² 代表氢原子或与 R¹ 共同形成邻苯二甲酰基； R³ 代表异丁基、正丁基或异丙基； R⁴ 代表一个正丁基或一个异丁基； X 代表直接键、蛋氨酸残基、亮氨酸残基或去甲亮氨酸残基；及 C 末端的 H 表示羧基以醛的形式被还原； 作为制备药物组合物的活性成分，可用于预防或治疗恶性高钙血症、骨髓鞘病或骨质疏松症。
• 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。
• Efficient delivery of therapeutic molecules to cells of the inner ear
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US11370823B2

  公开（公告）日：2022-06-28

  Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

  提供了诱导内耳细胞进入细胞周期和增殖的组合物。特别是，通过服用能激活 Myc 和 Notch 的组合物来诱导毛细胞增殖。通过抑制 Myc 和 Notch 的活性或激活 Atoh1，诱导支持细胞向毛细胞转分化。治疗方法包括在细胞内将这些分子输送到特定的治疗靶点。