(2S,3S)-N-(2-((1H-indol-3-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-amino-3-methylpentanamide | 1396009-46-3

• 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: (2S,3S)-N-(2-((1H-indol-3-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-amino-3-methylpentanamide
• 英文别名: (2S,3S)-2-amino-N-[2-(1H-indol-3-ylmethyl)-3H-benzimidazol-5-yl]-3-methylpentanamide
• CAS: 1396009-46-3
• 化学式: C₂₂H₂₅N₅O
• 分子量: 375.473
• InChiKey: FSLNBVIYKUVMJE-ZSEKCTLFSA-N

物化性质

• 沸点：
  739.5±55.0 °C(Predicted)
• 密度：
  1.292±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  99.6
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 5%-palladium/activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 23.0h， 生成 (2S,3S)-N-(2-((1H-indol-3-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-amino-3-methylpentanamide
  参考文献：
  名称：

  发现与 K-Ras 结合并抑制 Sos 介导的活化的小分子

  摘要：

  寻找片段：使用 NMR 光谱进行基于片段的筛选，以发现与 GTPase K-Ras 结合并调节核苷酸交换因子 Sos 活性的配体。关于这些片段衍生的命中如何与鸟苷二磷酸-K-Ras 复合物结合的结构数据（见图）为未来发现靶向 K-Ras 激活和信号传导的药物提供了一个起点。

  DOI：

  10.1002/anie.201201358

文献信息

• COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF
  申请人：BioTheryX, Inc.

  公开号：US20180170948A1

  公开（公告）日：2018-06-21

  The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1α, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.

  本发明提供了调节蛋白功能的化合物，以恢复蛋白稳态，包括细胞因子、CK1α、GSPT1、艾奥洛斯和/或伊卡洛斯活性和细胞间粘附。该发明提供了一种调节蛋白介导的疾病的方法，如细胞因子介导的疾病、障碍、状况或反应。提供了包括与其他细胞因子和炎症介质结合的组合物。提供了治疗、改善或预防与蛋白相关的疾病、障碍或状况的方法，包括与细胞因子相关的疾病、障碍和状况，包括炎症、纤维肌痛、类风湿性关节炎、骨关节炎、强直性脊柱炎、银屑病、银屑病关节炎、炎症性肠病、克罗恩病、溃疡性结肠炎、葡萄膜炎、炎症性肺病、慢性阻塞性肺病、阿尔茨海默病和癌症。
• [EN] OXOINDOLINE DERIVATIVES AS PROTEIN FUNCTION MODULATORS<br/>[FR] DÉRIVÉS D'OXOINDOLINE UTILISÉS COMME MODULATEURS DE LA FONCTION PROTÉIQUE
  申请人：BIOTHERYX INC

  公开号：WO2017201069A1

  公开（公告）日：2017-11-23

  The present invention provides chimeric compounds of formula (II) that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CKl-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.

  本发明提供了公式（II）的嵌合化合物，用于调节蛋白功能，恢复蛋白稳态，包括细胞因子、aiolos和/或ikaros活性，TNF-alpha活性，CKl-alpha活性和细胞间黏附。该发明提供了调节蛋白介导疾病的方法，如细胞因子介导的疾病、紊乱、状况或反应。提供了与其他细胞因子和炎症介质结合的组合物。提供了治疗、改善或预防蛋白介导疾病、紊乱和状况的方法，如细胞因子介导的疾病、紊乱和状况，包括炎症、纤维肌痛综合征、类风湿关节炎、骨关节炎、强直性脊柱炎、牛皮癣、银屑病性关节炎、炎症性肠病、克罗恩病、溃疡性结肠炎、葡萄膜炎、炎症性肺部疾病、慢性阻塞性肺疾病、阿尔茨海默病、器官移植排斥反应和癌症。
• A Photoaffinity‐Based Fragment‐Screening Platform for Efficient Identification of Protein Ligands
  作者：Emma K. Grant、David J. Fallon、Michael M. Hann、Ken G. M. Fantom、Chad Quinn、Francesca Zappacosta、Roland S. Annan、Chun‐wa Chung、Paul Bamborough、David P. Dixon、Peter Stacey、David House、Vipulkumar K. Patel、Nicholas C. O. Tomkinson、Jacob T. Bush

  DOI：10.1002/anie.202008361

  日期：2020.11.16

  termed PhABits (PhotoAffinity Bits), which utilizes a library of photoreactive fragments to covalently capture fragment–protein interactions. Hits can be profiled to determine potency and the site of crosslinking, and subsequently developed as reporters in a competitive displacement assay to identify novel hit matter. The PhABit platform is envisioned to be widely applicable to novel protein targets, identifying

  基因组分析的进步使人们能够鉴定与疾病有关的新蛋白质。为了验证这些目标，需要使用工具分子来证明配体具有改善疾病的作用。当前，由于仅报道了一部分蛋白质组的工具，配体发现平台对于利用基因组分析的见解至关重要。碎片筛选提供了一种探索化学空间的有效方法。这里展示的是一个称为PhABits（PhotoAffinity Bits）的片段筛选平台，该平台利用光反应片段库共价捕获片段-蛋白质相互作用。可以对命中进行分析以确定效力和交联位点，然后在竞争性替代测定中将其发展为报道基因，以鉴定新的命中物质。
• [EN] DEUTERATED COMPOUNDS AND CHIMERAS AND USES THEREOF<br/>[FR] COMPOSÉS DEUTÉRÉS ET CHIMÈRES ET LEURS UTILISATIONS
  申请人：BIOTHERYX INC

  公开号：WO2019173224A1

  公开（公告）日：2019-09-12

  The present disclosure provides compounds that modulate protein function and/or restore protein homeostasis. The disclosure provides methods of modulating protein-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other therapeutic agents, are provided.

  本公开提供了调节蛋白质功能和/或恢复蛋白质稳态的化合物。本公开提供了调节蛋白质介导的疾病、障碍、状况或反应的方法。还提供了与其他治疗剂组合使用的组合物。
• Compounds targeting proteins, compositions, methods, and uses thereof
  申请人：BioTheryX, Inc.

  公开号：US10040804B2

  公开（公告）日：2018-08-07

  The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1α, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.

  本发明提供了调节蛋白质功能的化合物，以恢复蛋白质的平衡，包括细胞因子、CK1α、GSPT1、aiolos 和/或 ikaros 活性以及细胞-细胞粘附性。本发明提供了调节蛋白质介导的疾病，如细胞因子介导的疾病、失调、病症或反应的方法。本发明提供了组合物，包括与其他细胞因子和炎症介质的组合物。提供了治疗、改善或预防与蛋白质相关的疾病、失调或病症的方法，例如与细胞因子相关的疾病、失调和病症，包括炎症、纤维肌痛、类风湿性关节炎、骨关节炎、强直性脊柱炎、银屑病、银屑病关节炎、炎症性肠病、克罗恩病、溃疡性结肠炎、葡萄膜炎、炎症性肺病、慢性阻塞性肺病、阿尔茨海默病和癌症。