2-cyclohexyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic Acid | 186320-22-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2-cyclohexyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic Acid
• CAS: 186320-22-9
• 化学式: C₂₃H₂₅NO₄
• 分子量: 379.456
• InChiKey: BWQQGHPODCJZDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  2-cyclohexyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic Acid 在 4-二甲氨基吡啶 、 二氢吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 12.0h， 生成 tert-butyl 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-cyclohexyl-2-(trifluoromethyl)butanoate
  参考文献：
  名称：

  N-羟基邻苯二甲酰亚胺酯与2-(三氟甲基)丙烯酸叔丁酯的无催化剂脱羧交叉偶联反应及其应用

  摘要：

  在这里，我们展示了一种通过可见光促进氧化还原活性酯与2-(三氟甲基)丙烯酸叔丁酯的脱羧交叉偶联来轻松合成含CF 3氨基酸的实用方法。该反应是由电子供体-受体 (EDA) 复合物的光化学活性驱动的，该复合物是由 Hantzsch 酯和氧化还原活性酯之间的非共价相互作用形成的。该方案的优点是合成简单、丰富的官能团耐受性和经济有效的反应系统。

  DOI：

  10.1039/d3ob02103c

文献信息

• Triaza- and tetraaza-anthracenedione derivates, their preparation and their use as pharmaceuticals
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1471066A1

  公开（公告）日：2004-10-27

  The present invention relates to triaza- and tetraaza-anthracenedione derivatives of the formula I, in which A, B and R1 to R5 have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They are useful in the treatment of various disease states including cardiovascular disorders such as atherosclerosis, thrombosis, coronary artery disease, hypertension and cardiac insufficiency. They upregulate the expression of the enzyme endothelial nitric oxide (NO) synthase and can be applied in conditions in which an increased expression of said enzyme or an increased NO level or the normalization of a decreased NO level is desired. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及式I的三氮杂和四氮杂蒽醌衍生物，其中A、B和R1至R5具有权利要求中所示的含义。式I的化合物是有价值的药理活性化合物。它们在治疗各种疾病状态中具有用处，包括心血管疾病，如动脉粥样硬化、血栓形成、冠状动脉疾病、高血压和心脏功能不全。它们上调内皮一氧化氮（NO）合酶的表达，并可应用于需要增加该酶的表达或增加NO水平或恢复降低的NO水平的情况。此外，本发明还涉及制备式I化合物的方法，它们的用途，特别是作为药物中的活性成分，以及包含它们的药物制剂。
• Structure-based peptide inhibitors of P53 aggregation as a new approach to cancer therapeutics
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10400010B2

  公开（公告）日：2019-09-03

  This invention relates, e.g., to an inhibitory peptide or CPP inhibitor which specifically binds to p53 having an aberrant conformation (e.g., is aggregated or misfolded) and inhibits p53 amyloidogenic aggregation or restores proper folding of the misfolded protein. Methods of using the inhibitory peptide or CPP inhibitor (e.g. to treat subjects having tumors that comprise aggregated p53) are described.

  本发明涉及一种抑制肽或CPP抑制剂，它能特异性地与具有异常构象（如聚集或错误折叠）的p53结合，并抑制p53的淀粉样聚集或恢复错误折叠蛋白的正常折叠。本文描述了使用抑制肽或 CPP 抑制剂（例如治疗具有包含聚集 p53 的肿瘤的受试者）的方法。
• Structure-based peptide inhibitors of alpha-synuclein aggregation
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10815271B2

  公开（公告）日：2020-10-27

  This invention relates to inhibitory peptides which bind to α-synuclein molecules and inhibit α-synuclein amyloidogenic aggregation, α-synuclein cytotoxicity, and spread of α-synuclein. Methods of making and using the inhibitory peptides (e.g. to treat subjects having conditions or diseases that are mediated by α-synuclein, such as Parkinson's disease, dementia with Lewy bodies, or MSA) are described.

  本发明涉及与α-突触核蛋白分子结合并抑制α-突触核蛋白淀粉样聚集、α-突触核蛋白细胞毒性和α-突触核蛋白扩散的抑制肽。本文介绍了抑制肽的制造和使用方法（例如治疗由α-突触核蛋白介导的病症或疾病，如帕金森病、路易体痴呆或MSA）。
• Structure-based peptide inhibitors that target the Tau VQIINK fibrillization segment
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10934332B2

  公开（公告）日：2021-03-02

  Aggregated Tau protein is associated with over 20 neurological disorders including Alzheimer's disease. Previous work has shown that Tau's sequence segments VQIINK (SEQ ID NO: 11) and VQIVYK (SEQ ID NO: 9) drive its aggregation, and that inhibitors based on the structure of the VQIVYK (SEQ ID NO: 9) segment partially inhibit Tau aggregation. Here we show that the VQIINK (SEQ ID NO: 11) segment is the more powerful driver of Tau aggregation. Two structures of this segment determined by the cryo EM method MicroED explain its more powerful seeding. Of practical significance, the understanding of the structures has led to the design of structure based peptide inhibitors that effectively inhibit Tau aggregation as well as the ability of exogenous Tau fibrils to seed intracellular Tau in mammalian cells into amyloid.

  Tau 蛋白的聚集与包括阿尔茨海默病在内的 20 多种神经系统疾病有关。以前的研究表明，Tau 的序列片段 VQIINK（SEQ ID NO: 11）和 VQIVYK（SEQ ID NO: 9）驱动其聚集，基于 VQIVYK（SEQ ID NO: 9）片段结构的抑制剂可部分抑制 Tau 的聚集。在这里，我们证明 VQIINK（SEQ ID NO: 11）区段是 Tau 聚集的更强大驱动力。通过低温电磁方法 MicroED 确定的该片段的两种结构解释了其更强大的播种作用。具有实际意义的是，通过对这些结构的了解，我们设计出了基于结构的多肽抑制剂，它们能有效抑制 Tau 的聚集以及外源 Tau 纤维在哺乳动物细胞中将细胞内 Tau 种子转化为淀粉样蛋白的能力。
• Inhibition of the aggregation of transthyretin by specific binding of peptides to aggregation-driving segments
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US11028128B2

  公开（公告）日：2021-06-08

  The invention disclosed herein relates to peptide inhibitors for transthyretin (TTR) aggregation and methods of inhibiting TTR aggregation, cytotoxicity, and/or TTR amyloidosis. Illustrative embodiments of the invention include a composition of matter comprising at least one peptide designed to inhibit the aggregation of TTR, with this peptide typically being coupled to a heterologous amino acid tag. A pharmaceutically acceptable carrier selected to be compatible with the inhibitory peptide may also be included. A method for blocking or inhibiting the aggregation of transthyretin TTR is also provided. The method comprises combining TTR with an effective amount of an inhibitory peptide or pharmaceutical composition, so that TTR aggregation and/or cytotoxicity is blocked or inhibited.

  本文公开的发明涉及转甲状腺素（TTR）聚集的多肽抑制剂和抑制TTR聚集、细胞毒性和/或TTR淀粉样变性的方法。本发明的示例性实施方案包括一种物质组合物，该物质组合物包含至少一种旨在抑制 TTR 聚集的多肽，该多肽通常与异源氨基酸标签相连。此外，还可包括一种药学上可接受的载体，该载体经选择可与抑制肽相容。还提供了一种阻断或抑制转甲状腺素 TTR 聚集的方法。该方法包括将 TTR 与有效量的抑制肽或药物组合物结合，从而阻断或抑制 TTR 的聚集和/或细胞毒性。