N2,N5-二[芴甲氧羰基]-L-鸟氨酸 | 201046-59-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N2,N5-二[芴甲氧羰基]-L-鸟氨酸
• 中文别名: N,N'-双-Fmoc-L-鸟氨酸；N,N'-双-FMOC-L-鸟氨酸
• 英文名称: Fmoc-Orn(Fmoc)-OH
• 英文别名: (2S)-2,5-bis(9H-fluoren-9-ylmethoxycarbonylamino)pentanoic acid
• CAS: 201046-59-5
• 化学式: C₃₅H₃₂N₂O₆
• 分子量: 576.649
• InChiKey: HFKOCIWEYMAENQ-YTTGMZPUSA-N

物化性质

• 沸点：
  830.7±65.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件：2-8℃，干燥密封

反应信息

• 作为反应物：
  描述：

  N2,N5-二[芴甲氧羰基]-L-鸟氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 、 N-甲基吡咯烷酮 为溶剂， 反应 2.5h， 生成 C₅H₁₂N₃OPol
  参考文献：
  名称：

  A fast entry to the novel medicinally-important 9-anilinoacridine peptidyls by solid phase organic synthesis (SPOS)

  摘要：

  A new approach to the synthesis of novel medicinally-important mono- and bis-9-anilinoacridine (9-AnA) peptidyl derivatives is described. The method generates efficiently 9-AnAs with variable spacer lengths and charged, polar or hydrophobic residues at desired positions, which can increase binding affinity, conformational stability, intracellular transport and/or biological activity. The synthetic routes reported in this work are both general and applicable, and significantly expand the scope of potential 9-aminoacridine (9-AA) anticancer candidates. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.05.023
• 作为产物：
  描述：

  L-鸟氨酸 、 氯甲酸-9-芴基甲酯 以provided the title product in 79% yield的产率得到N2,N5-二[芴甲氧羰基]-L-鸟氨酸
  参考文献：
  名称：

  Amino acid derivatives as HIV aspartyl protease inhibitors

  摘要：

  本发明涉及一类具有HIV天冬氨酸蛋白酶抑制作用的氨基酸衍生物。

  公开号：

  US06455587B1

文献信息

• A novel isocyanide based three component reactionElectronic Supplementary Information (ESI) available: experimental and spectroscopic data. See http://www.rsc.org/suppdata/cc/b3/b310962c/
  作者：Oliver T. Kern、William B. Motherwell

  DOI：10.1039/b310962c

  日期：——

  A three component reaction involving an isocyanide, a carboxylic acid and an epoxide or aziridine is described.

  描述了一种涉及异氰化物、羧酸和环氧化物或氮丙啶的三组分反应。
• [EN] PEPTIDE CONJUGATES AND METHODS OF USE<br/>[FR] CONJUGUÉS PEPTIDIQUES ET MÉTHODES D'UTILISATION
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2021113535A1

  公开（公告）日：2021-06-10

  Peptide conjugates comprising a peptide selected from a peptide that modulates the PYY receptor, a peptide that modulates both the GLP-1 receptor and the GCG receptor, a peptide that modulates both the GLP-1 receptor and the GIP receptor, and a peptide that modulates the GLP-1 receptor; and a staple attached to the peptide at a first amino acid and a second amino acid are disclosed herein. Also provided are peptide conjugates comprising prolactin-releasing peptide. The peptide conjugates may be used for treating conditions such as obesity. Further provided are stapled prolactin-releasing peptide.

  本文披露了包括以下内容的肽共轭物：选择自可调节PYY受体的肽、可调节GLP-1受体和GCG受体的肽、可调节GLP-1受体和GIP受体的肽、以及可调节GLP-1受体的肽；以及连接到肽的稳定剂，在第一个氨基酸和第二个氨基酸处连接。还提供了包括催乳素释放肽的肽共轭物。这些肽共轭物可用于治疗肥胖等疾病。此外，还提供了稳定的催乳素释放肽。
• [EN] MCL-1 INHIBITOR ANTIBODY-DRUG CONJUGATES AND METHODS OF USE<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT INHIBITEURS DE MCL-1 ET PROCÉDÉS D'UTILISATION
  申请人：NOVARTIS AG

  公开号：WO2022115451A1

  公开（公告）日：2022-06-02

  Anti-CD48 antibody-drug conjugates are disclosed. The anti-CD48 antibody-drug conjugates comprise an Mcl-1 inhibitor drug moiety and an anti-CD48 antibody or antigen-binding fragment thereof that binds an antigen target, e.g., an antigen expressed on a tumor or other cancer cell. The disclosure further relates to methods and compositions for use in the treatment of cancers by administering the antibody-drug conjugates provided herein. Linker-drug conjugates comprising an Mcl-1 inhibitor drug moiety and methods of making same are also disclosed.

  本文披露了抗CD48抗体药物结合物。该抗CD48抗体药物结合物包括Mcl-1抑制剂药物部分和抗CD48抗体或其抗原结合片段，其结合抗原靶点，例如在肿瘤或其他癌细胞上表达的抗原。本文进一步涉及使用所提供的抗体药物结合物治疗癌症的方法和组合物。还披露了包含Mcl-1抑制剂药物部分的连接体-药物结合物和制备方法。
• Design and synthesis of water-soluble prodrugs of rifabutin for intraveneous administration
  作者：Kevin Antraygues、Mathieu Maingot、Birgit Schellhorn、Vincent Trebosc、Marc Gitzinger、Benoit Deprez、Olivier Defert、Glenn E. Dale、Marilyne Bourotte、Sergio Lociuro、Nicolas Willand

  DOI：10.1016/j.ejmech.2022.114515

  日期：2022.8

  prevalent in many hospitals. Consequently, the World Health Organization made this bacterium a critical priority for the research and development of new antibiotics. Rifabutin, a semisynthetic product from the rifamycin class, was recently found to be very active in nutrient-limited eukaryotic cell culture medium against various A. baumannii strains, including extremely drug-resistant strains, with minimal

  鲍曼不动杆菌是一种革兰氏阴性细菌，可引起严重的医院获得性感染，例如血流感染或肺炎。此外，耐多药鲍曼不动杆菌在许多医院变得普遍。因此，世界卫生组织将这种细菌作为研发新抗生素的重中之重。Rifabutin 是一种来自利福霉素类的半合成产品，最近被发现在营养有限的真核细胞培养基中对各种鲍曼不动杆菌菌株（包括极耐药菌株）非常有效，最低抑制浓度低至 0.008 μg/mL . 此外，这种体外效力转化为体内功效。因此，利福布丁似乎是一种有吸引力的新型抗鲍曼不动杆菌抗生素。在这项工作中，我们的目标是设计和合成水溶性增加的利福布汀前药，以允许静脉内使用。开发了合成方法以选择性地官能化 21 位的羟基并提供 17 种前药。我们测量了前药的水溶性、在人和小鼠血浆中的稳定性以及它们在人血清中孵育后对鲍曼不动杆菌的抗菌活性。最后，在 CD1 小鼠中进行了利福布丁的药代动力学释放研究，其中三种选定的前药作为概念证明。
• Engineering of a Potent, Long-Acting NPY2R Agonist for Combination with a GLP-1R Agonist as a Multi-Hormonal Treatment for Obesity
  作者：Sam Lear、Elsa Pflimlin、Zhihong Zhou、David Huang、Sharon Weng、Van Nguyen-Tran、Sean B. Joseph、Shane Roller、Scott Peterson、Jing Li、Matthew Tremblay、Peter G. Schultz、Weijun Shen

  DOI：10.1021/acs.jmedchem.0c00740

  日期：2020.9.10

  Bariatric surgery results in increased intestinal secretion of hormones GLP-1 and anorexigenic PYY, which is believed to contribute to the clinical efficacy associated with the procedure. This observation raises the question whether combination treatment with gut hormone analogs might recapitulate the efficacy and mitigate the significant risks associated with surgery. Despite PYY demonstrating excellent efficacy and safety profiles with regard to food intake reduction, weight loss, and glucose control in preclinical animal models, PYY-based therapeutic development remains challenging given a low serum stability and half-life for the native peptide. Here, combined peptide stapling and PEG-fatty acid conjugation affords potent PYY analogs with >14 h rat half-lives, which are expected to translate into a human half-life suitable for once-weekly dosing. Excellent efficacy in glucose control, food intake reduction, and weight loss for lead candidate 22 in combination with our previously reported long-acting GLP-1 analog is demonstrated in a diet-induced obesity mouse model.