<(6-hydroxyhexyl)carbonimidoyl>biscarbamic acid, bis(1,1-dimethylethyl) ester | 221249-13-4

• 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: <(6-hydroxyhexyl)carbonimidoyl>biscarbamic acid, bis(1,1-dimethylethyl) ester
• 英文别名: bis-boc 6-guanidino-1-hexanol；N,N'-Bis(Boc)-N''-(6-hydroxyhexyl)guanidine；tert-butyl N-[N'-(6-hydroxyhexyl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 221249-13-4
• 化学式: C₁₇H₃₃N₃O₅
• 分子量: 359.466
• InChiKey: PRQGGVCRJADZTB-UHFFFAOYSA-N

物化性质

• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  <(6-hydroxyhexyl)carbonimidoyl>biscarbamic acid, bis(1,1-dimethylethyl) ester 在 三乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 18.25h， 生成 <(6-aminomethylhexyl)carbonimidoyl>bis-carbamic acid, bis(1,1-dimethylethyl)ester
  参考文献：
  名称：

  Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 1. Structural Modifications of the Hydroxyglycine Moiety

  摘要：

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm980431g
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 碳酸氢钠 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 168.0h， 生成 <(6-hydroxyhexyl)carbonimidoyl>biscarbamic acid, bis(1,1-dimethylethyl) ester
  参考文献：
  名称：

  设计和合成新型SCM-198类似物作为心脏保护剂：结构-活性关系研究和生物学评估。

  摘要：

  SCM-198（Leonurine）由于其对心肌梗死（MI）的心脏保护作用而引起了极大的关注。但是，到目前为止，尚无系统的修改和结构-活性关系（SAR）研究。在这项研究中，设计，合成了35种SCM-198类似物，并评估了它们的心脏保护作用。上的心肌细胞的细胞系的H9c2细胞生存力测定用H挑战2 ö 2表明几个类似物表现出比更有效的细胞保护作用SCM-198在1  μ M和10  μ M之间的浓度。在用1处理的细胞的LDH释放水平 μ中号140是可比较与细胞与10处理 μM SCM-198。因此，Bcl-2表达和caspase-3活化的结果表明14o的保护活性高于SCM-198。而且，在MI小鼠模型中，用14o预处理的小鼠的梗死面积比SCM-198小得多。机制研究表明14o改善了心脏形态，并减少了梗死边缘区域心肌细胞的凋亡，这已通过H＆E和TUNEL染色证明。

  DOI：

  10.1016/j.ejmech.2020.112469

文献信息

• [EN] CELL-PENETRATING, GUANIDINIUM-RICH OLIGOPHOSPHOTRIESTERS FOR DRUG AND PROBE DELIVERY<br/>[FR] OLIGOPHOSPHOTRIESTERS RICHES EN GUANIDINIUM À PÉNÉTRATION CELLULAIRE POUR L'ADMINISTRATION DE MÉDICAMENT ET DE SONDE
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2017083637A1

  公开（公告）日：2017-05-18

  Guanidinium-rich oligophosphotriesters transporter compounds and methods of making and using the same are provided. Also provided are pharmaceutical compositions that include the subject transporter compounds, where the transporter can be joined to a cargo of interest, and is formulated with a pharmaceutically acceptable excipient. Formulations may be provided in a unit dose, where the dose provides an amount of the compound effective to afford a desired therapeutic effect. Methods of using the subject transporter compounds to deliver a cargo moiety to a cell are provided, where the method can include contacting a target cell with the transporter compound. The subject methods can be performed in vitro or in vivo.

  提供了富含胍基的寡磷酸三酯转运化合物及其制备和使用方法。还提供了包括所述转运化合物的制药组合物，其中转运体可以与感兴趣的荷物结合，并且与药用可接受的赋形剂配制。可以提供单剂量的配方，其中剂量提供了有效的化合物量，以提供所需的治疗效果。提供了使用所述转运化合物将荷物基团传递至细胞的方法，其中该方法可以包括将转运化合物与目标细胞接触。所述方法可以在体外或体内执行。
• [EN] IMMOLATIVE CELL-PENETRATING COMPLEXES FOR NUCLEIC ACID DELIVERY<br/>[FR] COMPLEXES DE PÉNÉTRATION CELLULAIRE IMMOLATEURS POUR L'ADMINISTRATION D'ACIDES NUCLÉIQUES
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2018022930A1

  公开（公告）日：2018-02-01

  There are provided herein, inter alia, complexes, compositions and methods for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acid, into a cell. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

  本文提供了用于将治疗性、诊断性和成像剂（包括核酸）输送到细胞内的复合物、组合物和方法。这些复合物、组合物和方法可以促进寡核苷酸和多阴离子载体与靶细胞、组织和器官的复合、保护、传递和释放，无论是在体外还是体内。
• [EN] ANTIMICROBIAL GUANIDINIUM AND THIOURONIUM FUNCTIONALIZED POLYMERS<br/>[FR] POLYMÈRES FONCTIONNALISÉS PAR GUANIDINIUM ET THIOURONIUM ANTIMICROBIENS
  申请人：AGENCY SCIENCE TECH & RES

  公开号：WO2016186581A1

  公开（公告）日：2016-11-24

  Antimicrobial cationic polycarbonates and polyurethanes have been prepared comprising one or more pendent guanidinium and/or isothiouronium groups. Additionally, antimicrobial particles were prepared having a silica core linked to surface groups comprising a guanidinium and/or isothiouronium group. The cationic polymers and cationic particles can be potent antimicrobial agents against Gram-negative microbes, Gram-positive microbes, and/or fungi.

  已制备含有一个或多个侧链胍啉和/或异硫脲基团的抗菌阳离子聚碳酸酯和聚氨酯。此外，制备了含有硅核心的抗菌颗粒，其与表面基团相连，包括一个胍啉和/或异硫脲基团。这些阳离子聚合物和阳离子颗粒可以是对革兰氏阴性微生物、革兰氏阳性微生物和/或真菌具有强效抗菌作用的剂。
• PEPTIDE DERIVATIVES AND MEDICINAL COMPOSITIONS
  申请人：Nippon Shinyaku Co., Ltd.

  公开号：EP1275657A1

  公开（公告）日：2003-01-15

  An object of the present invention is to provide a novel nociceptin receptor agonist. The present invention relates to a peptide derivative represented by the following general formula (1):    (in which A represents alkylene, -(CH2)nCO- or a group represented by the following formula (2) or (3): wherein n represents an integer of 1 to 8; X and Y are same or different and each represents -CONH- or -CH2NH-; R1, R2 and R3 are same or different and each represents alkyl, aryl or heteroaryl; Z represents -CON(R4)R5 or -CH2N(R4)R5; and R4 and R5 are same or different and each represents hydrogen, alkyl, aryl or heteroaryl) or a pharmaceutically acceptable salt thereof. A pharmaceutical composition according to the present invention is useful as a nociceptin receptor agonist.

  本发明的目的是提供一种新型痛觉素受体激动剂。 本发明涉及一种由下式通式（1）代表的肽衍生物： (其中 A 代表亚烷基、-(CH2)nCO- 或下式(2)或(3)所代表的基团： 其中 n 代表 1 至 8 的整数；X 和 Y 相同或不同，各自代表-CONH-或-CH2NH-；R1、R2 和 R3 相同或不同，各自代表烷基、芳基或杂芳基；Z 代表-CON(R4)R5 或-CH2N(R4)R5；R4 和 R5 相同或不同，各自代表氢、烷基、芳基或杂芳基）或其药学上可接受的盐。 根据本发明的药物组合物可用作痛觉素受体激动剂。
• Cell-penetrating, guanidinium-rich oligophosphotriesters for drug and probe delivery
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10654875B2

  公开（公告）日：2020-05-19

  Guanidinium-rich oligophosphotriesters transporter compounds and methods of making and using the same are provided. Also provided are pharmaceutical compositions that include the subject transporter compounds, where the transporter can be joined to a cargo of interest, and is formulated with a pharmaceutically acceptable excipient. Formulations may be provided in a unit dose, where the dose provides an amount of the compound effective to afford a desired therapeutic effect. Methods of using the subject transporter compounds to deliver a cargo moiety to a cell are provided, where the method can include contacting a target cell with the transporter compound. The subject methods can be performed in vitro or in vivo.

  本发明提供了富含胍基的低聚磷酸酯转运体化合物及其制造和使用方法。此外，还提供了包括主题转运体化合物的药物组合物，其中转运体可与相关货物连接，并与药学上可接受的赋形剂配制。制剂可以单位剂量提供，其中的剂量提供有效的化合物量，以获得所需的治疗效果。提供了使用主题转运体化合物向细胞递送货物的方法，其中该方法可包括用转运体化合物接触靶细胞。所述方法可在体外或体内进行。