5-[(1R,2S,5S)-7-氧代-3-硫杂-6,8-二氮杂双环[3.3.0]辛-2-基]戊酰胺 | 6929-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫杂环戊烷
• 中文名称: 5-[(1R,2S,5S)-7-氧代-3-硫杂-6,8-二氮杂双环[3.3.0]辛-2-基]戊酰胺
• 英文名称: biotin
• 英文别名: 5-((3aS)-2-oxo-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl)-valeric acid amide；5-((3aS)-2-Oxo-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl)-valeriansaeure-amid；biotin amide；Biotinamid；Biotinamide；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanamide
• CAS: 6929-42-6
• 化学式: C₁₀H₁₇N₃O₂S
• 分子量: 243.33
• InChiKey: XFLVBMBRLSCJAI-ZKWXMUAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	biotin chloride	91853-90-6	C10H15ClN2O2S	262.76
  D-生物素甲酯	biotin methyl ester	608-16-2	C11H18N2O3S	258.342

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(2S,3S)-3-((S)-4-methyl-1-oxo-1-(4-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)butylamino)pentan-2-ylcarbamoyl)oxirane-2-carboxylic acid	149697-17-6	C24H39N5O7S	541.669

反应信息

• 作为反应物：
  描述：

  5-[(1R,2S,5S)-7-氧代-3-硫杂-6,8-二氮杂双环[3.3.0]辛-2-基]戊酰胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 (2S,3R)-ethyl 3-((S)-4-methyl-1-oxo-1-(4-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)butylamino)pentan-2-ylcarbamoyl)oxirane-2-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Optimization of Novel Epoxide Incorporating Peptidomimetics as Selective Calpain Inhibitors

  摘要：

  Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Call) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Call. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Call catalytic domain (Call(cat)), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Call inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Call with the genera l cysteine protease papain.

  DOI：

  10.1021/jm4006719
• 作为产物：
  描述：

  D-生物素甲酯 在 ammonium hydroxide 作用下， 生成 5-[(1R,2S,5S)-7-氧代-3-硫杂-6,8-二氮杂双环[3.3.0]辛-2-基]戊酰胺
  参考文献：
  名称：

  Amides and Amino Acid Derivatives of Biotin

  摘要：

  DOI：

  10.1021/ja01153a027

文献信息

• Water soluble multi-biotin-containing compounds
  申请人：Wilbur Scott D.

  公开号：US20060228325A1

  公开（公告）日：2006-10-12

  Water-soluble discrete multi-biotin-containing compounds with at least three (3) biotin moieties are disclosed. The water-soluble biotin-containing compounds may additionally comprise one or more moieties that confer resistance to cleavage by biotinidase or that is cleavable in vitro or in vivo. The discrete multi-biotin-containing compounds may include a reactive moiety that provides a site for reaction with yet another moiety, such as a targeting, diagnostic or therapeutic functional moiety. Biotinylation reagents comprising water-soluble linker moieties are also disclosed and may additionally comprise a biotinidase protective group. Methods for amplifying the number of sites for binding biotin-binding proteins at a selected target using multi-biotin compounds also are disclosed.

  可溶于水的离散多生物素含有化合物，至少含有三个（3）生物素基团。这些可溶于水的生物素含有化合物可能还包括一个或多个使其对生物素酶的裂解具有抗性的基团，或者在体外或体内可被裂解的基团。这些离散的多生物素含有化合物可能包括一个反应性基团，提供与另一个基团（如靶向、诊断或治疗功能基团）反应的位点。还公开了包含可溶于水的连接基团的生物素化试剂，可能还包括生物素酶保护基团。还公开了使用多生物素化合物扩增在选定靶点上结合生物素结合蛋白的位点数量的方法。
• [EN] METHODS FOR TREATING MELANOMA USING SMALL MOLECULES AND SMALL INTERFERING RNA (SIRNA)<br/>[FR] PROCÉDÉS DE TRAITEMENT DE MÉLANOME À L'AIDE DE PETITES MOLÉCULES ET DE PETITS ARN INTERFÉRENTS (ARNSI)
  申请人：UNIV NOVA SOUTHEASTERN

  公开号：WO2018112443A1

  公开（公告）日：2018-06-21

  The invention provides methods for treating cancers, such as melanoma and/or metastatic melanoma, using compounds that interact with and/or inhibit cellular proteins lamin A/C, ATP-dependent RNA helicase DDXl (DDXl), heterogeneous nuclear ribonuclear protein H1/H2 (hnRNP H2), and/or heterogeneous nuclear ribonuclear protein A2/B1 (hnRNP A2/B 1). The invention additionally provides a method for identifying compounds active against melanoma cells.

  该发明提供了一种治疗癌症的方法，如黑色素瘤和/或转移性黑色素瘤，使用与细胞蛋白lamin A/C，ATP依赖性RNA解旋酶DDXl（DDXl），异质核糖核酸蛋白H1/H2（hnRNP H2）和/或异质核糖核酸蛋白A2/B1（hnRNP A2/B1）相互作用和/或抑制的化合物。该发明还提供了一种识别对黑色素瘤细胞有效的化合物的方法。
• [EN] POLYOXAZOLINE ANTIBODY DRUG CONJUGATES<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT DE POLYOXAZOLINE
  申请人：SERINA THERAPEUTICS INC

  公开号：WO2016019340A1

  公开（公告）日：2016-02-04

  In the present disclosure, polymer conjugates, including polymer-antibody-drug conjugates (polymer ADCs) are described, as well as the use of such conjugates to treat human disease. The polymer conjugates can contain a large number of polymer-bound agents, thus effectively increasing the drug antibody ration (DAR) of the antibody significantly beyond the currently available technology. This may be of particular importance when antibodies to low density antigens are used as target antibodies. The described polymer-ADCs have improved pharmacokinetics and solubility relative to traditional ADCs. The linker between agent and the polymer can be tailored to provide release of toxin at the desired site and under the desired conditions within the tumor. An additional feature of the polymer-ADCs of the current disclosure is that a purification moiety can be attached to the polymer backbone to provide ease of purification of the polymer-ADCs.

  本公开描述了聚合物偶联物，包括聚合物-抗体-药物偶联物（聚合物ADCs），以及使用这些偶联物治疗人类疾病。该聚合物偶联物可以含有大量的聚合物结合剂，从而有效提高抗体的药物抗体比率（DAR），显著超过目前现有技术。当使用针对低密度抗原的抗体作为靶点抗体时，这一点可能尤为重要。与传统的ADC相比，所述聚合物ADC具有改善的药代动力学和溶解性。毒素与聚合物之间的连接器可以根据需要在肿瘤内特定部位和特定条件下释放毒素进行定制。当前公开的聚合物ADC的另一个特点是，可以在聚合物主链上附着一个纯化部分，以提供聚合物ADC的纯化便利。
• Near-Infrared Light-Initiated Molecular Superoxide Radical Generator: Rejuvenating Photodynamic Therapy against Hypoxic Tumors
  作者：Mingle Li、Jing Xia、Ruisong Tian、Jingyun Wang、Jiangli Fan、Jianjun Du、Saran Long、Xiangzhi Song、James W. Foley、Xiaojun Peng

  DOI：10.1021/jacs.8b08658

  日期：2018.11.7

  application for in vivo targeted hypoxic solid tumor ablation. Photomediated radical generation mechanism study shows that, even under severe hypoxic environment (2% O2), ENBS-B can generate considerable O2-• through type I photoreactions, and partial O2-• is transformed to high toxic OH· through SOD-mediated cascade reactions. These radicals synergistically damage the intracellular lysosomes, which subsequently

  缺氧是大多数实体瘤的普遍特征，被认为是传统光动力疗法 (PDT) 的“阿喀琉斯之踵”，严重损害了整体治疗效果。在此，我们开发了一种近红外 (NIR) 光触发分子超氧自由基 (O2-•) 发生器 (ENBS-B) 来克服这个棘手的问题，并揭示其抗缺氧作用背后的详细 O2-• 作用机制，并证实其在体内靶向缺氧实体瘤消融中的应用。光介导自由基生成机制研究表明，即使在严重缺氧环境（2% O2）下，ENBS-B也能通过I型光反应产生大量O2-•，部分O2-•通过SOD介导的级联反应转化为剧毒的OH·反应。这些自由基协同破坏细胞内溶酶体，随后触发癌细胞凋亡，呈现强大的缺氧 PDT 效力。体外共培养模型表明，受益于生物素配体，ENBS-B 在癌细胞中的细胞摄取比正常细胞高 87 倍，为个性化医疗提供了机会。静脉给药后，ENBS-B 能够特异性靶向肿瘤组织，并在低光剂量照射下完全抑制肿瘤生长。因此，我们假
• Phthalocyanine dyes
  申请人：LI-COR, Inc.

  公开号：US20040171827A1

  公开（公告）日：2004-09-02

  Fluorescent dyes are disclosed which are useful as reporter groups for labeling biomolecules. The silicon phthalocyanine dyes disclosed are preferably water soluble, isomericly pure, possess high quantum yield, and are useful in bioassays.

  荧光染料被披露，这些染料可作为标记生物分子的报告基团。所披露的硅酞菁染料最好是水溶性的，同分异构体纯净，具有高量子产率，并且在生物分析中很有用。