(9H-fluoren-9-yl)methyl dihydrogen phosphate

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (9H-fluoren-9-yl)methyl dihydrogen phosphate
• 英文别名: 9H-fluoren-9-ylmethyl dihydrogen phosphate
• 化学式: C₁₄H₁₃O₄P
• 分子量: 276.229
• InChiKey: BQDRQMYZLGTHJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (9H-fluoren-9-yl)methyl dihydrogen phosphate 在 三丁基焦磷酸铵 、 N,N'-羰基二咪唑 作用下， 生成 9-fluorenylmethyl triphosphate
  参考文献：
  名称：

  Structure-functional analysis of interactions of terminal deoxynucleotidyl transferase with new non-nucleoside substrates

  摘要：

  New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-(2-tripticencarbonyl)-4-aminobutyl; (2) 5-phenylsubstituted N-(2,4-dinitrophenyl)-4-aminobutyl; (3) N-(4-phenylbenzoyl)- and N-(4-(N-benzylamino)benzoyl)-2-aminoethyl groups, as well as (4) diphenylmethyl and fluorenyl groups were synthesized and studied as substrates of terminal deoxynucleotidyl transferase. With the exception of the two latter derivatives, all the analogues displayed substrate properties and could incorporate into the deoxyoligonucleotide 3'-end. As it was shown in biochemical experiments and by computer modeling, a linker joining the triphosphate and hydrophobic fragments of the molecule was necessary for these compounds to display substrate properties.

  DOI：

  10.1134/s1068162009030091
• 作为产物：
  描述：

  9-芴甲醇 在 四氯三氧化二磷 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以95%的产率得到(9H-fluoren-9-yl)methyl dihydrogen phosphate
  参考文献：
  名称：

  发现焦磷酸二酯作为位点特异性抗体-药物偶联物的可调、可溶和生物正交接头

  摘要：

  作为检查抗体-药物偶联物 (ADC) 在肿瘤学适应症之外的效用的努力的一部分，发现了一种新型焦磷酸酯接头，可以实现糖皮质激素的靶向递送。作为小分子，这些高可溶性磷酸酯药物接头被发现具有理想的正交特性：强大的血浆稳定性以及在溶酶体环境中快速释放有效载荷。在这些发现的基础上，在这种药物接头组合和一种抗人类 CD70 的抗体之间制造了位点特异性 ADC，CD70 是一种在免疫细胞中特异性表达但也在多种人类癌症中异常表达的受体。这些 ADC 的完整表征使流程能够进行体外概念验证，其中 ADC 1-22 和 1-37 被证明能够提供有效的、根据糖皮质激素受体介导的基因 mRNA 水平的变化，将糖皮质激素靶向递送至代表性细胞系。发现这些活动依赖于抗体、接头和有效载荷。初步机制研究支持这样一种观点，即活性需要溶酶体运输和酶促接头裂解，并且焦磷酸盐接头的效用对于内化 ADC 以及其他靶向递送平台可能是通用的。

  DOI：

  10.1021/jacs.5b12547

文献信息

• [EN] PHOSPHATE BASED LINKERS FOR INTRACELLULAR DELIVERY OF DRUG CONJUGATES<br/>[FR] LIEURS À BASE DE PHOSPHATES POUR INTRODUCTION INTRACELLULAIRE DE CONJUGUÉS MÉDICAMENTEUX
  申请人：MERCK SHARP & DOHME

  公开号：WO2015153401A1

  公开（公告）日：2015-10-08

  Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).

  描述了一种具有可调稳定性的磷酸酯基连接剂，用于药物共轭物的细胞内传递。这种磷酸酯基连接剂包括一个磷酸单酯、磷酸二酯、磷酸三酯或磷酸四酯基团（磷酸基团）和一个连接臂，包括一个调节元素和可选的间隔物。有效载荷以共价键连接到连接臂的远端的磷酸基团上，连接臂的近端的功能基团以共价键连接到细胞特异性靶向配体，如抗体。这些磷酸酯基连接剂在血液和细胞内环境（例如溶酶体区）中具有不同和可调的稳定性。
• Use of HSP20 for promoting wound healing and/or reducing scar formation
  申请人：ARIZONA BOARD OF REGENTS

  公开号：EP1808179A2

  公开（公告）日：2007-07-18

  The present invention provides methods for promoting wound healing and/or reducing scar formation, by administering to an individual in need thereof one or more of the heat shock protein 20-derived polypeptides disclosed herein.

  本发明提供了促进伤口愈合和/或减少疤痕形成的方法，方法是向有需要的个体施用一种或多种本文公开的热休克蛋白 20 衍生多肽。
• HSP20 peptides
  申请人：Arizona Board Of Regents

  公开号：EP2301563A2

  公开（公告）日：2011-03-30

  The present invention provides novel polypeptides comprising heat shock protein 20 (HSP20)-derived polypeptides to treat or inhibit smooth muscle vasospasm, as well to treat and inhibit smooth muscle cell proliferation and migration.

  本发明提供了由热休克蛋白 20（HSP20）衍生的多肽组成的新型多肽，用于治疗或抑制平滑肌血管痉挛，以及治疗和抑制平滑肌细胞增殖和迁移。
• Phosphate based linkers for intracellular delivery of drug conjugates
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10550190B2

  公开（公告）日：2020-02-04

  Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).

  本文描述了用于细胞内输送药物共轭物的稳定性可调的磷酸盐基连接体。磷酸盐基连接体包括一个单磷酸、二磷酸、三磷酸或四磷酸基团（磷酸盐基团）和一个连接臂，连接臂包括一个调谐元件和可选的间隔物。有效载荷与连接臂远端磷酸基团共价连接，连接臂近端官能团与细胞特异性靶向配体（如抗体）共价连接。这些基于磷酸盐的连接体在血液与细胞内环境（如溶酶体区）中具有不同的可调稳定性。
• Vasoactive polypeptides for smooth muscle relaxation
  申请人：Vanderbilt University

  公开号：US11149064B2

  公开（公告）日：2021-10-19

  A polypeptide, a pharmaceutical composition including a polypeptide, and a method for treating a condition using a polypeptide are provided. The polypeptide includes an amino acid sequence according to the general formula X1-X2-X3, wherein X1 and X3 are independently absent or comprise a transduction domain, X2 includes Z3, and Z3 is selected from the group consisting of serine or phosphoserine analogs. The pharmaceutical composition includes a polypeptide including an amino acid sequence according to the general formula X1-X2-X3 and one or more components selected from the group consisting of a pharmaceutically acceptable carrier, a calcium channel blocker, and a combination thereof. X1 and X3 are independently absent or comprise a transduction domain, X2 includes Z3, and Z3 is selected from the group consisting of serine or phosphoserine analogs. The method of treating a condition includes administering a polypeptide including an amino acid sequence according to the general formula X1-X2-X3 to a subject in need thereof, wherein X1 and X3 are independently absent or comprise a transduction domain, X2 includes Z3, and Z3 is selected from the group consisting of serine or phosphoserine analogs. Also provided is a biomedical device including a polypeptide.

  本发明提供了一种多肽、一种包括多肽的药物组合物以及一种使用多肽治疗疾病的方法。多肽包括根据通式X1-X2-X3的氨基酸序列，其中X1和X3独立地不存在或包括转导结构域，X2包括Z3，Z3选自由丝氨酸或磷酸丝氨酸类似物组成的组。药物组合物包括包括通式 X1-X2-X3 的氨基酸序列的多肽和一种或多种选自由药学上可接受的载体、钙通道阻滞剂及其组合组成的组的成分。X1和X3独立地不存在或包括转导结构域，X2包括Z3，Z3选自由丝氨酸或磷酸丝氨酸类似物组成的组。治疗疾病的方法包括向有需要的受试者施用包括根据通式 X1-X2-X3 的氨基酸序列的多肽，其中 X1 和 X3 独立地不存在或包括转导结构域，X2 包括 Z3，Z3 选自丝氨酸或磷酸丝氨酸类似物组成的组。还提供了一种包括多肽的生物医学装置。