4'-hydroxybiphenyl-4-acetic acid NHS ester | 1072896-40-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4'-hydroxybiphenyl-4-acetic acid NHS ester
• 英文别名: N-hydroxysuccinimide ester of 4'-hydroxybiphenyl-4-acetic acid；succinimido (4'-hydroxy-1,1'-biphenyl-4-yl)acetate；(2,5-Dioxopyrrolidin-1-yl) 2-[4-(4-hydroxyphenyl)phenyl]acetate
• CAS: 1072896-40-2
• 化学式: C₁₈H₁₅NO₅
• 分子量: 325.321
• InChiKey: DELXYNUYOFTLMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4'-hydroxybiphenyl-4-acetic acid NHS ester 、 p-methoxyphenyl (9-amino-3,5,9-trideoxy-5-glycolamido-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2->6)-β-D-galactopyranoside 在 碳酸氢钠 作用下， 以 水 、 乙腈 为溶剂， 反应 48.0h， 以72%的产率得到p-methoxyphenyl (3,5,9-trideoxy-5-glycolamido-9-(4'-hydroxy-4-biphenyl)-acetamido-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2->6)-β-D-galactopyranoside
  参考文献：
  名称：

  Design, Synthesis, and Structure−Affinity Relationships of Novel Series of Sialosides as CD22-Specific Inhibitors

  摘要：

  Sialosides incorporating substituted amides or amines at 9-position of sialic acid moiety have been synthesized and evaluated as CD22 inhibitors. Several derivatives exhibited inhibitory potency in sub- to low micromolar range (e. g., 8o, 9d, 9g, and 9k showed IC50 values 0.40, 0.47, 0.24, and 0.23 mu M, respectively, for hCD22, while 8p. 8q, and 9f, showed IC50 values 1.70, 2.90, and 4.10 mu M, respectively, for mCD22). The most significant result was the strongly enhanced affinity of 9g and 9k containing 9-(2' or 4'-hydroxy-4-biphenyl) methylamino substituents (600-fold more potent for hCD22 than the corresponding 9-hydroxy derivative; 7a). Molecular modeling study was carried out to get some insights into the molecular basis of CD22 inhibition. To the best of our knowledge, this is the first systematic structure-affinity relationship study on inhibition of CD22.

  DOI：

  10.1021/jm8000696
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 4'-羟基联苯-4-羧酸 在 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 为溶剂， 反应 24.0h， 生成 4'-hydroxybiphenyl-4-acetic acid NHS ester
  参考文献：
  名称：

  Design, Synthesis, and Structure−Affinity Relationships of Novel Series of Sialosides as CD22-Specific Inhibitors

  摘要：

  Sialosides incorporating substituted amides or amines at 9-position of sialic acid moiety have been synthesized and evaluated as CD22 inhibitors. Several derivatives exhibited inhibitory potency in sub- to low micromolar range (e. g., 8o, 9d, 9g, and 9k showed IC50 values 0.40, 0.47, 0.24, and 0.23 mu M, respectively, for hCD22, while 8p. 8q, and 9f, showed IC50 values 1.70, 2.90, and 4.10 mu M, respectively, for mCD22). The most significant result was the strongly enhanced affinity of 9g and 9k containing 9-(2' or 4'-hydroxy-4-biphenyl) methylamino substituents (600-fold more potent for hCD22 than the corresponding 9-hydroxy derivative; 7a). Molecular modeling study was carried out to get some insights into the molecular basis of CD22 inhibition. To the best of our knowledge, this is the first systematic structure-affinity relationship study on inhibition of CD22.

  DOI：

  10.1021/jm8000696

文献信息

• Design and Synthesis of a Multivalent Heterobifunctional CD22 Ligand as a Potential Immunomodulator
  作者：Hajjaj Abdu-Allah、Makoto Kiso、Kozo Watanabe、Shusaku Daikoku、Osamu Kanie、Takeshi Tsubata、Hiromune Ando、Hideharu Ishida

  DOI：10.1055/s-0030-1260151

  日期：2011.9

  We describe the design and synthesis of a trivalent CD22 ligand conjugated with a trivalent nitrophenol (ligand for decameric anti-nitrophenol immunoglobulin M). To generate such a bifunctional ligand, we designed and prepared two synthetic building blocks possessing different terminal functionalities. Coupling of these compounds afforded a trivalent azide-terminated scaffold. Ligation of the scaffold with an alkyne-terminated CD22 ligand by the use of click chemistry afforded the target trivalent cluster. We anticipate that our ligand will be valuable in a variety of applications, including targeting B cells and modulation of the humoral immune response.

  我们描述了与三价硝基苯酚（十聚抗硝基苯酚免疫球蛋白 M 的配体）缀合的三价 CD22 配体的设计和合成。为了生成这样的双功能配体，我们设计并制备了两种具有不同末端功能的合成结构单元。这些化合物的偶联提供了三价叠氮化物封端的支架。通过使用点击化学将支架与炔烃封端的 CD22 配体连接，得到目标三价簇。我们预计我们的配体将在多种应用中发挥价值，包括靶向 B 细胞和调节体液免疫反应。
• CD22-Antagonists with nanomolar potency: The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold
  作者：Hajjaj H.M. Abdu-Allah、Kozo Watanabe、Gladys C. Completo、Magesh Sadagopan、Koji Hayashizaki、Chiaki Takaku、Taichi Tamanaka、Hiromu Takematsu、Yasunori Kozutsumi、James C. Paulson、Takeshi Tsubata、Hiromune Ando、Hideharu Ishida、Makoto Kiso

  DOI：10.1016/j.bmc.2011.01.060

  日期：2011.3

  In earlier studies, we identified the C-9 amido derivative 1 (9-(4'-hydroxy-4-biphenyl)acetamido-9-deoxy-Neu5Gc alpha 2-6GalOMP) and the C-9 amino derivative 2 (9-(4'-hydroxy-4-biphenyl)methylamino-9-deoxy-Neu5Gc alpha 2-6GalOMP) have the most promising affinity for mouse CD22 and human CD22, respectively. Replacing the subterminal galactose residue (2-6Gal-OMP) of 1 with benzyl (5) or biphenylmethyl (6) as aglycone led to even higher potency for mCD22. In this study, both compounds showed improved potency and selectivity for CD22 (IC(50) 70 nM) and 712-fold more selective for CD22 than for MAG. The corresponding derivatives of 2, compounds 8 and 9, showed comparable activity to 2 but lower potency and selectivity than 5 and 6. Although compounds 5-9 are simple and small molecular weight antagonists, they showed much high potency and selectivity than the corresponding compounds having a 2-6Gal linkage. Both biological and computational docking simulation studies suggest that the 2-6GalOMP residues of 1 and 2 are not critical for binding process and could be replaced with hydrophobic non-carbohydrate moieties. The data presented herein has significant implications for the design and discovery of next-generation CD22-antagonists. (C) 2011 Elsevier Ltd. All rights reserved.
• Potent small molecule mouse CD22-inhibitors: Exploring the interaction of the residue at C-2 of sialic acid scaffold
  作者：Hajjaj H.M. Abdu-Allah、Kozo Watanabe、Koji Hayashizaki、Chiaki Takaku、Taichi Tamanaka、Hiromu Takematsu、Yasunori Kozutsumi、Takeshi Tsubata、Hideharu Ishida、Makoto Kiso

  DOI：10.1016/j.bmcl.2009.08.044

  日期：2009.10

  Our previous study revealed that compound 1 (9-(4'-hydroxy-4-biphenyl)acetamido-9-deoxy-Neu5Gc alpha 2-6GalOMP) has the most promising affinity for mCD22. Replacing the subterminal galactose residue of 1 with benzyl or biphenylmethyl as aglycone led to 38- and 20-fold higher potency, respectively. This discovery represents a new direction in inhibitor design suitable for pharmaceutical development. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of biotinylated sialoside to probe CD22–ligand interactions
  作者：Hajjaj H.M. Abdu-Allah、Kozo Watanabe、Koji Hayashizaki、Yuki Iwayama、Hiromu Takematsu、Yasunori Kozutsumi、Takeshi Tsubata、Hideharu Ishida、Makoto Kiso

  DOI：10.1016/j.tetlet.2009.05.044

  日期：2009.8

  Biotin conjugate of the most potent ligand for mouse CD22 was designed and synthesized. The key synthetic step involved the dual capability of Hanessian reaction for debenzylation and simultaneous conversion of the anomeric p-methoxyphenyl group into the corresponding phenylthioglycoside in one step. Competition enzyme-linked immunosorbent assay (ELISA) for testing the binding affinity of synthetic sialosides was developed based on this biotinylated ligand. (C) 2009 Elsevier Ltd. All rights reserved.