6-(benzyloxycarbonyl)-2-naphthoic acid | 128018-90-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(benzyloxycarbonyl)-2-naphthoic acid
• 英文别名: 6-phenylmethoxycarbonylnaphthalene-2-carboxylic acid
• CAS: 128018-90-6
• 化学式: C₁₉H₁₄O₄
• 分子量: 306.318
• InChiKey: CSSIRCDMVUHGEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(benzyloxycarbonyl)-2-naphthoic acid 在 manganese(IV) oxide 、 aluminum oxide 、 lithium hydroxide 、 硼烷四氢呋喃络合物 、 草酰氯 、 二甲基亚砜 、 三乙胺 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.08h， 生成 6-((bis-(tert-butyl))phosphono-difluoromethyl)-2-naphthoic acid
  参考文献：
  名称：

  Structure-based design and synthesis of small molecule protein–tyrosine phosphatase 1B inhibitors

  摘要：

  Protein-tyrosine phosphatase (PTP) inhibitors are attractive as potential signal transduction-directed therapeutics which may be useful in the treatment of a variety of diseases. We have previously reported the X-ray structure of 1,1-difluoro-1-(2-naphthalenyl)methyl] phosphonic acid (4) complexed with the human the protein-tyrosine phosphatase 1B (PTP1B) and its use in the design of an analogue which binds with higher affinity within the catalytic site (Burke, T. R., Jr. et al. Biochemistry 1996, 35, 15989). In the current study, new naphthyldifluoromethyl phosphonic acids were designed bearing acidic functionality intended to interact with the PTP1B Arg47, which is situated just outside the catalytic pocket. This residue has been shown previously to provide key interactions with acidic residues of phosphotyrosyl-containing peptide substrates. Consistent with trends predicted by molecular dynamics calculations, the new analogues bound with 7- to 14-fold higher affinity than the parent 4, in principal validating the design rationale. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00140-0
• 作为产物：
  描述：

  2,6-萘二羧酸 、 溴甲苯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以33%的产率得到6-(benzyloxycarbonyl)-2-naphthoic acid
  参考文献：
  名称：

  3-（β-d-吡喃葡萄糖基）-5-取代-1,2,4-三唑衍生物作为糖原磷酸化酶抑制剂的多学科研究：计算，合成，晶体学和动力学揭示了新的有效抑制剂

  摘要：

  已经揭示了3-（β- d-葡糖基葡糖基）-5-取代的1,2,4-三唑是开发有效的糖原磷酸化酶（GP）抑制剂的有效支架，但是其效力对其本质非常敏感。烷基/芳基5-取代基（Kun等人，Eur.J.Med.Chem.2014，76，567）。对于这些配体的训练集，量子力学极化的配体对接（QM-PLD）表现出良好的潜力，可以识别出更大的功效差异（预测指数PI = 0.82）和K i <10μM的有效抑制剂（AU-ROC） = 0.86）。因此，利用ZINC对接数据库对2335个新的类似物进行了计算机筛选，并选择了九个预测的候选物进行合成。这些化合物是在O中制备的-过苯甲酰化形式，可通过N-苄基-亚芳基羧酰亚胺基氯化物对5-β- d-吡喃葡萄糖基四唑进行环转化，将C-（β- d-吡喃葡萄糖基）甲酰胺ami与芳酰氯进行闭环，或将N-（β- d-吡喃葡糖基羰基）芳硫基羧酰胺通过肼，然后脱保护。针对兔肌肉

  DOI：

  10.1016/j.ejmech.2018.01.095

文献信息

• Phosphate mimics and methods of treatment using phosphatease inhibitors
  申请人：Sugen, Inc.

  公开号：US20040138255A1

  公开（公告）日：2004-07-15

  The invention relates to trifluoromethyl sulfonyl and trifluoromethyl sulfonamido compounds and the physiologically acceptable salts and the prodrugs thereof. These compounds are expected to modulate the activity of protein tyrosine enzymes which are related to cellular signal transduction, in particular, protein tyrosine phosphatase, and therefore are expected to be useful in the prevention and treatment of disorders associated with abnormal protein tyrosine enzyme related cellular signal transduction such as cancer, diabetes, immuno-modulation, neurologic degenerative diseases, osteoporosis and infectious diseases. The invention also relates to the use of compounds containing fluoromethyl sulfonyl groups as phosphate mimics. These mimics may be used to inhibit, regulate or modulate the activity of a phosphate binding protein in a cell.

  本发明涉及三氟甲基磺酰和三氟甲基磺酰胺化合物及其生理上可接受的盐和前药。这些化合物预计能够调节与细胞信号转导相关的蛋白酪氨酸酶的活性，特别是蛋白酪氨酸磷酸酶，因此预计在预防和治疗与异常蛋白酪氨酸酶相关的细胞信号转导障碍，如癌症、糖尿病、免疫调节、神经退行性疾病、骨质疏松症和传染病方面有用。本发明还涉及含有氟甲基磺酰基团的化合物作为磷酸酯模拟物的用途。这些模拟物可用于抑制、调节或调节细胞中的磷酸结合蛋白的活性。
• Phosphate mimics and methods of treatment using phosphatase inhibitors
  申请人：Sugen, Inc.

  公开号：US06596772B1

  公开（公告）日：2003-07-22

  The invention relates to trifluoromethyl sulfonyl and trifluoromethyl sulfonamido compounds and the physiologically acceptable salts and the prodrugs thereof. These compounds are expected to modulate the activity of protein tyrosine enzymes which are related to cellular signal transduction, in particular, protein tyrosine phosphatase, and therefore are expected to be useful in the prevention and treatment of disorders associated with abnormal protein tyrosine enzyme related cellular signal transduction such as cancer, diabetes, immuno-modulation, neurologic degenerative diseases, osteoporosis and infectious diseases. The invention also relates to the use of compounds containing fluoromethyl sulfonyl groups as phosphate mimics. These mimics may be used to inhibit, regulate or modulate the activity of a phosphate binding protein in a cell.

  本发明涉及三氟甲基磺酰和三氟甲基磺酰胺化合物及其生理上可接受的盐和前药。这些化合物预计能够调节与细胞信号转导相关的蛋白酪氨酸酶的活性，尤其是蛋白酪氨酸磷酸酶，因此预计能够在预防和治疗与异常蛋白酪氨酸酶相关的细胞信号转导紊乱的疾病，如癌症、糖尿病、免疫调节、神经退行性疾病、骨质疏松症和传染病方面有用。本发明还涉及含有氟甲基磺酰基团的化合物作为磷酸盐类似物的用途。这些类似物可用于抑制、调节或调节细胞中的磷酸盐结合蛋白的活性。
• Configurationally stable analogs of styrylxanthines as A2A adenosine receptor antagonist
  作者：CE Müller、U Schobert、J Hipp、U Geis、W Frobenius、M Pawlowski

  DOI：10.1016/s0223-5234(97)88913-1

  日期：1997.9

  Configurationally stable analogs of the potent, A(2A)-selective adenosine receptor (AR) antagonist 3,7-dimethyl-1-propargyl-8-styrylxanthine (8-styryl-DMPX, 3) were synthesized and investigated in radioligand binding assays for affinity to the high-affinity A(1)- and A(2A)-AR subtypes of rat brain. All derivatives prepared, including compounds in which the styryl double bond was replaced by a cyclopropane ring or a triple bond, or in which it was integrated into a (hetero) cyclic ring system, were less potent and less selective compared to the parent compound 3. The best compound of the present series was 8-(phenylethynyl)-DMPX (21), exhibiting a K-i value at A(2A)-AR of 300 nM and a > 10-fold selectivity versus A(1)-AR. In view of its configurational stability, 21 may be an interesting lead compound for the development of more potent A(2A) antagonists by introducing appropriate substituents in the phenyl ring. Based on conformational analysis of 8-styrylxanthine and 8-(2-naphthyl)xanthine derivatives, it is hypothesized that the bioactive conformation of (E)-8-styryl substituents with regard to the imidazole ring of the xanthine nucleus at A(2A)-AR may be nearly coplanar and cisoid, and may differ from the bioactive conformation of such xanthine derivatives at A(1)-AR.
• Plasmepsin II inhibition and antiplasmodial activity of Primaquine–Statine `double-drugs'
  作者：Sergio Romeo、Mario Dell'Agli、Silvia Parapini、Luca Rizzi、Germana Galli、Monica Mondani、Anna Sparatore、Donatella Taramelli、Enrica Bosisio

  DOI：10.1016/j.bmcl.2004.03.030

  日期：2004.6

  Statine-based inhibitors of Plasmepsin II (PLMII) coupled with Primaquine have been designed using the 'double-drug' approach. The IC50 values for PLMII inhibition ranged from 0.59 to 400 nM and the best IC50 value for inhibition of Plasmodium falciparum growth in vitro was 0.4 muM, which represent a remarkable improvement compared to other statine-based PLMII inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.
• Amino acid derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0346847B1

  公开（公告）日：1994-05-11