glucuronic acid | 912483-14-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: glucuronic acid
• 英文别名: galacturonic acid；Hexuronic Acid；3,4,5,6-tetrahydroxyoxane-2-carboxylic acid
• CAS: 912483-14-8
• 化学式: C₆H₁₀O₇
• mdl: MFCD00066842
• 分子量: 194.141
• InChiKey: AEMOLEFTQBMNLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  glucuronic acid 在 四氢吡咯 、 N-甲基吗啉 、 四(三苯基膦)钯 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.5h， 生成 Mln 8054 O-beta-D-glucuronide
  参考文献：
  名称：

  Synthesis of three isotopically labeled versions and a metabolite of Aurora A kinase inhibitor

  摘要：

  环-[14C]-4-[[9-氯-7-(2,6-二氟苯基)-5H-嘧啶并[5,4-d][2]苯并氮杂卓-2-基]氨基]-苯甲酸钠（1A，MLN8054）是一种极光 A 激酶抑制剂，由[14C]-氰酰胺分两步合成，总放射化学收率为 7%。中间体[14C]-4-胍基苯甲酸是通过将[14C]-氰酰胺与 4-氨基苯甲酸偶联制备的。羧基-[14C]-4-[[9-氯-7-(2,6-二氟苯基)-5H-嘧啶并[5,4-d][2]苯并氮杂卓-2-基]氨基]-苯甲酸钠（1B）由羧基-[14C]-4-胍基苯甲酸一步合成，放射化学收率为 35%。[D4,15N]-4-[[9-氯-7-(2,6-二氟苯基)-5H-嘧啶并[5,4-d][2]苯并氮杂卓-2-基]氨基]-苯甲酸（1C）由[15N2]-氰酰胺和[D4]-4-氨基苯甲酸分两步合成，总产率为 37%。主要代谢物 4-[[9-氯-7-（2,6-二氟苯基）-5H-嘧啶并[5,4-d][2]苯并氮杂卓-2-基]氨基]-苯甲酸的 β-酰基葡萄糖醛酸（14）由 D-葡萄糖醛酸经三个步骤合成，总产率为 1%。合成葡萄糖醛酸的关键中间体是由 4-[[9-氯-7-(2,6-二氟苯基)-5H-嘧啶并[5,4-d][2]苯并氮杂卓-2-基]氨基]-苯甲酸与葡萄糖醛酸烯丙基酯在 HATU 催化下偶联制备的。Copyright © 2009 John Wiley & Sons, Ltd. 版权所有。

  DOI：

  10.1002/jlcr.1607

文献信息

• Method of producing conjugate vaccines
  申请人：Finn Nicholas

  公开号：US20080213297A1

  公开（公告）日：2008-09-04

  The present invention relates to a method of production of a hydrazide modified sugar comprising a step of reacting a sugar with a hydrazide in a reaction solvent at a pH of between 3 and 5.5, wherein the solvent comprises an aqueous based solvent and an optional polar organic co-solvent. A further aspect of the invention relates to a method of production of a polysaccharide epitope carrier protein conjugate comprising the steps of: (a) reacting a polysaccharide epitope with a hydrazide to form a hydrazide modified polysaccharide epitope; (b) reacting the hydrazide modified polysaccharide epitope with a linker that has been pre-coupled to a carrier protein. Another aspect of the invention relates to a method of production of a sugar-dihydrazide-aldehyde adduct comprising the steps of: (a) producing a hydrazide modified sugar using a method according to the invention, wherein the hydrazide modified sugar includes a further unreacted hydrazide moiety; and (b) reacting the further hydrazide moiety with the aldehyde functionality of a linker group.

  本发明涉及一种生产含有肼改性糖的方法，包括在反应溶剂中将糖与肼在pH值在3至5.5之间反应的步骤，其中溶剂包括水基溶剂和可选的极性有机共溶剂。该发明的另一个方面涉及一种生产多糖表位载体蛋白共轭物的方法，包括以下步骤：(a)将多糖表位与肼反应，形成肼改性多糖表位；(b)将肼改性多糖表位与预先偶联到载体蛋白上的连接剂反应。该发明的另一个方面涉及一种生产糖-二肼-醛加合物的方法，包括以下步骤：(a)使用根据本发明的方法生产肼改性糖，其中肼改性糖包括进一步未反应的肼基团；(b)将进一步的肼基团与连接剂基团的醛功能基团反应。
• [EN] 5-ALA DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS DE 5-ALA ET LEUR UTILISATION
  申请人：UNIV GENEVE

  公开号：WO2016185368A1

  公开（公告）日：2016-11-24

  The present invention is directed to new 5-ALA derivatives, particles and formulation thereof, related methods of preparation and methods of use thereof. In particular, the invention relates to compounds of the invention, particles and formulation thereof useful in the treatment of a cancer and/or the diagnosis of a cancer cell such as in photodynamic therapy or photodynamic diagnosis.

  本发明涉及新的5-ALA衍生物，以及相关的制备方法、使用方法。具体而言，本发明涉及本发明的化合物、粒子和配方，用于治疗癌症和/或诊断癌细胞，例如在光动力疗法或光动力诊断中有用的粒子和配方。
• [EN] IMIDAZOLOTHIAZOLE COMPOUNDS AS MODULATORS OF PROTEIN KINASE<br/>[FR] COMPOSÉS IMIDAZOLOTHIAZOLES UTILISÉS COMME MODULATEURS DE PROTÉINE KINASES
  申请人：AMBIT BIOSCIENCE CORP

  公开号：WO2010054058A1

  公开（公告）日：2010-05-14

  Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.

  提供了用于调节受体激酶活性以及用于治疗、预防或改善由受体激酶介导的疾病或紊乱症状的化合物、组合物和方法。
• [EN] HEMIASTERLIN DERIVATIVES FOR CONJUGATION AND THERAPY<br/>[FR] DÉRIVÉS D'HÉMIASTERLINE POUR CONJUGAISON ET THÉRAPIE
  申请人：SUTRO BIOPHARMA INC

  公开号：WO2016123582A1

  公开（公告）日：2016-08-04

  Provided herein are hemiasterlin derivatives, conjugates thereof, compositions comprising the derivatives or conjugates thereof, methods of producing the derivatives and conjugates thereof, and methods of using the derivatives, conjugates, and compositions for the treatment of cell proliferation. The derivatives, conjugates, and compositions are useful in methods of treatment and prevention of cell proliferation and cancer, methods of detection of cell proliferation and cancer, and methods of diagnosis of cell proliferation and cancer. In an embodiment, the hemiasterlin derivatives are according to Formula 1000: or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein Ar, L, W1, W4, W5, SG, and R are as described herein.

  本文提供了半星菱素衍生物，以及与之结合的共轭物，包含这些衍生物或共轭物的组合物，生产这些衍生物和共轭物的方法，以及利用这些衍生物、共轭物和组合物治疗细胞增殖的方法。这些衍生物、共轭物和组合物在治疗和预防细胞增殖和癌症的方法中很有用，也可用于检测细胞增殖和癌症的方法，以及诊断细胞增殖和癌症的方法。在一个实施例中，半星菱素衍生物符合公式1000：或其药用可接受的盐、溶剂化合物或互变异构体，其中Ar、L、W1、W4、W5、SG和R如本文所述。
• In Vitro Interactions of Epacadostat and its Major Metabolites with Human Efflux and Uptake Transporters: Implications for Pharmacokinetics and Drug Interactions
  作者：Qiang Zhang、Yan Zhang、Jason Boer、Jack G. Shi、Peidi Hu、Sharon Diamond、Swamy Yeleswaram

  DOI：10.1124/dmd.116.074609

  日期：2017.6

  Epacadostat (EPAC) is a first-in-class, orally active inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 and has demonstrated promising clinical activity. In humans, three major plasma metabolites have been identified: M9 (a glucuronide-conjugate), M11 (a gut microbiota metabolite), and M12 (a secondary metabolite formed from M11). It is proposed, based on the human pharmacokinetics of EPAC, that the biliary excretion of M9, the most abundant metabolite, leads to the enterohepatic circulation of EPAC. Using various in vitro systems, we evaluated in the present study the vitro interactions of EPAC and its major metabolites with major drug transporters involved in drug absorption and disposition. EPAC is a substrate for efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), but it is not a substrate for hepatic uptake transporters [organic anion transporting polypeptides OATP1B1 and OATP1B3]. The low permeability of M9 suggests an essential role for transporters in its disposition. M9 is likely excreted from hepatocytes into bile via multidrug resistance–associated protein 2 (MRP2) and BCRP, excreted into blood via MRP3, and transported from blood back into hepatocytes via OATP1B1 and OATP1B3. M11 and M12 are not substrates for P-gp, OATP1B1 or OATP1B3, and M11, but not M12, is a substrate for BCRP. With respect to inhibition of drug transporters, the potential of EPAC, M9, M11, and M12 to cause clinical drug-drug interactions via inhibition of P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, or organic cation transporter 2 was estimated to be low. The current investigation underlines the importance of metabolite-transporter interactions in the disposition of clinically relevant metabolites, which may have implications for the pharmacokinetics and drug interactions of parent drugs.

  EPACadostat（EPAC）是一种首创的口服活性酶抑制剂，针对色氨酸2,3-双氧酶1，已显示出良好的临床活性。在人体中，已确认三种主要的血浆代谢物：M9（葡萄糖醛酸结合物）、M11（肠道微生物代谢物）和M12（由M11形成的二次代谢物）。根据EPAC在人体中的药代动力学，提出M9作为最丰富的代谢物通过胆汁排泄，导致EPAC的肠肝循环。在本研究中，我们使用各种体外系统评估了EPAC及其主要代谢物与参与药物吸收和分布的主要药物转运体的体外相互作用。EPAC是外排转运体P-糖蛋白（P-gp）和乳腺癌耐药蛋白（BCRP）的底物，但不是肝脏摄取转运体[有机阴离子转运多肽 OATP1B1 和 OATP1B3]的底物。M9的低渗透性表明转运体在其分布中的重要作用。M9可能通过多药耐药相关蛋白2（MRP2）和BCRP从肝细胞排泄到胆汁中，通过MRP3排泄到血液中，并通过OATP1B1和OATP1B3从血液运输回肝细胞。M11和M12不是P-gp、OATP1B1或OATP1B3的底物，而M11（而不是M12）是BCRP的底物。关于对药物转运体的抑制，EPAC、M9、M11和M12通过抑制P-gp、BCRP、OATP1B1、OATP1B3、OAT1、OAT3或有机阳离子转运体2引起临床药物相互作用的潜力被估计为低。这项研究强调了代谢物与转运体相互作用在临床相关代谢物分布中的重要性，这可能对母药的药代动力学和药物相互作用产生影响。