1-deoxy-1-<3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl>-β-D-ribofuranuronic acid | 3415-07-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-deoxy-1-<3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl>-β-D-ribofuranuronic acid
• 英文别名: 1-deoxy-1-(3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl)-β-D-ribofuranuronic acid；uridine-5’-uronic acid；uridine-5'-carboxylic acid；uridine-5'carboxylic acid；1-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-β-D-1-deoxy-ribofuranuronic acid；Uridin-5'-carbonsaeure；Uridine Uronic Acid；(2S,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolane-2-carboxylic acid
• CAS: 3415-07-4
• 化学式: C₉H₁₀N₂O₇
• 分子量: 258.188
• InChiKey: BMDRRZMODBSOPT-BNHYGAARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-deoxy-1-<3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl>-β-D-ribofuranuronic acid 在 甲酸 、 二苯基膦叠氮化物 、 三乙胺 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成
  参考文献：
  名称：

  Potential inhibitors of nucleotide biosynthesis. 1. Nitrosoureidonucleosides. 2

  摘要：

  Several nitrosoureidonucleosides (9a, 9b, 11a, 11b, 18 and 20) designed as inhibitors of enzymes that metabolize purine and pyrimidine nucleotides have been prepared and their chemical and biological properties studied. The low level of biological activity observed may be due to the unexpected stability of these nitrosoureas compared to biologically active compounds such as N-methyl-N-nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N'-nitrosourea (BCNU), and N,N'-dicyclohexyl-N-nitrosourea (DCyNU).

  DOI：

  10.1021/jm00134a011
• 作为产物：
  描述：

  tert-butyl 2',3'-O-isopropylideneuridine-5'-carboxylate 在 溶剂黄146 作用下， 反应 5.0h， 以79%的产率得到1-deoxy-1-<3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl>-β-D-ribofuranuronic acid
  参考文献：
  名称：

  Timoshchuk, V. A., Journal of Organic Chemistry USSR (English Translation), 1992, vol. 28, # 7, p. 1198 - 1204

  摘要：

  DOI：

文献信息

• [EN] SMALL MOLECULE INHIBITORS OF ALDH AND USES THEREOF<br/>[FR] INHIBITEURS À PETITES MOLÉCULES D'ALDH ET UTILISATIONS ASSOCIÉES
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2017223086A1

  公开（公告）日：2017-12-28

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a thiopyrimidinone structure which function as inhibitors of ALDH protein, and their use as therapeutics for the treatment of cancer and other diseases.

  这项发明属于药物化学领域。特别是，该发明涉及一类具有噻吩嘧啶酮结构的新颖小分子，它们作为ALDH蛋白的抑制剂，以及它们作为治疗癌症和其他疾病的疗法的使用。
• [EN] HETEROCYCLIC DERIVATIVES AS IAP BINDING COMPOUNDS<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES CONVENANT COMME COMPOSÉS SE LIANT AUX INHIBITEURS DE PROTÉINES D'APOPTOSE
  申请人：NUEVOLUTION AS

  公开号：WO2009152824A1

  公开（公告）日：2009-12-23

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates thereof, that bind to Inhibitor of Apoptosis Proteins (IAPs). The compounds of the invention may be used as diagnostic and therapeutic agents in the treatment of proliferative diseases, such as cancer, for promoting apoptosis in proliferating cells, and for sensitizing cells to inducers of apoptosis. The present invention furthermore provides a polymeric compound of formulas (VI) or (VII), comprising either at least two monomeric units of compounds of formula (I), or at least one monomeric unit of a compound of formula (I) and an entity E. The present invention further relates to pharmaceutical compositions comprising said compounds of formulas (I), (VI), and (VII) and the use of said compounds in medicine.

  本发明涉及式(I)的化合物，或其药学上可接受的盐、溶剂化合物，这些化合物与凋亡抑制蛋白(IAPs)结合。本发明的化合物可用作诊断和治疗剂，用于治疗增殖性疾病，如癌症，促进增殖细胞中的凋亡，并使细胞对凋亡诱导剂敏感。本发明还提供了具有式(VI)或(VII)的聚合物化合物，包括至少两个式(I)化合物的单体单位，或至少一个式(I)化合物的单体单位和实体E。本发明还涉及包含所述式(I)、(VI)和(VII)化合物的药物组合物以及在医学中使用所述化合物的用途。
• [EN] CEREBLON E3 LIGASE INHIBITORS<br/>[FR] INHIBITEURS DE LIGASE E3 CEREBLON
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2021041664A1

  公开（公告）日：2021-03-04

  The present disclosure provides compounds represented by Formula I: wherein R2a, R2b, R2c, R2d, R3, R13, and Z are as defined in the specification, and the salts and solvates thereof. Compounds of Formula I are cereblon (CRBN) ubiquitination inhibitors or monofunctional synthetic intermediates that can be used to prepare PROTAC molecules. CRBN ubiquitination inhibitors and PROTAC molecules are useful for the treatment of cancer and other diseases.

  本公开提供由下式表示的化合物：其中R2a、R2b、R2c、R2d、R3、R13和Z如规范中所定义，并且其盐和溶剂合物。式I的化合物是 cereblon (CRBN) 泛素化抑制剂或可用于制备PROTAC分子的单功能合成中间体。CRBN泛素化抑制剂和PROTAC分子可用于治疗癌症和其他疾病。
• Nitrosoureido nucleosides as potential inhibitors of nucleotide biosynthesis
  作者：Robert D. Elliott、H. Jeanette Thomas、Sue C. Shaddix、Doris J. Adamson、R. Wallace Brockman、James M. Riordan、John A. Montgomery

  DOI：10.1021/jm00396a039

  日期：1988.1

  Several nitrosoureido nucleosides (3a, 3b, 5a, 7a, 7c, and 10a) designed as inhibitors of enzymes that metabolize pyrimidine nucleotides have been prepared and their chemical and biological properties studied. The methylnitrosoureas 3a and 3b were not significantly cytotoxic to H.Ep.-2 and L1210 cells in vitro but showed moderate activity in the P388 mouse leukemia screen (79% ILS for 3a and 56% ILS

  已制备了几种设计为代谢嘧啶核苷酸的酶抑制剂的亚硝基脲核苷（3a，3b，5a，7a，7c和10a），并对其化学和生物学特性进行了研究。甲基亚硝基脲3a和3b在体外对H.Ep.-2和L1210细胞无明显细胞毒性，但在P388小鼠白血病筛查中显示中等活性（3a为79％ILS，3b为56％ILS）。（氯乙基）亚硝基脲7a和7c抑制L1210细胞增殖，对H.Ep.-2细胞具有细胞毒性，并在体内对P388表现出良好的活性（135％ILS具有一个30天存活率的7a和191％ILS具有两个7天的30天幸存者）。L1210细胞过夜暴露于7a和7c导致细胞肿大并伴有细胞溶解。扩大细胞中的高分子合成，尤其是RNA和蛋白质合成，相对于未处理的对照细胞，其显着增加。确定每种亚硝基脲在pH 7缓冲液中的半衰期，并将其与生物学活性进行比较。
• Synthesis and antiviral activities of new acyclic and “double-headed” nucleoside analogues
  作者：Xinying Zhang、Adel Amer、Xuesen Fan、Jan Balzarini、Johan Neyts、Erik De Clercq、Mark Prichard、Earl Kern、Paul F. Torrence

  DOI：10.1016/j.bioorg.2006.11.003

  日期：2007.6

  inhibition of orthopoxviruses by nucleoside analogues, a variety of novel chemical entities were synthesized. These included a series of pyrimidine 5-hypermodified acyclic nucleoside analogues based upon recently discovered new leads, and some previously unknown "double-headed" or "abbreviated" nucleosides. None of the synthetic products possessed significant activity against two representative orthopoxviruses;

  为了发展对核苷类似物抑制正痘病毒的构效关系的认识，合成了多种新颖的化学实体。这些包括基于最近发现的新先导的一系列嘧啶5-超修饰的无环核苷类似物，以及一些以前未知的“双头”或“缩写”核苷。没有一种合成产物对两种代表性的正痘病毒具有显着的活性。即牛痘病毒和牛痘病毒。它们还没有针对一系列其他DNA和RNA病毒的显着活性。就正痘病毒和疱疹病毒的结果而言，该结果可能表明核苷类似物5'-磷酸化具有抗病毒功效的必要性。