4-羟基-1-β-d-呋喃核糖苷-2[1H]吡啶酮 | 23205-42-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-羟基-1-β-d-呋喃核糖苷-2[1H]吡啶酮
• 中文别名: 4-羟基-1-Β-D-呋喃核糖苷-2(1H)吡啶酮；二氨基二苯基甲烷
• 英文名称: 3-deazauridine
• 英文别名: 3-Deazauridin；3-deazaUR；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxypyridin-2-one
• CAS: 23205-42-7
• 化学式: C₁₀H₁₃NO₆
• 分子量: 243.216
• InChiKey: CBOKZNLSFMZJJA-PEBGCTIMSA-N

物化性质

• 熔点：
  233-235°C
• 沸点：
  569.2±50.0 °C(Predicted)
• 密度：
  1.718±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（少许）、甲醇（少许）、水（少许）
• LogP：
  -1.693 (est)
• 稳定性/保质期：
  <p><b></b></p>

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  6

安全信息

• RTECS号：
  UV1148000
• 危险性防范说明：
  P261,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319
• 储存条件：
  <p><br></p>

制备方法与用途

合成制备方法 用途

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请提供具体的合成制备方法和用途内容，以便进一步润色。

反应信息

• 作为反应物：
  描述：

  4-羟基-1-β-d-呋喃核糖苷-2[1H]吡啶酮 、 1,3二氯-1,1,3,3-四异丙基二硅氧烷 以 吡啶 为溶剂， 反应 3.0h， 生成 3',5'-O-(1,1,3,3-tetraisopropyldisilox-1,3-diyl)-3-deazacytidine
  参考文献：
  名称：

  Robins, Morris J.; Wilson, John S.; Sawyer, Lindsay, Canadian Journal of Chemistry, 1983, vol. 61, p. 1911 - 1920

  摘要：

  DOI：
• 作为产物：
  描述：

  4-hydroxy-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2(1H)-pyridinone 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 4-羟基-1-β-d-呋喃核糖苷-2[1H]吡啶酮
  参考文献：
  名称：

  High-Throughput Five Minute Microwave Accelerated Glycosylation Approach to the Synthesis of Nucleoside Libraries

  摘要：

  [GRAPHICS]The Vorbruggen glycosylation reaction was adapted into a one-step 5 min/130 degrees C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl triflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield +/- SD was 26 +/- 16%, and the average purity +/- SD was 95 +/- 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.

  DOI：

  10.1021/jo061885l

文献信息

• [EN] AMINOPYRIMIDINE DERIVATIVES AS CTPS1 INHIBITORS<br/>[FR] DÉRIVÉS D'AMINOPYRIMIDINE UTILISÉS COMME INHIBITEURS DE CTPS1
  申请人：STEP PHARMA S A S

  公开号：WO2019180244A1

  公开（公告）日：2019-09-26

  Compounds of formula (I): (I) and related aspects.

  式(I)的化合物及相关方面。
• [EN] N-(5-(6-ETHOXYPYRAZIN-2-YL)PYRIDIN-2-YL)-4-(2-(METHYLSULFONAMIDO)PYRIMIDIN-4-YL) TETRAHYDRO-2H-PYRAN-4-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS HUMAN CTPS1 INHIBITORS FOR THE TREATMENT OF PROLIFERATIVE DISEASES<br/>[FR] DÉRIVÉS DE N-(5-(6-ÉTHOXYPYRAZIN-2-YL)PYRIDIN-2-YL)-4-(2-(MÉTHYLSULFONAMIDO)PYRIMIDIN-4-YL) TÉTRAHYDRO-2H-PYRAN-4-CARBOXAMIDE ET DES COMPOSÉS APPARENTÉS SERVANT D'INHIBITEURS DE CTPS1 HUMAINS POUR LE TRAITEMENT DE MALADIES PROLIFÉRATIVES
  申请人：STEP PHARMA S A S

  公开号：WO2020245664A1

  公开（公告）日：2020-12-10

  Compounds of formula (I) as human cytidine triphosphate synthase 1 ( CTPS1) inhibitors for the treatment of proliferative diseases, such as e.g. cancer, such as e.g. leukemia and lymphoma, e.g. inflammatory skin diseases such as psoriasis, or e.g. multiple sclerosis. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 64 to 80; examples; biological examples 1 and 2; e.g. compounds P140, P231 to P263; tables 1 to 10). Specific examples are e.g.: N-(5-(6-ethoxypyrazin-2-yl)pyridin-2-yl)-4-(2-(methylsulfonamido) pyrimidin-4-yl)tetrahydro-2H-pyran-4-carboxamide (Formula (II)), or 1-(2-(cyclopropanesulfonamido)pyrimidin-4-yl)-N-(5-(6- ethoxypyrazin-2-yl)pyridin-2-yl)cyclohexane-1-carboxamide (Formula (III)).

  化合物的化学式（I）作为人类胞嘧啶三磷酸合成酶1（CTPS1）抑制剂，用于治疗增殖性疾病，例如癌症，如白血病和淋巴瘤，例如炎症性皮肤病如牛皮癣，或多发性硬化症。本说明书披露了示例化合物的合成和表征，以及其药理学数据（例如，第64至80页；示例；生物学示例1和2；例如，化合物P140，P231至P263；表1至10）。具体示例包括：N-(5-(6-乙氧基吡嗪-2-基)吡啶-2-基)-4-(2-(甲磺酰胺基)嘧啶-4-基)四氢-2H-吡喃-4-羧酰胺（化学式（II）），或1-(2-(环丙磺酰胺基)嘧啶-4-基)-N-(5-(6-乙氧基吡嗪-2-基)吡啶-2-基)环己烷-1-羧酰胺（化学式（III））。
• [EN] COMPOUNDS FOR THE REDUCTION OF THE DELETERIOUS ACTIVITY OF EXTENDED NUCLEOTIDE REPEAT CONTAINING GENES<br/>[FR] COMPOSÉS POUR LA RÉDUCTION DE L'ACTIVITÉ DÉLÉTÈRE DE GÈNES CONTENANT UNE RÉPÉTITION DE NUCLÉOTIDES ÉTENDUE
  申请人：NUREDIS INC

  公开号：WO2020131573A1

  公开（公告）日：2020-06-25

  Aspects of the present disclosure include methods of reducing the deleterious impact of a target gene in a cell, such as the deleterious activity of a mutant extended nucleotide repeat (NR) containing target gene in a cell by contacting the cell with an effective amount of a tetrahydrocarbazole compound. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended NR containing target gene may be reduced, e.g., by reducing (and in some instances differentially, including selectively, reducing) the production or activity of toxic expression products (e.g., RNA or protein) encoded by the target gene. Kits and compositions for practicing the subject methods are also provided.

  本公开内容的方面包括减少目标基因在细胞中的有害影响的方法，例如通过将细胞与有效量的四氢咔唑化合物接触，减少含有突变延伸核苷酸重复序列（NR）的目标基因在细胞中的有害活性。突变延伸NR包含的目标基因的有害活性（例如，由此编码的产物的毒性和/或功能障碍）可以减少，例如，通过减少（在某些情况下包括选择性地减少）由目标基因编码的有毒表达产物（例如，RNA或蛋白质）的生产或活性。还提供了用于实施所述方法的试剂盒和组合物。
• Treatment of genitourinary tract disorders
  申请人：Ashton Paul

  公开号：US20050164994A1

  公开（公告）日：2005-07-28

  Genitourinary system disorders are treated with therapeutic agents, and optionally further with radiation treatments.

  生殖泌尿系统疾病可以用治疗性药物进行治疗，必要时还可以进一步进行放射治疗。
• Structure–Activity Relationship of Purine and Pyrimidine Nucleotides as Ecto-5′-Nucleotidase (CD73) Inhibitors
  作者：Anna Junker、Christian Renn、Clemens Dobelmann、Vigneshwaran Namasivayam、Shanu Jain、Karolina Losenkova、Heikki Irjala、Sierra Duca、Ramachandran Balasubramanian、Saibal Chakraborty、Frederik Börgel、Herbert Zimmermann、Gennady G. Yegutkin、Christa E. Müller、Kenneth A. Jacobson

  DOI：10.1021/acs.jmedchem.9b00164

  日期：2019.4.11

  Cluster of differentiation 73 (CD73) converts adenosine 5'-monophosphate to immunosuppressive adenosine, and its inhibition was proposed as a new strategy for cancer treatment. We synthesized 5'- O-[(phosphonomethyl)phosphonic acid] derivatives of purine and pyrimidine nucleosides, which represent nucleoside diphosphate analogues, and compared their CD73 inhibitory potencies. In the adenine series

  分化簇73（CD73）将5'-单磷酸腺苷转化为免疫抑制腺苷，其抑制作用被提出作为一种新的癌症治疗策略。我们合成了嘌呤和嘧啶核苷的5'-O-[（膦酰基甲基）膦酸]衍生物，它们代表核苷二磷酸类似物，并比较了它们对CD73的抑制作用。在腺嘌呤系列中，大多数核糖修饰和1-deaza和3-deaza都是有害的，但可以容忍7-deaza。耐受尿嘧啶被N3-甲基取代，但不能被较大的基团或2-硫代取代。不容许1，2-二膦酰基-乙基修饰。N4-（芳基）烷氧基-胞嘧啶衍生物，特别是具有庞大的苄氧基取代基的化合物，显示出增强的效力。最有效的抑制剂是5' -5-氟尿苷（4l），N4-苯甲酰基胞苷（7f），N4- [O-（4-苄氧基）]胞苷（9h）和N4- [O的O-[（膦酰基甲基）膦酸]衍生物-（4-萘-2-基甲氧基）]-胞苷（9e）（在人CD73上Ki值为5-10 nM）。在两种尿苷二磷酸激活的P2Y受体亚型上