5-氨基-3-[3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-2H-三唑并[4,5-e]嘧啶-7-酮 | 2133-80-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5-氨基-3-[3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-2H-三唑并[4,5-e]嘧啶-7-酮
• 英文名称: 8-azaguanosine
• 英文别名: 8-Aza-guanosin；Azaguanosine；5-amino-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6H-triazolo[4,5-d]pyrimidin-7-one
• CAS: 2133-80-4
• 化学式: C₉H₁₂N₆O₅
• 分子量: 284.231
• InChiKey: QOVIBFFZCVPCEI-UMMCILCDSA-N

物化性质

• 熔点：
  250-252 °C (decomp)(Solv: water (7732-18-5))
• 密度：
  2.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  168
• 氢给体数：
  5
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  5-氨基-3-[3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-2H-三唑并[4,5-e]嘧啶-7-酮 在 barium nitrite 、 溶剂黄146 作用下， 生成 3-β-D-ribofuranosyl-3,4-dihydro-[1,2,3]triazolo[4,5-d]pyrimidine-5,7-dione
  参考文献：
  名称：

  318.腺苷，肌苷，鸟苷和黄嘌呤的v-三唑并[ d ]嘧啶类似物的合成，以及鸟苷的新合成

  摘要：

  DOI：

  10.1039/jr9580001593
• 作为产物：
  描述：

  [(2R,3R,4R,5R)-5-(5-amino-7-oxo-6H-triazolo[4,5-d]pyrimidin-3-yl)-3,4-dibenzoyloxy-tetrahydrofuran-2-yl]methyl benzoate 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 5-氨基-3-[3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-2H-三唑并[4,5-e]嘧啶-7-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] NON-NUCLEOTIDE COMPOSITIONS AND METHOD FOR TREATING PAIN<br/>[FR] COMPOSITIONS NON-NUCLEOTIDIQUES ET PROCEDE DE TRAITEMENT DE LA DOULEUR
  申请人：INSPIRE PHARMACEUTICALS INC

  公开号：WO2005039590A1

  公开（公告）日：2005-05-06

  The present invention is directed to a method of treating pain. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a P2X receptor antagonist. The methods of the present invention are useful in reducing pain, such as traumatic pain, neuropathic pain, organ pain and/or pain associated with diseases. The P2X receptor antagonists useful for this invention are non-nucleotide compounds of general Formula I. Compounds of Formula I can be used alone to treat pain. Compounds of Formula I can also be used in conjunction with other therapeutic agents or adjunctive therapies commonly used to treat pain, thus enhancing the therapeutic effect of pain reduction.

  本发明涉及一种治疗疼痛的方法。该方法包括向受试者施用含有有效量P2X受体拮抗剂的药物组合物。本发明的方法对于减轻疼痛，如创伤性疼痛、神经病性疼痛、器官疼痛和/或与疾病相关的疼痛具有用处。本发明中用于该发明的P2X受体拮抗剂是一般式I的非核苷化合物。式I的化合物可以单独用于治疗疼痛。式I的化合物也可以与其他治疗剂或常用于治疗疼痛的辅助疗法结合使用，从而增强减轻疼痛的治疗效果。
• [EN] TETRAHYDRO-FURO`3,4-D!DIOXOLE COMPOUNDS AND COMPOSITIONS AND METHOD FOR INHIBITING PLATELET AGGREGATION<br/>[FR] COMPOSES TETRAHYDRO-FURO[3,4D]DIOXOLE, ET COMPOSITIONS ET PROCEDE POUR INHIBER UNE AGREGATION PLAQUETTAIRE
  申请人：INSPIRE PHARMACEUTICALS INC

  公开号：WO2005040174A1

  公开（公告）日：2005-05-06

  This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis or related disorders. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a non-nucleotide compound, preferably a P2Y12 receptor antagonist compound, wherein said amount is effective to inhibit platelet aggregation. The compounds useful for this invention include compounds of general Formulae I and III-XI, or salts, hydrates, and solvates thereof. The present invention also provides novel compounds according to Formulae I and III-XI.

  这项发明涉及一种预防或治疗与血小板聚集相关的疾病或症状的方法。该方法还涉及一种治疗血栓形成或相关疾病的方法。该方法包括向受试者施用含有有效量非核苷酸化合物的药物组合物，优选为P2Y12受体拮抗剂化合物，其中所述量有效地抑制血小板聚集。本发明有用的化合物包括一般式I和III-XI的化合物，或其盐、水合物和溶剂合物。本发明还提供了根据一般式I和III-XI的新化合物。
• [EN] CATIONIC LIPIDS AND USES THEREOF<br/>[FR] LIPIDES CATIONIQUES ET LEURS UTILISATIONS
  申请人：FACTOR BIOSCIENCE INC

  公开号：WO2021003462A1

  公开（公告）日：2021-01-07

  The present invention relates to novel cationic lipids of formula I, and more specifically formula IV. These are used, for example, in liposomes for the delivery of nucleic acids to cells.

  本发明涉及新型公式I的阳离子脂质，更具体地是公式IV。例如，这些脂质可用于脂质体中将核酸传递给细胞。
• Site-Selective Ribosylation of Fluorescent Nucleobase Analogs Using Purine-Nucleoside Phosphorylase as a Catalyst: Effects of Point Mutations
  作者：Alicja Stachelska-Wierzchowska、Jacek Wierzchowski、Agnieszka Bzowska、Beata Wielgus-Kutrowska

  DOI：10.3390/molecules21010044

  日期：——

  Enzymatic ribosylation of fluorescent 8-azapurine derivatives, like 8-azaguanine and 2,6-diamino-8-azapurine, with purine-nucleoside phosphorylase (PNP) as a catalyst, leads to N9, N8, and N7-ribosides. The final proportion of the products may be modulated by point mutations in the enzyme active site. As an example, ribosylation of the latter substrate by wild-type calf PNP gives N7- and N8-ribosides

  荧光 8-氮杂嘌呤衍生物，如 8-氮杂鸟嘌呤和 2,6-二氨基-8-氮杂嘌呤，以嘌呤核苷磷酸化酶 (PNP) 作为催化剂进行酶促核糖基化，产生 N9、N8 和 N7-核糖苷。产物的最终比例可以通过酶活性位点的点突变来调节。例如，野生型小牛 PNP 对后一种底物的核糖基化产生 N7 和 N8 核糖苷，而 N243D 突变体指导 N9 和 N7 位的核糖基取代。相同的突变体允许合成荧光 N7-β-d-核糖基-8-氮鸟嘌呤。大肠杆菌 PNP 的突变形式 D204N 也可用于获得 8-氮杂腺嘌呤和 2,6-二氨基-8-氮杂嘌呤的非典型核糖苷。8-氮杂嘌呤的 N7-和 N8-核糖苷可用于分析，如 N7-β-d-核糖基-2,6-二氨基-8-氮杂嘌呤所示，
• Enzymatic Synthesis of Highly Fluorescent 8-Azapurine Ribosides Using a Purine Nucleoside Phosphorylase Reverse Reaction: Variable Ribosylation Sites
  作者：Alicja Stachelska-Wierzchowska、Jacek Wierzchowski、Beata Wielgus-Kutrowska、Goran Mikleušević

  DOI：10.3390/molecules181012587

  日期：——

  Various forms of purine-nucleoside phosphorylase (PNP) were used as catalysts of enzymatic ribosylation of selected fluorescent 8-azapurines. It was found that the recombinant calf PNP catalyzes ribosylation of 2,6-diamino-8-azapurine in a phosphate-free medium, with ribose-1-phosphate as ribose donor, but the ribosylation site is predominantly N7 and N8, with the proportion of N8/N7 ribosylated products

  各种形式的嘌呤核苷磷酸化酶 (PNP) 被用作所选荧光 8-氮杂嘌呤的酶促核糖基化催化剂。发现重组小牛PNP在无磷酸盐培养基中催化2,6-二氨基-8-氮杂嘌呤核糖基化，1-磷酸核糖为核糖供体，但核糖基化位点主要为N7和N8，比例为N8/N7 核糖基化产物的显着依赖于反应条件。这两种产品都是荧光的。大肠杆菌 PNP 的应用产生了 N8 和 N9 取代的核糖苷的混合物。核糖基化 2,6-diamino-8-azapurine 的荧光已被简要表征。N9-β-d-核糖苷（λmax 365 nm）获得了最高的量子产率~0.9，而对于 N8-β-d-核苷，在~430 nm 处发射，发现荧光量子产率接近于0.4. 8-氮鸟嘌呤的核糖基化与作为催化剂的小牛 PNP 仅发生在 N9 上。相比之下，大肠杆菌 PNP 核糖基化 8-azaGua 主要在 N9，少量但高度荧光的产物在 N8/N7 核糖基化。