3,5-二氢咪唑并[2,1-b]嘌呤-4-酮 | 62962-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 3,5-二氢咪唑并[2,1-b]嘌呤-4-酮
• 英文名称: N²,3-ethenoguanine
• 英文别名: 1(3)H,5H-imidazo[2,1-b]purin-4-one；imidazo[2,1-b]purin-4(5H)-one；N²,3-Aethenoguanin；1H-Imidazo(2,1-b)purin-4(5H)-one；3,5-dihydroimidazo[2,1-b]purin-4-one
• CAS: 62962-42-9
• 化学式: C₇H₅N₅O
• 分子量: 175.15
• InChiKey: OSXKHFTZRHDUJN-UHFFFAOYSA-N

物化性质

• 密度：
  2.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,5-二氢咪唑并[2,1-b]嘌呤-4-酮 、 2'-脱氧胞嘧啶核苷 在 trans-N-deoxyribosylase from Lactobacillus helveticus 作用下， 以 水 为溶剂， 反应 15.0h， 生成 N²,3-Etheno-2'-deoxyguanosine 、
  参考文献：
  名称：

  将脱氧核糖加到鸟嘌呤和由瑞士乳杆菌反式-N-脱氧核糖基化酶修饰的DNA上。

  摘要：

  细菌反式-N-脱氧核糖基化酶的使用已被评估为合成含潜在诱变加合物的脱氧核糖核苷的一种替代方法。从瑞士乳杆菌中分离出粗制酶制剂，并将其与大肠杆菌嘌呤核苷磷酸化酶进行比较。如产物的NMR分析所示，与N7相比，在N9原子处的Gua的脱氧核糖基化中，反式N-脱氧核糖基化酶比嘌呤核苷磷酸化酶具有更高的区域选择性。5,6,7,9-四氢-7-乙酰氧基-9-氧代咪唑并[1,2-a]嘌呤可被反式-N-脱氧核糖基化酶有效地脱氧核糖基化，而根本不被嘌呤核苷磷酸化酶完全脱氧。反式-N-脱氧核糖基化酶的其他底物是N2-（2-氧乙基）Gua，嘧啶并[1,2-a]嘌呤-10（3H）-one，1，N2-ε-Gua，N2,3-ε-Gua ，3，N4-ε-Cyt，1，N6-ε-Ade，C8-甲基瓜瓜和C8-氨基瓜瓜，其中大多数以良好的收率得到了所需的异构体（与瓜9中的N9对应的氮键）。N7-烷基嘌呤和C8-（芳基氨基）取代的

  DOI：

  10.1021/tx9600661
• 作为产物：
  描述：

  O-6-苄基鸟嘌呤 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 124.0h， 生成 3,5-二氢咪唑并[2,1-b]嘌呤-4-酮
  参考文献：
  名称：

  4,5-Epoxy-2(E)-decenal-Induced Formation of 1,N⁶-Etheno-2‘-deoxyadenosine and 1,N²-Etheno-2‘-deoxyguanosine Adducts

  摘要：

  trans-4,5-Epoxy-2(E)-decenal reacted with 2'-deoxyadenosine to give 1,N-6-etheno-2'-deoxyadenosine as well as other 2'-deoxyadenosine adducts. It also reacted with 2'-deoxyguanosine to give 1,N-2-etheno-2'-deoxyguanosine and other 2'-deoxyguanosine adducts. Synthetic trans-4,5-epoxy-2(E)-decenal was quite stable under the reaction conditions that were used. It was not contaminated with 2,3-epoxyoctanal, a potential precursor to the formation of unsubstituted etheno adducts. Furthermore, using a sensitive LC/MS assay, it was possible to show that no 2,3-epoxyoctanal was formed during prolonged incubations of trans-4,5-epoxy-2(E)-decenal. Therefore, trans-4,5-epoxy-2(E)-decenal, a primary product of lipid peroxidation, is a precursor to the formation of 1,1,N-6-etheno-2'-deoxyadenosine and 1,N-2-etheno-2'-deoxyguanosine. There is no need for an additional oxidation step such as would be required if trans,trans-2,4-decadienal or 4-hydroxy-2-nonenal were the lipid hydroperoxide decomposition products that initiated the formation of unsubstituted etheno adducts. These findings provide an important link between a primary product of lipid peroxidation and a mutagenic DNA lesion that has been detected in human tissues.

  DOI：

  10.1021/tx010147j

文献信息

• Tri-Cyclic Nucleobase Analogs and their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives
  作者：Stachelska-Wierzchowska、Wierzchowski、Górka、Bzowska、Wielgus-Kutrowska

  DOI：10.3390/molecules24081493

  日期：——

  displayed intense fluorescence in neutral aqueous medium, and so did the corresponding ribosylation products. By contrast, PNP from calf spleens exhibited only modest activity towards 1,N6-etheno-isoguanine; the remaining compounds were not ribosylated by this enzyme. The enzymatic ribosylation of 1,N6-etheno-isoguanine using two forms of calf PNP (wild type and N243D) and E. coli PNP (wild type and D204N)

  使用标准方法制备和纯化鸟嘌呤、O6-甲基鸟嘌呤和异鸟嘌呤的乙烯衍生物。在反向（合成）途径中，将标题化合物作为来自各种来源的嘌呤核苷磷酸化酶的潜在底物进行检测。发现 1,N2-乙烯-鸟嘌呤和 1,N6-乙烯-异鸟嘌呤是大肠杆菌嘌呤核苷磷酸化酶 (PNP) 的优良底物，而 O6-甲基-N2,3-乙烯-鸟嘌呤表现出中等活性与这种酶。后两种化合物在中性水性介质中显示出强烈的荧光，相应的核糖基化产物也是如此。相比之下，来自小牛脾脏的 PNP 对 1,N6-乙烯异鸟嘌呤仅表现出适度的活性；其余的化合物没有被这种酶核糖基化。1的酶促核糖基化，N6-乙烯异鸟嘌呤使用两种形式的小牛 PNP（野生型和 N243D）和大肠杆菌 PNP（野生型和 D204N）得到三种不同的产物，根据 NMR 分析和与异鸟苷产物的比较进行鉴定与氯乙醛反应，得到基本上单一的化合物，明确鉴定为 N9-核糖苷。以野生型大肠杆菌酶为催化剂
• Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts
  作者：Anne-Mari Ruohola、Niangoran Koissi、Sanna Andersson、Ilona Lepistö、Kari Neuvonen、Satu Mikkola、Harri Lönnberg

  DOI：10.1039/b405117c

  日期：——

  Reactions of 9-ethylguanine, 2′-deoxyguanosine and guanosine with bromomalondialdehyde in aqueous buffers over a wide pH-range were studied. The main products were isolated and characterized by 1H and 13C NMR and mass spectroscopy. The final products formed under acidic and basic conditions were different, but they shared the common feature of being derived from glyoxal. Among the 1 : 1 adducts, 1,N2-(trans-1,2-dihydroxyethano)guanine adduct (6) predominated at pH < 6 and N2-carboxymethylguanine adduct (10a,b) at pH > 7. In addition to these, an N2-(4,5-dihydroxy-1,3-dioxolan-2-yl)methylene adduct (11a,b) and an N2-carboxymethyl-1,N2-(trans-1,2-dihydroxyethano)guanine adduct (12) were obtained at pH 10. The results of kinetic experiments suggest that bromomalondialdehyde is significantly decomposed to formic acid and glycolaldehyde under the conditions required to obtain guanine adducts. Glycolaldehyde is oxidized to glyoxal, which then modifies the guanine base more readily than bromomalondialdehyde. Besides the glyoxal-derived adducts, 1,N2-ethenoguanine (5a–c) and N2,3-ethenoguanine adducts (4a–c) were formed as minor products, and a transient accumulation of two unstable intermediates, tentatively identified as 1,N2-(1,2,2,3-tetrahydroxypropano) (8) and 1,N2-(2-formyl-1,2,3-trihydroxypropano) (9) adducts, was observed.

  研究了 9-乙基鸟嘌呤、2'-脱氧鸟苷和鸟苷与溴丙二醛在水性缓冲液中在宽 pH 范围内的反应。主要产物通过1H和13C NMR和质谱进行分离和表征。在酸性和碱性条件下形成的最终产物不同，但它们具有共同的特征，即衍生自乙二醛。在 1:1 加合物中，pH < 6 时主要为 1,N2-(反式-1,2-二羟基乙醇)鸟嘌呤加合物 (6)，pH > 7 时主要为 N2-羧甲基鸟嘌呤加合物 (10a,b)。 N2-(4,5-二羟基-1,3-二氧戊环-2-基)亚甲基加合物 (11a,b) 和 N2-羧甲基-1,N2-(反式-1,2-二羟基乙醇)鸟嘌呤加合物 (12 ）在pH 10下获得。动力学实验结果表明，在获得鸟嘌呤加合物所需的条件下，溴丙二醛显着分解为甲酸和乙醇醛。乙醇醛被氧化成乙二醛，然后乙二醛比溴丙二醛更容易修饰鸟嘌呤碱基。除了乙二醛衍生的加合物外，还形成了次要产物 1,N2-乙烯基鸟嘌呤 (5a–c) 和 N2,3-乙烯基鸟嘌呤加合物 (4a–c)，以及两种不稳定中间体的短暂积累，初步鉴定为 1,N2 -(1,2,2,3-四羟基丙酸) (8)和1,N2-(2-甲酰基-1,2,3-三羟基丙酸) (9)观察到加合物。
• Condensed purine derivatives
  申请人：KYOWA HAKKO KOGYO KABUSHIKI KAISHA

  公开号：EP0423805A2

  公开（公告）日：1991-04-24

  There are disclosed condensed purine derivatives represented by formula: alkyl or benzyl; each of X¹ and X² independently represents hydrogen, lower alkyl, aralkyl or phenyl; and n is an integer of 0 or 1; R¹ represents hydrogen, lower alkyl, alicyclic alkyl, noradamantan-3-yl, dicyclopropylmethyl or styryl; and R² represents hydrogen, lower alkyl or alicyclic alkyl; or a pharmaceutically acceptable salt thereof. The derivatives and pharmaceutically acceptable salts are useful as diuretics, renal protecting agents, antiallergic agents and hypotensives.

  公开了由式表示的缩合嘌呤衍生物： 烷基或苄基；X¹和X²各自独立地代表氢、低级烷基、芳烷基或苯基；n为0或1的整数；R¹代表氢、低级烷基、脂环烷基、去甲金刚烷-3-基、二环丙基甲基或苯乙烯基；R²代表氢、低级烷基或脂环烷基；或其药学上可接受的盐。这些衍生物和药学上可接受的盐可用作利尿剂、肾脏保护剂、抗过敏剂和降血压剂。
• Organic compounds
  申请人：Fienberg Allen A.

  公开号：US10010553B2

  公开（公告）日：2018-07-03

  The present invention relates to a new use of phosphodiesterase 1 (PDE1) inhibitors for the treatment of psychosis, schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder, delusional disorder, mania, or bipolar disorder.

  本发明涉及一种磷酸二酯酶1（PDE1）抑制剂的新用途，用于治疗精神病、精神分裂症、情感分裂症、精神分裂症、精神病性障碍、妄想性障碍、躁狂症或双相情感障碍。
• Combinations of PDE1 inhibitors and NEP inhibitors and associated methods
  申请人：Intra-Cellular Therapies, Inc.

  公开号：US10285992B2

  公开（公告）日：2019-05-14

  The invention relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) and inhibitors of Neprilysin (NEP) useful for the treatment of certain cardiovascular diseases or related disorders, e.g., hypertension, congestive heart disease, and post-myocardial infarction. In another embodiment, the invention relates to the combination of inhibitors of PDE1 and inhibitors of NEP for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways in the cardiovascular system (e.g., in cardiac tissue or in arterial smooth muscle).

  本发明涉及磷酸二酯酶1（PDE1）抑制剂和Neprilysin（NEP）抑制剂的组合，用于治疗某些心血管疾病或相关疾病，如高血压、充血性心脏病和心肌梗塞后。在另一个实施方案中，本发明涉及 PDE1 抑制剂和 NEP 抑制剂的组合，用于治疗以心血管系统（如心脏组织或动脉平滑肌）中各种 cGMP/PKG 介导的通路被破坏或损害为特征的疾病或紊乱。