5-amino-1-<2',3'-O-(1-methylethylidene)-β-D-ribofuranosyl>imidazole-4-carbonitrile | 6612-90-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑核糖核苷和核糖核苷酸
• 英文名称: 5-amino-1-<2',3'-O-(1-methylethylidene)-β-D-ribofuranosyl>imidazole-4-carbonitrile
• 英文别名: 5-amino-1-(2',3'-O-isopropylidene-β-D-ribofuranosyl)-1H-imidazole-4-carbonitrile；5-amino-1-(2',3'-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carbonitrile；5-amino-4-cyano-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole；5-amino-1-(O²,O³-isopropylidene-β-D-ribofuranosyl)-1H-imidazole-4-carbonitrile；5-amino-1-[(2,3-O-(1-methylethylidene)-β-D-ribofuranosyl)]-1H-imidazole-4-carbonitrile；5-Amino-4-cyan-1-(2',3'-O-isopropyliden-β-D-ribofuranosyl)-imidazol；1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-aminoimidazole-4-carbonitrile
• CAS: 6612-90-4
• 化学式: C₁₂H₁₆N₄O₄
• 分子量: 280.283
• InChiKey: FEKSXDGHWREFIS-TURQNECASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-amino-1-<2',3'-O-(1-methylethylidene)-β-D-ribofuranosyl>imidazole-4-carbonitrile 在 咪唑 、 二(氰基苯)二氯化钯 、 二碘甲烷 、 potassium tert-butylate 、 氨 、 sodium hydride 、 亚硝酸异戊酯 作用下， 以 甲醇 、 乙二醇二甲醚 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 45.17h， 生成 4-Amino-1-(5′-O-sulfamoyl-β-D-ribofuranosyl)-1H-imidazo[4,5-c]pyridine
  参考文献：
  名称：

  Bisubstrate Inhibitors of Biotin Protein Ligase in Mycobacterium tuberculosis Resistant to Cyclonucleoside Formation

  摘要：

  Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is the leading cause of bacterial infectious disease mortality. Biotin protein ligase (BirA) globally regulates lipid metabolism in Mtb through the posttranslational biotinylation of acyl coenzyme A carboxylases (ACCs) involved in lipid biosynthesis and is essential for Mtb survival. We previously developed a rationally designed bisubstrate inhibitor of BirA that displays potent enzyme inhibition and whole cell activity against multidrug resistant and extensively drug resistant Mtb strains. Here we present the design, synthesis, and evaluation of a focused series of inhibitors, which are resistant to cyclonucleoside formation, a key decomposition pathway of our initial analogue. Improved chemical stability is realized through replacement of the adenosyl N-3 nitrogen and C-5' oxygen atom with carbon as well as incorporation of a bulky group on the nucleobase to prevent the required synconformation necessary for proper alignment of N-3 with C-5'.

  DOI：

  10.1021/ml400328a
• 作为产物：
  描述：

  5-Amino-1-((3aR,4R,6R,6aR)-6-hydroxymethyl-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-1H-imidazole-4-carboxylic acid amide 在 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以45%的产率得到5-amino-1-<2',3'-O-(1-methylethylidene)-β-D-ribofuranosyl>imidazole-4-carbonitrile
  参考文献：
  名称：

  Synthesis of bredinin from 1-.BETA.-D-ribofuranosyl-5-aminoimidazole-4-carboxamide by a photo-reaction.

  摘要：

  光解1-β-D-呋喃核糖基-5-氨基咪唑-4-甲酰胺（AICA-核糖苷）得到2-氨基-N-(β-D-呋喃核糖基)马来二酰胺，后者经乙氧基三甲酸酯处理环化得到强力免疫抑制核苷类抗生素1-β-D-呋喃核糖基-5-羟基咪唑-4-甲酰胺（bredinin）。

  DOI：

  10.1248/cpb.34.3653

文献信息

• Synthesis of bredinin from 1-.BETA.-D-ribofuranosyl-5-aminoimidazole-4-carboxamide by a photo-reaction.
  作者：KIYOFUMI FUKUKAWA、SATOSHI SHUTO、TAKAO HIRANO、TOHRU UEDA

  DOI：10.1248/cpb.34.3653

  日期：——

  Photolysis of 1-β-D-ribofuranosyl-5-aminoimidazole-4-carboxamide (AICA-riboside) gave 2-amino-N-(β-D-ribofuranosyl)malondiamide, which was cyclized by treatment with ethyl orthoformate to furnish 1-β-D-ribofuranosyl-5-hydroxyimidazole-4-carboxamide (bredinin), a potent immunosuppressive nucleoside antibiotic.

  光解1-β-D-呋喃核糖基-5-氨基咪唑-4-甲酰胺（AICA-核糖苷）得到2-氨基-N-(β-D-呋喃核糖基)马来二酰胺，后者经乙氧基三甲酸酯处理环化得到强力免疫抑制核苷类抗生素1-β-D-呋喃核糖基-5-羟基咪唑-4-甲酰胺（bredinin）。
• A general synthesis of 5,7-diaminoimidazo[4,5-<i>b</i>]pyridine ribosides ("2-amino-1-deazaadenosines") from 5-amino-4-imidazolecarboxamide riboside (AICA riboside)
  作者：John E. Francis、Michael A. Moskal

  DOI：10.1139/v92-166

  日期：1992.5.1

  synthesis of 5-substituted 5,7-diaminoimidazo[4,5-b]pyridines from 5-amino-4-imidazolecarboxamide riboside (AICA riboside) was designed to prepare isosteres of substituted 2-aminoadenosines that are selective adenosine A2 receptor agonists. AICA riboside was converted to a hydroxyl-protected 5-amino-4-imidazolecarbonitrile riboside and reacted with an N,N-disubstituted acetamide in the presence of

  从 5-氨基-4-咪唑甲酰胺核苷（AICA 核糖苷）合成 5-取代的 5,7-二氨基咪唑并[4,5-b] 吡啶，旨在制备选择性腺苷 A2 受体的取代 2-氨基腺苷的等排体激动剂。AICA 核苷转化为羟基保护的 5-氨基-4-咪唑甲腈核苷，并在磷酰氯存在下与 N,N-二取代乙酰胺反应。氢化钠处理完成了闭环并引入了 7-氨基。在标准条件下除去羟基保护基团。乙酰胺被一个苄基部分的 N-取代通过氢解产生 5-N-取代的衍生物，而 N,N-二苄基乙酰胺产生 5,7-二氨基化合物。从 N,N-二取代丙酰胺获得 6-甲基类似物。
• Imidazo[4,5-b]pyridine derivatives as cardiovascular agents
  申请人：Ciba-Geigy Corporation

  公开号：US04977144A1

  公开（公告）日：1990-12-11

  Disclosed are the compounds of the formula ##STR1## wherein R represents hydrogen, lower alkyl, aryl or aryl-lower alkyl; R.sub.1 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -alkenyl, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, or optionally lower alkyl substituted (C.sub.3 -C.sub.7 -cycloalkyl, bicycloheptyl, bicycloheptenyl, adamantyl, tetrahydropyranyl or tetrahydrothiopyranyl)-lower alkyl, or diaryl-lower alkyl; R.sub.2 represents hydrogen or lower alkyl; R.sub.3 represents hydroxymethyl or --CONHR.sub.4 in which R.sub.4 represents hydrogen, lower alkyl, aryl-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl or hydroxy-lower alkyl; pharmaceutically acceptable ester derivatives thereof in which one or more of the hydroxy groups are esterified in form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; methods of preparation; pharmaceutical compositions; and their use as adenosine-2 agonists in mammals.

  公开的化合物如下所示：其中R代表氢、低碳烷基、芳基或芳基-低碳烷基；R.sub.1代表氢、低碳烷基、C.sub.3-C.sub.7-烯基、碳环或杂环芳基、碳环或杂环芳基-低碳烷基、C.sub.3-C.sub.7-环烷基，或者可选地低碳烷基取代的(C.sub.3-C.sub.7-环烷基、双环庚基、双环庚烯基、金刚烷基、四氢吡喃基或四氢硫代吡喃基)-低碳烷基，或二芳基-低碳烷基；R.sub.2代表氢或低碳烷基；R.sub.3代表羟甲基或--CONHR.sub.4，其中R.sub.4代表氢、低碳烷基、芳基-低碳烷基、C.sub.3-C.sub.7-环烷基、C.sub.3-C.sub.7-环烷基-低碳烷基或羟基-低碳烷基；其药学上可接受的酯衍生物，其中一个或多个羟基以药学上可接受的酯形式酯化；以及其药学上可接受的盐；制备方法；药物组合物；以及它们在哺乳动物中作为腺苷-2受体激动剂的用途。
• Certain imidazo[4,5-b]pyridine derivatives
  申请人：CIBA-GEIGY AG

  公开号：EP0354180A2

  公开（公告）日：1990-02-07

  Disclosed are imidazo[4,5-b]pyridine derivatives of the formula I wherein R₁, R₂ and R₃ are as defined in the specification, which exhibit valuable pharmacological properties, especially as adenosine-2 (A-2) receptor agonists, and the preparation thereof.

  所公开的是式 I 的咪唑并[4,5-b]吡啶衍生物 其中 R₁、R₂ 和 R₃ 如说明书中所定义，这些衍生物具有重要的药理特性，特别是作为腺苷-2 (A-2) 受体激动剂，以及其制备方法。
• REESE, COLIN B.;SANGHVI, YOGESH S.;KURODA, REIKO, J. CHEM. SOC. PERKIN TRANS., 1,(1987) N 7, 1527-1531
  作者：REESE, COLIN B.、SANGHVI, YOGESH S.、KURODA, REIKO

  DOI：——

  日期：——