5-iodo-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide | 118744-90-4

• 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-iodo-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide
• 英文别名: 5-iodo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-imidazole-4-carboxamide；5-Iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-imidazole-4-carboxamide；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(4-carbamoyl-5-iodoimidazol-1-yl)oxolan-2-yl]methyl acetate
• CAS: 118744-90-4
• 化学式: C₁₅H₁₈IN₃O₈
• 分子量: 495.228
• InChiKey: JFPFBQTYSWZFCA-SDBHATRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  149
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-iodo-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide 生成 5-(3-hydroxy-1-propynyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide
  参考文献：
  名称：

  MATSUDA, AKIRA;MINAKAWA, NORIAKI;SASAKI, TAKUMA;UEDA, TOHRU, CHEM. AND PHARM. BULL., 36,(1988) N 7, C. 2730-2733

  摘要：

  DOI：
• 作为产物：
  描述：

  阿卡地新 在 4-二甲氨基吡啶 、 二碘甲烷 、 三乙胺 、 亚硝酸异戊酯 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 5-iodo-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide
  参考文献：
  名称：

  核苷和核苷酸。96. 5-乙炔基-1-β-D-呋喃呋喃基嘧啶咪唑-4-羧酰胺（EICAR）及其衍生物的合成和抗肿瘤活性。

  摘要：

  在存在下，5-碘-1-（2,3,5-三-O-乙酰基-β-D-核呋喃呋喃糖基）咪唑-4-羧酰胺（8）的钯催化交叉偶联反应在含三乙胺的乙腈中的双（苄腈）二氯化钯以高收率得到了所需的5-炔基衍生物9。但是，当使用（三甲基甲硅烷基）乙炔时，唯一可分离的产物是不希望的二聚体，即1，2-双（4-氨基甲酰基-1-β-D-呋喃呋喃基氨基咪唑-5-基）乙炔衍生物10a。为了避免这种二聚物的形成，在没有三乙胺的情况下，使用三甲基-[（三丁基锡烷基）乙炔基]硅烷进行反应，以高收率得到所需的5-（2-三甲基甲硅烷基）乙炔基衍生物9a。此外，5-iodo-1-（2,3，具有（三甲基甲硅烷基）乙炔的5-三-O-乙酰基-β-D-呋喃呋喃糖基）咪唑-4-碳三化合物（12）也提供了所需的核苷13a。这些化合物的脱保护提供了5-炔基-1-β-D-呋喃呋喃基嘧啶唑-4-羧酰胺（6b-k）和-甲腈​​（14b-f）。其中，5-乙

  DOI：

  10.1021/jm00106a045

文献信息

• NOVEL CONDENSED IMIDAZOLE DERIVATIVE
  申请人：Dainippon Sumitomo Pharma Co., Ltd.

  公开号：EP1690863A1

  公开（公告）日：2006-08-16

  Disclosed is a compound represented by the formula (1) below which has a high DPP-IV inhibitory activity and is improved in safety, toxicity and the like. Also disclosed is a prodrug of such a compound and pharmaceutically acceptable salts of them. (In the formula, R1 represents a hydrogen atom, an optionally substituted alkyl group or the like; R2 and R3 independently represent a hydrogen atom, an optionally substituted alkyl group or the like; R4 and R5 independently represent a hydrogen atom, an optionally substituted alkyl group or the like: R6 represents a hydrogen atom, an optionally substituted aryl group or the like; and -Y-NH2, represents a group represented by the following formula (A): (wherein m is 0, 1 or 2; and R7 may not exist or one or two R7 may exist and independently represent an optionally substituted alkyl group or the like) or the like.]

  揭示了一种化合物，其化学式如下（1），具有较高的DPP-IV抑制活性，并在安全性、毒性等方面得到改善。还披露了这种化合物的前药和其药用可接受的盐。（在该式中，R1代表氢原子、可选择取代的烷基或类似物；R2和R3独立代表氢原子、可选择取代的烷基或类似物；R4和R5独立代表氢原子、可选择取代的烷基或类似物；R6代表氢原子、可选择取代的芳基或类似物；-Y-NH2代表由以下式（A）表示的基团：（其中m为0、1或2；R7可能不存在，或一个或两个R7可以存在且独立代表可选择取代的烷基或类似物）或类似物。）
• Imidazole derivatives, process for production thereof, and use thereof
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：US05059590A1

  公开（公告）日：1991-10-22

  Disclosed are imidazole derivatives represented by formula [I]: ##STR1## wherein R is a hydrogen atom or ##STR2## wherein R.sup.2 is a hydrogen atom or a hydroxy protecting group, R.sup.2 protecting either a single hydroxy or two hydroxies together when R.sup.2 is a hydroxy protecting group, and R.sup.3 is a hydrogen atom or OR.sup.2 ; A is CONH.sub.2 or CN; and R.sup.1 is a hydrogen atom, lower alkyl, hydroxy lower alkyl, or phenyl. Also disclosed are six processes for producing these novel compounds among which a typical process comprises reacting a starting imidazole compound having a halogen at the 5-position thereof with an acetylene derivative to alkynylate the 5-position. Furthermore, the compounds having remarkable antitumor activities and therefore can provide novel antitumor agents.

  已披露的咪唑衍生物如下所示：其中R是氢原子或其中R.sup.2是氢原子或羟基保护基团，R.sup.2在R.sup.2是羟基保护基团时可以保护单个羟基或两个羟基，R.sup.3是氢原子或OR.sup.2；A是CONH.sub.2或CN；R.sup.1是氢原子、较低的烷基、羟基较低的烷基或苯基。还披露了六种制备这些新化合物的方法，其中一种典型的方法包括将在其5-位置具有卤素的起始咪唑化合物与乙炔衍生物反应以炔基化5-位置。此外，这些化合物具有显著的抗肿瘤活性，因此可以提供新的抗肿瘤药物。
• The design, synthesis and antileukemic activity of 5-alkynyl-1-.BETA.-D-ribofuranosylimidazole-4-carboxamides.
  作者：Akira Matsuda、Noriaki Minakawa、Takuma Sasaki、Tohru Ueda

  DOI：10.1248/cpb.36.2730

  日期：——

  The design, synthesis and antileukemic activity of 5-alkynel-1-β-D-ribofuranosylimidazole-4-carboxamides (6) are described. The cross-coupling reaction of 5-iodo-1-(2, 3, 5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide (8) with various terminal alkynes in the persence of bis(benzonitrile)palladium dichloride and triethylamine in acetonitrile gave 5-alkylnyl derivatives (9) in high yields. Coupling of 8 with (trimethylsilyl)acetylene gave hte undesired dimer (10). Instead of (trimethylsilyl)acetylene, treatment of trimethyl[(tributyl-satannyl)ethynyl]silane with 8 in the absence of triethylamine produced the desired 5-[2-(trimethylsilyl)ethynyl] derivative (9f) in 77% yield. Deblocking of these nucleosides (9) gave the target nucleosides (6a-f). Among them, 5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxyamide (6f) is the most potent inhibitor of the growth of murine L1210 cells in vitro (IC50=0.18 μg/ml).

  描述了 5-炔基-1-β-D-呋喃核糖基咪唑-4-甲酰胺 (6) 的设计、合成和抗白血病活性。 5-碘-1-(2,3,5-三-O-乙酰基-β-D-呋喃核糖基)咪唑-4-甲酰胺(8)与各种末端炔烃在双(苯甲腈)存在下的交叉偶联反应)二氯化钯和三乙胺在乙腈中以高产率得到5-烷基衍生物(9)。 8与(三甲基甲硅烷基)乙炔偶联得到不需要的二聚体(10)。在不存在三乙胺的情况下，用8代替(三甲基甲硅烷基)乙炔处理三甲基[(三丁基-饱和烷基)乙炔基]硅烷，产生所需的5-[2-(三甲基甲硅烷基)乙炔基]衍生物(9f)，收率77%。这些核苷 (9) 的解封闭得到目标核苷 (6a-f)。其中，5-乙炔基-1-β-D-核呋喃基咪唑-4-羧酰胺(6f)是体外小鼠L1210细胞生长最有效的抑制剂(IC50=0.18 μg/ml)。
• Nucleosides and nucleotides 179. Ring-expanded purine nucleosides. The synthesis and cytotoxicity of imidazo[4,5-c]azepine nucleosides
  作者：Noriaki Minakawa、Takuma Sasaki、Akira Matsuda

  DOI：10.1016/s0040-4020(98)00832-1

  日期：1998.10

  The synthesis of ring-expanded imidazo[4,5-c]azepine nucleosides (3–6) is described. Treatment of 5-iodoimidazole derivative 9 with methyl acrylate in the presence of a palladium catalyst gave (10), appropriate manipulation of which gave (3). The ring-expanded guanosine derivative 4 was prepared in a manner similar to the synthesis of 3. The ring-expanded inosine derivatives 5 and 6 were obtained from

  描述了扩环的咪唑并[4,5- c ]氮杂氮杂核苷（3–6）的合成。在钯催化剂的存在下用丙烯酸甲酯处理5-碘咪唑衍生物9，得到（10），对其进行适当的操作得到（3）。以类似于3的合成的方式制备环扩的鸟苷衍生物4。从（21）通过钯催化的氢解获得环膨胀的肌苷衍生物5和6。还描述了这些环扩核苷的细胞毒性。
• Novel condensed imidazole derivative
  申请人：Nakahira Hiroyuki

  公开号：US20070105890A1

  公开（公告）日：2007-05-10

  Disclosed is a compound represented by the formula (1) below which has a high DPP-IV inhibitory activity and is improved in safety, toxicity and the like. Also disclosed is a prodrug of such a compound and pharmaceutically acceptable salts of them. (In the formula, R 1 represents a hydrogen atom, an optionally substituted alkyl group or the like; R 2 and R 3 independently represent a hydrogen atom, an optionally substituted alkyl group or the like; R 4 and R 5 independently represent a hydrogen atom, an optionally substituted alkyl group or the like: R 6 represents a hydrogen atom, an optionally substituted aryl group or the like; and —Y—NH 2 , represents a group represented by the following formula (A): (wherein m is 0, 1 or 2; and R 7 may not exist or one or two R 7 may exist and independently represent an optionally substituted alkyl group or the like) or the like.]

  公开了一种化合物，其表示为以下式（1），具有较高的DPP-IV抑制活性并且在安全性、毒性等方面得到改善。还公开了这种化合物的前药和它们的药学上可接受的盐。（在该式中，R1表示氢原子，可选择性取代的烷基或类似物; R2和R3独立地表示氢原子，可选择性取代的烷基或类似物; R4和R5独立地表示氢原子，可选择性取代的烷基或类似物：R6表示氢原子，可选择性取代的芳基或类似物; 而—Y—NH2表示由以下式（A）表示的基团：（其中m为0、1或2；而R7可能不存在或一个或两个R7可能存在且独立地表示可选择性取代的烷基或类似物）或类似物。）