2-[2,3-O-(1-甲基乙亚基)-beta-D-呋喃核糖基]-4-噻唑甲酰胺 | 60084-11-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-[2,3-O-(1-甲基乙亚基)-beta-D-呋喃核糖基]-4-噻唑甲酰胺
• 英文名称: 2-(2',3'-O-isopropylidene-β-D-ribofuranosyl)thiazole-4-carboxamide
• 英文别名: 2-(2',3'-isopropylidene-β-D-ribofuranosyl)thiazole-4-carboxamide；2-(2,3-O-isopropylidene-β-D-ribofuranosyl)thiazole-4-carboxamide；2',3'-O-isopropylidene-tiazofurin；2',3'-O-isopropylidenethiazofurin；2',3'-O-isopropylidenetiazofurin；2-(O²,O³-isopropylidene-β-D-ribofuranosyl)-thiazole-4-carboxylic acid amide；2-[2,3-O-(1-Methylethylidene)-beta-D-ribofuranosyl]-4-thiazolecarboxamide；2-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1,3-thiazole-4-carboxamide
• CAS: 60084-11-9
• 化学式: C₁₂H₁₆N₂O₅S
• 分子量: 300.335
• InChiKey: QAXZUYHAABBXMH-FNCVBFRFSA-N

物化性质

• 熔点：
  119-121 °C(Solv: acetone (67-64-1))
• 沸点：
  539.6±50.0 °C(Predicted)
• 密度：
  1.373±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[2,3-O-(1-甲基乙亚基)-beta-D-呋喃核糖基]-4-噻唑甲酰胺 在 吡啶 、 Dowex 50-X₈ 、 水 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 反应 20.0h， 生成 adenosine 5'- 5'<*>5'-ester with 2-β-D-ribofuranosyl-4-thiazolecarboxamide
  参考文献：
  名称：

  The Practical Synthesis of a Methylenebisphosphonate Analogue of Benzamide Adenine Dinucleotide:  Inhibition of Human Inosine Monophosphate Dehydrogenase (Type I and II)

  摘要：

  beta-Methylene-BAD (8), a nonhydrolyzable analogue of benzamide adenine dinucleotide (BAD), was synthesized as potential inhibitor of human inosine monophosphate dehydrogenase (IMPDH). Treatment of 2',3'-O-isopropylideneadenosine 5'-methylenebisphosphonate (15) with DCC afforded P-1,P-4-bis(2',3'-O-isopropylideneadenosine) 5'-P-1,P-2:P-3,P-4-dimethylenetetrakisphosphonate (17). This compound was further converted with DCC to an active intermediate 18 which upon reaction with 3-(2',3'-O-isopropylidene-beta-D-ribofuranosyl)benzamide (19) gave, after hydrolysis and deisopropylidenation, the desired beta-methylene-BAD (8) in 95% yield. In a similar manner, treatment of 18 with 2',3'-O-isopropylidenetiazofurin (21) followed by hydrolysis and deprotection afforded beta-methylene-TAD (5) in 91% yield. Compound 8 (IC50 = 0.665 mu M) was found to be a 6-8 times less potent inhibitor of IMPDH than 5 (IC50 = 0.107 mu M) and was almost equally potent against IMPDH type I and type II. Although TAD and beta-methylene-TAD were bound by LADH with the same affinity, the binding affinity of 8 toward LADH (K-i = 333 mu M) was found to be 50-fold lower than that of the parent pyrophosphate 7 (K-i = 6.3 mu M).

  DOI：

  10.1021/jm960641y
• 作为产物：
  描述：

  ethyl 2-(2',3',3''-tri-O-benzoyl-β-D-apiofuranosyl)thiazole-4-carboxylate 在 盐酸 、 氨 、 原甲酸三乙酯 作用下， 以 甲醇 为溶剂， 生成 2-[2,3-O-(1-甲基乙亚基)-beta-D-呋喃核糖基]-4-噻唑甲酰胺
  参考文献：
  名称：

  Synthesis of C-glycosyl thiazoles

  摘要：

  DOI：

  10.1021/jo00888a005

文献信息

• Synthesis and biological activity of some new 5′-O-acyl tiazofurin derivatives
  作者：Vjera Pejanović、Vesna Piperski、Dragana Uglješić-Kilibarda、Jelena Tasić、Mirjana Dačević、Ljubica Medić-Mijačević、Esmir Gunić、Mirjana Popsavin、Velimir Popsavin

  DOI：10.1016/j.ejmech.2006.01.005

  日期：2006.4

  Three new 5'-O-acyl tiazofurin derivatives 2-4 were synthesized and evaluated for their antiproliferative activity against different tumour cell lines as well as for their ability to induce apoptosis in C6 cells in vitro. Apart of the antitumour assays, the cell membrane permeation of 2-4 and their intracellular metabolism in C6 cells in vitro was also studied in order to evaluate their potential as

  合成了三种新的5'-O-酰基噻唑啉衍生物2-4，并评估了其对不同肿瘤细胞系的抗增殖活性以及在体外诱导C6细胞凋亡的能力。除抗肿瘤试验外，还研究了C6细胞中2-4的细胞膜渗透及其细胞内代谢，以评估其作为噻唑呋林生物等排体或前药的潜力。
• Synthesis of thiazole-4-carboxamide-adenine difluoromethylenediphosphonates substituted with fluorine at C-2′ of the adenosine
  作者：Andrzej Zatorski、Pawell Lipla、Nevena Mollova、Karl H. Schram、Barry M. Goldstein、Kyoichi A. Watanabe、Krzysztof W. Pankiewicz

  DOI：10.1016/0008-6215(93)84063-c

  日期：1993.10

  Synthesis of an analogue 3 of thiazole-4-carboxamide adenine-dinucleotide (TAD) in which the beta-oxygen atom of the pyrophosphate bridge is replaced by a difluoromethylene group has been achieved. Likewise, 2'-deoxy-2'-fluoroadenosine containing analogues of TAD (4) and its difluoromethylenediphosphonate congener (5) have been synthesized. Adenosine 5'-difluoromethylenediphosphonate (8) was prepared

  已经合成了噻唑-4-羧酰胺腺嘌呤二核苷酸（TAD）的类似物3，其中焦磷酸桥的β-氧原子被二氟亚甲基取代。同样，已经合成了含有2'-脱氧-2'-氟腺苷的TAD类似物（4）及其二氟亚甲基二膦酸盐同类物（5）。腺苷5'-二氟亚甲基二膦酸酯（8）是由5'-O-甲苯磺酰基腺苷（6）和三（四正丁基铵）二氟亚甲基二膦酸酯（7）通过改进的Poulter方法制备的。通过用原甲酸三乙酯处理将化合物8转化为2'，3'-环状碳酸酯9。用2'，3'处理9 在DCC存在下，在吡啶中的-O-异亚丙基亚氮杂呋喃（10）得到二核苷酸11和异亚丙基保护的二腺苷四膦酸酯12的混合物。将11脱保护后，所需的β-二氟亚甲基TAD（3）通过HPLC分离为次要化合物。产品。获得了Ap4A的类似物二腺苷四膦酸腺苷12作为主要成分。或者，将2'，3'-O-异丙基亚氮杂呋喃酯（10）甲苯磺酸化，并通过与7偶合，将产物13进一步转化为相应的二
• Potent Inhibitors of Human Inosine Monophosphate Dehydrogenase Type II. Fluorine-Substituted Analogs of Thiazole-4-carboxamide Adenine Dinucleotide
  作者：Andrzej Zatorski、Barry M. Goldstein、Thomas D. Colby、Jeffery P. Jones、Krzysztof W. Pankiewicz

  DOI：10.1021/jm00007a007

  日期：1995.3

  best cofactor-type inhibitor, beta-CH2-TAD (Ki = 0.11 microM). Interestingly, the level of inhibition of horse liver alcohol dehydrogenase by these compounds was found to be much lower (0.1 mM for 1 and 2 and no inhibition up to 10 mM for 3). These findings show that inhibition of tumor-induced inosine monophosphate dehydrogenase type II is selective and may be of therapeutic interest.

  噻唑-4-羧酰胺腺嘌呤二核苷酸（TAD）（1-3）的三个类似物分别在腺嘌呤核苷的C2'（核糖和阿拉伯糖构型）和C3'（核糖构型）中含有氟原子。由2'-脱氧-2'-氟腺苷（9），9-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）-腺嘌呤（17）和3的相应5'-单磷酸盐高收率合成'-deoxy-3'-氟腺苷（14）。通过将被保护的噻唑呋喃磷酸化，然后用羰基二咪唑处理并进行HPLC纯化，获得纯的2'，3'-O-异亚丙基-噻唑呋喃5'-磷酸咪唑啉（8）。8在DMF-d7中（由1H和31P NMR监测）中的9与9的反应得到所需的二核苷酸12，在脱异丙基化之后，其收率为82％，为1。在主要产品12的HPLC纯化过程中，还分离出少量对称的二核苷酸AppA（10，7.2％）和TRppTR（11，8.0％）。以类似的方式，通过将8与14和C偶联，得到化合物2和3。分别以80％和76％的收率排名第17位。我们早
• Synthesis, conformational analysis, and biological activity of new analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) as IMP dehydrogenase inhibitors
  作者：Palmarisa Franchetti、Loredana Cappellacci、Michela Pasqualini、Riccardo Petrelli、Vetrichelvan Jayaprakasan、Hiremagalur N. Jayaram、Donald B. Boyd、Manojkumar D. Jain、Mario Grifantini

  DOI：10.1016/j.bmc.2005.01.007

  日期：2005.3

  T-3'-MeAD (2) containing, respectively, a methyl group at the ribose 2'-C-, and 3'-C-position of the adenosine moiety, were prepared as potential selective human inosine monophosphate dehydrogenase (IMPDH) type II inhibitors. The synthesis of heterodinucleotides was carried out by CDI-catalyzed coupling reaction of unprotected 2'-C-methyl- or 3'-C-methyl-adenosine 5'-monophosphate with 2',3'-O-isopr

  噻唑-4-羧酰胺腺嘌呤二核苷酸（TAD）类似物T-2'-MeAD（1）和T-3'-MeAD（2）分别在核糖2'-C-和3'-处含有甲基制备腺苷部分的C位作为潜在的选择性人肌苷单磷酸脱氢酶（IMPDH）II型抑制剂。杂二核苷酸的合成是通过CDI催化未保护的2'-C-甲基-或3'-C-甲基-腺苷5'-单磷酸酯与2'，3'-O-异亚丙基-噻唑啉5'-的偶联反应进行的一磷酸，然后脱异丙基。作为重组人IMPDH和I型II抑制剂的二核苷酸1和2的生物学评估导致了良好的活性。相对于NAD底物，T-2'-MeAD和T-3'-MeAD对同工酶的抑制是非竞争性的。T-3'的结合 -MeAD与母体化合物TAD相当，而T-2'-MeAD被证明是较弱的抑制剂。然而，在抑制IMPDH同工酶方面未发现显着差异。发现T-2'-MeAD和T-3'-MeAD抑制K562细胞的生长（IC（50）分别为30.7和65.0μM）。
• A New Tiazofurin Pronucleotide: Synthesis and Biological Evaluation of<i>Cyclo</i>Saligenyl-Tiazofurin Monophosphate
  作者：L. Cappellacci、G. Barboni、P. Franchetti、C. Martini、H. N. Jayaram、M. Grifantini

  DOI：10.1081/ncn-120022674

  日期：2003.10

  Synthesis and biological activities of cyclosaligenyl-tiazofurin monophosphate (CycloSal-TRMP), a new tiazofurin pronucleotide, are reported. CycloSal-TRMP proved to be active in vitro against human myelogenous leukemia K562 cell line and as A1 adenosine receptor agonist.

  据报道，一种新的噻唑呋喃原核苷酸，即环saligenyl-tiazofurin单磷酸酯（CycloSal-TRMP）的合成和生物学活性。CycloSal-TRMP被证明在体外对人骨髓性白血病K562细胞具有活性，并作为A1腺苷受体激动剂。