2-(2',3'-O-isopropylidene-5'-monophosphate-β-D-ribofuranosyl)thiazole-4-carboxamide | 162756-36-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(2',3'-O-isopropylidene-5'-monophosphate-β-D-ribofuranosyl)thiazole-4-carboxamide
• 英文别名: 2-(2',3'-isopropylidene-β-D-ribofuranosyl)thiazole-4-carboxamide 5'-phosphate；2',3'-O-isopropylidenetiazofurin 5'-monophosphate；[(3aR,4R,6R,6aR)-4-(4-carbamoyl-1,3-thiazol-2-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl dihydrogen phosphate
• CAS: 162756-36-7
• 化学式: C₁₂H₁₇N₂O₈PS
• 分子量: 380.315
• InChiKey: TUPIYTIKWOJLNL-FNCVBFRFSA-N

物化性质

• 沸点：
  662.4±65.0 °C(predicted)
• 密度：
  1.541±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-(2',3'-O-isopropylidene-5'-monophosphate-β-D-ribofuranosyl)thiazole-4-carboxamide 在 三辛胺 、 溶剂黄146 作用下， 反应 2.42h， 生成 噻唑-4-甲酰胺腺嘌呤二核苷酸
  参考文献：
  名称：

  Synthesis of thiazole-4-carboxamide adenine dinucleotide. A powerful inhibitor of IMP dehydrogenase

  摘要：

  The chemical synthesis of thiazole-4-carboxamide adenine dinucleotide (TAD), previously identified as the active anabolite of the oncolytic 2-beta-D-ribofuranosylthiazole-4-carboxamide (TR), has been achieved by three different approaches: (1) incubation of adenosine 5'-monophosphate (AMP) and 2-beta-D-ribofuranosylthiazole-4-carboxamide 5'-monophosphate (TRMP) with excess DCC in aqueous pyridine, (2) reaction of adenosine 5'-phosphoromorpholidate with TRMP in pyridine, and (3) reaction of adenosine-5'-phosphoric di-n-butylphosphinothioic anhydride with TRMP in the presence of AgNO3. While the first approach produced only traces of TAD, the last two afforded 31 and 16% yields, respectively, of isolated TAD. The synthetic material was indistinguishable from biosynthesized TAD as judged by its HPLC behavior, NMR, UV and mass spectra, enzymatic resistance to alkaline phosphatase and susceptibility to venom phosphodiesterase, IMP dehydrogenase inhibitory activity, and cytotoxicity. TAD and TR were equally effective against murine P388 leukemia when employed at equimolar doses.

  DOI：

  10.1021/jm00360a025
• 作为产物：
  描述：

  噻唑呋林 在 盐酸 、 三氯氧磷 作用下， 以 various solvent(s) 为溶剂， 反应 3.0h， 生成 2-(2',3'-O-isopropylidene-5'-monophosphate-β-D-ribofuranosyl)thiazole-4-carboxamide
  参考文献：
  名称：

  Synthesis of thiazole-4-carboxamide adenine dinucleotide. A powerful inhibitor of IMP dehydrogenase

  摘要：

  The chemical synthesis of thiazole-4-carboxamide adenine dinucleotide (TAD), previously identified as the active anabolite of the oncolytic 2-beta-D-ribofuranosylthiazole-4-carboxamide (TR), has been achieved by three different approaches: (1) incubation of adenosine 5'-monophosphate (AMP) and 2-beta-D-ribofuranosylthiazole-4-carboxamide 5'-monophosphate (TRMP) with excess DCC in aqueous pyridine, (2) reaction of adenosine 5'-phosphoromorpholidate with TRMP in pyridine, and (3) reaction of adenosine-5'-phosphoric di-n-butylphosphinothioic anhydride with TRMP in the presence of AgNO3. While the first approach produced only traces of TAD, the last two afforded 31 and 16% yields, respectively, of isolated TAD. The synthetic material was indistinguishable from biosynthesized TAD as judged by its HPLC behavior, NMR, UV and mass spectra, enzymatic resistance to alkaline phosphatase and susceptibility to venom phosphodiesterase, IMP dehydrogenase inhibitory activity, and cytotoxicity. TAD and TR were equally effective against murine P388 leukemia when employed at equimolar doses.

  DOI：

  10.1021/jm00360a025

文献信息

• 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）。
• Synthesis of thiazole-4-carboxamide adenine dinucleotide. A powerful inhibitor of IMP dehydrogenase
  作者：Gulilat Gebeyehu、Victor E. Marquez、James A. Kelley、David A. Cooney、Hiremagalur N. Jayaram、David G. Johns

  DOI：10.1021/jm00360a025

  日期：1983.6

  The chemical synthesis of thiazole-4-carboxamide adenine dinucleotide (TAD), previously identified as the active anabolite of the oncolytic 2-beta-D-ribofuranosylthiazole-4-carboxamide (TR), has been achieved by three different approaches: (1) incubation of adenosine 5'-monophosphate (AMP) and 2-beta-D-ribofuranosylthiazole-4-carboxamide 5'-monophosphate (TRMP) with excess DCC in aqueous pyridine, (2) reaction of adenosine 5'-phosphoromorpholidate with TRMP in pyridine, and (3) reaction of adenosine-5'-phosphoric di-n-butylphosphinothioic anhydride with TRMP in the presence of AgNO3. While the first approach produced only traces of TAD, the last two afforded 31 and 16% yields, respectively, of isolated TAD. The synthetic material was indistinguishable from biosynthesized TAD as judged by its HPLC behavior, NMR, UV and mass spectra, enzymatic resistance to alkaline phosphatase and susceptibility to venom phosphodiesterase, IMP dehydrogenase inhibitory activity, and cytotoxicity. TAD and TR were equally effective against murine P388 leukemia when employed at equimolar doses.