噻唑-4-甲酰胺腺嘌呤二核苷酸 | 83285-83-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 中文名称: 噻唑-4-甲酰胺腺嘌呤二核苷酸
• 英文名称: Tiazofurin adenine dinucleotide
• 英文别名: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(4-carbamoyl-1,3-thiazol-2-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate
• CAS: 83285-83-0
• 化学式: C₁₉H₂₅N₇O₁₄P₂S
• 分子量: 669.46
• InChiKey: INQLNSVYIFCUML-QZTLEVGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  356
• 氢给体数：
  8
• 氢受体数：
  20

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	adenosine 5'-phosphoric di-n-butylphosphinothioic anhydride	57816-25-8	C18H31N5O7P2S	523.487
  5'-腺嘌呤核苷酸	5'-adenosine monophosphate	61-19-8	C10H14N5O7P	347.224
  ——	adenosine 5'-monophosphate morpholidate	7331-13-7	C14H21N6O7P	416.331
  ——	2-(2',3'-O-isopropylidene-5'-monophosphate-β-D-ribofuranosyl)thiazole-4-carboxamide	162756-36-7	C12H17N2O8PS	380.315
  ——	tiazofurin 5'-monophosphate	83161-83-5	C9H13N2O8PS	340.251
  2-[2,3-O-(1-甲基乙亚基)-beta-D-呋喃核糖基]-4-噻唑甲酰胺	2-(2',3'-O-isopropylidene-β-D-ribofuranosyl)thiazole-4-carboxamide	60084-11-9	C12H16N2O5S	300.335
  噻唑呋林	tiazofurin	60084-10-8	C9H12N2O5S	260.271

反应信息

• 作为产物：
  描述：

  噻唑呋林 在 吡啶 、 silver nitrate 、 formamide 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 84.0h， 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

文献信息

• Ribavirin, tiazofurin, and selenazofurin: mononucleotides and nicotinamide adenine dinucleotide analogs. Synthesis, structure, and interactions with IMP dehydrogenase
  作者：Gulilat Gebeyehu、Victor E. Marquez、Anne Van Cott、David A. Cooney、James A. Kelley、Hiremagalur N. Jayaram、Gurpreet S. Ahluwalia、Robert L. Dion、Yvonne A. Wilson、David G. Johns

  DOI：10.1021/jm00379a018

  日期：1985.1

  A series of dinucleotides, analogous to nicotinamide adenine dinucleotide but containing the five-membered base nucleosides tiazofurin (1a), selenazofurin (1b), ribavirin (2), and AICAR (3) in place of nicotinamide ribonucleoside, were prepared in greater than 50% yield by reacting the corresponding nucleotide imidazolidates (6a-d) with adenosine 5'-monophosphate (AMP). The symmetric dinucleotides of tiazofurin (TTD, 8e) and selenazofurin (SSD, 8f) were also prepared by a similar methodology. These dinucleotides were characterized by 1H NMR and fast atom bombardment MS and were evaluated for their inhibitory potency against a partially purified preparation of tumoral inosine monophosphate dehydrogenase (IMPD) from P388 cells. The order of potency found was SAD (8b) greater than TAD (8a) much greater than SSD (8f) congruent to TTD (8e) congruent to RAD (8c) much much greater than ZAD (8d). On kinetic analysis none of the dinucleotides produced competitive inhibition of IMPD with NAD as a variable substrate. In addition to their superior IMPD inhibitory activity, SAD and TAD appear to be the only dinucleotides, besides NAD, that are formed naturally by the NAD pyrophosphorylase from P388 lymphoblasts.
• 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.