IsoddA | 127682-75-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: IsoddA
• 英文别名: <(2R-cis)-4-(6-aminopurin-9-yl)tetrahydrofuran-2-yl>methanol；6-amino-9-[(3R,5R)-5-(hydroxymethyl)tetrahydrofuran-3-yl]purine；(2R,4R)-4-(6'-amino-9'H-purin-9'-yl)tetrahydrofuran-2-methanol；iso-ddA；(2R-cis)-4-(6-amino-9H-purin-9-yl)tetrahydro-2-furanmethanol；[(2R,4R)-4-(6-aminopurin-9-yl)oxolan-2-yl]methanol
• CAS: 127682-75-1
• 化学式: C₁₀H₁₃N₅O₂
• 分子量: 235.246
• InChiKey: FJKGKWDFDNULCJ-RNFRBKRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  IsoddA 在 N-甲基咪唑 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (S)-2-{[(2R,4R)-4-(6-Amino-purin-9-yl)-tetrahydro-furan-2-ylmethoxy]-hydroxy-phosphorylamino}-propionic acid; compound with triethyl-amine
  参考文献：
  名称：

  Decomposition Pathways and in Vitro HIV Inhibitory Effects of IsoddA Pronucleotides:  Toward a Rational Approach for Intracellular Delivery of Nucleoside 5‘-Monophosphates

  摘要：

  The decomposition pathways and kinetics in various biological media and the in vitro anti-HIV-1 and anti-HIV-2 activities of four derivatives of the 5'-mononucleotide of isoddA incorporating carboxylate esterase-labile transient phosphate protecting groups are reported and compared: namely, two mononucleoside aryl phosphoramidate derivatives 1a,b and two mononucleoside phosphotriester derivatives incorporating two S-acyl-2-thioethyl groups 2a,b. All four compounds show better antiviral activity, compared to the parent nucleoside analog isoddA. The results highlight that both types of compounds act as pronucleotides, i.e. they exert their antiviral effect via intracellular delivery of the 5'-mononucleotide of isoddA. The results may give insights for the design of new more efficient pronucleotides.

  DOI：

  10.1021/jm9507338
• 作为产物：
  描述：

  1,4-戊二烯 在 potassium osmate(VI) 、 氢化奎宁 1,4-(2,3-二氮杂萘)二醚 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 18-冠醚-6 、 四丁基氟化铵 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 101.5h， 生成 IsoddA
  参考文献：
  名称：

  Enantiospecific Total Synthesis of l-2‘,3‘-Dideoxyisonucleosides via Regioselective Opening of Optically Active C₂-Symmetric 1,4-Pentadiene Bis-epoxide¹

  摘要：

  A new method for the synthesis of L-2',3'-dideoxyisonucleosides is described. The readily available, optically active C-2-symmetric bis-epoxide (2S,4S)-1,2:4,5-diepoxypentane (5) was prepared by a short route from readily available starting materials. The key step of the new synthesis is the opening of 5 with nucleophiles, which proceeds highly regioselectively; e.g., reaction with sodium sulfide affords a 5:1 mixture of the tetrahydrothiophenediol 9a and the tetrahydrothiopyrandiol 14, and reaction with sodium hydroxide gives exclusively the tetrahydrofurandiol 9b via a preferred 5-exo cyclization. These five-membered diols 9a,b can be converted in only four steps into the modified dideoxyuridine and adenosine isonucleosides 4a-c, one of which (4c) has shown good antiviral activity. In addition, we have examined the opening of the analogous six carbon bis-epoxide, (2S,5S)-1,2:5,6-diepoxyhexane (23), which affords a 3:1 mixture of the hexahydrothiepinediol 24 and the tetrahydrothiopyrandiol 25 with sodium sulfide via a preferred 7-endo cyclization. An alternate route to these two optically active bis-epoxides 5 and 23 was also examined, namely the asymmetric dihydroxylation of 1,4-pentadiene and 1,5-hexadiene followed by selective sulfonylation and epoxide : formation. The asymmetric reaction produces a nearly 1:1 mixture of optically active and meso tetrols, e.g., 28-9 and 32-3. Unfortunately, the tetrols, their simple derivatives, and the final sulfonates and epoxides could not be readily separated by Rnv simple means.

  DOI：

  10.1021/jo9721655

文献信息

• Isomeric dideoxynuclesides
  申请人：Hoffmann-La Roche Inc.

  公开号：US05126347A1

  公开（公告）日：1992-06-30

  Isomeric derivatives of 2',3'-dideoxyadenosine and 2',3'-dideoxyguanosine wherein the adenine or guanine base is attached to the 1' position of the iso-dideoxysugar residue by the 9-N position, the novel intermediates used in the synthesis of these compounds, and a method for treating a subject infected with a retrovirus by administering the compounds of the invention.

  2'，3'-二去氧腺苷和2'，3'-二去氧鸟苷的同分异构衍生物，其中腺嘌呤或鸟嘌呤碱基通过9-N位置连接到异-二去氧糖残基的1'位置，用于合成这些化合物的新中间体，以及通过给予本发明化合物治疗感染逆转录病毒的受试者的方法。
• Synthesis and Evaluation of the Anti-HIV Activity of Aza and Deaza Analogs of IsoddA and Their Phosphates as Prodrugs
  作者：Palmarisa Franchetti、Loredana Cappellacci、Mario Grifantini、Lea Messini、Ghassan Abu Sheikha、Anna Giulia Loi、Enzo Tramontano、Antonella De Montis、Maria Grazia Spiga、Paolo La Colla

  DOI：10.1021/jm00047a011

  日期：1994.10

  2-trichloroethyl) phosphate] triesters and 5'-phenyl phosphoramidate derivatives which, acting as membrane soluble prodrugs, could release the free phosphate form inside the cell. The 5'-(phenylmethoxy)alaninyl phosphate derived from 8-aza-isoddA was found active against HIV-1 and HIV-2 with a potency similar to that of isoddA, while the anti-HIV potency of 5'-(phenylmethoxy)alaninyl phosphate of isoddA proved

  抗HIV剂2'，3'-dideoxy-3'-oxoadenosine（isoddA）的某些aza和deaza类似物（8-aza-，8-aza-1-deaza，8-aza-3-deaza-，1 -deaza-和3-deaza-isoddA）已合成，并且在体外对HIV没有活性。通过合成一系列5'-[磷酸双（2,2,2-三氯乙基）]三酯和5'-苯基来检验这些异核苷无活性可能是由于它们对细胞核苷激酶亲和力较弱的假设。可用作膜可溶前药的氨基磷酸酯衍生物可以释放细胞内的游离磷酸盐形式。发现源自8-氮杂-isoddA的5'-（苯基甲氧基）丙氨酰磷酸对HIV-1和HIV-2有活性，其功效与isoddA相似，而抗HIV的功效为5' 证明isoddA的-（苯基甲氧基）丙氨酸磷酸酯显着高于isoddA的磷酸，特别是针对HIV-2，与AZT相似。进一步的证据表明，通过合成其5'-三磷酸衍生物可以得到8-aza-i
• Isomere Dideoxynucleoside, ihre Herstellung und Verwendung für Heilmittel
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0383239A1

  公开（公告）日：1990-08-22

  Die Verbindungen der Formel worin A 6-Amino-9H-purin-9-yl oder 2-Amino-6-hydroxy-9H-­purin-9-yl darstellt, worin die Aminogruppe durch NHC(O)R² oder N=CHR³R⁴ ersetzt sein kann und R OH oder OC(O)R¹ ist, wobei R¹, R², R³ und R⁴ unabhängig voneinander geradkettiges oder verzweigtes C₁₋₂₀-Alkyl, C₁₋₁₂-­Alkoxyalkyl, substituiertes oder unsubstituiertes Phenoxy-­C₁₋₄-alkyl, Phenyl oder Phenyl das durch Halogen, C₁₋₄-­Alkoxy, Nitro, Hydroxy, Carboxyl oder Alkylamino substi­tuiert ist, bedeuten und pharmazeutisch anwendbare Salze davon sind als Mittel zur Behandlung retroviraler Infek­tionen, wie HIV, von Wert.

  式中的化合物 其中 A 为 6-氨基-9H-嘌呤-9-基或 2-氨基-6-羟基-9H-嘌呤-9-基，其中氨基可被 NHC(O)R² 或 N=CHR³R⁴ 取代，R 为 OH 或 OC(O)R¹、其中 R¹、R²、R³ 和 R⁴ 相互独立地为直链或支链 C₁₋₂₀-烷基、C₁₋₁₂-烷氧基烷基、取代或未取代的苯氧基-C₁₋₄-烷基、苯基或被卤素、C₁₋₄-烷氧基、硝基、羟基、羧基或烷基氨基取代的苯基，以及它们的药用盐具有治疗逆转录病毒感染（如 HIV）的价值。
• Jones, Martin F.; Noble, Stewart A.; Robertson, Colin A., Journal of the Chemical Society. Perkin transactions I, 1992, # 11, p. 1427 - 1436
  作者：Jones, Martin F.、Noble, Stewart A.、Robertson, Colin A.、Storer, Richard、Highcock, Rona M.、Lamont, R. Brian

  DOI：——

  日期：——
• Synthesis of iso-ddA, member of a novel class of anti-HIV agents
  作者：Donna M. Huryn、Barbara C. Sluboski、Steve Y. Tam、Louis J. Todaro、Manfred Weigele

  DOI：10.1016/s0040-4039(01)93867-5

  日期：1989.1