2',3'-isopropylidene-2-aminoadenosine | 30685-38-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3'-isopropylidene-2-aminoadenosine
• 英文别名: 2',3'-O-isopropylidene-2-aminoadenosine；((3aR,4R,6R,6aR)-6-(2,6-diamino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol；[(3aR,4R,6R,6aR)-4-(2,6-diaminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 30685-38-2
• 化学式: C₁₃H₁₈N₆O₄
• 分子量: 322.324
• InChiKey: GHTKDSBSFMMOKE-IOSLPCCCSA-N

物化性质

• 沸点：
  667.1±65.0 °C(Predicted)
• 密度：
  1.93±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  144
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2',3'-isopropylidene-2-aminoadenosine 在 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 四丁基氟化铵 、 溶剂黄146 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 22.0h， 生成
  参考文献：
  名称：

  Synthesis and complementary self-association of novel lipophilic π-conjugated nucleoside oligomers

  摘要：

  一系列由天然和非天然碱基构成的亲脂性核苷类化合物，这些化合物与短寡苯乙炔片段进行π共轭，并已合成并测量了它们各自的结合常数。

  DOI：

  10.1039/c5ob00098j
• 作为产物：
  描述：

  2',3'-O-异丙亚基鸟苷 在 吡啶 、 4-二甲氨基吡啶 、 氨 、 N,N-二甲基苯胺 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 32.25h， 生成 2',3'-isopropylidene-2-aminoadenosine
  参考文献：
  名称：

  2-(N-Acyl) and 2-N-acyl-N6-substituted analogues of adenosine and their affinity at the human adenosine receptors

  摘要：

  A series of 2-(N-acyl) and 2-(N-acyl)-N-6-alkyladenosine analogues have been synthesized from the intermediate 2-amino-6-chloroadenosine derivatives (2b and 7) and evaluated for their affinity at the human A(1), A(2A), and A(3) receptors. We found that 2-(N-acyl) derivatives of adenosine showed relatively low affinity at A(2A) and A(3) receptors, while the N-6-cyclopentyl substituent in 4h and 4i induced high potency [A(1) (K-i) = 20.7 and 31.8 nM respectively] at the A(1) receptor and resulted therefore in increased selectivity for this subtype. The general synthetic methods and their binding studies are presented herein. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.011

文献信息

• Synthesis and Evaluation of Analogues of 5‘-([(<i>Z</i>)-4-Amino-2-butenyl]methylamino)-5‘-deoxyadenosine as Inhibitors of Tumor Cell Growth, Trypanosomal Growth, and HIV-1 Infectivity
  作者：Canio J. Marasco,、Debora L. Kramer、John Miller、Carl W. Porter、Cyrus J. Bacchi、Donna Rattendi、Louis Kucera、Nathan Iyer、Ralph Bernacki、Paula Pera、Janice R. Sufrin

  DOI：10.1021/jm0201621

  日期：2002.11.1

  antineoplastic activity of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine. However, di-O-acetylation of the parent compound produced a potential prodrug that caused markedly pronounced inhibition of trypanosomal and neoplastic cell growth and viability. Moreover, the acetylated derivative of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine did inhibit HIV-1 growth and infectivity

  设计并合成了一系列明确定义的5'-（[（（Z）-4-氨基-2-丁烯基]甲基氨基）-5'-脱氧腺苷类似物，以进一步确定抑制S-腺苷甲硫氨酸脱羧酶的最佳结构要求并有可能增强甚至分离它们的抗增殖和抗锥虫活性。大多数结构修饰对5'-（[（（Z）-4-氨基-2-丁烯基]甲基氨基）-5'-脱氧腺苷的抗锥虫活性和抗肿瘤活性均具有有害影响。但是，母体化合物的二-O-乙酰化作用会产生潜在的前药，从而显着抑制锥虫和肿瘤细胞的生长和活力。此外，5'-（[[（Z）-4-氨基-2-丁烯基]甲基氨基）-5'-脱氧腺苷的乙酰化衍生物确实抑制了HIV-1的生长和感染力，
• Probing Binding Requirements of Type I and Type II Isoforms of Inosine Monophosphate Dehydrogenase with Adenine-Modified Nicotinamide Adenine Dinucleotide Analogues
  作者：Liqiang Chen、Guangyao Gao、Krzysztof Felczak、Laurent Bonnac、Steven E. Patterson、Daniel Wilson、Eric M. Bennett、Hiremagalur N. Jayaram、Lizbeth Hedstrom、Krzysztof W. Pankiewicz*

  DOI：10.1021/jm070568j

  日期：2007.11.1

  2-ethyl TAD analogue 33 [Ki = 1 nM (type I), Ki = 14 nM (type II)] was found to be the most potent. It did not inhibit three other cellular dehydrogenases up to 50 microM. Mycophenolic adenine bis(phosphonate)s containing a 2-phenyl (37) or 2-ethyl group (38), were prepared as metabolically stable compounds, both nanomolar inhibitors. Compound 38 [Ki = 16 nM (type I), Ki = 38 nM (type II)] inhibited proliferation

  已经合成了在腺嘌呤环的C 2处含有取代基的新型噻唑呋林腺嘌呤二核苷酸（TAD）类似物25-33，作为人IMP-脱氢酶的两种同工型的抑制剂。发现2-乙基TAD类似物33 [Ki ＝ 1nM（I型），Ki ＝ 14nM（II型）]是最有效的。它不抑制其他三种直至50 microM的细胞脱氢酶。制备含有2-苯基（37）或2-乙基（38）的霉酚腺嘌呤双（膦酸酯）作为代谢稳定的化合物，均为纳摩尔抑制剂。化合物38 [Ki = 16 nM（I型），Ki = 38 nM（II型）]比噻唑呋林（IC50 = 12.4 microM）或霉酚酸（IC50 = 7.7）更有效地抑制白血病K562细胞（IC50 = 1.1 microM）的增殖。 microM）。
• Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues
  作者：Xiao Luo、Meng Li、Kaiyu Zhan、Wei Yang、Lihe Zhang、KeWei Wang、Peilin Yu、Liangren Zhang

  DOI：10.1111/cbdd.13119

  日期：2018.2

  Transient receptor potential melastatin‐2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5′‐diphosphoribose analogues were synthesized, and their activities and selectivity were evaluated. Whole‐cell patch‐clamp recordings were employed for screen and evaluation of synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2 inhibitors with IC50 of 5.7 and 5.4 μm, respectively. Both 7i and 8a inhibited TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2 inhibitors can serve as new pharmacological tools for further investigation and validation of TRPM2 channel as a drug target, and the summarized structure–activity relationship (SAR) may also provide insights into further improving existing inhibitors as potential lead compounds.
• Nucleic Acid-Related Compounds. 88. Efficient Conversions of Ribonucleosides into Their 2',3'-Anhydro, 2'(and 3')-Deoxy, 2',3'-Didehydro-2',3'-dideoxy, and 2',3'-Dideoxynucleoside Analogs
  作者：Morris J. Robins、John S. Wilson、Danuta Madej、Nicholas H. Low、Fritz Hansske、Stanislaw F. Wnuk

  DOI：10.1021/jo00129a034

  日期：1995.12

  Treatment of purine, pyrimidine, and modified purine (antibiotic) ribonucleosides with 2-acetoxy-2-methylpropanoyl (alpha-acetoxyisobutyryl) bromide in acetonitrile gave mixtures of 2',3'-bromohydrin acetates with different O5' substituents. Significant amounts of 5'-unprotected (hydroxyl) bromo acetates were obtained in some cases, and formation of 2',3'-O-isopropylidene derivatives as minor byproducts was detected for the first time. Acid-catalyzed nucleophilic displacement of chloride by bromide occurred with 2-amino-6-chloropurine riboside, but no substitution of fluoride by bromide was detected with 6-amino-2-fluoropurine riboside. Treatment of the trans bromo acetate mixtures obtained from purine-type nucleosides with Dowex 1 x 2 (OH-) in methanol gave the 2',3'-anhydro (ribo epoxide) compounds. Radical-mediated hydrogenolytic debromination and deprotection gave 2'- and 3'-deoxynucleosides. Treatment of the bromo acetate mixtures with zinc-copper couple or acetic acid-activated zinc effected reductive elimination, and deprotection gave 2',3'-didehydro-2',3'-dideoxy compounds which were hydrogenated to give 2',3'-dideoxynucleosides. A number of these analogues have potent inhibitory activity against AIDS and hepatitis B viruses. New C-13 NMR data for several types of unsaturated-sugar nucleosides are tabulated. These procedures are directly applicable for the preparation of L-didehydro-dideoxy and L-dideoxy nucleoside analogues.
• Synthesis and complementary self-association of novel lipophilic π-conjugated nucleoside oligomers
  作者：J. Camacho-García、C. Montoro-García、A. M. López-Pérez、N. Bilbao、S. Romero-Pérez、D. González-Rodríguez

  DOI：10.1039/c5ob00098j

  日期：——

  A series of lipophilic nucleosides comprising natural and non-natural bases that are π-conjugated to a short oligophenylene–ethynylene fragment has been synthesized and their respective association constants measured.

  一系列由天然和非天然碱基构成的亲脂性核苷类化合物，这些化合物与短寡苯乙炔片段进行π共轭，并已合成并测量了它们各自的结合常数。