2-iodo-N⁶-methyl-9-(β-D-ribofuranosyl)adenine | 377774-42-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-iodo-N⁶-methyl-9-(β-D-ribofuranosyl)adenine
• 英文别名: 2-iodo-N⁶-methyladenosine；2-iodo-6-N-methyladenosine；2-iodo-N6-methylAdo；Adenosine, 2-iodo-N-methyl-；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[2-iodo-6-(methylamino)purin-9-yl]oxolane-3,4-diol
• CAS: 377774-42-0
• 化学式: C₁₁H₁₄IN₅O₄
• 分子量: 407.168
• InChiKey: VAALRCZOBOJZJI-KQYNXXCUSA-N

物化性质

• 沸点：
  746.8±70.0 °C(Predicted)
• 密度：
  2.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-iodo-N⁶-methyl-9-(β-D-ribofuranosyl)adenine 在 copper(II) sulfate 、 sodium ascorbate sodium azide 、 sodium carbonate 、 copper(II) sulfate 、 sodium ascorbate 、 L-脯氨酸 作用下， 以 水 、 叔丁醇 为溶剂， 反应 10.0h， 生成 2-(4-cyclopentylmethyl-1,2,3-triazol-1-yl)-N⁶-methyl-9-(β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  2-Triazole-Substituted Adenosines:  A New Class of Selective A₃ Adenosine Receptor Agonists, Partial Agonists, and Antagonists

  摘要：

  “点击化学”被用来合成两类2-(1,2,3-三氮唑基)腺苷衍生物(1-14)。测定其在人A1、A2A和A3腺苷受体上的结合亲和力及其在A3腺苷受体上的相对效能。一些三氮唑-1-基衍生物显示出低纳摩尔级的A3受体亲和力、高水平的A3/A2A选择性比值以及中等到高的A3/A1比值。1,2,3-三氮唑-4-基衍生物的A3受体亲和力通常较低。在腺嘌呤C2位的位阻较大基团往往降低相对A3受体效能。因此，几个5'-OH衍生物似乎成为选择性A3受体拮抗剂，即化合物10，与A1受体相比具有260倍的结合选择性，并在A3受体模型中显示出特征的结合模式。相应的5'-乙基脲酰胺衍生物通常显示出较高的A3受体亲和力，并表现为空气满拮抗剂，即化合物17，具有910倍的A3/A1选择性。因此，N6-取代的2-(1,2,3-三氮唑基)-腺苷衍生物构成了一类基于核苷的高效且高选择性的A3受体拮抗剂、部分激动剂和激动剂的新颖化合物。

  DOI：

  10.1021/jm0608208
• 作为产物：
  描述：

  2',3',5'-三-O-乙酰-6-氯-2-碘嘌呤核苷 、 甲胺 反应 1.0h， 以69%的产率得到2-iodo-N⁶-methyl-9-(β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  合成新型强效和选择性A3腺苷受体放射性配体的合成方法。

  摘要：

  合成2-苯基乙炔基腺苷及其N6-甲基衍生物，并在结合测定中在稳定转染到CHO细胞上的人腺苷受体上进行评估。结果表明，N6-甲基-2-苯基乙炔基腺苷对A3受体亚型具有很高的亲和力和选择性。因此，建立了另一种合成tri化的N6-甲基-2-苯基乙炔基腺苷的替代方法，以在最后一步中引入tri化的甲胺。

  DOI：

  10.1081/ncn-100002428

文献信息

• N-Alkoxysulfamide, N-hydroxysulfamide, and sulfamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
  作者：Jeewoo Lee、Sung Eun Kim、Ji Young Lee、Su Yeon Kim、Sang Uk Kang、Seung Hwan Seo、Moon Woo Chun、Taehee Kang、Soo Young Choi、Hea Ok Kim

  DOI：10.1016/s0960-894x(03)00020-9

  日期：2003.3

  A series of sulfamate surrogates of methionyl and isoleucyl adenylate have been investigated as MetRS and IleRS inhibitors by modifications of the sulfamate linker and adenine moieties. The discovery of 2-iodo Ile-NHSO(2)-AMP (58) as a potent Escherichia coli IleRS inhibitor revealed that a significant hydrophobic interaction between the 2-substituent of Ile-NHSO(2)-AMP and the adenine binding site

  通过修饰氨基磺酸酯连接基和腺嘌呤部分，已经研究了一系列甲硫基和异亮氨酰腺苷的氨基磺酸替代物作为MetRS和IleRS抑制剂。2-碘Ile-NHSO（2）-AMP（58）作为强效大肠杆菌IleRS抑制剂的发现表明，Ile-NHSO（2）-AMP的2-取代基与H2O2的腺嘌呤结合位点之间存在显着的疏水相互作用IleRS为酶提供了强大的效力。
• Synthesis and Biological Evaluation of 2-Alkynyl-<i>N</i>⁶-methyl-5′-<i>N</i>-methylcarboxamidoadenosine Derivatives as Potent and Highly Selective Agonists for the Human Adenosine A₃ Receptor
  作者：Rosaria Volpini、Michela Buccioni、Diego Dal Ben、Catia Lambertucci、Carmen Lammi、Gabriella Marucci、Anna T. Ramadori、Karl-Norbert Klotz、Gloria Cristalli

  DOI：10.1021/jm900754g

  日期：2009.12.10

  N6-methyl-2-phenylethynylMECA (10) showing a subnanomolar affinity and about 100000-fold selectivity vs AA1R and AA2AR. Furthermore, the new nucleosides showed to be full agonists, the N6-methyl-2-(2-pyridinyl)ethynylMECA (13) being the most potent in the series.

  一系列新的2-芳炔-N 6 -甲基- MECAs 10 - 13的合成和在放射性配体结合研究，并在提供强大的替代放射性同位素使用一个新的Eu-GTP功能测定评价。这些新化合物具有对AA高亲和力和选择性3，其中R Ñ 6 -甲基-2- phenylethynylMECA（10示出了亚纳摩尔亲和力与约100000倍的选择性VS AA）1 R和AA 2A R.此外，新的核苷显示作为完全激动剂，N 6-甲基-2-（2-吡啶基）乙炔基MECA（13）是该系列中最有效的。
• SYNTHETIC PROCEDURE FOR THE PREPARATION OF NOVEL POTENT AND SELECTIVE A₃ADENOSINE RECEPTOR RADIOLIGANDS
  作者：R. Volpini、S. Costanzi、C. Lambertucci、S. Vittori、G. Cristalli

  DOI：10.1081/ncn-100002428

  日期：2001.3.31

  receptors stably transfected on CHO cells. Results showed that the N6-methyl-2-phenylethynyladenosine is endowed with very high affinity and selectivity at A3 receptor subtype. Hence, an alternative procedure for the synthesis of tritiated N6-methyl-2-phenylethynyladenosine was set up to introduce tritiated methylamine in the final step.

  合成2-苯基乙炔基腺苷及其N6-甲基衍生物，并在结合测定中在稳定转染到CHO细胞上的人腺苷受体上进行评估。结果表明，N6-甲基-2-苯基乙炔基腺苷对A3受体亚型具有很高的亲和力和选择性。因此，建立了另一种合成tri化的N6-甲基-2-苯基乙炔基腺苷的替代方法，以在最后一步中引入tri化的甲胺。
• Purine and deazapurine nucleosides: synthetic approaches, molecular modelling and biological activity
  作者：Gloria Cristalli、Stefano Costanzi、Catia Lambertucci、Sara Taffi、Sauro Vittori、Rosaria Volpini

  DOI：10.1016/s0014-827x(03)00019-3

  日期：2003.3

  A number of ligands for the adenosine binding sites has been obtained by using nucleoside convergent and divergent synthesis. Most of our nucleosides have been synthesized by coupling 2,6-dichloropurine (1), 2,6-dichloro-1-deazapurine (2), 2,6-dichloro-3-deazapurine (3) with ribose, 2- and 3-deoxyribose and 2,3-dideoxyribose derivatives. The use of these versatile synthons allowed the introduction of various substituents in 2- and/or 6-positions. The glycosylation site and the anomeric configuration of the obtained nucleosides were assigned on the basis of spectroscopic studies and confirmed by molecular models. A series of potent adenosine receptor ligands has been obtained by using divergent approaches, mostly starting from guanosine. Substitutions in 2, 6, 8, and 5' position of adenosine molecule led to ligands selective for the different adenosine receptor subtypes. Furthermore, we investigated the molecular bases of the different behavior of 2- and 8-alkynyl adenosines, by means of NMR experiments and molecular modeling studies. With docking experiments, we demonstrated that the two class of molecules should have different binding modes that explain their different degree of affinity and the shift of their activity from agonistic (2-substituted derivatives) to antagonistic (8-substituted derivatives).
• <i>N</i>⁶-Alkyl-2-alkynyl Derivatives of Adenosine as Potent and Selective Agonists at the Human Adenosine A₃ Receptor and a Starting Point for Searching A_2B Ligands
  作者：Rosaria Volpini、Stefano Costanzi、Catia Lambertucci、Sara Taffi、Sauro Vittori、Karl-Norbert Klotz、Gloria Cristalli

  DOI：10.1021/jm0109762

  日期：2002.7.1

  A series of N-6-alkyl-2-alkynyl derivatives of adenosine (Ado) have been synthesized and evaluated for their affinity at human A(1), A(2A), and A(3) receptors and for their potency at A(2B) adenosine receptor subtypes. The corresponding 2-(1-alkynyl) derivatives of 5'-N-ethylcarboxamidoadenosine (NECA) and Ado are used as reference compounds. Binding studies demonstrated that the activities of 2-alkynylAdos were slightly increased for the adenosine A, receptor and slightly decreased for both A(3) and A(2B) subtypes compared to those of their corresponding NECA derivatives, whereas the A(2A) receptor affinities of the two series of nucleosides were similar. The presence of a methyl group on N-6 of the 2-alkynyladenosines, inducing an increase in affinity at the human A(3) receptor and a decrease at the other subtypes, resulted in an increase in A(3) selectivity. In particular, 2-phenylethynyl-N-6-methylAdo (8b) showed an A(3) affinity in the low nanomolar range (K-i(A(3)) = 3.4 nM), with a A(1)/A(3) and A(2A)/A(3) selectivity of about 500 and 2500, respectively. These findings motivated us to search for the preparation of new selective radioligands for the A(3) subtype; hence, a procedure to introduce a tritiated alkylamino group in these molecules was carried out. As far as the potency at the A(2B) receptor, the type of 2-alkynyl chain and the presence of the ethylcarboxamido group on the sugar seem to be very important; in fact, the (S)-2-phenylhydroxypropynylNECA [(S)-PHPNECA, 1e, EC50(A(2B)) = 0.22 muM] proved to be one of the most potent A(2B) agonist reported so far. On the other hand, the (S)-2-phenylhydroxypropynyl-N-6-ethylAdo (9e, EC50(A(2B)) = 0.73 muM) showed a significantly increase of potency at the A(2B) subtype in comparison with the N-6-methyl, N-6-isopropyl, and the unsubstituted adenosine derivatives, although it resulted in being less potent than (S)PHPNECA (le, EC50(A(2B)) = 0.22 muM). These observations suggest that the introduction of an ethyl group in the N-6-position and an ethylcarboxamido substituent in the 4'-position of (S)2-phenylhydroxypropynyladenosine could lead to a compound endowed with high potency at the A(2B) receptor.