PEAdo | 90596-70-6

• 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: PEAdo
• 英文别名: 2-phenylethynyladenosine；(2R,3R,4S,5R)-2-(6-amino-2-(phenylethynyl)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol；(2R,3R,4S,5R)-2-[6-amino-2-(2-phenylethynyl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 90596-70-6
• 化学式: C₁₈H₁₇N₅O₄
• 分子量: 367.364
• InChiKey: BARJSNBJYYNDDG-XKLVTHTNSA-N

物化性质

• 熔点：
  215-216 °C
• 沸点：
  773.3±70.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  PEAdo 在 二碘甲烷 、 亚硝酸异戊酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以37%的产率得到6-iodo-2-(phenylethyn-1-yl)-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
• 作为产物：
  描述：

  2',3',5'-三-O-乙酰-6-氯-2-碘嘌呤核苷 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 氨 作用下， 以 甲醇 、 三乙胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 PEAdo
  参考文献：
  名称：

  钯催化的2-碘腺苷与末端炔烃的交叉偶联：2-炔基腺苷的合成和生物活性。

  摘要：

  2-碘腺苷（2）与末端炔烃在双（三苯基膦）氯化钯和碘化亚铜存在下，在三乙胺和N,N-二甲基甲酰胺中反应，得到了优良产率的2-炔基腺苷（3a-h）。几种化合物在大鼠被动皮肤过敏反应（PCA）中表现出高活性作为抑制剂。其中，2-(3-羟丙炔基)-和2-(3-羟丁炔基)-腺苷（3d, f）远比双钠氮芥（DSCG）更有效。

  DOI：

  10.1248/cpb.33.1766

文献信息

• Structure−Activity Relationships of Adenine and Deazaadenine Derivatives as Ligands for Adenine Receptors, a New Purinergic Receptor Family
  作者：Thomas Borrmann、Aliaa Abdelrahman、Rosaria Volpini、Catia Lambertucci、Edgars Alksnis、Simone Gorzalka、Melanie Knospe、Anke C. Schiedel、Gloria Cristalli、Christa E. Müller

  DOI：10.1021/jm9006356

  日期：2009.10.8

  Adenine derivatives bearing substituents in the 2-, N6-, 7-, 8-, and/or 9-position and a series of deazapurines were synthesized and investigated in [3H]adenine binding studies at the adenine receptor in rat brain cortical membrane preparations (rAde1R). Steep structure−activity relationships were observed. Substitution in the 8-position (amino, dimethylamino, piperidinyl, piperazinyl) or in the 9-position

  合成并研究了在[ 3]中带有2-，N 6-，7-，8和/或9位取代基的腺嘌呤衍生物和一系列脱氮嘌呤。H]腺嘌呤在大鼠大脑皮层膜制剂（rAde1R）中对腺嘌呤受体的结合研究。观察到陡峭的结构-活性关系。最好的取代是在8位（氨基，二甲基氨基，哌啶基，哌嗪基）或9位（2-吗啉代乙基）中带有碱性残基或在6位氨基官能团处引入极性取代基（羟基，氨基，乙酰基）是最好的修改。在稳定表达rAde1R的1321N1星形细胞瘤细胞的腺苷酸环化酶测定中，对所选腺嘌呤衍生物的功能评估表明，所研究的所有化合物均为激动剂或部分激动剂。在人类胚胎肾脏（HEK293）细胞的结合研究中还对化合物的子集进行了研究，该细胞还表达了高亲和力的腺嘌呤结合位点。人细胞系的结构亲和力关系与rAde1R相似，但不完全相同。特别是，N 6-乙酰腺嘌呤（25，K i大鼠：2.85μM; K i人：0.515μM）和8-氨基腺嘌呤（33，K i
• 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).
• Nucleosides and nucleotides. 107. 2-(Cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects
  作者：Toichi Abiru、Takanori Miyashita、Yohko Watanabe、Toyofumi Yamaguchi、Haruhiko Machida、Akira Matsuda

  DOI：10.1021/jm00090a017

  日期：1992.6

  Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100-mu-g/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.
• <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.
• Effects of 5‘-Phosphate Derivatives of 2-Hexynyl Adenosine and 2-Phenylethynyl Adenosine on Responses of Human Platelets Mediated by P2Y Receptors
  作者：Gloria Cristalli、Gian Marco Podda、Stefano Costanzi、Catia Lambertucci、Anna Lecchi、Sauro Vittori、Rosaria Volpini、Maddalena L. Zighetti、Marco Cattaneo

  DOI：10.1021/jm0493562

  日期：2005.4.1

  Newly synthesized mono-, di-, and triphosphate of 2-alkynyl adenosines showed very different behavior in human platelet P2Y receptor models, according to the different alkynyl chains. In fact, 2-hexynyladenosine di- (5) and triphosphate (7) induced platelet shape change and aggregation and inhibited PGE(1)-induced increase in platelet cyclic AMP. On the contrary, the corresponding 2-phenylethynyladenosine di- (6) and triphosphate (8) did not induce platelet shape change or aggregation, but inhibited platelet aggregation induced by ADP.