AAG 129 | 113628-03-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: AAG 129
• 英文别名: (2R,3R,4S,5R)-2-[7-(cyclopentylamino)imidazo[4,5-b]pyridin-3-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol；(2R,3R,4S,5R)-2-[7-(cyclopentylamino)imidazo[4,5-b]pyridin-3-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 113628-03-8
• 化学式: C₁₆H₂₂N₄O₄
• 分子量: 334.375
• InChiKey: YBZHWDBTBCHQTH-XKVFNRALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5,7-dichloro-3-(β-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridine 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 乙醇 为溶剂， 135.0 ℃ 、344.73 kPa 条件下， 反应 32.0h， 生成 AAG 129
  参考文献：
  名称：

  腺苷受体激动剂：腺苷衍生物的1-deaza类似物的合成和生物学评估。

  摘要：

  为了寻找更具选择性的A1腺苷受体激动剂，N6-[（R）-（-）-1-甲基-2-苯乙基] -1-脱氮杂腺苷（1-deaza-R-PIA，3a），N6-环戊基-从5,7-二氯-3-β-D合成了1-deazaadenosine（1-deazaCPA，3b），N6-cyclohexyl-1-deazaadenosine（1-deazaCHA，3c）和相应的2-氯衍生物2a-c。 -核呋喃糖基-3H-咪唑并[4,5-b]吡啶。另一方面，制备了N-乙基-1′-脱氧-1′-（1-deaza-6-氨基-9H-嘌呤-9-基）-β-D-呋喃呋喃核糖酰胺（1-deazaNECA，10）。为了寻找更具选择性的A2激动剂，从7-硝基-3-β-D-呋喃呋喃糖基-3H-咪唑并[4,5-b]吡啶中合成了吡咯烷酮。在腺苷酸环化酶和放射性配体结合研究中已经确定了所有deaza类似物对腺苷受体的活性。1-DeazaNECA被证

  DOI：

  10.1021/jm00401a018

文献信息

• Adenosine receptor agonists: synthesis and biological evaluation of 1-deaza analogs of adenosine derivatives
  作者：Gloria Cristalli、Palmarisa Franchetti、Mario Grifantini、Sauro Vittori、Karl Norbert Klotz、Martin J. Lohse

  DOI：10.1021/jm00401a018

  日期：1988.6

  N6-substituted 1-deazaadenosines largely retain the A1 agonist activity of their parent compounds, but lose some of their A2 agonist activity. This results in A1-selective compounds, of which N6-cyclopentyl-2-chloro-1-deazaadenosine (1-deaza-2-Cl-CPA, 2b) was identified as the most selective agonist at A1 adenosine receptors so far known. The activity of all 1-deaza analogues confirms that the presence

  为了寻找更具选择性的A1腺苷受体激动剂，N6-[（R）-（-）-1-甲基-2-苯乙基] -1-脱氮杂腺苷（1-deaza-R-PIA，3a），N6-环戊基-从5,7-二氯-3-β-D合成了1-deazaadenosine（1-deazaCPA，3b），N6-cyclohexyl-1-deazaadenosine（1-deazaCHA，3c）和相应的2-氯衍生物2a-c。 -核呋喃糖基-3H-咪唑并[4,5-b]吡啶。另一方面，制备了N-乙基-1′-脱氧-1′-（1-deaza-6-氨基-9H-嘌呤-9-基）-β-D-呋喃呋喃核糖酰胺（1-deazaNECA，10）。为了寻找更具选择性的A2激动剂，从7-硝基-3-β-D-呋喃呋喃糖基-3H-咪唑并[4,5-b]吡啶中合成了吡咯烷酮。在腺苷酸环化酶和放射性配体结合研究中已经确定了所有deaza类似物对腺苷受体的活性。1-DeazaNECA被证
• Potent and Selective Ligands for Adenosine Binding Sites
  作者：G. Cristalli、E. Camaioni、E. Di Francesco、A. Eleuteri、S. Vittori、R. Volpini

  DOI：10.1080/07328319708006189

  日期：1997.7

  A number of selective ligands for the different binding sites of adenosine have been synthesized and tested in several pharmacological models. The aim of these synthetic efforts is both to improve the knowledge of structure-activity relationships in the adenosine-related biological systems and to develop drugs from some of these molecules.
• CRISTALLI, GLORIA;FRANCHETTI, PALMARISA;GRIFANTINI, MARIO;VITTORI, SAURO;+, J. MED. CHEM., 31,(1988) N 6, 1179-1183
  作者：CRISTALLI, GLORIA、FRANCHETTI, PALMARISA、GRIFANTINI, MARIO、VITTORI, SAURO、+

  DOI：——

  日期：——
• <i>N</i>-Cycloalkyl Derivatives of Adenosine and 1-Deazaadenosine as Agonists and Partial Agonists of the A₁ Adenosine Receptor
  作者：Sauro Vittori、Anna Lorenzen、Christina Stannek、Stefano Costanzi、Rosaria Volpini、Adriaan P. IJzerman、Jakobien K. Von Frijtag Drabbe Kunzel、Gloria Cristalli

  DOI：10.1021/jm9911231

  日期：2000.1.1

  A number of cycloalkyl substituents (from C-3 to C-8) have been int-reduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guanosine 5'-triphosphate (GTP) shift and the maximal induction of guanosine 5'-(gamma-thio)triphosphate ([S-35]GTP gamma S) binding to G proteins in rat brain membranes were used to determine the intrinsic activity of these nucleosides at the A(1) adenosine receptor. All compounds of the ribose-bearing series proved to be full agonists, the 1-deaza derivatives showing affinities for the Al receptor about 10-fold lower than the corresponding adenosines. On the other hand, all the 2'-deoxyribose derivatives bind to the A(1) receptor with affinities in the high nanomolar range, with the 2-chloro substituted compounds showing slightly higher affinities than the 2-unsubstituted counterparts. In terms of the potencies, the most potent compounds proved to be those bearing four- and five-membered rings. Both GTP shifts and [S-35]-GTP gamma S experiments showed that most of the 2'-deoxyadenosine derivatives are partial agonists, The 2'-deoxyadenosine derivatives which were identified as partial agonists consistently detected fewer Az receptors in the high-affinity state than full agonists. However, it is worthwhile noting that there was not a simple Linear relationship between receptor occupancy and activation. These results indicate that a critical density of A(1) adenosine receptors in the high-affinity state is required for G protein activation.