(2R,3S,4R,5R)-2-Hydroxymethyl-5-[6-(2-naphthalen-2-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol | 101565-84-8

• 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: (2R,3S,4R,5R)-2-Hydroxymethyl-5-[6-(2-naphthalen-2-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol
• CAS: 101565-84-8
• 化学式: C₂₂H₂₃N₅O₄
• 分子量: 421.456
• InChiKey: NTXJYQJDMKXBMU-WGQQHEPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.25
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  125.55
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  2-萘-2-乙胺 、 6-氯嘌呤核苷 在 三乙胺 作用下， 以 乙醇 为溶剂， 以75 %的产率得到(2R,3S,4R,5R)-2-Hydroxymethyl-5-[6-(2-naphthalen-2-yl-ethylamino)-purin-9-yl]-tetrahydro-furan-3,4-diol
  参考文献：
  名称：

  腺苷类似物作为正常孢子形成和持久性所需的艰难梭菌特异性 DNA 腺嘌呤甲基转移酶抑制剂的系统设计

  摘要：

  迫切需要针对内生孢子传播的艰难梭菌感染的抗毒剂。艰难梭菌特异性 DNA 腺嘌呤甲基转移酶 (CamA) 是有效孢子形成所必需的，并影响在结肠中的持久性。CamA 的活性位点是保守的，并且与数百种相关的S-腺苷-L-甲硫氨酸(SAM) 依赖性甲基转移酶的活性位点非常相似，这使得选择性抑制剂的设计更具挑战性。我们探索了 SAM 腺苷部分的溶剂暴露边缘，并系统地设计了 42 个在腺苷 C6 氨基 (N6) 上带有取代基的腺苷类似物。我们比较了这些不同化合物的抑制特性和结合亲和力，并展示了在底物 DNA 存在下 CamA 与其中 14 种化合物形成复合物的晶体结构。这些抑制剂中最有效的化合物39（IC 50 ∼ 0.4 μM 和K D ∼ 0.2 μM）对 CamA 具有选择性，对抗密切相关的细菌和哺乳动物 DNA 和 RNA 腺嘌呤甲基转移酶、蛋白质赖氨酸和精氨酸甲基转移酶以及人腺苷受体。

  DOI：

  10.1021/acs.jmedchem.2c01789

文献信息

• Dog coronary artery adenosine receptor. Structure of the N6-aryl subregion
  作者：Shozo Kusachi、Robert D. Thompson、Noboyuki Yamada、Daniel T. Daly、R. A. Olsson

  DOI：10.1021/jm00156a016

  日期：1986.6

  Previous structure-coronary vasoactivity correlations of the N6-alkyladenosine analogues of N6-[(R)-1-phenyl-2-propyl]adenosine, 1, support the hypothesis that the coronary artery A2 adenosine receptor contains an N6 region of specialized structure. The part of this receptor region that binds the 2-propyl moiety of 1 determines stereoselectivity and contributes to coronary vasoactivity. The present study uses 92 adenosine analogues containing an aryl group in the N6 substituent to test the hypothesis that the N6 receptor region contains an aryl subregion that binds the phenyl moiety of 1 and thereby contributes to its coronary vasoactivity. N6-Aralkyladenosines are often more potent than their alkyl congeners. Two methylene residues seem to provide optimum separation of the aryl group from N6. Among adenosines with semirigid N6 substituents, N6-[(1R,2S)-trans-2-phenylcyclohexyl]adenosine was uniquely active, evidence that when 1 occupies the receptor, the axis of the propyl C-1 to phenyl C-1 bond is nearly in the plane described by N6 and propyl C-1 and C-2. The torsion angle around this bond is unknown. Replacing the phenyl group of N6-2-phenethyladenosine with a thienyl or a 3-pyridyl group raises activity. The structure-activity relationships of the N6-(arylethyl)-, the N6-(arylmethyl)-, and the N6-phenyladenosines differ strinkingly from each other. Taken together, such results support the idea that the N6 region of the dog coronary artery A2 adenosine receptor includes an aryl subregion.