2-chloro-N⁶-(3-iodobenzyl)-9-<5-(methylcarbamoyl)-2,3-O-(thiocarbonyl)-β-D-ribofuranosyl>adenine

• 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-chloro-N⁶-(3-iodobenzyl)-9-<5-(methylcarbamoyl)-2,3-O-(thiocarbonyl)-β-D-ribofuranosyl>adenine
• 英文别名: (3aR,4R,6S,6aS)-4-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-N-methyl-2-sulfanylidene-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide
• 化学式: C₁₉H₁₆ClIN₆O₄S
• 分子量: 586.797
• InChiKey: PWCUFBYAXYFCHR-IPJQOSJUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  145
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N,N'-硫羰基二咪唑 、 1-[2-氯-6-[[(3-碘苯基)甲基]氨基]-9h-嘌呤-9-基]-1-脱氧-N-甲基-beta-d-呋喃核糖酰胺 在 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到2-chloro-N⁶-(3-iodobenzyl)-9-<5-(methylcarbamoyl)-2,3-O-(thiocarbonyl)-β-D-ribofuranosyl>adenine
  参考文献：
  名称：

  Structure-Activity Relationships of 9-Alkyladenine and Ribose-Modified Adenosine Derivatives at Rat A3 Adenosine Receptors

  摘要：

  9-Alkyladenine derivatives and ribose-modified N-6-benzyladenosine derivatives were synthesized in an effort to identify selective ligands for the rat A(3) adenosine receptor and leads for the development of antagonists. The derivatives contained structural features previously determined to be important for A(3) selectivity in adenosine derivatives, such as an N-6-(3-iodobenzyl) moiety, and were further substituted at the 2-position with halo, amino, or thio groups. Affinity was determined in radioligand binding assays at rat brain A(3) receptors stably expressed in Chinese hamster ovary (CHO) cells, using [I-125]]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamid)), and at rat brain A(1) and A(2a) receptors using [H-3]-N-6-PIA ((R)-N-6-phenylisopropyladenosine) and [H-3]CGS 21680 (2-[[[4-(2-carboxyethyl)-phenyl]ethyl]amino]-5'-(N-ethylcarbamoyl)adenosine), respectively. A series of N-6-(3-iodobenzyl) 2-amino derivatives indicated that a small 2-alkylamino group, e.g., methylamino, was favored at A(3) receptors. N-6-(3-Iodobenzyl)-9-methyl-2-(methylthio)adenine was 61-fold more potent than the corresponding 2-methoxy ether at A(3) receptors and of comparable affinity at A(1) and A(2a) receptors, resulting in a 3-6-fold selectivity for A(3) receptors. A pair of chiral N-6-(3-iodobenzyl) 9-(2,3-dihydroxypropyl) derivatives showed stereoselectivity, with the R-enantiomer favored at A(3) receptors by 5.7-fold. 2-Chloro-9-(beta-D-erythrofuranosyl)-N-6-(3-iodobenzyl)adenine had a K-i value at A(3) receptors of 0.28 mu M. 2-Chloro-9-[2-amino-2,3-dideoxy-beta-D-5-(methylcarbamoyl)-arabinofuranosyl]-N-6-(3-iodobenzyl)adenine was moderately selective for A(1) and A(3) VS A(2a) receptors. A 3'-deoxy analogue of a highly A(3)-selective adenosine derivative retained selectivity in binding and was a full agonist in the inhibition of adenylyl cyclase mediated via cloned rat A(3) receptors expressed in CHO cells. The 3'-OH and 4'-CH2OH groups of adenosine are not required for activation at A(3) receptors. A number of 2',3'-dideoxyadenosines and 9-acyclic-substituted adenines appear to inhibit adenylyl cyclase at the allosteric ''P'' site.

  DOI：

  10.1021/jm00010a017

文献信息

• Structure-Activity Relationships of 9-Alkyladenine and Ribose-Modified Adenosine Derivatives at Rat A3 Adenosine Receptors
  作者：Kenneth A. Jacobson、Suhaib M. Siddiqi、Mark E. Olah、Xiao-duo Ji、Neli Melman、Kamala Bellamkonda、Yacov Meshulam、Gary L. Stiles、Hea O. Kim

  DOI：10.1021/jm00010a017

  日期：1995.5

  9-Alkyladenine derivatives and ribose-modified N-6-benzyladenosine derivatives were synthesized in an effort to identify selective ligands for the rat A(3) adenosine receptor and leads for the development of antagonists. The derivatives contained structural features previously determined to be important for A(3) selectivity in adenosine derivatives, such as an N-6-(3-iodobenzyl) moiety, and were further substituted at the 2-position with halo, amino, or thio groups. Affinity was determined in radioligand binding assays at rat brain A(3) receptors stably expressed in Chinese hamster ovary (CHO) cells, using [I-125]]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamid)), and at rat brain A(1) and A(2a) receptors using [H-3]-N-6-PIA ((R)-N-6-phenylisopropyladenosine) and [H-3]CGS 21680 (2-[[[4-(2-carboxyethyl)-phenyl]ethyl]amino]-5'-(N-ethylcarbamoyl)adenosine), respectively. A series of N-6-(3-iodobenzyl) 2-amino derivatives indicated that a small 2-alkylamino group, e.g., methylamino, was favored at A(3) receptors. N-6-(3-Iodobenzyl)-9-methyl-2-(methylthio)adenine was 61-fold more potent than the corresponding 2-methoxy ether at A(3) receptors and of comparable affinity at A(1) and A(2a) receptors, resulting in a 3-6-fold selectivity for A(3) receptors. A pair of chiral N-6-(3-iodobenzyl) 9-(2,3-dihydroxypropyl) derivatives showed stereoselectivity, with the R-enantiomer favored at A(3) receptors by 5.7-fold. 2-Chloro-9-(beta-D-erythrofuranosyl)-N-6-(3-iodobenzyl)adenine had a K-i value at A(3) receptors of 0.28 mu M. 2-Chloro-9-[2-amino-2,3-dideoxy-beta-D-5-(methylcarbamoyl)-arabinofuranosyl]-N-6-(3-iodobenzyl)adenine was moderately selective for A(1) and A(3) VS A(2a) receptors. A 3'-deoxy analogue of a highly A(3)-selective adenosine derivative retained selectivity in binding and was a full agonist in the inhibition of adenylyl cyclase mediated via cloned rat A(3) receptors expressed in CHO cells. The 3'-OH and 4'-CH2OH groups of adenosine are not required for activation at A(3) receptors. A number of 2',3'-dideoxyadenosines and 9-acyclic-substituted adenines appear to inhibit adenylyl cyclase at the allosteric ''P'' site.