5'-deoxy-5'-<(2-hydroxyethyl)thio>adenosine | 37094-86-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-deoxy-5'-<(2-hydroxyethyl)thio>adenosine
• 英文别名: 5'-deoxy-5'-(hydroxyethylthio)adenosine；5'-deoxy-5'-hydroxyethylthioadenosine；S-(2-hydroxy-ethyl)-5'-thio-adenosine；5'-S-(2-hydroxyethyl)-5'-thioadenosine；5'-Deoxy-5'-(2-hydroxy-ethylthio)adenosin；5'-Hydroxyethylthio-5'-deoxyadenosin；(2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-(2-hydroxyethylsulfanylmethyl)oxolane-3,4-diol
• CAS: 37094-86-3
• 化学式: C₁₂H₁₇N₅O₄S
• 分子量: 327.364
• InChiKey: XECCOMIMOJOGCO-WOUKDFQISA-N

物化性质

• 沸点：
  722.0±70.0 °C(Predicted)
• 密度：
  1.87±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-deoxy-5'-<(2-hydroxyethyl)thio>adenosine 在 六甲基磷酰三胺 、 二溴亚砜 作用下， 反应 3.0h， 以4.2%的产率得到5'-deoxy-5'-<(2-bromoethyl)thio>adenosine
  参考文献：
  名称：

  通过5'-脱氧-5'-（甲硫基）腺苷的5'-卤代烷基类似物靶向5'-脱氧-5'-（甲硫基）腺苷磷酸化酶。

  摘要：

  合成了一系列5'-脱氧-5'-（甲硫基）腺苷（MTA）的5'-卤代烷基修饰的类似物（多胺生物合成的核苷副产物）：5'-deoxy-5'-[（2-一氟乙基）硫代]腺苷（10），5'-脱氧-5'-[（2-氯乙基）硫代]腺苷（4），5'-脱氧-5'-[（2-溴乙基）硫代]腺苷（5）和5'-脱氧-5'-[（3-单氟丙基）硫代]腺苷（13）。根据它们用作小鼠肝脏MTA磷酸化酶底物的能力，对其中的一些类似物进行了表征，证明它们在含MTA磷酸化酶（鼠L5178Y和人MOLT-4）和MTA磷酸化酶缺陷（鼠尿）中具有抑制生长的作用。 L1210和人CCRF-CEM）白血病细胞系。含有MTA磷酸化酶的肿瘤细胞系，尤其是人类来源的 被发现对这些类似物的治疗更为敏感。在类似物系列中，有10种是每种测试细胞系中最有效的生长抑制剂。相对于MTA，类似物，尤其是化合物10，表现出降低的改变多胺池的能力，机械上表明在MT

  DOI：

  10.1021/jm00112a039
• 作为产物：
  描述：

  腺苷 在 吡啶 、 氯化亚砜 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 5'-deoxy-5'-<(2-hydroxyethyl)thio>adenosine
  参考文献：
  名称：

  组蛋白甲基转移酶DOT1L含腺苷抑制剂的合成及构效关系研究

  摘要：

  组蛋白 3-赖氨酸 79 (H3K79) 甲基转移酶 DOT1L 已被发现是具有 MLL（混合谱系白血病）基因易位的急性白血病的药物靶点。总共设计和合成了 55 种含腺苷的化合物，其中鉴定了几种有效的 DOT1L 抑制剂，K i值低至 0.5 nM。与其他三种组蛋白甲基转移酶相比，这些化合物还显示出高选择性（> 4500 倍）。讨论了这些化合物对 DOT1L 的抑制活性的构效关系 (SAR)。强效 DOT1L 抑制剂对 MLL 易位白血病细胞系 MV4;11 和 THP1 的增殖具有选择性活性，EC 504–11 μM 的值。等温滴定量热研究表明，两种代表性抑制剂以高亲和力与 DOT1L:核小体复合物结合，仅与酶辅因子 SAM（S-腺苷-1-甲硫氨酸）竞争，而不与底物核小体竞争。

  DOI：

  10.1021/jm300917h

文献信息

• COMPOUNDS USEFUL AGAINST KINETOPLASTIDEAE PARASITES
  申请人：Davioud-Charvet Elisabeth

  公开号：US20120214996A1

  公开（公告）日：2012-08-23

  Dibenzylidene and heterobenzylideneacetone derivatives, related 4-piperidones, related 4-thiopyranones and the corresponding sulfinyl- and sulfonyl-analogues for their use for prophylaxis or treatment of trypanosomiasis and leishmaniasis.

  二苄基亚烷和杂二苄基亚烷乙酮衍生物，相关的4-哌啶酮，相关的4-噻opyranones以及相应的亚磺酰基和磺酰基类似物，用于预防或治疗锥虫病和利什曼病。
• Novel Trypanocidal Analogs of 5′-(Methylthio)-Adenosine
  作者：Janice R. Sufrin、Arthur J. Spiess、Canio J. Marasco、Donna Rattendi、Cyrus J. Bacchi

  DOI：10.1128/aac.00480-07

  日期：2008.1

  The purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma

  嘌呤核苷 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) 是多胺途径代谢物 5'-deoxy-5'-(methylthio)-adenosine (MTA) 的类似物。HETA 是正在进行的选择性靶向锥虫杀灭剂开发的先导结构。合成了 13 种新型 HETA 类似物，并检查了它们对血流形式的布氏布氏锥虫 LAB 110 EATRO 和至少一种耐药性布氏锥虫临床分离株的体外锥虫杀灭活性。还在无细胞试验中评估了新化合物作为锥虫 MTA 磷酸化酶底物的活性。该组中最有效的类似物是 5'-deoxy-5'-(羟乙硫基)-tubercidin，其体外细胞毒性（50% 抑制浓度 [IC50]，10 nM）是 HETA 的 45 倍（IC50，450 nM) 对抗喷他脒抗性临床分离株 KETRI 269。结构-活性分析表明，锥虫 MTA 磷酸化酶对 HETA
• Method and probes for detecting nucleoside transporter and method for
  申请人：The Governors of the University of Alberta

  公开号：US05236902A1

  公开（公告）日：1993-08-17

  The present invention is directed to compounds capable of binding to the es nucleoside transporter of animal cells having the general formula: ##STR1## wherein n is 1-12; E is H, halogen, NH.sub.2, OH, OCH.sub.3, O(CH.sub.2).sub.n CH.sub.3 (where n is 1 to 12), SH, SR (where R is CH.sub.3 or (CH.sub.2).sub.n CH.sub.3 and n is 1 to 12); A is HN, S, O, Se; X is N or C; Y is N or C; Z is N or C; R.sub.1 is H or acyl; R.sub.2 is C1 to C20 substituted or unsubstituted alkyl or heteroalkyl; substituted or unsubstituted aliphatic carbocycle or heterocycle; substituted or unsubstituted arene or heteroarene, aryl or substituted aryl; heteroaryl or substituted heteroaryl; R.sub.3 is H, halogen, NO.sub.2, N.sub.3, SH, SR (where R is CH.sub.3 or (CH.sub.2).sub.n CH.sub.3 and n is 1 to 12); R.sub.4 is H, OH is halogen; R.sub.5 is H, OH, halogen, N.sub.3, acetal, hemiacetal and R.sub.6 is H, --C.dbd.O--HN.sub.2 or --C.dbd.N when X is C and R.sub.6 is H when X is N.

  本发明涉及一种具有以下一般式的能够结合动物细胞的es核苷酸转运体的化合物：##STR1## 其中n为1-12；E为H、卤素、NH.sub.2、OH、OCH.sub.3、O(CH.sub.2).sub.n CH.sub.3（其中n为1至12）、SH、SR（其中R为CH.sub.3或（CH.sub.2).sub.n CH.sub.3，n为1至12）；A为HN、S、O、Se；X为N或C；Y为N或C；Z为N或C；R.sub.1为H或酰基；R.sub.2为C1至C20取代或未取代的烷基或杂烷基；取代或未取代的脂环或杂环烷基；取代或未取代的芳烃或杂芳烃、芳基或取代的芳基；杂芳基或取代的杂芳基；R.sub.3为H、卤素、NO.sub.2、N.sub.3、SH、SR（其中R为CH.sub.3或（CH.sub.2).sub.n CH.sub.3，n为1至12）；R.sub.4为H、OH或卤素；R.sub.5为H、OH、卤素、N.sub.3、缩醛、半缩醛；R.sub.6为H、--C.dbd.O--HN.sub.2或--C.dbd.N（当X为C时），当X为N时，R.sub.6为H。
• Antitrypanosomal activity of purine nucleosides can be enhanced by their conversion to O-acetylated derivatives
  作者：J R Sufrin、D Rattendi、A J Spiess、S Lane、C J Marasco、C J Bacchi

  DOI：10.1128/aac.40.11.2567

  日期：1996.11

  Fifteen purine nucleosides and their O-acetylated ester derivatives were examined for in vitro antitrypanosomal activity against the LAB 110 EATRO isolate of Trypanosoma brucei brucei and two clinical isolates of Trypanosoma brucei rhodesiense. Initial comparisons of activity were made for the LAB 110 EATRO isolate. Three nucleoside analogs exhibited no significant activity (50% inhibitory concentrations [IC50s] of > 100 microM), whether they were O acetylated or unacetylated; three nucleosides showed almost equal activity (IC50s of < 5 microM) for the parent compound and the O-acetylated derivative; nine nucleosides showed significantly improved activity (> or = 3-fold) upon O acetylation; of these nine analogs, six displayed activity at least 10-fold greater than that of their parent nucleosides. The most significant results were those for four apparently inactive compounds which, upon O acetylation, displayed IC50s of < or = 25 microM. When the series of compounds was tested against T. brucei rhodesiense isolates (KETRI 243 and KETRI 269), their antitrypanosomal effects were comparable to those observed for the EATRO 110 strain. Thus, our studies of purine nucleosides have determined that O acetylation consistently improved their in vitro antitrypanosomal activity. This observed phenomenon was independent of their cellular enzyme targets (i.e., S-adenosylmethionine, polyamine, or purine salvage pathways). On the basis of our results, the routine preparation of O-acetylated purine nucleosides for in vitro screening of antitrypanosomal activity is recommended, since O acetylation transformed several inactive nucleosides into compounds with significant activity, presumably by improving uptake characteristics. O-acetylated purine nucleosides may offer in vivo therapeutic advantages compared with their parent nucleosides, and this possibility should be considered in future evaluations of this structural class of trypanocides.

  本研究对15种嘌呤核苷及其O-乙酰化酯衍生物在体外抗非洲锥虫病活性方面进行了研究，包括LAB 110 EATRO亚型的Trypanosoma brucei brucei和两种Trypanosoma brucei rhodesiense的临床分离株。首先比较了LAB 110 EATRO亚型的活性。其中三种核苷类似物没有显著活性（50%抑制浓度[IC50]大于100微米），无论它们是否被乙酰化；三种核苷显示出几乎相等的活性（IC50小于5微米）的母化合物和O-乙酰化衍生物；九种核苷在O-乙酰化后显示出显著改善的活性（大于或等于3倍）；在这九种类似物中，有六种显示出至少比其母核苷高10倍的活性。最显着的结果是四个表面上无活性的化合物，在O-乙酰化后显示出IC50小于或等于25微米的活性。当这一系列化合物对T. brucei rhodesiense分离物（KETRI 243和KETRI 269）进行测试时，它们的抗非洲锥虫病效果与EATRO 110株观察到的相当。因此，我们对嘌呤核苷的研究确定了O-乙酰化一直改善它们的体外抗非洲锥虫病活性。这种观察到的现象与它们的细胞酶靶点（即S-腺苷甲硫氨酸、多胺或嘌呤拯救途径）无关。基于我们的结果，建议常规制备O-乙酰化嘌呤核苷进行体外筛选抗非洲锥虫病活性，因为O-乙酰化将几种无活性的核苷转化为具有显著活性的化合物，可能通过改善摄取特性。与其母核苷比较，O-乙酰化嘌呤核苷在体内治疗上可能具有优势，这一可能性应在对这种结构类的锥虫药物进行未来评估时予以考虑。
• Design, synthesis, and biological evaluation of novel human 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP) substrates
  作者：Pei-Pei Kung、Luke R. Zehnder、Jerry J. Meng、Stanley W. Kupchinsky、Donald J. Skalitzky、M. Catherine Johnson、Karen A. Maegley、Anne Ekker、Leslie A. Kuhn、Peter W. Rose、Laura A. Bloom

  DOI：10.1016/j.bmcl.2005.03.107

  日期：2005.6

  The structure-based design, chemical synthesis, and biological evaluation of novel MTAP substrates are described. These compounds incorporate various C5'-moieties and are shown to have different k(cat)/K values compared with the natural MTAP substrate (MTA). (c) 2005 Elsevier Ltd. All rights reserved.