(2S,3S,4R,5R)-2-(2-氨基乙基硫基甲基)-5-[6-[(4-硝基苯基)甲基氨基]嘌呤-9-基]四氢呋喃-3,4-二醇 | 130117-76-9

• 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
• 中文名称: (2S,3S,4R,5R)-2-(2-氨基乙基硫基甲基)-5-[6-[(4-硝基苯基)甲基氨基]嘌呤-9-基]四氢呋喃-3,4-二醇
• 英文名称: 5'-S-(2-aminoethyl)-6-N-(4-nitrobenzyl)-5'-thioadenosine
• 英文别名: SAENTA；(2S,3S,4R,5R)-2-(2-aminoethylsulfanylmethyl)-5-[6-[(4-nitrophenyl)methylamino]purin-9-yl]oxolane-3,4-diol
• CAS: 130117-76-9
• 化学式: C₁₉H₂₃N₇O₅S
• 分子量: 461.502
• InChiKey: OAFPVFZXWPVEBS-NVQRDWNXSA-N

物化性质

• 熔点：
  >67°C (dec.)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  203
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-nitrophenyl 6-(trifluoroacetamido)hexanoate 、 (2S,3S,4R,5R)-2-(2-氨基乙基硫基甲基)-5-[6-[(4-硝基苯基)甲基氨基]嘌呤-9-基]四氢呋喃-3,4-二醇 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以47%的产率得到6-N-(4-nitrobenzyl)-5'-S-{2-[6-(trifluoroacetamido)hexanamido]ethyl}-5'-thioadenosine
  参考文献：
  名称：

  Improved Syntheses of 5′-S-(2-Aminoethyl)-6-N-(4-nitrobenzyl)-5′-thioadenosine (SAENTA), Analogues, and Fluorescent Probe Conjugates: Analysis of Cell-Surface Human Equilibrative Nucleoside Transporter 1 (hENT1) Levels for Prediction of the Antitumor Efficacy of Gemcitabine

  摘要：

  5'-S-(2-Aminoethyl)-6-N-(4-nitrobenzyl)-5'-thioadenosine (SAENTA), 5'-S-(2-acetamidoethyl)-6-N-[(4-substituted)benzyl]-5'-thioadenosine analogues, 5'-S-[2-(6-aminohexanamido)lethyl-6-N-(4-nitrobenzyl)-5'-thioadenosine (SAHENTA), and related compounds were synthesized by S(N)Ar displacement of fluoride from 6-fluoropurine intermediates with 4-(substituted)benzylamines. Conjugation of the pendant amino groups of SAENTA and SAHENTA with fluorescein-5-yl isothiocyanate (FITC) gave fluorescent probes that bound at nanomolar concentrations specifically to human equilibrative nucleoside transporter 1 (hENT1) produced in recombinant form in model expression systems and in native form in cancer cell lines. Transporter binding effects were studied and the ability of the probes to predict the potential antitumor efficacy of 2'-deoxy-2',2'-difluorocylidine (gemcitabine) was demonstrated.

  DOI：

  10.1021/jm100432w
• 作为产物：
  描述：

  2',3'-di-O-acetyl-6-N-(4-nitrobenzyl)-5'-S-[2-(trifluoroacetamido)ethyl]-5'-thioadenosine 在 ammonium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 (2S,3S,4R,5R)-2-(2-氨基乙基硫基甲基)-5-[6-[(4-硝基苯基)甲基氨基]嘌呤-9-基]四氢呋喃-3,4-二醇
  参考文献：
  名称：

  Improved Syntheses of 5′-S-(2-Aminoethyl)-6-N-(4-nitrobenzyl)-5′-thioadenosine (SAENTA), Analogues, and Fluorescent Probe Conjugates: Analysis of Cell-Surface Human Equilibrative Nucleoside Transporter 1 (hENT1) Levels for Prediction of the Antitumor Efficacy of Gemcitabine

  摘要：

  5'-S-(2-Aminoethyl)-6-N-(4-nitrobenzyl)-5'-thioadenosine (SAENTA), 5'-S-(2-acetamidoethyl)-6-N-[(4-substituted)benzyl]-5'-thioadenosine analogues, 5'-S-[2-(6-aminohexanamido)lethyl-6-N-(4-nitrobenzyl)-5'-thioadenosine (SAHENTA), and related compounds were synthesized by S(N)Ar displacement of fluoride from 6-fluoropurine intermediates with 4-(substituted)benzylamines. Conjugation of the pendant amino groups of SAENTA and SAHENTA with fluorescein-5-yl isothiocyanate (FITC) gave fluorescent probes that bound at nanomolar concentrations specifically to human equilibrative nucleoside transporter 1 (hENT1) produced in recombinant form in model expression systems and in native form in cancer cell lines. Transporter binding effects were studied and the ability of the probes to predict the potential antitumor efficacy of 2'-deoxy-2',2'-difluorocylidine (gemcitabine) was demonstrated.

  DOI：

  10.1021/jm100432w

文献信息

• Selective cellular targeting: multifunctional delivery vehicles, multifunctional prodrugs, use as antineoplastic drugs
  申请人：Drug Innovation & Design, Inc.

  公开号：US20030138432A1

  公开（公告）日：2003-07-24

  The present invention relates to the compositions, methods, and applications of a novel approach to selective cellular targeting. The purpose of this invention is to enable the selective delivery and/or selective activation of effector molecules to target cells for diagnostic or therapeutic purposes. The present invention relates to multi-functional prodrugs or targeting vehicles wherein each functionality is capable of enhancing targeting selectivity, affinity, intracellular transport, activation or detoxification. The present invention also relates to ultra-low dose, multiple target, multiple drug chemotherapy and targeted immunotherapy for cancer treatment.

  本发明涉及一种新的选择性细胞靶向的组合物、方法和应用。本发明的目的是为了实现对目标细胞的选择性输送和/或选择性激活效应分子，以进行诊断或治疗。本发明涉及多功能前药或靶向载体，其中每个功能都能增强靶向选择性、亲和力、细胞内转运、激活或解毒。本发明还涉及超低剂量、多靶点、多药物化疗和靶向免疫疗法，用于癌症治疗。
• 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结构的化合物，能够结合到动物细胞的es核苷酸转运体上：##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到12）、SH、SR（其中R为CH.sub.3或（CH.sub.2）.sub.n CH.sub.3且n为1到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到C20的取代或未取代的烷基或杂烷基；取代或未取代的脂环烃或杂环烃；取代或未取代的芳烃或杂芳烃、芳基或取代芳基；杂芳基或取代杂芳基；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且n为1到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。
• Novel Nucleoside Transport Inhibitors
  申请人：Buolamwini Kwesi John

  公开号：US20070293444A1

  公开（公告）日：2007-12-20

  Compounds or compositions that are inhibitors and/or ligands of nucleoside transporters; and methods of treating cancer, heart disease and stroke, as well as AIDS and other infectious diseases

  抑制核苷酸转运体的化合物或组合物；以及治疗癌症、心脏病和中风，以及艾滋病和其他传染病的方法。
• SELECTIVE CELLULAR TARGETING: MULTIFUNCTIONAL DELIVERY VEHICLES
  申请人：Drug Innovation & Design, Inc.

  公开号：EP1255567A1

  公开（公告）日：2002-11-13
• US5236902A
  申请人：——

  公开号：US5236902A

  公开（公告）日：1993-08-17