9-(4-acetoxybutyl)adenine | 5845-41-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-(4-acetoxybutyl)adenine
• 英文别名: 4-(6-Aminopurin-9-yl)butyl acetate
• CAS: 5845-41-0
• 化学式: C₁₁H₁₅N₅O₂
• 分子量: 249.272
• InChiKey: CPCCOVIILIGQEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  95.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-(4-acetoxybutyl)adenine 在 三甲基氯硅烷 、 四溴化碳 、 sodium methylate 、 三苯基膦 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 为溶剂， 反应 23.5h， 生成 9-(4-diethoxyphosphonylbutyl)-N⁶-benzoyladenine
  参考文献：
  名称：

  Rosenberg, Ivan; Holy, Antonin; Masojidkova, Milena, Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 11B, p. 2753 - 2777

  摘要：

  DOI：
• 作为产物：
  描述：

  腺嘌呤 、 alkaline earth salt of/the/ methylsulfuric acid 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以88%的产率得到9-(4-acetoxybutyl)adenine
  参考文献：
  名称：

  7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors

  摘要：

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).

  DOI：

  10.1021/jm051146h

文献信息

• An acyl-SAM analog as an affinity ligand for identifying quorum sensing signal synthases
  作者：Kenji Kai、Hiroki Fujii、Rui Ikenaka、Mitsugu Akagawa、Hideo Hayashi

  DOI：10.1039/c4cc03094j

  日期：——

  We here report the affinity purification of N-acylhomoserine lactone synthases using beads conjugated with an enzyme inhibitor, which was designed based on the catalytic intermediate acyl-SAM.

  我们在这里报告了利用与酶抑制剂共轭的珠子亲和纯化N-酰基脱氨酪氨酸乳酸合成酶，该酶抑制剂是基于催化中间体酰基-SAM设计的。
• [EN] ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'ADÉNINE EN TANT QU'INHIBITEURS DE PROTÉINE KINASES
  申请人：BCI PHARMA

  公开号：WO2017191297A1

  公开（公告）日：2017-11-09

  The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.

  本发明涉及一种适用于作为激酶抑制剂的化合物，其符合一般式(I) [化合物(C)，以下简称]，或其N-氧化物、药学上可接受的盐、药学上可接受的溶剂，或其立体异构体，式(I)中A、R1、R2、R3、R3'、R4、R4'、X、Y、Z、T的定义如权利要求所述。本发明还涉及一种体外抑制蛋白激酶活性的方法，包括将蛋白激酶与式(I)的化合物，或其N-氧化物、药学上可接受的盐、药学上可接受的溶剂，或其立体异构体接触。本发明还涉及式(I)的化合物本身，以及其作为药物的用途，以及用于治疗由蛋白激酶介导的疾病的方法，所述疾病包括癌症、炎症性疾病、心血管疾病、病毒感染性疾病、循环系统疾病、纤维增殖性疾病和疼痛敏化性疾病。
• Synthesis and Pharmacological Evaluation of Novel Adenine–Hydrogen Sulfide Slow Release Hybrids Designed as Multitarget Cardioprotective Agents
  作者：Nikolaos Lougiakis、Andreas Papapetropoulos、Evangelos Gikas、Spyridon Toumpas、Panagiotis Efentakis、Rudolf Wedmann、Anastasia Zoga、Zhongmin Zhou、Efstathios K. Iliodromitis、Alexios-Leandros Skaltsounis、Milos R. Filipovic、Nicole Pouli、Panagiotis Marakos、Ioanna Andreadou

  DOI：10.1021/acs.jmedchem.5b01223

  日期：2016.3.10

  This work deals with the design, synthesis, and evaluation of the cardioprotective properties of a number of novel hybrid compounds combining the adenine nucleus with a suitable H2S slow-releasing moiety, coupled via a stable ether bond. The H2S release rate of the hybrids and their ability to increase cGMP were estimated in vitro. The most promising derivatives 4 and 11, both containing 4-hydroxythiobenzamide

  这项工作涉及腺嘌呤核与合适的H 2 S缓释部分结合并通过稳定的醚键结合的许多新型杂化化合物的设计，合成和心脏保护性能的评估。在体外估计了杂种的H 2 S释放速率及其增加cGMP的能力。选择最有希望的衍生物4和11，它们都含有4-羟基硫代苯甲酰胺部分作为H 2 S供体，用于进一步的体内评价。他们释放H 2的能力使用新的经过充分验证的UPLC-DAD方法记录体内的S。在持续缺血结束时给药时，两种化合物均显着减少了梗塞面积。机理研究表明，与腺嘌呤或4-羟基硫代苯甲酰胺相比，它们具有增强的心脏保护作用。它们激活了缺血心肌中的PKG / PLN途径，表明这两种药效基团的组合通过触发心脏保护作用的两种分子途径的组合而产生协同的心脏保护活性。
• Selective Oxidation of Uracil and Adenine Derivatives by the Catalytic System MeReO3/H2O2 and MeReO3/Urea Hydrogen Peroxide
  作者：Raffaele Saladino、Paola Carlucci、Maria Chiara Danti、Claudia Crestini、Enrico Mincione

  DOI：10.1016/s0040-4020(00)00974-1

  日期：2000.12

  Methyltrioxorhenium (MTO) is a useful and selective catalyst for the oxidation of uracil and purine derivatives using environmentally friendly hydrogen peroxide (H2O2, 30% water solution) or hydrogen peroxide/urea adduct (UHP) as oxygen atom donors. In particular, the MTO/UHP system constitutes a convenient combination to convert uracil derivatives into the biologically relevant 5,6-oxiranyl-5,6-dihydrouracils

  甲基三（MTO）为尿嘧啶和嘌呤衍生物的使用环境友好的过氧化氢的氧化的有用的和选择性的催化剂（H 2 ö 2为氧原子供体，30％的水溶液）或过氧化氢/尿素加合（UHP）。尤其是，MTO / UHP系统构成了方便的组合，可以以高收率将尿嘧啶衍生物转化为生物学上相关的5,6-环氧乙烷基-5,6-二氢尿嘧啶。嘌呤衍生物被选择性氧化为相应的1-氧化物，在吡嗪-2-羧酸（PCA）存在下可获得最佳收率。也报道了质粒pBG1的氧化是由催化系统MTO / H 2 O 2介导的双链DNA切割的第一个实例。
• Intramolecular Cyclization of Some Acyclic Nucleoside Analogs
  作者：Zlatko Janeba、Antonín Holý、Hana Votavová、Milena Masojídková

  DOI：10.1135/cccc19960442

  日期：——

  Reaction of stereoisomeric 8-bromo-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (8) with concentrated aqueous ammonia, sodium hydride, potassium tert-butoxide, or 1,8-diazabicyclo[5,4,0]undec-7-ene afforded 4e-O,8-anhydro-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines 9 (derivatives of 1,3-oxazepino[2,3-e]adenine). The CD spectra of optically active stereoisomers of 9 have been studied and it was found that for threo isomers 9a and 9b their character corresponds to 5'-O,8-cycloadenosine. The compounds 9 were also prepared by oxidative cyclization of 9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (7) with lead(IV) acetate in benzene. Reaction of 9-(4-hydroxybutyl)adenine (14) with lead(IV) acetate smoothly afforded the seven-membered ring derivative, 4'-O,8-anhydro-9-(4-hydroxybutyl)adenine (15); no anhydro products with five-, six-, and eight-membered ring were found. 2',3'-O-Isopropylideneinosine (16) reacted with lead(IV) acetate to give 5'-O,8-cyclo-2',3'-O-isopropylideneinosine (17) whereas 9-(4-hydroxybutyl)hypoxanthine (18) afforded no cyclic products.

  立体异构体8-溴-9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤（8）与浓氨水、氢化钠、叔丁醇钾或1,8-二氮杂双环[5,4,0]十一烯反应，得到4e-O,8-去水-9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤9（1,3-噁唑并[2,3-e]腺嘌呤的衍生物）。对9的光学活性立体异构体的CD光谱进行了研究，发现对于threo异构体9a和9b，它们的特征对应于5'-O,8-环腺苷。化合物9也可以通过9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤（7）与醋酸铅（IV）在苯中氧化环化制备而成。9-(4-羟基丁基)腺嘌呤（14）与醋酸铅（IV）反应顺利地得到七元环衍生物4'-O,8-去水-9-(4-羟基丁基)腺嘌呤（15）；没有发现五元、六元和八元环的去水产物。2',3'-O-异丙基核苷（16）与醋酸铅（IV）反应，得到5'-O,8-环-2',3'-O-异丙基核苷（17），而9-(4-羟基丁基)次黄嘌呤（18）没有产生环状产物。