N⁶,N⁶,N⁶-trimethyladeninium chloride | 13020-83-2

• 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: N⁶,N⁶,N⁶-trimethyladeninium chloride
• 英文别名: N,N,N-trimethyl-9H-purin-6-aminium chloride；purin-6-yltrimethylammonium chloride；Purin-6-yl-trimethyl-ammonium-chloride；Trimethylpurin-6-ylammonium；Trimethylpurin-6-ylammonium chloride；trimethyl(7H-purin-6-yl)azanium;chloride
• CAS: 13020-83-2
• 化学式: C₈H₁₂N₅*Cl
• 分子量: 213.67
• InChiKey: JSVIFNMHKUROQN-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.45
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  N⁶,N⁶,N⁶-trimethyladeninium chloride 在 四丁基氟化铵 作用下， 以 二甲基亚砜 为溶剂， 反应 336.0h， 以80%的产率得到6-氟嘌呤
  参考文献：
  名称：

  The New Convenient Synthesis of 6-Fluoropurine and Its 7-/9-Unsubstituted Analogues

  摘要：

  6-Fluoropurine and its 7-/9-unsubstituted analogues have good biological activity and serve as important pharmaceutical intermediates. This paper describes a new and convenient synthesis of 6-fluoropurine and its 7-/9-unsubstituted analogues, by first replacing the chlorine atoms with trimethylammonio groups through the reaction of 6-chloropurine and its 7-/9-unsubstituted analogues with trimethylamine, and then replacing the trimethylammonio groups with fluorine atoms using safe and cheap TBAF center dot 3H(2)O as fluorinating agent at room temperature. Compared with reported methods, the new synthesis has milder conditions, shorter reaction times, simpler post-processing and higher (or similar) yields.

  DOI：

  10.3987/com-12-12583
• 作为产物：
  描述：

  6-氯嘌呤 、 三甲胺 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 以90%的产率得到N⁶,N⁶,N⁶-trimethyladeninium chloride
  参考文献：
  名称：

  The New Convenient Synthesis of 6-Fluoropurine and Its 7-/9-Unsubstituted Analogues

  摘要：

  6-Fluoropurine and its 7-/9-unsubstituted analogues have good biological activity and serve as important pharmaceutical intermediates. This paper describes a new and convenient synthesis of 6-fluoropurine and its 7-/9-unsubstituted analogues, by first replacing the chlorine atoms with trimethylammonio groups through the reaction of 6-chloropurine and its 7-/9-unsubstituted analogues with trimethylamine, and then replacing the trimethylammonio groups with fluorine atoms using safe and cheap TBAF center dot 3H(2)O as fluorinating agent at room temperature. Compared with reported methods, the new synthesis has milder conditions, shorter reaction times, simpler post-processing and higher (or similar) yields.

  DOI：

  10.3987/com-12-12583

文献信息

• [EN] O<6>-SUBSTITUTED GUANINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND THEIR USE IN TREATING TUMOUR CELLS<br/>[FR] DERIVES DE GUANINE SUBSTITUEE EN POSITION O<6>, LEUR PROCEDE DE PREPARATION ET LEUR APPLICATION AU TRAITEMENT DES CELLULES TUMORALES
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：WO1994029312A1

  公开（公告）日：1994-12-22

  (EN) O^_6-hetarylalkyl- or naphthylalkylguanine derivatives of formula (I) wherein Y is H, ribosyl, deoxyribosyl, or R'XCHR'', wherein X is O or S, R'' and R''' are alkyl, or substituted derivatives thereof; R' is H, or alkyl or hydroxyalkyl; R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hereto atom chosen from O, N or S, or a substituted derivative thereof; or (ii) naphthyl or a substituted derivative thereof; and pharmaceutically acceptable salts thereof, exhibit the ability to deplete O^_6-alkylguanine-DNA alkyltransferase (ATase) activity. A process for preparation of the compounds is described. The compounds have utility in combination with alkylating agents in the chemotherapeutic treatment of tumour cells.(FR) Dérivés de naphtylalkylguanine ou hétarylalkylguanine substituée en position O^_6, répondant à la formule (I), dans laquelle Y représente H, ribosyle, désoxyribosyle ou R'XCHR'', où X représente O ou S, R' et R'' représentent alkyle, ou leurs dérivés substitués; R' représente H, alkyle ou hydroxyalkyle; R représente (i) un groupe cyclique possédant au moins un hétérocycle pentagonal ou hexagonal éventuellement condensé avec un carbocycle ou hétérocycle, le ou chaque hétérocycle possédant au moins un hétéroatome choisi parmi O, N et S, ou son dérivé substitué; ou (ii) naphtyle ou son dérivé substitué; et leurs sels pharmaceutiquement acceptables; pouvant diminuer l'activité de l'O^_6-alkylguanine-ADN alkyltransférase (Atase). On décrit un procédé de préparation de ces composés. Lesdits composés sont utilisables en association avec des agents d'alkylation dans le traitement chimiothérapeutique des cellules tumorales.

  化合物公式（I）中，O^_6-萜基烷基或萘基烷基鸟嘌呤衍生物，其中Y为H，核糖基，脱氧核糖基或R'XCHR''，其中X为O或S，R''和R'''为烷基或其取代衍生物；R'为H，烷基或羟基烷基；R为（i）至少具有一个5-或6-成员杂环环的环状基团，可选地与碳环或杂环融合，或其取代衍生物，其中每个杂环环至少具有一个来自O，N或S的杂原子；或（ii）萘基或其取代衍生物；及其药学上可接受的盐，具有降低O^_6-烷基鸟嘌呤-DNA烷基转移酶（ATase）活性的能力。描述了制备该化合物的过程。该化合物在联合烷基化剂治疗肿瘤细胞方面具有实用价值。
• [EN] PYRIMIDINE DERIVATIVES AND GUANINE DERIVATIVES, AND THEIR USE IN TREATING TUMOUR CELLS<br/>[FR] DERIVES DE LA PYRIMIDINE ET DERIVES DE LA GUANINE, ET LEUR UTILISATION POUR TRAITER DES CELLULES TUMORALES
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：WO1997020843A1

  公开（公告）日：1997-06-12

  (EN) The invention provides compounds exhibiting the ability to deplete O6-alkylguanine-DNA alkyltransferase (ATase) activity in tumour cells. The compounds include certain pyrimidine derivatives of formula (II), wherein R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hetero atom chosen from O, N, or S, or a substituted derivative thereof; or (ii) phenyl or a substituted derivative thereof, R2 is selected from H, C1-C5 alkyl, halogen or NH2, R4 and R5 which are the same or different are selected from H, NH-Y' or NOn wherein Y' is H, ribosyl, deoxyribosyl, arabinosyl, (a) wherein X is O or S, R' is alkyl and R''' is H or alkyl, or substituted derivatives thereof, n = 1 or 2 or R4 and R5 together with the pyrimidine ring form a 5-or 6-membered ring structure containing one or more hetero atoms, and pharmaceutically acceptable salts thereof. They include certain guanine derivatives of formula (XIII), wherein R6 is as defined at (i) for R above and Y' is as defined above.(FR) L'invention concerne des composés capables de neutraliser l'activité de la O6-alkylguanine-ADN transférase (ATase) dans les cellules tumorales. Parmi ces composés, il y a certains dérivés de la pyrimidine ayant la formule (II). Dans cette formule, R est (i) un groupe cyclique ayant au moins un noyau hétérocyclique à 5 ou 6 éléments, éventuellement fusioné avec un cycle carboxylique ou hétérocyclique, le ou chaque noyau hétérocyclique ayant au moins un hétéroatome choisi parmi O, N ou S ou un dérivé substitué; ou (ii) phényle ou un dérivé substitué de celui-ci, R2 est choisi parmi H, C1-C5 alkyle, halogène ou NH2, R4 et R5 qui sont les mêmes ou différents sont choisis parmi H, NH-Y' ou NOn, où Y' est H, ribosyle, désoxyribosyle, arabinosyle, un radical de la formule (a), dans laquelle X est O ou S, R'' est un alkyle et R''' est H ou alkyle ou un alkyle substitué, n = 1 ou 2 ou R4 et R5 forment avec le cycle de la pyridine une structure à 5 ou 6 éléments contenant un ou plusieurs hétéroatomes. L'invention concerne également les sels de ces composés acceptables sur le plan pharmaceutique. L'invention concerne en outre les dérivés de la guanadine de la formule XIII, où R6 est défini comme R en (i) et Y' est comme défini ci-dessus.

  本发明提供了一种能够降低肿瘤细胞中O6-烷基鸟嘌呤-DNA烷基转移酶(ATase)活性的化合物。这些化合物包括以下公式(II)中的某些嘧啶衍生物，其中R是(i)至少具有一个5-或6-成员杂环环的环状基团，可选地与碳环或杂环融合，或其取代衍生物，该杂环中的每个杂环至少有一个从O、N或S中选择的杂原子；或(ii)苯基或其取代衍生物，R2选择自H、C1-C5烷基、卤素或NH2，R4和R5相同或不同，选择自H、NH-Y'或NOn，其中Y'是H、核糖基、去氧核糖基、阿拉伯糖基、(a)式中的基团，其中X是O或S，R'是烷基，R'''是H或烷基，或其取代衍生物，n=1或2，或R4和R5与嘧啶环一起形成一个含有一个或多个杂原子的5-或6-成员环结构，以及其在药学上可接受的盐。它们包括以下公式(XIII)中的某些鸟嘌呤衍生物，其中R6如上所述的R(i)，Y'如上所述。
• ANTI-HEPATITIS B VIRUS AGENT
  申请人：DAIKIN INDUSTRIES, LTD.

  公开号：EP3939655A1

  公开（公告）日：2022-01-19

  The present disclosure aims to provide an anti-hepatitis B virus agent, and a prophylactic or therapeutic agent for a hepatitis B virus-related disease, each comprising a nucleic acid analogue as an active ingredient. The above object can be attained by an anti-hepatitis B virus agent, or a prophylactic or therapeutic agent for a hepatitis B virus-related disease, each comprising, as an active ingredient, a compound represented by the following formula (1): wherein R is a halogen atom, an amino group, a methoxy group, or a cyano group, or its prodrug, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

  本公开旨在提供一种抗乙型肝炎病毒制剂，以及一种乙型肝炎病毒相关疾病的预防或治疗制剂，每种制剂都包含一种核酸类似物作为活性成分。 抗乙型肝炎病毒制剂或乙型肝炎病毒相关疾病的预防或治疗制剂可通过以下方法实现上述目的，每种制剂都包含由下式（1）代表的化合物作为活性成分： 其中 R 是卤素原子、氨基、甲氧基或 氰基、 或其原药，或其药学上可接受的盐，或 其溶液。
• Novel 6-alkoxypurine 2',3'-dideoxynucleosides as inhibitors of the cytopathic effect of the human immunodeficiency virus
  作者：Charlene L. Burns、Marty H. St. Clair、Lloyd W. Frick、Thomas Spector、Devron R. Averett、Michael L. English、Timothy J. Holmes、Thomas A. Krenitsky、George W. Koszalka

  DOI：10.1021/jm00055a009

  日期：1993.2

  Twenty-one 6-alkoxypurine 2',3'-dideoxynucleosides were enzymatically synthesized with nucleoside phosphorylases purified from E. coli. Eighteen analogs exhibited anti-HIV-1 activity in MT4 cells. Two analogs,6-(hexyloxy)-(17) and 6-(heptyloxy)-(18) purine 2',3'-dideoxynucleoside, were as potent as 2',3'-dideoxyinosine (ddI, didanosine, Videx). Although the antiviral activities of 17 and 18 were equivalent, 18 was more cytotoxic. Analogs containing less than four carbons in the 6-alkoxypurine substituent exhibited weak anti-HIV-1 activity. Analogs containing more than seven carbons in the 6-alkoxypurine substituent were too cytotoxic to be effectively evaluated for antiviral activity. Several 6-alkoxypurine 2',3'-dideoxynucleosides were evaluated for substrate activity with calf intestinal adenosine deaminase (ADA). Increasing the carbon chain length of the 6-alkoxypurine substituent decreased the rate of dealkoxylation. The best substrate in this series was 6-methoxypurine 2',3'-dideoxynucleoside (1); however, the rate of dealkoxylation of 100 muM 1 was 0.17 % of the rate of deamination of 100 muM 2',3'-dideoxyadenosine. Compound 17, the most potent anti-HIV-1 analog, was not a substrate for ADA. EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), a potent inhibitor of ADA, had little effect on the antiviral activities of 17 and ddI. In contrast, coformycin, a potent inhibitor of both ADA and AMP deaminase, dramatically decreased the antiviral activity of 17, but not the antiviral activity of ddI. Thus, AMP deaminase appeared to be involved in the anabolism of 17. The pharmacokinetic profile of 17, the most promising analog in this series, was determined in the rat. At least seventeen metabolites of 17, including ddI, were detected in plasma samples. This analog also had poor oral bioavailability.
• Reactivity of 6-Halopurine Analogs with Glutathione as a Radiotracer for Assessing Function of Multidrug Resistance-Associated Protein 1
  作者：Toshimitsu Okamura、Tatsuya Kikuchi、Kiyoshi Fukushi、Toshiaki Irie

  DOI：10.1021/jm901332c

  日期：2009.11.26

  6-Bromo-7-[C-11]methylpurine is reported to react with glutathione via glutathione S-transferases in the brain and to be converted into a substrate for multidrug resistance-associated protein 1 (MRP1), an efflux pump. The compound with a rapid conversion rate allows quantitative assessment of MRP1 function, but this rate is probably susceptible to interspecies differences. Hence, for application to different species, including humans, it is necessary to adjust the conversion rate by modifying the chemical structure. We therefore designed 6-Halo-9-(or 7)-[C-14]methylpurine (halogen: F, Cl, Br, or I), and evaluated them in vitro with respect to enzymatic reactivity with glutathione using brain homogenates from the mouse, rat, or monkey. There was a marked difference in reactivity between these species. Changes in the position of the methyl group and halogen on N-methyl-6-halopurine provided various compounds possessing wide-ranging reactivity with glutathione. In conclusion, the adjustment of reactivity of 6-bromo-7-[C-11]methylpurine may allow assessment of MRP1 function in the brain in various species.

表征谱图