N⁸,N⁸-dimethyl-9H-purine-6,8-diamine | 61908-19-8

• 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: N⁸,N⁸-dimethyl-9H-purine-6,8-diamine
• 英文别名: N8,N8-dimethyl-9H-purine-6,8-diamine；8-(N,N-Dimethylamino)adenine；8-(Dimethylamino)adenine；8-dimethylaminoadenine；8-N,8-N-dimethyl-7H-purine-6,8-diamine
• CAS: 61908-19-8
• 化学式: C₇H₁₀N₆
• mdl: MFCD00514711
• 分子量: 178.197
• InChiKey: IJLZPLBXRPFQHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  83.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N⁸,N⁸-dimethyl-9H-purine-6,8-diamine 在 Dowex 50X₈ 、 caesium carbonate 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 (S)-9-(2,3-Dihydroxypropyl)-8-(dimethylamino)adenine
  参考文献：
  名称：

  Synthesis of 8-Amino- and N-Substituted 8-Aminoadenine Derivatives of Acyclic Nucleoside and Nucleotide Analogs

  摘要：

  8-氨基腺嘌呤衍生物2可通过一锅法从8-溴腺嘌呤1经过8-叠氮腺嘌呤制备而得。在乙醇中，8-溴腺嘌呤1与甲胺或二甲胺反应生成相应的N⁹-取代的8-(甲基氨基)腺嘌呤3和8-(二甲胺基)腺嘌呤4。将8-氨基腺嘌呤（2a）与不同的烷基化试剂进行烷基化反应可得到N⁹-取代的8-氨基腺嘌呤衍生物2，而将8-(二甲胺基)腺嘌呤（4a）进行烷基化反应则会得到相应的N⁹-取代的8-(二甲胺基)腺嘌呤4及其N³-取代的异构体5的混合物。通过对(S)-8-溴-9-{2-[(二异丙氧磷酰)-甲氧基]-3-羟基丙基}腺嘌呤（1c）进行对烷基化反应，然后用甲醇氨或甲胺溶液处理制备了8,3'-N-缺水腺嘌呤衍生物7。

  DOI：

  10.1135/cccc20010517
• 作为产物：
  描述：

  8-dimethylamino-2',3'-O-isopropylideneadenosine-5'-carboxylic acid 在 盐酸 作用下， 以 水 为溶剂， 生成 N⁸,N⁸-dimethyl-9H-purine-6,8-diamine
  参考文献：
  名称：

  Akhrem, A. A.; Ermolenko, T. M.; Timoshchuk, V. A., Journal of Organic Chemistry USSR (English Translation), 1985, vol. 21, p. 1639 - 1644

  摘要：

  DOI：

文献信息

• Synthesis of Acyclic Adenine 8,N-Anhydronucleosides
  作者：Kateřina Meszárosová、Antonín Holý、Milena Masojídková

  DOI：10.1135/cccc20001109

  日期：——

  9-(4-Hydroxybutyl)adenine (10) was obtained by reaction of adenine with 4-[(2-tetrahydropyran-2-yl)oxy]butyl chloride (7) in the presence of DBU. 8-Bromo-9-(4-hydroxybutyl)adenine (13) was prepared by bromination of 10 or by alkylation of 8-bromoadenine (11) with 4-bromoethyl acetate followed by methanolysis. Tosylation of compound 13 afforded the 4-tosyloxy derivative 15 which gave on heating with methylamine or cyclopropylamine 6-methyl- (17a) or 6-cyclopropyl-7,8,9,10-tetrahydro-6H-[1,3]diazepino[1,2-e]purin-4-amine (17b), while the reaction with hydrazine afforded 7,8,9,10-tetrahydro-6H-[1,3]diazepino[1,2-e]purine-4,6-diamine (17d). Treatment of compound 13 with thionyl chloride gave 9-(4-chlorobutyl)-8-chloroadenine (18) as the main product which was transformed to 17b, 6-propyl-7,8,9,10-tetrahydro-6H-[1,3]diazepino[1,2-e]purin-4-amine (17c) or 7,8,9,10-tetrahydro-6H-[1,3]diazepino[1,2-e]purin-4-amine (17e) by reaction with cyclopropylamine, propylamine or ammonia, respectively. Compound 17e was quite stable both in acid and alkaline solutions, at room temperature or at 90 °C. Compound 13 was converted to 9-(4-hydroxybutyl)-8-methylaminoadenine (19) by reaction with methylamine. Compound 19 failed to undergo intramolecular cyclization to diazepine 17a on treatment with diphenyl carbonate, bis(4-nitrophenyl) carbonate or 1,1'-carbonyldiimidazole.

  9-(4-羟基丁基)腺嘌呤（10）是通过腺嘌呤与4-[(2-四氢呋喃-2-基)氧基]丁基氯化物（7）在DBU存在下反应得到的。8-溴-9-(4-羟基丁基)腺嘌呤（13）通过10的溴化或8-溴腺嘌呤（11）与4-溴乙酸乙酯烷基化后随后进行甲醇解得到。化合物13的对甲苯磺酰化得到4-对甲苯磺酰氧基衍生物15，加热与甲基胺或环丙胺反应得到6-甲基-（17a）或6-环丙基-7,8,9,10-四氢-6H-[1,3]二氮杂吡咯[1,2-e]嘌呤-4-胺（17b），而与肼反应得到7,8,9,10-四氢-6H-[1,3]二氮杂吡咯[1,2-e]嘌呤-4,6-二胺（17d）。化合物13与氯化亚砜反应得到9-(4-氯丁基)-8-氯腺嘌呤（18）作为主要产物，经转化得到17b，6-丙基-7,8,9,10-四氢-6H-[1,3]二氮杂吡咯[1,2-e]嘌呤-4-胺（17c）或7,8,9,10-四氢-6H-[1,3]二氮杂吡咯[1,2-e]嘌呤-4-胺（17e），分别与环丙胺、丙胺或氨反应。化合物17e在酸性和碱性溶液中，在室温或90°C下都相当稳定。化合物13通过与甲基胺反应转化为9-(4-羟基丁基)-8-甲基氨基腺嘌呤（19）。化合物19在与二苯基碳酸酯、双(4-硝基苯基)碳酸酯或1,1'-羰基二咪唑处理时未能发生分子内环化反应形成二氮杂吡咯17a。
• Structure−Activity Relationships of Adenine and Deazaadenine Derivatives as Ligands for Adenine Receptors, a New Purinergic Receptor Family
  作者：Thomas Borrmann、Aliaa Abdelrahman、Rosaria Volpini、Catia Lambertucci、Edgars Alksnis、Simone Gorzalka、Melanie Knospe、Anke C. Schiedel、Gloria Cristalli、Christa E. Müller

  DOI：10.1021/jm9006356

  日期：2009.10.8

  Adenine derivatives bearing substituents in the 2-, N6-, 7-, 8-, and/or 9-position and a series of deazapurines were synthesized and investigated in [3H]adenine binding studies at the adenine receptor in rat brain cortical membrane preparations (rAde1R). Steep structure−activity relationships were observed. Substitution in the 8-position (amino, dimethylamino, piperidinyl, piperazinyl) or in the 9-position

  合成并研究了在[ 3]中带有2-，N 6-，7-，8和/或9位取代基的腺嘌呤衍生物和一系列脱氮嘌呤。H]腺嘌呤在大鼠大脑皮层膜制剂（rAde1R）中对腺嘌呤受体的结合研究。观察到陡峭的结构-活性关系。最好的取代是在8位（氨基，二甲基氨基，哌啶基，哌嗪基）或9位（2-吗啉代乙基）中带有碱性残基或在6位氨基官能团处引入极性取代基（羟基，氨基，乙酰基）是最好的修改。在稳定表达rAde1R的1321N1星形细胞瘤细胞的腺苷酸环化酶测定中，对所选腺嘌呤衍生物的功能评估表明，所研究的所有化合物均为激动剂或部分激动剂。在人类胚胎肾脏（HEK293）细胞的结合研究中还对化合物的子集进行了研究，该细胞还表达了高亲和力的腺嘌呤结合位点。人细胞系的结构亲和力关系与rAde1R相似，但不完全相同。特别是，N 6-乙酰腺嘌呤（25，K i大鼠：2.85μM; K i人：0.515μM）和8-氨基腺嘌呤（33，K i
• SYNTHESIS OF 8-AMINO AND 8-SUBSTITUTED AMINO DERIVATIVES OF ACYCLIC PURINE NUCLEOSIDE AND NUCLEOTIDE ANALOGS. ALKYLATION OF 8-SUBSTITUTED PURINE BASES
  作者：Z. Janeba、A. Holý

  DOI：10.1081/ncn-100002498

  日期：2001.3.31

  Two synthetic approaches were used for preparation of 8-amino-, 8-methyl- amino-, and 8-dimethylaminoadenine and -guanine analogs of PME and HPMP series: (a) direct modification of 8-bromopurine acyclic nucleotide analogs at the 8-position of the base, (b) alkylation of 8-modified purine bases with alkylation agents.

  使用两种合成方法制备PME和HPMP系列的8-氨基-，8-甲基-氨基和8-二甲基氨基腺嘌呤和-鸟嘌呤类似物：（a）在8-位直接修饰8-溴嘌呤无环核苷酸类似物碱的位置，（b）用烷基化剂使8-修饰的嘌呤碱烷基化。
• XAYAKAVA, AKIO;JONEHDA, BUNRO;XIGUTI, MASATSUGU
  作者：XAYAKAVA, AKIO、JONEHDA, BUNRO、XIGUTI, MASATSUGU

  DOI：——

  日期：——
• Synthesis of 8-Amino- and N-Substituted 8-Aminoadenine Derivatives of Acyclic Nucleoside and Nucleotide Analogs
  作者：Zlatko Janeba、Antonín Holý、Milena Masojídková

  DOI：10.1135/cccc20010517

  日期：——

  8-Aminoadenine derivatives2were obtained from 8-bromoadenines1in one-pot reactionvia8-azidoadenines. Reaction of 8-bromoadenines1with methylamine or dimethylamine in ethanol afforded the correspondingN⁹-substituted 8-(methylamino)adenines3and 8-(dimethylamino)adenines4. Alkylation of 8-aminoadenine (2a) with diverse alkylation agents affordedN⁹-substituted 8-aminoadenine derivatives2, and alkylation of 8-(dimethylamino)adenine (4a) gave mixtures of the correspondingN⁹-substituted 8-(dimethylamino)adenines4and theirN³-substituted regioisomers5. 8,3'-N-Anhydro derivatives7were prepared by tosylation of (S)-8-bromo-9-2-[(diisopropoxyphosphoryl)- methoxy]-3-hydroxypropyl}adenine (1c) followed by treatment with methanolic ammonia or methylamine solution.

  8-氨基腺嘌呤衍生物2可通过一锅法从8-溴腺嘌呤1经过8-叠氮腺嘌呤制备而得。在乙醇中，8-溴腺嘌呤1与甲胺或二甲胺反应生成相应的N⁹-取代的8-(甲基氨基)腺嘌呤3和8-(二甲胺基)腺嘌呤4。将8-氨基腺嘌呤（2a）与不同的烷基化试剂进行烷基化反应可得到N⁹-取代的8-氨基腺嘌呤衍生物2，而将8-(二甲胺基)腺嘌呤（4a）进行烷基化反应则会得到相应的N⁹-取代的8-(二甲胺基)腺嘌呤4及其N³-取代的异构体5的混合物。通过对(S)-8-溴-9-2-[(二异丙氧磷酰)-甲氧基]-3-羟基丙基}腺嘌呤（1c）进行对烷基化反应，然后用甲醇氨或甲胺溶液处理制备了8,3'-N-缺水腺嘌呤衍生物7。