6-氨基-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮 | 2537-04-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 6-氨基-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮
• 中文别名: 6氨基-1H-吡唑并[3,4-D]嘧啶-4(7H)酮；6氨基-1H-吡唑并[3,4-D〕嘧啶-4(7H)酮
• 英文名称: 6-amino-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one
• 英文别名: 6-Amino-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-on；6-amino-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one；6-Amino-1H-pyrazolo[3,4-d]pyrimidin-4(7H)-one；6-amino-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one
• CAS: 2537-04-4
• 化学式: C₅H₅N₅O
• 分子量: 151.128
• InChiKey: BZUZJVLPAKJIBP-UHFFFAOYSA-N

物化性质

• 密度：
  2.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-氨基-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮 在 palladium on activated charcoal 、 四(三苯基膦)钯 copper(l) iodide 、 氢气 、 溴 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， 25.0~105.0 ℃ 、344.73 kPa 条件下， 反应 116.0h， 生成 Dimethyl N-<4-<2-(2-amino-4(3H)-oxo-7H-pyrazolo<3,4-d>pyrimidin-5-yl)ethyl>benzoyl>-L-glutamate
  参考文献：
  名称：

  Synthesis of pyrazolo 3,4-pyrimidine analogues of the potent agent N-4-2-2-amino-4 3-oxo-7-pyrrolo 2,3-pyrimidin-5-yl ethylbenzoyl-L-glutamic acid (LY231514)

  摘要：

  Several pyrazolo[3,4-d]pyrimidine analogues of the potent antitumor agent N-{4-12-(2-amino-4(3H)-oxo-7H-pyrrolo [2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid (LY231514, 5) have been prepared. A principal synthetic step proved to be a palladium-catalyzed C-C coupling of the 5-halo-substituted pyrazolo[3,4-d]pyrimidines 12-15 with dimethyl 4-ethynylbenzoyl-L-glutamate (16). An additional pyrazolo[3,4-d]pyrimidine analogue of 5 possessing an isofolic acid bridge unit (-NHCH2-) was prepared by reductive alkylation of diethyl 4-formylbenzoyl-L-glutamate (31) with 2-methyl-5-amino-4(3H)-oxo-7H-pyrazolo[3,4-d]pyrimidine (30). Only compound 26 proved to have in vitro cell growth inhibitory activity.

  DOI：

  10.1016/s0040-4020(01)80479-8
• 作为产物：
  描述：

  6-氨基-2-(2-脱氧-Β-D-呋喃核糖)-2,5-二氢-4H-吡唑并-[3,4-D]-PYRIMIDIN-4-ONE 在 盐酸 作用下， 以 水 为溶剂， 生成 6-氨基-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮
  参考文献：
  名称：

  8-Aza-7-脱氮鸟嘌呤和相关的吡唑并[3,4- d ]嘧啶的2'-脱氧核糖呋喃糖苷的合成

  摘要：

  所述Ñ（1） -和Ñ（2） - （2'- deoxyribofuranosides）1和2，分别为8-氮杂-7-脱氮鸟嘌呤的制备通过相转移的糖基化在存在或不存在卜4 NHSO 4作为6-氨基-4-甲氧基-1 H-吡唑并[3,4- d ]嘧啶（7c）与2-脱氧-3,5-二-O-（对甲苯甲酰基）-α-D-赤型-的催化剂戊呋喃糖酰氯（10）。以类似的方式，但是没有催化剂并且使用THF作为有机相，6-氨基-4-氯核苷11b和12b从7a合成并分别转化为N（1）-和N（2）-取代的4-thioxo类似物17a和18a。的比率Ñ（1） -至Ñ（2）-glycosylation为2：1 7C和1：1为图7a，即 取决于核碱基的结构。与N（1）化合物相比，N（2）-（β-D-2'-脱氧核糖呋喃糖苷）的H +催化N-糖基水解速率大大降低。但是，N（1）-核苷1它是2'-脱氧鸟苷的等排物，具有足够的稳定性，可稍后用于固相寡核苷酸合成。

  DOI：

  10.1002/hlca.19860690714

文献信息

• [EN] HETEROCYCLIC GTP CYCLOHYDROLASE 1 INHIBITORS FOR THE TREATMENT OF PAIN<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA GTP CYCLOHYDROLASE 1 POUR LE TRAITEMENT DE LA DOULEUR
  申请人：HERCULES TECHNOLOGY MAN CO V INC

  公开号：WO2011035009A1

  公开（公告）日：2011-03-24

  The present invention relates to the field of small molecule heterocyclic inhibitors of GTP cyclohydrolase (GCH-I), or a tautomer, prodrug, or pharmaceutically acceptable salt thereof. The invention also features pharmaceutical compositions of the compounds and the medical use of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, or neuropathic pain).

  本发明涉及小分子杂环抑制剂对GTP环化酶（GCH-I）的，或其互变异构体、前药或药用可接受盐。该发明还涉及这些化合物的药物组合物以及这些化合物用于治疗或预防疼痛（例如炎症性疼痛、伤害性疼痛、功能性疼痛或神经病理性疼痛）的医疗用途。
• Synthesis of 7-Halogenated 8-Aza-7-deaza-2′-deoxyguanosines and Related Pyrazolo[3,4-d]pyrimidine 2′-Deoxyribonucleosides
  作者：Frank Seela、Georg Becher

  DOI：10.1055/s-1998-4483

  日期：1998.2

  The synthesis of 7-bromo and 7-iodo derivatives of 8-aza-7-deaza-2′-deoxyguanosine (2, 3) as well as the halogenated 4-alkoxy derivatives 4 a - c and 5 a - c is described. Glycosylation of the halogenated pyrazolo[3,4-d]pyrimidine anions of 7 a -c or 8 a - c with 2-deoxy-3,5-di-O-(p-toluoyl)-α-d-erythro-pentofuranosyl chloride (9) yields regioisomeric glycosylation products, the N(1)-isomers 10 a - c and 11 a - c as well as the N(2)-compounds 12 a - c. The latter isomers lose their halogen during the glycosylation in the presence of non-anhydrous KOH. Anhydrous conditions (NaH) furnished 10 c, 11 c together with the halogenated N(2)-isomers 13 a,b. Compounds 10 a - c, and 11 a - c were deprotected and converted to the 4-alkoxy nucleosides 4 a - c and 5 a - c. The N(1)-nucleosides 4 c and 5 c were hydrolyzed to give the 7-bromo or 7-iodo derivatives of 8-aza-7-deaza-2′-deoxyguanosines 2 and 3. Different from regular 2′-deoxyribonucleosides the sugar moiety of pyrazolo[3,4-d]pyrimidine 2′-deoxyribonucleosides shows a preferred N-type pucker (3T2) in solution, a conformation which is also detected in the solid state.

  描述了8-氮杂-7-脱氮-2′-去氧鸟苷（2, 3）的7-溴和7-碘衍生物的合成，以及卤化的4-烷氧基衍生物4a-c和5a-c。将7a-c或8a-c的卤化吡唑[3,4-d]嘧啶阴离子与2-去氧-3,5-二-O-(对甲苯酰基)-α-d-赤糖善氟糖氯化物（9）进行糖苷化反应，得到区域异构糖苷化产物，N(1)-异构体10a-c和11a-c，以及N(2)-化合物12a-c。后者异构体在无水氢氧化钾存在下糖苷化时失去卤素。在无水条件下（氢化钠）生成了10c、11c以及卤化的N(2)-异构体13a,b。化合物10a-c和11a-c被去保护并转化为4-烷氧基核糖苷4a-c和5a-c。N(1)-核糖苷4c和5c被水解，得到8-氮杂-7-脱氮-2′-去氧鸟苷的7-溴或7-碘衍生物2和3。与常规的2′-去氧核糖核苷不同，吡唑[3,4-d]嘧啶2′-去氧核糖核苷的糖部分在溶液中显示出优先的N型扭曲（3T2），这种构象在固态中也得到了验证。
• Robins, Journal of the American Chemical Society, 1957, vol. 79, p. 6407,6412
  作者：Robins

  DOI：——

  日期：——
• Modifications on the heterocyclic base of acyclovir: syntheses and antiviral properties
  作者：Lilia M. Beauchamp、Bart L. Dolmatch、Howard J. Schaeffer、Peter Collins、D. J. Bauer、Paul M. Keller、James A. Fyfe

  DOI：10.1021/jm00146a002

  日期：1985.8

  A group of compounds was prepared in which variations of the ring portion of the acyclovir (ACV) structure were made. These modifications included monocyclic (isocytosine, triazole, imidazole), bicyclic (8-azapurine, pyrrolo[2,3-d]pyrimidine, pyrazolo[3,4-d]pyrimidine) and tricyclic (linear benzoguanine) congeners. The derivatives were evaluated against herpes simplex virus type 1 (HSV-1) by the plaque-inhibition and plaque-reduction methods with only the 8-azapurine analogue 28 showing some activity. In a test measuring the ability of these compounds to inhibit the HSV-1 thymidine kinase, 28 and the tricyclic derivative 38 exhibited competition with ACV for binding to the enzyme. The inability of the group to exert significant antiherpetic action is attributed to their lack of phosphorylation to the requisite triphosphate stage.
• Synthesis of 2?-Deoxyribofuranosides of 8-Aza-7-deazaguanine and Related Pyrazolo[3,4-d]pyrimidines
  作者：Frank Seela、Herbert Steker

  DOI：10.1002/hlca.19860690714

  日期：1986.10.29

  N(1)-and N(2)-substituted 4-thioxo analogues 17a and 18a, respectively. The ratio of N(1)- to N(2)-glycosylation was 2:1 for 7c and 1:1 for 7a, viz. depending on the nucleobase structure. The rate of the H+-catalyzed N-glycosyl hydrolysis was strongly decreased for the N(2)-(β-D-2′-deoxyribofuranosides) as compared to the N(1)-compounds. However, the N(1)-nucleoside 1, which is an isostere of 2′-deoxyguanosine

  所述Ñ（1） -和Ñ（2） - （2'- deoxyribofuranosides）1和2，分别为8-氮杂-7-脱氮鸟嘌呤的制备通过相转移的糖基化在存在或不存在卜4 NHSO 4作为6-氨基-4-甲氧基-1 H-吡唑并[3,4- d ]嘧啶（7c）与2-脱氧-3,5-二-O-（对甲苯甲酰基）-α-D-赤型-的催化剂戊呋喃糖酰氯（10）。以类似的方式，但是没有催化剂并且使用THF作为有机相，6-氨基-4-氯核苷11b和12b从7a合成并分别转化为N（1）-和N（2）-取代的4-thioxo类似物17a和18a。的比率Ñ（1） -至Ñ（2）-glycosylation为2：1 7C和1：1为图7a，即 取决于核碱基的结构。与N（1）化合物相比，N（2）-（β-D-2'-脱氧核糖呋喃糖苷）的H +催化N-糖基水解速率大大降低。但是，N（1）-核苷1它是2'-脱氧鸟苷的等排物，具有足够的稳定性，可稍后用于固相寡核苷酸合成。

表征谱图