2-(bis-tert-butoxycarbonyl)amino-9-hydroxy-6-methoxypurine | 124077-18-5

• 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: 2-(bis-tert-butoxycarbonyl)amino-9-hydroxy-6-methoxypurine
• 英文别名: 2-[di-(t-butoxycarbonyl)]amino-9-hydroxy-6-methoxypurine；2-[(bis-t-butoxycarbonyl)amino]-9-hydroxy-6-methoxypurine；2-[Bis-(t-butoxycarbonyl)amino]-9-hydroxy-6-methoxypurine；tert-butyl N-(9-hydroxy-6-methoxypurin-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
• CAS: 124077-18-5
• 化学式: C₁₆H₂₃N₅O₆
• 分子量: 381.389
• InChiKey: AMESKLYATZTGNU-UHFFFAOYSA-N

物化性质

• 沸点：
  534.5±60.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-(bis-tert-butoxycarbonyl)amino-9-hydroxy-6-methoxypurine 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 2-氨基-9-(3-羟基丙氧基)-3H-嘌呤-6-酮
  参考文献：
  名称：

  9-羟基嘌呤的合成：新型抗病毒无环核苷的中间体

  摘要：

  描述了2-[（（双-叔丁氧基羰基）氨基] -9-羟基-6-甲氧基嘌呤（）和9-羟基-6-邻苯二甲酰亚胺嘌呤（）的合成方法。这些9-羟基嘌呤是作为潜在抗病毒剂合成9-烷氧基鸟嘌呤和9-烷氧基腺嘌呤衍生物的有用中间体。

  DOI：

  10.1016/0040-4039(90)80104-t
• 作为产物：
  描述：

  N-(4,6-二氯-5-甲酰基氨基-嘧啶-2-基)-甲酰胺 在 palladium on activated charcoal 4-二甲氨基吡啶 、 乙酸二乙氧基甲酯 、 氨 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二乙二醇二甲醚 为溶剂， 生成 2-(bis-tert-butoxycarbonyl)amino-9-hydroxy-6-methoxypurine
  参考文献：
  名称：

  9-羟基嘌呤的合成：新型抗病毒无环核苷的中间体

  摘要：

  描述了2-[（（双-叔丁氧基羰基）氨基] -9-羟基-6-甲氧基嘌呤（）和9-羟基-6-邻苯二甲酰亚胺嘌呤（）的合成方法。这些9-羟基嘌呤是作为潜在抗病毒剂合成9-烷氧基鸟嘌呤和9-烷氧基腺嘌呤衍生物的有用中间体。

  DOI：

  10.1016/0040-4039(90)80104-t

文献信息

• Novel acyclonucleotides: synthesis and antiviral activity of alkenylphosphonic acid derivatives of purines and a pyrimidine
  作者：Michael R. Harnden、Ann Parkin、Martin J. Parratt、Robert M. Perkins

  DOI：10.1021/jm00062a006

  日期：1993.5

  nitrogen-oxygen bond. The phosphonoalkenyl-substituted compounds 7a-c, 8a-c, 9, 10, and 12 were prepared either by Mitsunobu coupling of alcohols with purine or pyrimidine derivatives or by alternative alkylations of the heterocyclic bases. The (phosphonoalkenyl) oxy derivatives 7d-g, 8d-g, and 11 were synthesized by coupling of alcohols with 9-hydroxypurines or a 1-hydroxypyrimidine under Mitsunobu conditions

  合成了嘌呤和嘧啶的一系列膦酰基烯基和（膦酰基烯基）氧基衍生物。这些化合物是首先报道的无环核苷酸，其结合了α，β-不饱和膦酸部分作为磷酸酯模拟物，并且包括其中无环取代基被氮连接至嘌呤的N-9或嘧啶的N-1的化合物。 -碳或氮-氧键。膦酰基烯基取代的化合物7a-c，8a-c，9、10和12是通过醇与嘌呤或嘧啶衍生物的Mitsunobu偶联或通过杂环碱基的替代烷基化来制备的。（膦烯基）氧基衍生物7d-g，8d-g和11是通过在Mitsunobu条件下将醇与9-羟基嘌呤或1-羟基嘧啶偶联而合成的。测试了新型无环核苷酸对1型和2型单纯疱疹（HSV-1和HSV-2），水痘带状疱疹病毒（VZV），巨细胞病毒（CMV），维斯纳病毒和1型人类免疫缺陷病毒（HIV-1）的活性。鸟嘌呤衍生物具有中等至极强的细胞毒性，但腺嘌呤对细胞的毒性较小。在测试浓度下，直链系列中的（Z）异构体对疱疹病毒或HIV-1没有活性。
• Antiviral purine derivatives
  申请人：Beecham Group p.l.c.

  公开号：US05108994A1

  公开（公告）日：1992-04-28

  Compounds of formula (I), and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is hydroxy or amino; R.sub.2 is hydrogen or amino; R.sub.3 is hydrogen, hydroxymethyl or acyloxymethyl; R.sub.4 is a group of formula: ##STR2## wherein R.sub.5 and R.sub.6 are independently selected from hydrogen, C.sub.1-6 alkyl and optionally substituted phenyl; or R.sub.3 and R.sub.4 together are: ##STR3## wherein R.sub.6 is as defined above; having antiviral activity, processes for their preparation and their pharmaceutical use.

  式(I)的化合物及其药学上可接受的盐：##STR1##其中R.sub.1是羟基或氨基；R.sub.2是氢或氨基；R.sub.3是氢、羟甲基或醋氧甲基；R.sub.4是下式的基团：##STR2##其中R.sub.5和R.sub.6分别选自氢、C.sub.1-6烷基和可选择取代的苯基；或R.sub.3和R.sub.4一起是：##STR3##其中R.sub.6如上所定义；具有抗病毒活性，其制备方法及其药用。
• Antiviral phosphono-alken derivatives of purines
  申请人：Beecham Group p.l.c.

  公开号：US05356886A1

  公开（公告）日：1994-10-18

  The present invention provides antiviral compounds of Formula (I), and pharmaceutically acceptable salts thereof: ##STR1## wherein X is --CH.sub.2 O or --CH.sub.2 ; R.sub.1 is hydroxy or amino; R.sub.2 is hydrogen or amino; R.sub.3 is hydrogen, hydroxymethyl or acyloxymethyl, wherein the acyl group of said acyloxymethyl is selected from the group consisting of C.sub.1-7 alkanoyl and benzoyl optionally substituted in the phenyl ring by one, two or three substituents selected from the group consisting of fluoro, chloro, bromo, C.sub.1-4 alkyl and C.sub.1-4 alkoxy, wherein the alkyl moiety of said C.sub.1-4 alkyl and C.sub.1-4 alkoxy substituents is selected from the group consisting of methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, R.sub.4 is a group of formula: ##STR2## wherein R.sub.5 and R.sub.6 are independent selected from hydrogen, C.sub.1-6 alkyl and phenyl optionally substituted by one, two or three substituents selected from the group consisting of fluoro, chloro, bromo, C.sub.1-4 alkyl and C.sub.1-4 alkoxy, wherein the alkyl moiety of said C.sub.1-4 alkyl and C.sub.1-4 alkoxy substituents is selected from the group consisting of methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl.

  本发明提供了化合物的抗病毒化合物的公式(I)，以及其药用可接受的盐：其中X为--CH.sub.2 O或--CH.sub.2；R.sub.1为羟基或氨基；R.sub.2为氢或氨基；R.sub.3为氢，羟甲基或乙酰氧甲基，其中所述乙酰氧甲基的酰基选自由C.sub.1-7烷酰和苯甲酰组成的群，该苯环可选择地被一个、两个或三个取代基选自氟、氯、溴、C.sub.1-4烷基和C.sub.1-4烷氧的群取代，其中所述C.sub.1-4烷基和C.sub.1-4烷氧取代基的烷基部分选自甲基、乙基、正丙基、异丙基、正丁基、异丁基、异戊基和叔丁基，R.sub.4为下式的基团：其中R.sub.5和R.sub.6独立地选自氢、C.sub.1-6烷基和苯基，该苯基可选择地被一个、两个或三个取代基选自氟、氯、溴、C.sub.1-4烷基和C.sub.1-4烷氧的群取代，其中所述C.sub.1-4烷基和C.sub.1-4烷氧取代基的烷基部分选自甲基、乙基、正丙基、异丙基、正丁基、异丁基、异戊基和叔丁基。
• Antiviral phosphonylalkoxy purines
  申请人：Beecham p.l.c.

  公开号：US05166198A1

  公开（公告）日：1992-11-24

  A compound of formula (I), or a pharmaceutically acceptable salt thereof: ##STR1## wherein R.sub.1 is hydroxy or amino; R.sub.2 is hydrogen or amino; R.sub.3 is hydrogen, hydroxymethyl or acyloxymethyl; R.sub.4 is hydrogen or (when R.sub.3 =H and Z is a bond or CH.sub.2) hydroxy, acyloxy, hydroxymethyl or acyloxymethyl; Z is a bond, or a group CHR.sub.8 wherein R.sub.8 is hydrogen, or (when R.sub.3 =R.sub.4 =H), R.sub.8 is hydroxy, acyloxy, hydroxymethyl or acyloxymethyl; R.sub.5 is a group of formula: ##STR2## wherein R.sub.6 and R.sub.7 are independently selected from hydrogen, C.sub.1-6 alkyl and optionally substituted phenyl.

  化合物的化学式（I），或其药学上可接受的盐：其中R₁为羟基或氨基；R₂为氢或氨基；R₃为氢、羟甲基或醋酰氧甲基；R₄为氢或（当R₃=H且Z为键或CH₂时）羟基、醋酰氧基、羟甲基或醋酰氧甲基；Z为键，或基团CHR₈，其中R₈为氢，或（当R₃=R₄=H时），R₈为羟基、醋酰氧基、羟甲基或醋酰氧甲基；R₅为下列基团：其中R₆和R₇分别选自氢、C₁-₆烷基和可选择取代的苯基。
• Process for preparing purines
  申请人：Beecham Group p.l.c.

  公开号：US04910307A1

  公开（公告）日：1990-03-20

  A process for the preparation of compounds of formula (I), and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is hydrogen or CH.sub.2 OH; R.sub.2 is hydrogen or, (when R.sub.1 is hydrogen), hydroxy or CH.sub.2 OH; R.sub.3 is CH.sub.2 OH or, (when R.sub.1 and R.sub.2 are both hydrogen), CH(OH)CH.sub.2 OH; R.sub.4 is hydrogen, hydroxy, amino or OR.sub.5 wherein R.sub.5 is C.sub.1-6 alkyl, phenyl or phenyl C.sub.1-2 alkyl either of which phenyl moieties may be substituted by one or two halo, C.sub.1-4 alkyl or C.sub.1-4 alkoxy groups; and in which any OH groups in R.sub.1, R.sub.2 and/or R.sub.3 may be in the form of O-acyl, phosphate, cyclic acetal or cyclic carbonate derivatives thereof; which process comprises the reaction of a compound of formula (II): ##STR2## wherein R.sub.4 ' is R.sub.4 or a group or atom convertible thereto and R.sub.x is amino or protected amino; with a compound of formula (III): R.sub.3 'CHR.sub.2 'CHR.sub.1 'Q (III) wherein Q is a leaving group and R.sub.1 ', R.sub.2 ' and R.sub.3 ' are R.sub.1, R.sub.2 and R.sub.3 respectively or R.sub.1, R.sub.2 and/or R.sub.3 wherein the OH group(s) is/are in protected form; and thereafter converting R.sub.4 ' when other than R.sub.4, to an R.sub.4 moiety or converting R.sub.4 ' when R.sub.4 to other R.sub.4 ; if necessary converting R.sub.1 ', R.sub.2 ' or R.sub.3 ' to R.sub.1, R.sub.1 and R.sub.3 respectively and optionally forming a pharmaceutically acceptable salt, O-acyl, phosphate, cyclic acetal or cyclic carbonate derivative thereof.

  一种制备化合物（I）及其药用可接受盐的方法：其中R.sub.1为氢或CH.sub.2 OH；R.sub.2为氢或（当R.sub.1为氢时）羟基或CH.sub.2 OH；R.sub.3为CH.sub.2 OH或（当R.sub.1和R.sub.2都为氢时）CH(OH)CH.sub.2 OH；R.sub.4为氢、羟基、氨基或OR.sub.5，其中R.sub.5为C.sub.1-6烷基、苯基或苯基C.sub.1-2烷基，其中任一苯基团可能被一个或两个卤素、C.sub.1-4烷基或C.sub.1-4烷氧基取代；在其中R.sub.1、R.sub.2和/或R.sub.3中的任何羟基可以是其O-酰基、磷酸酯、环缩醛或环碳酸酯衍生物形式；该方法包括化合物（II）与化合物（III）的反应：其中R.sub.4'为R.sub.4或可转化为的基团或原子，R.sub.x为氨基或保护氨基；化合物（III）中的R.sub.3'CHR.sub.2'CHR.sub.1'Q（III），其中Q为脱离基团，R.sub.1'、R.sub.2'和R.sub.3'分别为R.sub.1、R.sub.2和R.sub.3或R.sub.1、R.sub.2和/或R.sub.3，其中羟基以保护形式存在；然后将R.sub.4'转化为非R.sub.4时的R.sub.4基团或将R.sub.4'转化为R.sub.4时的其他R.sub.4；如有必要，将R.sub.1'、R.sub.2'或R.sub.3'转化为R.sub.1、R.sub.1和R.sub.3，然后可选择形成药用可接受盐、O-酰基、磷酸酯、环缩醛或环碳酸酯衍生物。