N¹-cyclohexylmethylthymine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N¹-cyclohexylmethylthymine
• 英文别名: 1-(Cyclohexylmethyl)-5-methylpyrimidine-2,4-dione
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: BAARUIIACXPYNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  胸腺嘧啶 、 溴甲基环己烷 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 以47%的产率得到N¹-cyclohexylmethylthymine
  参考文献：
  名称：

  Hydrogen bonding between adenine and 2,4-difluorotoluene is definitely not present, as shown by concentration-dependent NMR studies

  摘要：

  合氯仿可溶核苷碱基衍生物N9-环己基甲基腺嘌呤（A）和N1-环己基甲基胸苷（T）已被合成，旨在研究A与胸苷模仿物2,4-二氟甲苯（F）在CDCl3高浓度下的氢键相互作用。浓度依赖性的1H NMR实验表明，在F存在的情况下，A发生自聚集，而不是与F配对。这些结果强有力地支持了Kool关于腺嘌呤与2,4-二氟甲苯之间缺乏氢键相互作用的假设。

  DOI：

  10.1039/a910295g

文献信息

• Pyrimidinedione, pyrimidinetrione, triazinedione, tetrahydroquinazolinedione derivatives as alpha-1-adrenergic receptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0748800A2

  公开（公告）日：1996-12-18

  The present invention relates to novel α1-adrenoceptor antagonists of the formula I in which: R1 is acetylamino, amino, cyano, trifluoroacetylamino, halo, hydro, hydroxy, nitro, methylsulfonylamino, 2-propynyloxy, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl, (C1-6)alkyloxy, (C3-6)cycloalkyloxy, (C3-6)cycloalkyl(C1-4)alkyloxy and (C1-4)alkylthio (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, aryl(C1-4)alkyl, heteroaryl, heteroaryl(C1-4)alkyl, aryloxy, aryl(C1-4)alkyloxy, heteroaryloxy and heteroaryl(C1-4)alkyloxy (which aryl and heteroaryl are optionally further substituted with one to two radicals independently selected from halo and cyano); R2 is cyano, halo, hydro, hydroxy or a group selected from (C1-6)alkyl and (C1-6)alkyloxy (which group is optionally further substituted with one to three halogen atoms); R3 and R4 are both hydro or methyl or together are ethylene; and R5 is a group selected from Formulae (a), (b), (c) and (d): in which: X is C(O), CH2 or CH(OH); Y is CH2 or CH(OH); Z is N or C(R9), wherein R9 is hydro, (C1-6)alkyl or hydroxy; R6 is hydro, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl); R7 is (C1-6)alkanoyl, carbamoyl, cyano, di(C1-6)alkylamino, halo, hydro, hydroxy, hydroxyiminomethyl, (C1-6)alkylsulfonyl, (C1-6)alkylthio, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C1-6)alkyloxy and (C1-6)alkyloxy(C1-4)alkyl (which group is optionally further substituted with one to three radicals selected from halo, hydroxy or (C1-6)alkyloxy) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl) or R7 and R9 together are tetramethylene; and each R8 is independently hydro, hydroxy, methyl or ethyl; and the pharmaceutically acceptable salts and N-oxides thereof.

  本发明涉及式 I 的新型 α1 肾上腺素受体拮抗剂 其中 R1为乙酰氨基、氨基、氰基、三氟乙酰氨基、卤代、氢、羟基、硝基、甲磺酰氨基、2-丙炔氧基、选自(C1-6)烷基、(C3-6)环烷基、(C3-6)环烷基(C1-4)烷基、(C1-6)烷氧基、(C3-6)环烷氧基的基团、(C1-6)烷氧基、(C3-6)环烷氧基、(C3-6)环烷基(C1-4)烷氧基和(C1-4)烷硫基（该基团可选择进一步被一至三个卤原子取代）或选自芳基的基团、芳基、芳基（C1-4）烷基、杂芳基、杂芳基（C1-4）烷基、芳氧基、芳基（C1-4）烷氧基、杂芳氧基和杂芳基（C1-4）烷氧基（其中芳基和杂芳基可任选地被一至两个独立选自卤原子和氰基的基团进一步取代）； R2 是氰基、卤代、氢基、羟基或选自 (C1-6) 烷基和 (C1-6) 烷氧基的基团（该基团可任选进一步被一至三个卤素原子取代）； R3 和 R4 都是羟基或甲基，或一起是乙烯；以及 R5 是选自式(a)、(b)、(c)和(d)的基团： 其中 X 是 C(O)、CH2 或 CH(OH)； Y 是 CH2 或 CH(OH)； Z 是 N 或 C(R9)，其中 R9 是氢、(C1-6)烷基或羟基； R6 是氢、选自(C1-6)烷基、(C3-6)环烷基、(C3-6)环烷基(C1-4)烷基（该基团可任选进一步被一至三个卤原子取代）或选自芳基、杂芳基、芳基(C1-4)烷基和杂芳基(C1-4)烷基（该芳基和杂芳基可任选进一步被一至三个选自卤素、氰基、(C1-6)烷氧基、(C1-6)烷基和芳基的基团取代）的基团； R7 是(C1-6)烷酰基、氨基甲酰基、氰基、二(C1-6)烷基氨基、卤素、氢、羟基、羟基亚氨基甲基、(C1-6)烷基磺酰基、(C1-6)烷硫基、选自(C1-6)烷基、(C3-6)环烷基、(C1-6)烷氧基和(C1-6)烷氧基(C1-4)烷基的基团（该基团可选择进一步被选自卤素、羟基或(C1-6)烷氧基的一至三个基团取代）、羟基或(C1-6)烷氧基)或选自芳基、杂芳基、芳基(C1-4)烷基和杂芳基(C1-4)烷基的基团(其中芳基和杂芳基可选择进一步被一至三个选自卤代、氰基、(C1-6)烷氧基、(C1-6)烷基和芳基的基团取代)或 R7 和 R9 一起为四亚甲基；每个 R8 独立地是氢、羟基、甲基或乙基；以及它们的药学上可接受的盐和 N-氧化物。
• Pyrimidinedione, pyrimidinetrione, triazinedione derivatives as alpha-1-adrenergic receptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0748800B1

  公开（公告）日：2001-05-09
• US5859014A
  申请人：——

  公开号：US5859014A

  公开（公告）日：1999-01-12
• Hydrogen bonding between adenine and 2,4-difluorotoluene is definitely not present, as shown by concentration-dependent NMR studies
  作者：Kathrin S. Schmidt、Roland K. O. Sigel、Dmitri V. Filippov、Gijs A. van der Marel、Bernhard Lippert、Jan Reedijk

  DOI：10.1039/a910295g

  日期：——

  The chloroform-soluble nucleobase derivatives N9-cyclohexylmethyladenine (A) and N1-cyclohexylmethylthymine (T) have been synthesized in order to study hydrogen-bonding interactions between A and the thymidine mimic 2,4-difluorotoluene (F) in CDCl3 at high concentrations. Concentration-dependent 1H NMR experiments show that in the presence of F, A undergoes self-association rather than pairing with F. These results strongly support the assumptions made by Kool with regard to the lack of hydrogen bonding between adenine and 2,4-difluorotoluene.

  合氯仿可溶核苷碱基衍生物N9-环己基甲基腺嘌呤（A）和N1-环己基甲基胸苷（T）已被合成，旨在研究A与胸苷模仿物2,4-二氟甲苯（F）在CDCl3高浓度下的氢键相互作用。浓度依赖性的1H NMR实验表明，在F存在的情况下，A发生自聚集，而不是与F配对。这些结果强有力地支持了Kool关于腺嘌呤与2,4-二氟甲苯之间缺乏氢键相互作用的假设。