2-anilino-6-chloro-9-(2,3-epoxypropyl)purine | 161363-30-0

• 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-anilino-6-chloro-9-(2,3-epoxypropyl)purine
• 英文别名: 6-chloro-9-(oxiran-2-ylmethyl)-N-phenylpurin-2-amine
• CAS: 161363-30-0
• 化学式: C₁₄H₁₂ClN₅O
• 分子量: 301.735
• InChiKey: PHDIECUOWIBXMI-UHFFFAOYSA-N

物化性质

• 沸点：
  543.8±60.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-anilino-6-chloro-9-(2,3-epoxypropyl)purine 在 sodium hydroxide 作用下， 反应 2.0h， 以61%的产率得到9-(2,3-dihydroxypropyl)-N₂-phenylguanine
  参考文献：
  名称：

  Synthesis, Properties, and Pharmacokinetic Studies of N2-Phenylguanine Derivatives as Inhibitors of Herpes Simplex Virus Thymidine Kinases

  摘要：

  Two series of selective inhibitors of herpes simplex virus types 1 and 2 (HSV1,2) thymidine kinases (TK) have been developed as potential treatment of recurrent virus infections. Among compounds related to the potent base analog N-2-[m-(trifluoromethyl)phenyl]guanine (mCF(3)PG), none was a more potent inhibitor than mCF(3)PG itself. Compounds related to the nucleoside N-2-phenyl-2'-deoxyguanosine (PhdG), but with alkyl, hydroxyalkyl, and related substituents at the 9-position in place of the glycosyl group of PhdG, retained significant but variable inhibitory potencies against the HSV TKs. The most potent inhibitor of HSV1 TK among 9-substituted derivatives, 9-(4-hydroxybutyl)-N-2-phenylguanine (HBPG), was a competitive inhibitor with respect to the substrate thymidine but was not itself a substrate for the enzyme. Water solubilities and 1-octanol:water partition coefficients for the 9-substituted N-2-phenylguanines were linearly but oppositely related to the sum of hydrophobic fragmental constants (Sigma f) of the 9-substituents. Four of the inhibitors were given as solutions to mice by iv and ip routes, and the time course of their plasma concentrations was determined by HPLC analysis of the parent compounds. HBPG was completely absorbed by the ip route, and the plasma concentration could be prolonged by use of suspension formulations. HBPG is a candidate for animal trials of the ability of TK inhibitors to prevent recurrent herpes virus infections.

  DOI：

  10.1021/jm00001a010
• 作为产物：
  描述：

  6-chloro-N-phenyl-9H-purin-2-amine 、 环氧溴丙烷 以 氯仿 、 乙腈 、 mineral oil 为溶剂， 以3.8%的产率得到2-anilino-6-chloro-9-(2,3-epoxypropyl)purine
  参考文献：
  名称：

  Drugs to prevent recurrent herpes virus infections

  摘要：

  揭示了防止复发的单纯疱疹病毒感染的N.sup.2-取代烷基鸟嘌呤和N.sup.2-取代苯基鸟嘌呤化合物。由于它们在体内能够抑制单纯疱疹病毒胸苷激酶，这些化合物将防止、减少或减轻人类复发性HSV感染的频率或严重程度。N.sup.2-烷基鸟嘌呤化合物的结构如下：其中R.sub.1是正常或支链C.sub.n H.sub.2n+1（其中n为1-12）；R.sub.2是H、2-去氧核糖呋喃糖基、（CH.sub.2).sub.n OH（其中n为2-5）、CH.sub.2 CH(OH)CH.sub.2 OH、（CH.sub.2).sub.n --COOH（其中n为1-4）、CH.sub.2 CH(OH)CH.sub.2 --O--COR.sub.4、（CH.sub.2).sub.n --O--COR.sub.4（其中n为2-5）或（CH.sub.2).sub.n CO--OR.sub.4（其中n为1-4）；R.sub.4是CH.sub.3、CH.sub.2 CH.sub.3、CH.sub.2 CH.sub.2 NH.sub.2、CH.sub.2 CH.sub.2 N(C.sub.2 H.sub.5).sub.2或CH.sub.2 CH.sub.2 CO.sub.2 H；R.sub.3是OH、H、Cl或NH.sub.2，或其互变异构体或药学上可接受的盐。N.sup.2-取代苯基鸟嘌呤化合物具有类似结构，其中R.sub.1是苯基或在3和4位置用H、疏水性或电子提取基团或CH.sub.2 CH.sub.3取代的苯基。

  公开号：

  US05646155A1

文献信息

• [EN] FUSED IMIDAZOLE COMPOUNDS<br/>[FR] COMPOSÉS D'IMIDAZOLE CONDENSÉS
  申请人：ONO PHARMACEUTICAL CO

  公开号：WO2015115673A1

  公开（公告）日：2015-08-06

  The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABAA α5) and act as GABAA α5 negative allosteric modulators (GABAA α5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABAA α5 such as Alzheimer's disease.

  本发明提供了由式(I)表示的化合物，其药学上可接受的盐，N-氧化物，溶剂合物或前药（其中字符如描述中所定义）。由式(I)表示的化合物对γ-氨基丁酸A受体亚单位α5（GABAA α5）具有亲和力和选择性，并作为GABAA α5负向变构调节剂（GABAA α5 NAM）发挥作用，因此它们在预防和/或治疗与GABAA α5相关的疾病，如阿尔茨海默病中是有用的。
• Fused imidazole compounds
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US10016439B2

  公开（公告）日：2018-07-10

  The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABAA α5) and act as GABAA α5 negative allosteric modulators (GABAA α5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABAA α5 such as Alzheimer's disease.

  本发明提供了式(I)代表的化合物、其药学上可接受的盐、其N-氧化物、其溶液剂或其原药（其中特征如描述中所定义）。式（I）代表的化合物对γ-氨基丁酸A受体亚基α5（GABAA α5）具有亲和性和选择性，可作为GABAA α5负异位调节剂（GABAA α5 NAM），因此可用于预防和/或治疗与GABAA α5相关的疾病，如阿尔茨海默病。
• DRUGS TO PREVENT RECURRENT HERPES VIRUS INFECTIONS
  申请人：UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER

  公开号：EP0794781A1

  公开（公告）日：1997-09-17
• EP0794781A4
  申请人：——

  公开号：EP0794781A4

  公开（公告）日：1998-04-22
• FUSED IMIDAZOLE COMPOUNDS
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP3099672A1

  公开（公告）日：2016-12-07