[(2R,3S,5S)-5-(2,4-dioxo-5-thiophen-2-ylpyrimidin-1-yl)-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate | 127235-41-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: [(2R,3S,5S)-5-(2,4-dioxo-5-thiophen-2-ylpyrimidin-1-yl)-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
• CAS: 127235-41-0
• 化学式: C₂₉H₂₆N₂O₇S
• 分子量: 546.601
• InChiKey: XBPKZKJTLSDJHJ-ARNLJNQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  140
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(2R,3S,5S)-5-(2,4-dioxo-5-thiophen-2-ylpyrimidin-1-yl)-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate 在 sodium methylate 作用下， 以70%的产率得到5-thien-2-yl-1-(α-D-2-deoxyribofuranos-1-yl)uracil
  参考文献：
  名称：

  5-(5-Bromothien-2-yl)-2'-deoxyuridine and 5-(5-chlorothien-2-yl)-2'-deoxyuridine are equipotent to (E)-5-(2-bromovinyl)-2'-deoxyuridine in the inhibition of herpes simplex virus type I replication

  摘要：

  2'-Deoxyuridines with a five-membered heterocyclic substituent in the 5-position were synthesized by palladium-catalyzed coupling reactions of 5-iodo-2'-deoxyuridine with the activated heteroaromatics. Further modification of the compound with the 5-thien-2-yl substituent gave 5-(5-bromothien-2-yl)-2'-deoxyuridine and 5-(5-chlorothienyl-2-yl)-2'-deoxyuridine. Both compounds show potent and selective activity against herpes simplex virus type 1 and varicella-zoster virus.

  DOI：

  10.1021/jm00112a011
• 作为产物：
  描述：

  1-Α-氯-3,5-二-O-对甲苯甲酰基-2-脱氧-D-呋喃核糖 在 吡啶 、 四(三苯基膦)钯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 23.0h， 生成 [(2R,3S,5S)-5-(2,4-dioxo-5-thiophen-2-ylpyrimidin-1-yl)-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
  参考文献：
  名称：

  5-(5-Bromothien-2-yl)-2'-deoxyuridine and 5-(5-chlorothien-2-yl)-2'-deoxyuridine are equipotent to (E)-5-(2-bromovinyl)-2'-deoxyuridine in the inhibition of herpes simplex virus type I replication

  摘要：

  2'-Deoxyuridines with a five-membered heterocyclic substituent in the 5-position were synthesized by palladium-catalyzed coupling reactions of 5-iodo-2'-deoxyuridine with the activated heteroaromatics. Further modification of the compound with the 5-thien-2-yl substituent gave 5-(5-bromothien-2-yl)-2'-deoxyuridine and 5-(5-chlorothienyl-2-yl)-2'-deoxyuridine. Both compounds show potent and selective activity against herpes simplex virus type 1 and varicella-zoster virus.

  DOI：

  10.1021/jm00112a011

文献信息

• Pyrimidine nucleosides
  申请人：Medivir Aktiebolag

  公开号：EP0357571A2

  公开（公告）日：1990-03-07

  Compounds of the formula wherein R¹ is OH, NH₂; R² is a heteroaromatic or aromatic substituent as defined in claim 1; R³ is H, OH, F, OCH₃; R⁴ is H, F, OH or an ether or ester residue thereof, OCH₃, CN, C≡CH, N₃; R⁵ is OH or an ether or ester residue thereof including mono-, di- and triphosphate esters; wherein n is O or 1 and M is hydrogen or a pharmaceutically acceptable counterion such as sodium, potassium, ammonium or alkylammonium; and pharmaceutically acceptable salts thereof; and pharmaceutical compositions comprising said compounds can be used for therapeutic and/or prophylactic treatment of virus infections such as AIDS. Compounds of the formula wherein R¹ and R² are as defined above, are new precursor compounds.

  式中的化合物 其中 R¹ 是 OH、NH₂； R² 是如权利要求 1 所定义的杂芳香族或芳香族取代基； R³ 是 H、OH、F、OCH₃；R⁴ 是 H、F、OH 或其醚或酯残基、OCH₃、CN、C≡CH、N₃； R⁵ 是 OH 或其醚或酯残基，包括单、二和三磷酸酯； 其中 n 是 O 或 1，M 是氢或药学上可接受的反离子，如钠、钾、铵或烷基铵；及其药学上可接受的盐；包含所述化合物的药物组合物可用于病毒感染（如艾滋病）的治疗和/或预防性治疗。 式中化合物 其中 R¹ 和 R² 如上定义，是新的前体化合物。
• Pyrimidine derivatives, process for their preparation and their use as precursors
  申请人：Medivir Aktiebolag

  公开号：EP0691333A2

  公开（公告）日：1996-01-10

  1. A compound of the formula wherein the radicals R¹ and R² are defined as follows: R¹: OH, NH₂; R²: wherein X is O, S, N-R⁷, Se; R⁶ is H, straight or branched C₁₋₁₀ alkyl, F, Cl, Br, I, X-R⁷, -CH=CH-R⁷, -C=C-R⁷, CO₂R⁷, CH₂X-R⁷; R⁷ is H, straight or branched C₁₋₅ alkyl, phenyl; with the following provisos: (a) when R¹ is OH, then R² is not: 2-thienyl, 3-thienyl, 2-selenienyl, 3-selenienyl, 2-pyridyl, 3-pyridyl, 2-imidazolyl, 4-imidazolyl, 2-furyl, 2-methyl-3-furyl, 2-amino-4-thiazolyl, with R⁶ being H, alkyl, or alkoxy; (b) when R¹ is NH₂, then R² is not: with R⁶ being H, F, Cl, or alkoxy.

  1.式中化合物 其中自由基 R¹ 和 R² 定义如下： R¹:OH、NH₂； R²: 其中 X 是 O、S、N-R⁷、Se； R⁶ 是 H、直链或支链 C₁₋₁₀烷基、F、Cl、Br、I、 x-r⁷，-ch=ch-r⁷，-c=c-r⁷，co₂r⁷，ch₂x-r⁷； R⁷ 是 H、直链或支链 C₁₋₅烷基、苯基； 但书如下： (a) 当 R¹ 是 OH 时，R² 不是：2-噻吩基、3-噻吩基、2-硒硒基、3-硒硒基、2-吡啶基、3-吡啶基、2-咪唑基、4-咪唑基、2-呋喃基、2-甲基-3-呋喃基、2-氨基-4-噻唑基、 其中 R⁶ 为 H、烷基或烷氧基； (b) 当 R¹ 是 NH₂ 时，R² 不是： R⁶ 为 H、F、Cl 或烷氧基。
• Synthesis of Mimics to Thymidine and 5-(2″-Thienyl)-2′-Deoxyuridine Triphosphates
  作者：Ulf Wellmar、Anna-Britta Hörnfeldt、Salo Gronowitz、Nils Gunnar Johansson

  DOI：10.1080/07328319608002034

  日期：1996.5

  Dicarboxylic acid 5'-monoesters of thymidine and 5-(2-thienyl)-2 ''-deoxyuridine have been synthesised and evaluated as triphosphate mimics. Glutaric (25, 29), adipic (26, 30), pimelic (27, 31) and trans-1,4-cyclohexane dicarboxylic acids (28, 32) were employed to vary the distance between two carboxylate functions and were structurally compared to the triphosphate moiety by molecular modelling. The glutarate and adipate derivatives can assume conformations fitting the triphosphate, and the thienyl compounds 29 and 30 were the ones having overall best inhibitory activities against DNA pol alpha and HIV-1 RT.
• US5440040A
  申请人：——

  公开号：US5440040A

  公开（公告）日：1995-08-08
• US5576429A
  申请人：——

  公开号：US5576429A

  公开（公告）日：1996-11-19