5-propynyl-3',5'-di-O-p-toluyl-2'-deoxyuridine | 84558-92-9

• 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: 5-propynyl-3',5'-di-O-p-toluyl-2'-deoxyuridine
• 英文别名: 2'-Deoxy-3',5'-di-O-p-Toluoyl-5propynyluridine；[(2R,3S,5R)-5-(2,4-dioxo-5-prop-1-ynylpyrimidin-1-yl)-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
• CAS: 84558-92-9
• 化学式: C₂₈H₂₆N₂O₇
• 分子量: 502.524
• InChiKey: YMFWSWGLBYJBHR-RBZQAINGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-propynyl-3',5'-di-O-p-toluyl-2'-deoxyuridine 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以94%的产率得到5-丙炔-2-脱氧尿苷
  参考文献：
  名称：

  核酸相关化合物。40. 5-炔基尿嘧啶核苷的合成和生物学活性。

  摘要：

  末端炔与5-碘-1-（2,3,5-三-Op-甲苯基-β-D-阿拉伯呋喃糖基）尿嘧啶和5-碘-3'，5'-二-Op-甲苯基-2'的偶联-脱氧尿苷在三乙胺中易于催化量的双（三苯基膦）-钯（II）氯化物和碘化铜（I）进行。使所得产物脱保护，得到5-炔基-1-β-D-阿拉伯呋喃糖基尿嘧啶和5-炔基-2'-脱氧尿苷核苷。5-乙炔基，其次是5-丙炔基，产品具有最高的抗病毒效力，其中2'-脱氧衍生物比阿拉伯糖基化合物更有效。活性在己炔基处弱，而在庚炔基处消失。包含ω-羟基功能减弱了抗病毒作用。测试的5-炔基尿嘧啶核苷均没有足够的选择性足以胜任候选抗病毒药。

  DOI：

  10.1021/jm00359a008
• 作为产物：
  描述：

  5-iodo-3',5'-di-O-p-toluyl-2'-deoxyuridine 、 丙炔 在 copper(l) iodide 、 四(三苯基膦)钯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-propynyl-3',5'-di-O-p-toluyl-2'-deoxyuridine
  参考文献：
  名称：

  Design and Studies of Novel 5-Substituted Alkynylpyrimidine Nucleosides as Potent Inhibitors of Mycobacteria

  摘要：

  We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitro. 5-Decynyl, 5-dodecynyl, and 5-tetradecynyl derivatives showed the highest antimycobacterial potency against M. bovis and M. avium, with the 2'-deoxyribose derivatives being more effective than the ribose analogues. Nucleosides bearing short alkynyl side chains 5-ethynyl, 5-propynyl, 5-pentynyl, and 5-heptynyl were mostly not inhibitory. Incorporation of a phenylethynyl function at the 5-position diminished the antimicrobial effect. Furthermore, related bicyclic analogues (20-24) were devoid of antimycobacterial activity, indicating that an acyclic side chain at the C-5 position of the pyrimidine ring is essential for potent activity. Compounds 1-17 were synthesized by the Pd-catalyzed coupling reactions of respective alkynes with 5-iodo derivatives of 2'-deoxyuridine, 2'-deoxycytidine, and uridine. Intramolecular cyclization of 1 and 3-6 in the presence of Cu afforded the corresponding bicyclic compounds 20-24. The investigated nucleosides are recognized here for the first time to be potent inhibitors of mycobacteria. This class of compounds could be of interest for lead optimization as antimycobacterial agents.

  DOI：

  10.1021/jm058167w

文献信息

• Antiviral compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0417560A1

  公开（公告）日：1991-03-20

  The present invention relates to certain 5-substituted pyrimidine nucleosides of formula (I) and pharmaceutically acceptable derivatives thereof and their use in the treatment of varicella zoster virus, cytomegalovirus and Epstein Barr virus infections. Also provided are pharmaceutical formulations and processes for the preparation of the compounds according to the invention. wherein X represents an ethynylene group; R¹ represents an oxo or imino group; R² represents hydrogen, or a C₁₋₂ alkyl or a C₃₋₄ branched or cycloalkyl group; R³ represents a hydrogen atom or an acyl group optionally substituted by one or more halogen, alkyl, hydroxy or alkoxy substituents; and R⁴ represents a hydrogen atom or a hydroxy group; providing that (a) when R¹ is imino, R³ is hydrogen and R⁴ is hydrogen or hydroxy, R² does not represent a hydrogen atom, and (b) when R¹ is oxo; R³ is hydrogen and R⁴ is hydrogen or hydroxy, R² does not represent hydrogen, methyl, ethyl or isopropyl; or a pharmaceutically acceptable derivative thereof.

  本发明涉及某些式（I）的 5-取代嘧啶核苷及其药学上可接受的衍生物，以及它们在治疗水痘带状疱疹病毒、巨细胞病毒和 Epstein Barr 病毒感染中的用途。此外，还提供了根据本发明制备化合物的药物制剂和工艺。 其中 X 代表乙炔基；R¹ 代表氧代或亚氨基；R² 代表氢，或 C₁₋₂烷基或 C₃₋₄ 支链或环烷基；R³ 代表氢原子或任选被一个或多个卤素、烷基、羟基或烷氧基取代基取代的酰基；R⁴ 代表氢原子或羟基；条件是：(a) 当 R¹ 为亚氨基，R³ 为氢，R⁴ 为氢或羟基时，R² 不代表氢原子；(b) 当 R¹ 为氧代，R³ 为氢，R⁴ 为氢或羟基时，R² 不代表氢、甲基、乙基或异丙基；或其药学上可接受的衍生物。
• 1-( -D-Arabinofuranosyl)-5-propynyluracil as a VZV-antiviral compound
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0486477A2

  公开（公告）日：1992-05-20

  The present invention relates to certain 5-substituted pyrimidine nucleosides and pharmaceutically acceptable derivatives thereof and their use in the treatment and prophylaxis of varicella zoster virus, cytomegalovirus and Epstein Barr virus infections. Also provided are pharmaceutical formulations and processes for the preparation of the compounds according to the invention.

  本发明涉及某些 5-取代嘧啶核苷及其药学上可接受的衍生物，以及它们在治疗和预防水痘带状疱疹病毒、巨细胞病毒和爱泼斯坦巴氏病毒感染中的用途。此外，还提供了根据本发明制备化合物的药物制剂和工艺。
• US5028596A
  申请人：——

  公开号：US5028596A

  公开（公告）日：1991-07-02
• Design and Studies of Novel 5-Substituted Alkynylpyrimidine Nucleosides as Potent Inhibitors of Mycobacteria
  作者：Dinesh Rai、Monika Johar、Tracey Manning、B. Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm058167w

  日期：2005.11.1

  We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitro. 5-Decynyl, 5-dodecynyl, and 5-tetradecynyl derivatives showed the highest antimycobacterial potency against M. bovis and M. avium, with the 2'-deoxyribose derivatives being more effective than the ribose analogues. Nucleosides bearing short alkynyl side chains 5-ethynyl, 5-propynyl, 5-pentynyl, and 5-heptynyl were mostly not inhibitory. Incorporation of a phenylethynyl function at the 5-position diminished the antimicrobial effect. Furthermore, related bicyclic analogues (20-24) were devoid of antimycobacterial activity, indicating that an acyclic side chain at the C-5 position of the pyrimidine ring is essential for potent activity. Compounds 1-17 were synthesized by the Pd-catalyzed coupling reactions of respective alkynes with 5-iodo derivatives of 2'-deoxyuridine, 2'-deoxycytidine, and uridine. Intramolecular cyclization of 1 and 3-6 in the presence of Cu afforded the corresponding bicyclic compounds 20-24. The investigated nucleosides are recognized here for the first time to be potent inhibitors of mycobacteria. This class of compounds could be of interest for lead optimization as antimycobacterial agents.
• Nucleic acid related compounds. 40. Synthesis and biological activities of 5-alkynyluracil nucleosides
  作者：Erik De Clercq、Johan Descamps、Jan Balzarini、Jerzy Giziewicz、Philip J. Barr、Morris J. Robins

  DOI：10.1021/jm00359a008

  日期：1983.5

  5-alkynyl-2'-deoxyuridine nucleosides. The 5-ethynyl, followed by 5-propynyl, products had the highest antiviral potency, with the 2'-deoxy derivatives being more effective than the arabinosyl compounds. Activity was weak at hexynyl and disappeared at heptynyl. Inclusion of an omega-hydroxy function diminished the antiviral effect. None of the 5-alkynyluracil nucleosides tested had sufficient selectivity

  末端炔与5-碘-1-（2,3,5-三-Op-甲苯基-β-D-阿拉伯呋喃糖基）尿嘧啶和5-碘-3'，5'-二-Op-甲苯基-2'的偶联-脱氧尿苷在三乙胺中易于催化量的双（三苯基膦）-钯（II）氯化物和碘化铜（I）进行。使所得产物脱保护，得到5-炔基-1-β-D-阿拉伯呋喃糖基尿嘧啶和5-炔基-2'-脱氧尿苷核苷。5-乙炔基，其次是5-丙炔基，产品具有最高的抗病毒效力，其中2'-脱氧衍生物比阿拉伯糖基化合物更有效。活性在己炔基处弱，而在庚炔基处消失。包含ω-羟基功能减弱了抗病毒作用。测试的5-炔基尿嘧啶核苷均没有足够的选择性足以胜任候选抗病毒药。