2',3'-didehydro-2',3'-dideoxy-5-chlorouridine | 120815-05-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 2',3'-didehydro-2',3'-dideoxy-5-chlorouridine
• 英文别名: 5-Chloro-2',3'-didehydro-2',3'-dideoxyuridine；5-chloro-1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione
• CAS: 120815-05-6
• 化学式: C₉H₉ClN₂O₄
• 分子量: 244.634
• InChiKey: JYNQRQBBMYJMLF-CAHLUQPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-丙氨酸甲酯盐酸盐 、 4-溴苯基二氯磷酸酯 、 2',3'-didehydro-2',3'-dideoxy-5-chlorouridine 在 TEA 作用下， 以 二氯甲烷 为溶剂， 以1.44 %的产率得到methyl ((4-bromophenoxy)(((2S,5R)-5-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methoxy)phosphoryl)-L-alaninate
  参考文献：
  名称：

  HALO-DEHYDRO-3'-DEOXYURACIL PHOSPHORAMIDATES AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS

  摘要：

  Substituted halo-dehydro-3'-deoxyuracil phosphoramidates and related compounds, pharmaceutical compositions, their use for inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase activity, and their use in the treatment of medical disorders, such as cancer, are disclosed herein.

  公开号：

  WO2024107850A1
• 作为产物：
  描述：

  1-[(2R,5S)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,5-dihydrofuran-2-yl]-5-chloropyrimidine-2,4-dione 以16%的产率得到
  参考文献：
  名称：

  ROSOWSKY, ANDRE;PAI, NIRANJAN N., NUCLEOSIDES AND NUCLEOTIDES, 10,(1991) N, C. 837-851

  摘要：

  DOI：

文献信息

• Synthesis and anti-HIV evaluation of 2',3'-dideoxyribo-5-chloropyrimidine analogs: reduced toxicity of 5-chlorinated 2',3'-dideoxynucleosides
  作者：Arthur Van Aerschot、Dirk Everaert、Jan Balzarini、Koen Augustyns、Liu Jie、Gerard Janssen、Oswald Peeters、Norbert Blaton、Camiel De Ranter

  DOI：10.1021/jm00168a046

  日期：1990.6

  While chlorination of 2',3'-dideoxycytidine removed the anti-HIV activity, introduction of a chlorine at the C-5 position of 3'-fluoro-, 3'-azido- or 2',3'-didehydro-2',3'-dideoxycytidine led to reduced cytotoxicity with only slightly reduced anti-HIV activity. X-ray analysis showed compound 11 to have two molecules in the asymmetric unit with chi = -168.8 (3) degrees and -131.3 (3) degrees and P = 179

  鉴于2'，3'-dideoxy-3'-fluoro-5-chlorouridine（11）的选择性抗HIV活性，合成了8个2'，3'-dideoxy-5-chloropyrimidines并评估了它们对MT-4细胞中1型人类免疫缺陷病毒（HIV-1）复制的抑制活性。注意到2，3-二脱氧核糖呋喃糖，3-叠氮基-2，3-二脱氧核糖呋喃糖和3-氟-2，3-二脱氧核糖呋喃糖的5-氯尿嘧啶衍生物的选择性显着改善，这主要是由于该化合物对宿主细胞。虽然氯化2'，3'-二脱氧胞苷可消除抗HIV活性，但在3'-氟-，3'-叠氮基或2'，3'-二氢-2'的C-5位置引入了氯，3'-二脱氧胞苷导致细胞毒性降低，而抗HIV活性仅略微降低。X射线分析表明化合物11在不对称单元中具有两个分子，分别为chi = -168.8（3）度和-131.3（3）度，P = 179（1）度和163（1）度。因此显示与3'-叠氮基-3'-脱氧胸苷（AZT）没有相似之处。
• AERSCHOT, ARTHUR VAN;EVERAERT, DIRK;BALZARINI, JAN;AUGUSTYNS, KOEN;JIE, L+, J. MED. CHEM., 33,(1990) N, C. 1833-1839
  作者：AERSCHOT, ARTHUR VAN、EVERAERT, DIRK、BALZARINI, JAN、AUGUSTYNS, KOEN、JIE, L+

  DOI：——

  日期：——
• ROSOWSKY, ANDRE;PAI, NIRANJAN N., NUCLEOSIDES AND NUCLEOTIDES, 10,(1991) N, C. 837-851
  作者：ROSOWSKY, ANDRE、PAI, NIRANJAN N.

  DOI：——

  日期：——
• HALO-DEHYDRO-3'-DEOXYURACIL PHOSPHORAMIDATES AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS
  申请人：[en]ROME THERAPEUTICS, INC.

  公开号：WO2024107850A1

  公开（公告）日：2024-05-23

  Substituted halo-dehydro-3'-deoxyuracil phosphoramidates and related compounds, pharmaceutical compositions, their use for inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase activity, and their use in the treatment of medical disorders, such as cancer, are disclosed herein.