N-tert-butyloxycarbonyl-2,4-dichloropyrrolo[3,2-d]pyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: N-tert-butyloxycarbonyl-2,4-dichloropyrrolo[3,2-d]pyrimidine
• 英文别名: tert-butyl 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine-5-carboxylate；tert-butyl 2,4-dichloropyrrolo[3,2-d]pyrimidine-5-carboxylate
• 化学式: C₁₁H₁₁Cl₂N₃O₂
• 分子量: 288.133
• InChiKey: KQVURGSYPAAJEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-tert-butyloxycarbonyl-2,4-dichloropyrrolo[3,2-d]pyrimidine 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.25h， 生成 C₂₂H₂₁ClN₄O₃
  参考文献：
  名称：

  Lead Optimization and Avoidance of Metabolic-perturbing Motif Developing Novel Diarylpyrimidines as Potent HIV-1 NNRTIs

  摘要：

  DOI：

  10.1021/acs.jmedchem.2c00576
• 作为产物：
  描述：

  (E)-6-(2-(dimethylamino)vinyl)-5-nitropyrimidin-2,4-dione 在 苯膦酰二氯 、 4-二甲氨基吡啶 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 N-tert-butyloxycarbonyl-2,4-dichloropyrrolo[3,2-d]pyrimidine
  参考文献：
  名称：

  Antiproliferative activities of halogenated pyrrolo[3,2-d]pyrimidines

  摘要：

  In vitro evaluation of the halogenated pyrrolo[3,2-d]pyrimidines identified antiproliferative activities in compounds 1 and 2 against four different cancer cell lines. Upon screening of a series of pyrrolo[3, 2-d] pyrimidines, the 2,4-Cl compound 1 was found to exhibit antiproliferative activity at low micromolar concentrations. Introduction of iodine at C7 resulted in significant enhancement of potency by reducing the IC50 into sub-micromolar levels, thereby suggesting the importance of a halogen at C7. This finding was further supported by an increased antiproliferative effect for 4 as compared to 3. Cell-cycle and apoptosis studies conducted on the two potent compounds 1 and 2 showed differences in their cytotoxic mechanisms in triple negative breast cancer MDA-MB-231 cells, wherein compound 1 induced cells to accumulate at the G2/M stage with little evidence of apoptotic death. In contrast, compound 2 robustly induced apoptosis with concomitant G2/M cell cycle arrest in this cell model. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.025

文献信息

• [EN] HIGH-ACTIVITY WNT PATHWAY INHIBITOR COMPOUND<br/>[FR] COMPOSÉ INHIBITEUR DE LA VOIE WNT À HAUTE ACTIVITÉ<br/>[ZH] 一种高活性Wnt通路抑制剂化合物
  申请人：ADLAI NORTYE BIOPHARMA CO LTD

  公开号：WO2022089454A1

  公开（公告）日：2022-05-05

  提供了一种具有式(I)结构的抑制Wnt通路活性的化合物、包含所述化合物的药物组合物以及所述化合物在预防和/或治疗癌症、肿瘤、炎症性疾病、自身免疫性疾病或免疫介导性疾病中的用途。
• 10.1016/j.ejmech.2024.116649
  作者：Wu, Chengyong、Zhang, Lele、Zhou, Zhilan、Tan, Lun、Wang, Zhijia、Guo, Cuiyu、Wang, Yuxi

  DOI：10.1016/j.ejmech.2024.116649

  日期：——

  Guided by the X-ray cocrystal structure of the lead compound 4a, we developed a series of thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines demonstrating potent antiproliferative activity against four tumor cell lines. Two analogs, 13 and 25d, exhibited IC50 values around 1 nM and overcame P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). At low concentrations, 13 and 25d inhibited

  在先导化合物 4a 的 X 射线共晶结构的引导下，我们开发了一系列噻吩并[3,2-d] 嘧啶和杂环熔融嘧啶，显示出对四种肿瘤细胞系的强效抗增殖活性。两个类似物 13 和 25d 的 IC50 值约为 1 nM，并克服了 P-糖蛋白 （P-gp） 介导的多药耐药性 （MDR）。在低浓度下，13 和 25d 抑制 SKOV3 细胞在体外的集落形成和微管蛋白聚合。此外，机制研究表明，13 和 25d 诱导 SKOV3 细胞 G2/M 期阻滞和凋亡，以及在低浓度下对肿瘤细胞迁移和侵袭的剂量依赖性抑制。最值得注意的是，阐明了化合物 4a 、 25a 和与微管蛋白复合物中最佳分子 13 的 X 射线共晶结构。本研究确定噻吩并[3,2-d]嘧啶和杂环稠合嘧啶是具有强大抗增殖活性的秋水仙碱结合位点抑制剂 （CBSI） 的代表。
• PYRIMIDINE PYRROLE COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION, AND USES THEREOF
  申请人：Xiamen University

  公开号：EP3290420B1

  公开（公告）日：2020-12-09
• Antiproliferative activities of halogenated pyrrolo[3,2-d]pyrimidines
  作者：Kartik W. Temburnikar、Christina R. Ross、Gerald M. Wilson、Jan Balzarini、Brian M. Cawrse、Katherine L. Seley-Radtke

  DOI：10.1016/j.bmc.2015.06.025

  日期：2015.8

  In vitro evaluation of the halogenated pyrrolo[3,2-d]pyrimidines identified antiproliferative activities in compounds 1 and 2 against four different cancer cell lines. Upon screening of a series of pyrrolo[3, 2-d] pyrimidines, the 2,4-Cl compound 1 was found to exhibit antiproliferative activity at low micromolar concentrations. Introduction of iodine at C7 resulted in significant enhancement of potency by reducing the IC50 into sub-micromolar levels, thereby suggesting the importance of a halogen at C7. This finding was further supported by an increased antiproliferative effect for 4 as compared to 3. Cell-cycle and apoptosis studies conducted on the two potent compounds 1 and 2 showed differences in their cytotoxic mechanisms in triple negative breast cancer MDA-MB-231 cells, wherein compound 1 induced cells to accumulate at the G2/M stage with little evidence of apoptotic death. In contrast, compound 2 robustly induced apoptosis with concomitant G2/M cell cycle arrest in this cell model. (C) 2015 Elsevier Ltd. All rights reserved.
• Lead Optimization and Avoidance of Metabolic-perturbing Motif Developing Novel Diarylpyrimidines as Potent HIV-1 NNRTIs
  作者：Yanying Sun、Zhenzhen Zhou、Da Feng、Lanlan Jing、Fabao Zhao、Zhao Wang、Tao Zhang、Hao Lin、Hao Song、Erik De Clercq、Christophe Pannecouque、Peng Zhan、Xinyong Liu、Dongwei Kang

  DOI：10.1021/acs.jmedchem.2c00576

  日期：2022.12.8