2--2.3-dihydro-2-phosphapyrimidin-2-oxid | 97211-96-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2--2.3-dihydro-2-phosphapyrimidin-2-oxid
• 英文别名: bis-(2-chloro-ethyl)-(2-oxo-2,3-dihydro-1H-2λ⁵-naphtho[1,8-de][1,3,2]diazaphosphinin-2-yl)-amine；Phosphoric triamide,N-bis(2-chloroethyl)-N',N''-1,8-naphthylene-；N,N-bis(2-chloroethyl)-3-oxo-2,4-diaza-3λ5-phosphatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaen-3-amine
• CAS: 97211-96-6
• 化学式: C₁₄H₁₆Cl₂N₃OP
• 分子量: 344.18
• InChiKey: MOLJTXDTPDVVAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  双(2-氯乙基)氨基磷酰二氯 、 1,8-二氨基萘 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以56%的产率得到2--2.3-dihydro-2-phosphapyrimidin-2-oxid
  参考文献：
  名称：

  Fluorescent cyclic phosphoramide mustards and their cytotoxicity against cancer and cancer stem cells

  摘要：

  Two fluorescent cyclic phosphoramides, 1,3-dihydronaphtho[1,8-cd][1,2,6]phosphdiazine-2-oxide-(2-bis (2-chloroethyl)amide) (1) and 2,3-dihydro-2-oxo-1H-anthra[1,2-d][1,3,2]diazaphosphole-6,11-dione-2 [N,N-bis(2-chloroethyl)]amide (2) were synthesized and characterized using standard analytical techniques. The single crystal X-ray diffraction studies of 1 showed that it crystallizes in triclinic space group P 1. The comparison of the bond distances and angles data of the single crystal structure of 1 with the theoretical value obtained from DFT calculations show that they are well commensurate with each other. H-1 and P-31 NMR studies reveal that 1 is more stable than 2 towards hydrolysis and formation of the active phosphoramide. 1 showed no dissociation in 48 h but 25% dissociation of 2 was observed using DMSO-phosphate buffer pH 7.4 (8:2 viv). Compound 1 and 2 exhibit blue (lambda(em) = 375 nm) and orange fluorescence (lambda(em) = 585 nm) respectively. However, the ligand of 2 daq exhibits red fluorescence (lambda(em) = 635 nm) in its free form. 1 and 2 showed cytotoxicity to cancer cells (MCF-7, A549, HepG2 and HeLaWF) and the toxicity enhanced in vitro, in presence of the cellular reducing agent ascorbic acid. The fluorescent imaging study of 2 showed that the intact compound enters organelles like mitochondria within 1 h of treatment. The compound localizes in other organelles too and upon 10 h incubation red emissions from endoplasmic reticulum, mitochondria and lysozome suggests that the ligand daq dissociated from 2. Compound 2 depolarises the mitochondria. Both 1 and 2 are efficient in killing the slow growing cancer stem cells (CSCs), known to cause cancer relapse. 1 and 2 also exhibit excellent anti cell migratory activity at IC10 dosage even after 48 h of removal of the compounds and causes cell death by apoptosis. (C) 2019 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2019.05.046

文献信息

• ZIMMER; SILL, Arzneimittel-Forschung/Drug Research, 1964, vol. 14, p. 150 - 151
  作者：ZIMMER、SILL

  DOI：——

  日期：——
• Venugopal; Reddy; Bavaji, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 9, p. 822 - 827
  作者：Venugopal、Reddy、Bavaji

  DOI：——

  日期：——