phenyl methoxyphenylalaninyl phosphorochloridate | 147907-42-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: phenyl methoxyphenylalaninyl phosphorochloridate
• 英文别名: phenyl-(methoxy-L-phenylalaninyl)-phosphorochloridate；methyl (2S)-2-[[chloro(phenoxy)phosphoryl]amino]-3-phenylpropanoate
• CAS: 147907-42-4
• 化学式: C₁₆H₁₇ClNO₄P
• 分子量: 353.742
• InChiKey: HKAUOJUVHWWNSI-NGMICRHFSA-N

物化性质

• 沸点：
  468.5±55.0 °C(Predicted)
• 密度：
  1.301±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  白杨素 、 phenyl methoxyphenylalaninyl phosphorochloridate 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 以51.9%的产率得到N-((phenoxy)((5-hydroxy-2-phenyl-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-phenylalanine methyl ester
  参考文献：
  名称：

  Phosphoramidate protides of five flavones and their antiproliferative activity against HepG2 and L-O2 cell lines

  摘要：

  A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 mu mol/L, 5.5 mu mol/L and 6.6 mu mol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.02.012
• 作为产物：
  描述：

  L-苯丙氨酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 phenyl methoxyphenylalaninyl phosphorochloridate
  参考文献：
  名称：

  氨基磷酸酯ProTide技术的应用显着提高了碳环腺苷衍生物的抗病毒效力。

  摘要：

  我们报告了氨基磷酸酯原核苷酸（ProTide）技术在抗病毒剂碳环L-d4A（L-Cd4A）中的应用。L-Cd4A的苯基甲基丙氨酸基母体ProTide是通过格利雅（Grignard）介导的磷酰氯反应制备的，得到的化合物具有显着改善的抗HIV（2600倍）和HBV活性。我们描述了ProTide的芳基，酯和氨基酸区域的修饰，以及这些变化如何影响抗病毒活性和代谢稳定性。注意到针对HIV和HBV的SAR分别且不同。另外，由D-核苷D-Cd4A和双脱氧类似物L-CddA和D-CddA制备ProTide。与母体药物相比，这些化合物显示出更适度的效能改善。综上所述，当将ProTide方法应用于L-Cd4A时，在体外的效价提高了9000倍，非常成功，抗HIV的能力提高了。为了临床前候选人的选择，我们使用食蟹猴肝脏和肠道S9馏分进行了代谢稳定性研究。

  DOI：

  10.1021/jm060776w

文献信息

• ProTides of BVdU as potential anticancer agents upon efficient intracellular delivery of their activated metabolites
  作者：Sahar Kandil、Jan Balzarini、Stephanie Rat、Andrea Brancale、Andrew D. Westwell、Christopher McGuigan

  DOI：10.1016/j.bmcl.2016.10.077

  日期：2016.12

  cancer, however their limitations in terms of cellular uptake, nucleoside kinase-mediated activation and catabolism are well-documented. The monophosphate pro-nucleotides known as ProTides represents a powerful strategy for bypassing the dependence on active transport and nucleoside kinase-mediated activation. Herein, we report the structural tuning of BVdU ProTides. Forty six phosphoramidates were

  核苷是治疗癌症的主要化疗药物，但其在细胞摄取、核苷激酶介导的激活和分解代谢方面的局限性已有充分记录。被称为 ProTides 的单磷酸前核苷酸代表了一种绕过对主动转运和核苷激酶介导的激活的依赖的强大策略。在此，我们报告了 BVdU ProTides 的结构调整。制备了 46 种氨基磷酸酯，并针对三种不同的癌细胞系进行了生物学评估；鼠白血病 (L1210)、人 CD 4 + T 淋巴细胞 (CEM) 和人宫颈癌 (HeLa)。与 BVdU 相比，针对 L1210 细胞的效力增强了 20 倍。有趣的是，与无活性的母体 BVdU 相比，许多 ProTides 对 CEM 和 HeLa 细胞表现出较低的微摩尔活性。ProTides 对非致瘤性人肺成纤维细胞培养物显示出即使有可测量的毒性，也很差。报道了四对非对映异构体混合物的分离以及它们的光谱特性、生物活性和酶活化率的比较。
• 含硫类化合物、其药物组合物及应用
  申请人：上海日馨医药科技股份有限公司

  公开号：CN117417301A

  公开（公告）日：2024-01-19

  本发明公开了一种含硫类化合物、其药物组合物及应用。本发明提供了一种物质A在制备Aβ40和/或Aβ42蛋白抑制剂或药物中的应用；所述的药物为用于治疗和/或由Aβ40和/或Aβ42蛋白介导的疾病的药物或者用于治疗和/或预防神经退行性疾病或衰老的药物，所述的物质A选自如式A1等所示的化合物或其药学上可接受的盐。本发明的化合物，对Aβ40及Aβ42蛋白具有良好的抑制作用，有望治疗和/或预防神经退行性疾病或衰老药物。#imgabs0#
• Phosphoramidate Protides of Carbocyclic 2′,3′‐Dideoxy‐2′,3′‐Didehydro‐7‐Deazaadenosine with Potent Activity Against HIV and HBV
  作者：Kristjan S. Gudmundsson、Zhicheng Wang、Susan M. Daluge、Lance C. Johnson、Richard Hazen、Lynn D. Condreay、Christopher McGuigan

  DOI：10.1081/ncn-200040678

  日期：2004.1.12

  Synthesis of phosphoramidate protides of carbocyclic D- and L-2',3'-dideoxy-2',3' -didehydro-7-deazaadenosine by treatment of the nucleoside with phosphorochloridates in the presence of pyridine and t-BuMgCl is described. Several of these protides showed significantly improved antiviral potency over the parent nucleosides against both HIV and HBV.
• Phosphoramidate and phosphate prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies
  作者：Yuzeng Liang、Janarthanan Narayanasamy、Raymond F. Schinazi、Chung K. Chu

  DOI：10.1016/j.bmc.2005.11.008

  日期：2006.4

  A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M 184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents
  作者：Qinggang Ji、Zhiqiang Ge、Zhixing Ge、Kaizhi Chen、Hualong Wu、Xiaofei Liu、Yanrong Huang、Lvjiang Yuan、Xiaolan Yang、Fei Liao

  DOI：10.1016/j.ejmech.2015.11.027

  日期：2016.1

  A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the K-m of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-N-acetylglucosamine, and the result of the K-i showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 p,g/mL to 2 mu g/MI while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational. (C) 2015 Elsevier Masson SAS. All rights reserved.