Oral Delivery of Propofol with Methoxymethylphosphonic Acid as the Delivery Vehicle

被引：65

作者：

Wei, Yonggang ^{[1
]}

Qiu, Guanpeng ^{[1
]}

Lei, Bailin ^{[1
]}

Qin, Linlin ^{[1
]}

Chu, Hongzhu ^{[1
]}

Lu, Yonghua ^{[1
]}

Zhu, Guozhi ^{[1
]}

Gao, Qiu ^{[1
]}

Huang, Qingping ^{[1
]}

Qian, Guofei ^{[1
]}

Liao, Pengfei ^{[1
]}

Luo, Xinfeng ^{[1
]}

Zhang, Xiaowei ^{[1
]}

Zhang, Chen ^{[1
]}

Li, Yao ^{[1
]}

Zheng, Suxin ^{[1
]}

Yu, Yan ^{[1
]}

Tang, Pingming ^{[1
]}

Ni, Jia ^{[1
]}

Yan, Pangke ^{[1
]}

Zhou, Yi ^{[1
]}

Li, Pan ^{[1
]}

Huang, Xia ^{[1
]}

Gong, Aisheng ^{[1
]}

Liu, Jianyu ^{[1
]}

机构：

[1] Haisco Pharmaceut Grp Co Ltd, 136 Baili Rd, Chengdu 611130, Sichuan, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 60卷 / 20期

关键词：

ARYLOXY PHOSPHORAMIDATE TRIESTERS; PHOSPHATE DERIVATIVES; RATS; AZT; BIOAVAILABILITY; INHIBITORS; MIGRAINE; PRODRUGS; CELLS; HIV;

D O I：

10.1021/acs.jmedchem.7b01133

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Phosphonamidate 3a of methoxymethylphosphonic acid (MMPA) with propofol (l) and L-alanine ethyl ester was found to be an efficient scaffold for the oral delivery of compound 1. The synthesis and evaluation of MMPA based phosphonamidates of compound 1, HSK3486 (2), and other phenolic drugs revealed the general application of MMPA as the effective delivery vehicle for phenolic drugs. On the basis of plasma concentrations of compound 1 and SN38 (14), the oral bioavailability of compound 3a and 15 in beagle dogs was found to be 97.6% and 34.1%, respectively.

引用

页码：8580 / 8590

页数：11

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