Oral Delivery of Propofol with Methoxymethyl­phosphonic Acid as the Delivery Vehicle

Oral Delivery of Propofol with Methoxymethyl­phosphonic Acid as the Delivery Vehicle

Phosphonamidate 3a of methoxymethyl­phosphonic acid (MMPA) with propofol (1) 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...

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Veröffentlicht in:Journal of medicinal chemistry 2017-10, Vol.60 (20), p.8580-8590
Hauptverfasser: Wei, Yonggang, Qiu, Guanpeng, Lei, Bailin, Qin, Linlin, Chu, Hongzhu, Lu, Yonghua, Zhu, Guozhi, Gao, Qiu, Huang, Qingping, Qian, Guofei, Liao, Pengfei, Luo, Xinfeng, Zhang, Xiaowei, Zhang, Chen, Li, Yao, Zheng, Suxin, Yu, Yan, Tang, Pingming, Ni, Jia, Yan, Pangke, Zhou, Yi, Li, Pan, Huang, Xia, Gong, Aisheng, Liu, Jianyu
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Sprache:eng
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Zusammenfassung:Phosphonamidate 3a of methoxymethyl­phosphonic acid (MMPA) with propofol (1) 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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.7b01133