Design, synthesis, and bioavailability evaluation of coumarin-based prodrug of meptazinol.
Based on the known coumarin-based prodrug system, a new meptazinol (Z)-3-[2-(propionyloxy) phenyl]-2-propenoic ester (3) was designed and synthesized as prodrug to minimize the first-pass effect of meptazinol (1) and improve the oral bioavailability. The prodrug (3) showed a 4-fold increase in oral bioavailability over the parent drug meptazinol in rats.
Xie
Qiong
Q
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
Wang
Xiaolin
X
Wang
Xinghai
X
Jiang
Zhiqiang
Z
Qiu
Zhuibai
Z
D000818:Animals; D001682:Biological Availability; D003374:Coumarins / Q000737:chemistry*; D015195:Drug Design; D008621:Meptazinol / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats
D003374:Coumarins; D011355:Prodrugs; D008621:Meptazinol; C030123:coumarin