Design, synthesis, and sustained-release property of 1,3-cyclic propanyl phosphate ester of 18β-glycyrrhetinic acid.
A new class of potential prodrugs, 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid, was designed and synthesized through the key reaction of 18β-glycyrrhetic acid with 1,3-cyclic propanyl phosphate ester catalysed by lithium diisopropylamide. The sustained-release properties of 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid in vivo were also investigated. The animal experiments showed that 18β-glycyrrhetic acid was released from 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid at a steady rate in rats and the plasma concentrations of 18β-glycyrrhetic acid were nearly stable. The result indicated that 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid have sustained-release properties to avoid the quick metabolism of 18β-glycyrrhetic acid. These prodrugs are highlighted as a promising new strategy to improve 18β-glycyrrhetic acid metabolism.
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Pharmacy, Ocean University of China, Qingdao 266003, China.
Weizhi
W
Sun
Weibing
W
Peng
Guoqiang
G
Li
Tao
T
Jiang
D000818:Animals; D002384:Catalysis; D015195:Drug Design; D004952:Esters; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011437:Propylamines / Q000737:chemistry; D051381:Rats; D013237:Stereoisomerism
D004952:Esters; D011355:Prodrugs; D011437:Propylamines; C119129:18alpha-glycyrrhetinic acid; C007442:diisopropylamine; D006034:Glycyrrhetinic Acid