916918-81-5Relevant articles and documents
Phenolic esters of O-desmethylvenlafaxine with improved Oral bioavailability and brain uptake
Zhang, Yang,Yang, Yan,Zhao, Sen,Yang, Zhichao,Yang, Hong,Fawcett, J. Paul,Li, Youxin,Gu, Jingkai,Sun, Tiemin
, p. 14920 - 14934 (2014/01/17)
O-Desmethylvenlafaxine (desvenlafaxine, ODV) is a recently approved antidepressant which in some clinical studies failed to meet a satisfactory end-point. The aim of this study was to prepare a series of phenolic esters of ODV and evaluate their potential as ODV prodrugs with improved brain uptake. Fifteen phenolic esters (compounds 1a-o) were synthesized and their pharmacokinetic profiles evaluated in rat. The four compounds producing the highest relative bioavailability of ODV in rat (compounds 1c, 1e, 1n, 1o) were then studied to evaluate their brain uptake. Of these four compounds, compound 1n (the piperonylic acid ester of ODV) demonstrated the highest Cmax of ODV both in the rat hypothalamus and total brain. Finally the pharmacokinetics of 1n were evaluated in beagle dog where the increase in relative bioavailability of ODV was found to be as great as in rat. This high relative bioavailability of ODV coupled with its good brain penetration make 1n the most promising candidate for development as an ODV prodrug.
COMPOUNDS, PREPARATION PROCESS, AND USES THEREOF USED FOR INTERRUPTING REUPTAKE OF 5-HYDROXYTRYPTAMINE AND NOREPINEPHRINE OR TREATING DISEASES SUCH AS DEPRESSION ET AL.
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Page/Page column 7-8, (2008/06/13)
The present invention discloses compounds of formula (I), their optical isomers or pharmaceutically acceptable salts thereof, their preparation and uses thereof, wherein the definitions of R1, R2, R3 and R4 are shown in the description. These compounds ar
