Title of article :
Designing rapid onset selective serotonin re-uptake inhibitors. Part 1: Structure–activity relationships of substituted (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthaleneamine
Author/Authors :
Donald S. Middleton، نويسنده , , Mark Andrews، نويسنده , , Paul Glossop، نويسنده , , Geoffrey Gymer، نويسنده , , Alan Jessiman، نويسنده , , Patrick S. Johnson، نويسنده , , Malcolm MacKenny، نويسنده , , Michael J. Pitcher، نويسنده , , Tony Rooker، نويسنده , , Alan Stobie، نويسنده , , Kim Tang، نويسنده , , B. Paul Morgan، نويسنده ,
Abstract :
A series of sertraline analogues 4–39 which possess polar groups on the fused tetrahydronaphthalene ring, targeting reduced Vd as a strategy to reduce Tmax and increase rate of elevation of central 5-HT levels, were prepared. These studies led to the successful identification of 22a, which demonstrated equivalent pharmacology and metabolic stability to 1, but which possessed greatly reduced Vd leading to significantly shorter Tmax, in rat pharmacokinetic studies.
