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.

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Middleton DS, Andrews M, Glossop P, Gymer G, Jessiman A, Johnson PS, Mackenny M, Pitcher MJ, Rooker T, Stobie A, Tang K, Morgan P

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.

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1434-9. Epub 2005 Nov 28.

PubMed ID

16314097 [ View in PubMed

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Abstract

A series of sertraline analogues 4-39 which possess polar groups on the fused tetrahydronaphthalene ring, targeting reduced V(d) as a strategy to reduce T(max) 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 V(d) leading to significantly shorter T(max), in rat pharmacokinetic studies.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Sertraline	Sodium-dependent dopamine transporter	IC 50 (nM)	310	N/A	N/A	Details
Sertraline	Sodium-dependent serotonin transporter	IC 50 (nM)	3	N/A	N/A	Details