Bicyclo[2.2.1]heptanes as novel triple re-uptake inhibitors for the treatment of depression

Lorraine Axford; John R Boot; Terrence M Hotten; Martine Keenan; Fionna M Martin; Sandra Milutinovic; Nick A Moore; Michael F O'Neill; Ian A Pullar; David E Tupper; Kristel R Van Belle; Vincent Vivien

doi:10.1016/s0960-894x(03)00660-7

Bicyclo[2.2.1]heptanes as novel triple re-uptake inhibitors for the treatment of depression

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3277-80. doi: 10.1016/s0960-894x(03)00660-7.

Authors

Lorraine Axford¹, John R Boot, Terrence M Hotten, Martine Keenan, Fionna M Martin, Sandra Milutinovic, Nick A Moore, Michael F O'Neill, Ian A Pullar, David E Tupper, Kristel R Van Belle, Vincent Vivien

Affiliation

¹ Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK.

PMID: 12951108
DOI: 10.1016/s0960-894x(03)00660-7

Abstract

A series of substituted naphthyl containing chiral [2.2.1] bicycloheptanes were prepared utilizing asymmetric Diels-Alder chemistry. This paper describes structure-activity relationships in this series. The N-methyl 2-naphthyl analogue (16d) and its des-methyl analogue (17d) are active triple re-uptake inhibitors both in vivo and in vitro.

MeSH terms

Animals
Antidepressive Agents / chemistry*
Antidepressive Agents / metabolism
Antidepressive Agents / therapeutic use
Binding Sites / drug effects
Binding Sites / physiology
Bridged Bicyclo Compounds / chemistry*
Bridged Bicyclo Compounds / metabolism
Bridged Bicyclo Compounds / therapeutic use
Depression / drug therapy*
Depression / metabolism
Mice
Neurotransmitter Uptake Inhibitors / chemistry*
Neurotransmitter Uptake Inhibitors / metabolism
Neurotransmitter Uptake Inhibitors / therapeutic use
Synaptosomes / drug effects
Synaptosomes / metabolism

Substances

Antidepressive Agents
Bridged Bicyclo Compounds
Neurotransmitter Uptake Inhibitors
bicyclo(2.2.1)heptene