Kristin Lynne Meagher

Studies toward the discovery of the next generation of antidepressants. Part 2: Incorporating a 5-HT1A antagonist component into a class of serotonin reuptake inhibitors

The design and synthesis of a novel series of indole derivatives (9) having dual 5-HT transporter reuptake and 5-HT(1A) antagonist activity are described.

Studies towards the next generation of antidepressants. Part 1: indolylcyclohexylamines as potent serotonin reuptake inhibitors

A series of indolylcyclohexylamines possessing potent and selective serotonin reuptake inhibition is reported. The most interesting compounds proved to have subnanomolar 5-HT transporter activity, and exhibited moderate 5-HT(1A) affinity.

A new efficient synthesis of 3-(4-pyridinyl)methylindoles

Abstract A new efficient method for the preparation of 3-(4-pyridinyl)methylindoles has been developed. The new method involves coupling of indoles with 4-pyridinecarboxaldehyde to give 3-indolyl 4-pyridinyl methanols, which upon treatment with triethylsilane in the presence of trifluoroacetic acid afford 3-(4-pyridinyl)methylindoles in 64–76% overall yield.

Studies toward the discovery of the next generation of antidepressants. Part 6: Dual 5-HT1A receptor and serotonin transporter affinity within a class of arylpiperazinyl-cyclohexyl indole derivatives.

Based on the previously reported discovery lead, 3-(cis-4-(4-(1H-indol-4-yl)piperazin-1-yl)cyclohexyl)-5-fluoro-1H-indole (2), a series of related arylpiperazin-4-yl-cyclohexyl indole analogs were synthesized then evaluated as 5-HT transporter inhibitors and 5-HT(1A) receptor antagonists. The investigation of the structure-activity relationships revealed the optimal pharmacophoric elements required for activities in this series. The best example from this study, 5-(piperazin-1-yl)quinoline analog (trans-20), exhibited equal binding affinities at 5-HT transporter (K(i)=4.9nM), 5-HT(1A) receptor (K(i)=6.2nM) and functioned as a 5-HT(1A) receptor antagonist.