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Journals and Conferences
The possible role of 5-HT(6) receptor antagonists in the treatment of learning and memory disorders has stimulated significant recent work in this area. The first selective antagonists of this receptor were identified by Roche (Ro 04-6790 and Ro 63-0563) and SmithKline Beecham (SB-271046), although they only had poor to modest brain penetration,… (More)
A series of N(1)-arylsulfonyltryptamines were found to be potent ligands of the human serotonin 5-HT(6) receptor with the 5-methoxy-1-benzenesulfonyl analogue (19) having the highest affinity. Additionally, it was discovered that a group such as 3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl in the 2-position of the indole ring (43) can replace the arylsulfonyl… (More)
The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat… (More)
A new class of potent NK3R antagonists based on the N',2-diphenylquinoline-4-carbohydrazide core is described. In an ex vivo assay in gerbil, the lead compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30 mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK properties.
Several 5-HT(1D/1B) receptor agonists are now entering the marketplace as treatments for migraine. This paper describes the development of selective h5-HT(1D) receptor agonists as potential antimigraine agents which may produce fewer side effects. A series of 3-[3-(piperidin-1-yl)propyl]indoles has been synthesized which has led to the identification of 80… (More)
2,5-Dihydro-3H-pyrazolo[4,3-c]pyridin-3-ones are GABAA receptor benzodiazepine binding site ligands, which can exhibit functional selectivity for the alpha3 subtype over the alpha1 subtype. SAR studies to optimize this functional selectivity are described.
It has previously been reported that a 3-(3-(piperazin-1-yl)propyl)indole series of 5-HT1D receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pKa of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this… (More)
There is increasing evidence that compounds with selectivity for gamma-aminobutyric acid(A) (GABA(A)) alpha2- and/or alpha3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABA(A) alpha2/alpha3 subtype-selective agonists leading to the… (More)
2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones are GABAA receptor benzodiazepine binding site ligands with functional selectivity for the alpha3 subtype over the alpha1 subtype. SAR studies to optimise this functional selectivity are described.