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5-HT(6) receptor antagonists: lead optimisation and biological evaluation of N-aryl and N-heteroaryl 4-amino-benzene sulfonamides.
TLDR
Compounds with a logD profile indicative of brain penetration have been subjected to in vivo testing for reversal of a scopolamine-induced retention deficit in a passive avoidance paradigm and RO-04-6790 (6a) has been identified. Expand
Identification of essential residues involved in the glutamate binding pocket of the group II metabotropic glutamate receptor.
TLDR
Results suggest that Ser-148 and Arg-183 may be important for the 3D structure and/or are involved in closure of the domain, and Asp-146, which is also remote from the binding site, was shown to be involved in the differential binding affinity of [(3)H]LY354740 for mGlu2 versus mGLU3 receptors. Expand
In vitro binding characteristics of a new selective group II metabotropic glutamate receptor radioligand, [3H]LY354740, in rat brain.
TLDR
The pharmacology, tissue distribution, and sensitivity to guanosine-5'-O-(3-thiotriphosphate show that [3H]LY354740 binding probably occurs to group II mGlu receptors in rat brain. Expand
The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction.
TLDR
The unique pharmacological profiles and optimal pharmacokinetic profiles resulted in in vivo activity in selected cognition models and the identification of two clinical leads functioning as novel potent and selective GABAA alpha5 inverse agonists. Expand
The role of 5-HT2C receptors in affective disorders.
TLDR
Results are consistent with an important hypothesis proposing that 5-HT has a complex, dual action on the neural mechanism of anxiety by either facilitating or inhibiting different kinds of anxiety in different brain regions and suggest that5-HT(2C) receptor subtypes play an important role in the therapeutic properties of SSRIs. Expand
Substituted piperidines--highly potent renin inhibitors due to induced fit adaptation of the active site.
The identification, synthesis and activity of a novel class of piperidine renin inhibitors is presented. The most active compounds show activities in the picomolar range and are among the most potentExpand
Piperidine renin inhibitors: from leads to drug candidates.
TLDR
Treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status, and two candidate compounds 14 and 23 display potent and long-lasting blood pressure lowering effects. Expand
Distribution and abundance of metabotropic glutamate receptor subtype 2 in rat brain revealed by [3H]LY354740 binding in vitro and quantitative radioautography: Correlation with the sites of
TLDR
This extensive study paves the way for investigations of the regional expression and regulation of mGlu2 receptors in human CNS diseases, such as Alzheimer's disease, which may reveal their functional roles and identify potential therapeutic drug targets. Expand
Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists.
TLDR
The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK(1) receptor antagonists is described, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration. Expand
Distribution and abundance of metabotropic glutamate receptor subtype 2 in rat brain revealed by [3H]LY354740 binding in vitro and quantitative radioautography: correlation with the sites of
TLDR
This extensive study paves the way for investigations of the regional expression and regulation of mGlu2 receptors in human CNS diseases, such as Alzheimer's disease, which may reveal their functional roles and identify potential therapeutic drug targets. Expand
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