Brown D.G.,Astrazeneca |
Bernstein P.R.,Astrazeneca |
Griffin A.,Astrazeneca |
Wesolowski S.,Astrazeneca |
And 18 more authors.
Journal of Medicinal Chemistry | Year: 2014
A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only σ2 (62% at 10 μM). Compound 6s demonstrated free-plasma exposures above the IC50 (∼50×) with a brain-to-plasma ratio of ∼3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition. © 2014 American Chemical Society.
Bolduc M.,Laval University |
Bergeron J.,Laval University |
Michaud A.,Laval University |
Pelchat N.,Laval University |
And 3 more authors.
Tetrahedron Asymmetry | Year: 2012
2-Substituted glycerol derivatives 4a-g were resolved by acylation with vinyl butyrate in the presence of lipases in organic media. The reverse reaction, the enzymatic hydrolysis of the corresponding butyrates 5a-g, was also highly stereoselective and provided the opposite enantiomers. High enantioselectivities (ee >90%) and good isolated yields were obtained for all substrates using the appropriate lipase. Pseudomonas cepacia lipase or the closely related Pseudomonas sp. lipase were the most efficient enzymes for the resolution of substrates bearing smaller aliphatic groups. Candida antarctica lipase B was more suitable as the biocatalyst in the resolution of more sterically demanding aromatic substrates. 2-Benzylglycerol derivatives were resolved in the presence of Rhizopus sp. lipase. © 2012 Elsevier Ltd. All rights reserved.
Turcotte-Savard M.-O.,OmegaChem |
Mahe O.,Laval University |
Paquin J.-F.,Laval University
Chimica Oggi/Chemistry Today | Year: 2013
The syntheses of dialkylaminodifluorosulfinium tetrafluoroborate salts are described These reagents first used for the deoxyfluorination of alcohols were also shown to fluorinate aldehydes ketones carboxylic acids and glycosyl groups Alternatively dialkylaminodifluorosulfinium tetrafluoroborate salts were recently shown to act as activating agents for hydroxyl carbonyl and carboxyl groups in a variety of transformations leading to non-fluorinated products © 2013 Sigma-Aldrich Co LLC.