320348-18-3Relevant academic research and scientific papers
Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters as potent and long-acting muscarinic antagonists with potential for minimal systemic exposure after inhaled administration: Identification of (3R)-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2. 2.2]octane bromide (aclidinium bromide)
Prat, María,Fernández, Dolors,Buil, M. Antonia,Crespo, María I.,Casals, Gaspar,Ferrer, Manuel,Tort, Laia,Castro, Jordi,Monleón, Juan M.,Gavaldà, Amadeu,Miralpeix, Montserrat,Ramos, Israel,Doménech, Teresa,Vilella, Dolors,Antón, Francisca,Huerta, Josep M.,Espinosa, Sonia,López, Manuel,Sentellas, Sonia,González, Marisa,Albertí, Joan,Segarra, Victor,Cárdenas, Alvaro,Beleta, Jorge,Ryder, Hamish
experimental part, p. 5076 - 5092 (2010/03/01)
The objective of this work was to discover a novel, long-acting muscarinicM3 antagonist for the inhaled treatment of chronic obstructive pulmonary disease (COPD), with a potentially improved risk-benefit profile compared with current antimuscarinic agents. A series of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters were synthesized and evaluated. On the basis of its overall profile, (3R)-3-{[hydroxy(di-2-thienyl) acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (aclidiniumbromide) emerged as a candidate for once-daily maintenance treatment of COPD. This compound is a potent muscarinic antagonist, with long duration of action in vivo, and was found to have a rapid hydrolysis in human plasma, minimizing the potential to induce class-related systemic side effects. Aclidinium bromide is currently in phase III development for maintenance treatment of patients with COPD.
Asymmetric Addition of Organometallics to Chiral Ketooxazolines. Preparation of Enantiomerically Enriched α-Hydroxy Acids
Meyers, A. I.,Slade, Joel
, p. 2785 - 2791 (2007/10/02)
Addition of Grignard and organolithium reagents to chiral α-ketooxazolines results in α-substituted α-hydroxyoxazoline derivatives which on hydrolytic removal of the chiral auxiliary groups give rise to α-substituted α-hydroxy acids in 30-87 percent enantiomeric excess (ee).Studies on the various parameters (solvents, temperature, substituents) were undertaken to reach optimum asymmetric induction.
