1216-44-0Relevant articles and documents
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
supporting information; 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.
Medicaments for inhalation comprising an anticholinergic and a betamimetic
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, (2008/06/13)
A pharmaceutical composition comprising an anticholinergic and a betamimetic of formula 2 optionally together with a pharmaceutically acceptable excipient, the anticholinergic and the betamimetic optionally in the form of their enantiomers, mixtures of their enantiomers, their racemates, their solvates, or their hydrates, processes for preparing them, and their use in the treatment of asthma, COPD, or other inflammatory or obstructive respiratory complaints.
Anticholinergics, processes for the preparation thereof, and pharmaceutical compositions
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Page 9, (2010/01/31)
A compound of formula 1 wherein: X? is an anion with a single negative charge; A and B, which are identical or different, are each —O—, —S—, —NH—, —CH2—, —CH═CH—, or —N(C1-C4-alkyl)-; R is hydrogen, hydroxy, —C1-C4-alkyl, —C1-C4-alkyloxy, —C1-C4-alkylene-halogen, —O—C1-C4-alkylene-halogen, —C1-C4-alkylene-OH, —CF3, —CHF2, —C1-C4-alkylene-C1-C4-alkyloxy, —O—COC1-C4-alkyl, —O—COC1-C4-alkylene-halogen, —C1-C4-alkylene-C3-C6-cycloalkyl, —O—COCF3, or halogen; R1 and R2, which are identical or different, are each —C1-C5-alkyl, which is optionally substituted by —C3-C6-cycloalkyl, hydroxy, or halogen, or R1 and R2 together are a —C3-C5-alkylene bridge; R3, R4, R3′, and R4′, which are identical or different, are each hydrogen, C1-C4-alkyl, C1-C4-alkyloxy, hydroxy, —CF3, —CHF2, —CN, —NO2, or halogen; Rx and Rx′, which are identical or different, are each hydrogen, C1-C4-alkyl, C1-C4-alkyloxy, hydroxy, —CF3, —CHF2, —CN, —NO2, or halogen, or Rx and Rx′ together are a single bond or a bridging group selected from —O—, —S—, —NH—, —CH2—, —CH2—CH2—, —N(C1-C4-alkyl)-, —CH(C1-C4-alkyl)-, and —C(C1-C4-alkyl)2-, or a pharmacologically acceptable acid addition salt thereof, processes for preparing, them and their use in pharmaceutical compositions.