tiotropium has been researched along with Pulmonary-Disease--Chronic-Obstructive* in 3 studies
3 other study(ies) available for tiotropium and Pulmonary-Disease--Chronic-Obstructive
| Article | Year |
|---|---|
Discovery of M
In this paper, we report the discovery of dual M Topics: Animals; Cyclic Nucleotide Phosphodiesterases, Type 4; Dose-Response Relationship, Drug; Drug Discovery; Guinea Pigs; Male; Molecular Structure; Phosphodiesterase 4 Inhibitors; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Inbred BN; Rats, Sprague-Dawley; Receptor, Muscarinic M3; Structure-Activity Relationship | 2021 |
Discovery of (R)-1-(3-((2-chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, batefenterol): first-in-class dual pharmac
Through application of our multivalent approach to drug discovery we previously reported the first discovery of dual pharmacology MABA bronchodilators, exemplified by 1. Herein we describe the subsequent lead optimization of both muscarinic antagonist and β2 agonist activities, through modification of the linker motif, to achieve 24 h duration of action in a guinea pig bronchoprotection model. Concomitantly we targeted high lung selectivities, low systemic exposures and identified crystalline forms suitable for inhalation devices. This article culminates with the discovery of our first clinical candidate 12f (TD-5959, GSK961081, batefenterol). In a phase 2b trial, batefenterol produced statistical and clinically significant differences compared to placebo and numerically greater improvements in the primary end point of trough FEV1 compared to salmeterol after 4 weeks of dosing in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Animals; Carbamates; CHO Cells; Cricetulus; Drug Discovery; Guinea Pigs; HEK293 Cells; Humans; Lung; Models, Molecular; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones | 2015 |
Molecular hybridization yields triazole bronchodilators for the treatment of COPD.
A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. Topics: Adrenergic beta-2 Receptor Agonists; Animals; Biological Availability; Bronchoconstriction; Bronchodilator Agents; CHO Cells; Cricetulus; Dogs; Humans; Ipratropium; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Rats; Receptor, Muscarinic M3; Salmeterol Xinafoate; Tiotropium Bromide; Triazoles | 2015 |