Discovery Of Muscarinic Acetylcholine Receptor Antagonist and Beta-2 Adrenoceptor Agonist (MABA) Dual Pharmacology Molecules
Hughes AD.
RDD Europe 2013. Volume 1, 2013: 47-58.
Abstract:
The most frequently used bronchodilators in the treatment of chronic obstructive pulmonary disease (COPD) are inhaled beta-2 adrenergic receptor (β2) agonists and muscarinic acetylcholine receptor antagonists. Combinations of the two provide even greater improvement in lung function than either mechanism alone due to their complementary nature. By applying our multivalent approach to drug discovery, we designed muscarinic antagonist (MA) and β2 agonist (BA) dual pharmacology bronchodilators by linking several muscarinic and β2 pharmacophores in various ways. MABA molecules exhibiting bronchoprotection and extended duration of action in animal models are featured. The first MABA compound to enter the clinic (GSK-961081/TD-5959) recently completed Phase 2b studies in COPD patients.
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