title: Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules.
abstract: We sought to design dual pharmacology bronchodilators targeting both the M(3) muscarinic acetylcholine and beta-2 adrenergic (β(2)) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptors.
authors.affiliation: Theravance, Inc., South San Francisco, CA 94080, USA. ahughes@theravance.com
authors.forename: Adam D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Kay H
authors.initials: KH
authors.lastname: Chin
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Dunham
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Jasper
authors.forename: Kristin E
authors.initials: KE
authors.lastname: King
authors.forename: Tae Weon
authors.initials: TW
authors.lastname: Lee
authors.forename: Mathai
authors.initials: M
authors.lastname: Mammen
authors.forename: Jerri
authors.initials: J
authors.lastname: Martin
authors.forename: Tod
authors.initials: T
authors.lastname: Steinfeld
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry; D011976:Receptors, Muscarinic / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D018343:Receptors, Adrenergic, beta-2; D011976:Receptors, Muscarinic