Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules

Adam D Hughes; Kay H Chin; Sarah L Dunham; Jeffrey R Jasper; Kristin E King; Tae Weon Lee; Mathai Mammen; Jerri Martin; Tod Steinfeld

doi:10.1016/j.bmcl.2011.01.043

Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1354-8. doi: 10.1016/j.bmcl.2011.01.043. Epub 2011 Jan 18.

Authors

Adam D Hughes¹, Kay H Chin, Sarah L Dunham, Jeffrey R Jasper, Kristin E King, Tae Weon Lee, Mathai Mammen, Jerri Martin, Tod Steinfeld

Affiliation

¹ Theravance, Inc., South San Francisco, CA 94080, USA. [email protected]

PMID: 21310610
DOI: 10.1016/j.bmcl.2011.01.043

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.

MeSH terms

Adrenergic beta-2 Receptor Agonists / chemical synthesis*
Adrenergic beta-2 Receptor Agonists / chemistry
Adrenergic beta-2 Receptor Agonists / pharmacology*
Bronchodilator Agents / chemical synthesis
Bronchodilator Agents / chemistry
Bronchodilator Agents / pharmacology
Drug Design*
Humans
Molecular Structure
Muscarinic Antagonists / chemical synthesis*
Muscarinic Antagonists / chemistry
Muscarinic Antagonists / pharmacology*
Receptors, Adrenergic, beta-2* / chemistry
Receptors, Muscarinic* / chemistry
Structure-Activity Relationship

Substances

Adrenergic beta-2 Receptor Agonists
Bronchodilator Agents
Muscarinic Antagonists
Receptors, Adrenergic, beta-2
Receptors, Muscarinic