title: Design, synthesis and evaluation of dual pharmacology β2-adrenoceptor agonists and PDE4 inhibitors.
abstract: A novel series of formoterol-phthalazinone hybrids were synthesised and evaluated as dual pharmacology β2-adrenoceptor agonists and PDE4 inhibitors. Most of the hybrids displayed high β2-adrenoceptor agonist and moderate PDE4 inhibitory activities. The most potent compound, (R,R)-11c, exhibited agonist (EC50=1.05nM, pEC50=9.0) and potent PDE4B2 inhibitory activities (IC50=0.092μM).
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Jiangsu Hansoh Pharmaceutical Research Institute Co., Ltd, Lianyungang 222000, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Shan
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Kefang
authors.initials: K
authors.lastname: Lai
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: lixs@mail.sysu.edu.cn.
authors.forename: Xingshu
authors.initials: X
authors.lastname: Li
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004983:Ethanolamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006801:Humans; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D004983:Ethanolamines; D058988:Phosphodiesterase 4 Inhibitors; D010793:Phthalazines; D018343:Receptors, Adrenergic, beta-2; D011994:Recombinant Proteins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D000068759:Formoterol Fumarate
keywords: Bronchodilator; Chronic obstructive pulmonary disease (COPD); PDE4 inhibitor; β(2)-Adrenoceptor agonist