title: Novel and potent adenosine 3',5'-cyclic phosphate phosphodiesterase III inhibitors: thiazolo[4,5-b][1,6]naphthyridin-2-ones.
abstract: The transformation of 3-bromo-1,6-naphthyridin-2(1H)-ones 8 to thiazolo[4,5-b][1,6]naphthyridin-2(1H)-ones 12 resulted in a 2-9-fold increase in cAMP phosphodiesterase (PDE) III inhibitory potency. Unlike the secondary binding sites on the cAMP PDE III isozyme which interact with the methyl group of milrinone (2) and CI-930 (4), the site which interacts with the 5-substituents of 1,6-naphthyridin-2(1H)-ones and the 8-substituents of thiazolo[4,5-b][1,6]naphthyridin-2(1H)-ones 12 is able to accommodate a diverse group of substituents which have different steric and electronic requirements.
authors.affiliation: Department of Medicinal Chemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania 19426, USA.
authors.forename: B
authors.initials: B
authors.lastname: Singh
authors.forename: E R
authors.initials: ER
authors.lastname: Bacon
authors.forename: G Y
authors.initials: GY
authors.lastname: Lesher
authors.forename: S
authors.initials: S
authors.lastname: Robinson
authors.forename: P O
authors.initials: PO
authors.lastname: Pennock
authors.forename: D C
authors.initials: DC
authors.lastname: Bode
authors.forename: E D
authors.initials: ED
authors.lastname: Pagani
authors.forename: R G
authors.initials: RG
authors.lastname: Bentley
authors.forename: M J
authors.initials: MJ
authors.lastname: Connell
authors.forename: L T
authors.initials: LT
authors.lastname: Hamel
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009287:Naphthyridines; D015105:3',5'-Cyclic-AMP Phosphodiesterases