title: First dual M3 antagonists-PDE4 inhibitors: synthesis and SAR of 4,6-diaminopyrimidine derivatives.
abstract: SAR around 4,6-diaminopyrimidine derivatives allowed the discovery of the first potent dual M(3) antagonists and PDE4 inhibitors. Various chemical modulations around that scaffold led to the discovery of ucb-101333-3 which is characterized by the most interesting profile on both targets.
authors.affiliation: Global Chemistry, UCB, R&D, Chemin du Foriest, B-1420 Braine-L'Alleud, Belgium. laurent.provins@ucb-group.com
authors.forename: Laurent
authors.initials: L
authors.lastname: Provins
authors.forename: Bernard
authors.initials: B
authors.lastname: Christophe
authors.forename: Pierre
authors.initials: P
authors.lastname: Danhaive
authors.forename: Jacques
authors.initials: J
authors.lastname: Dulieu
authors.forename: Véronique
authors.initials: V
authors.lastname: Durieu
authors.forename: Michel
authors.initials: M
authors.lastname: Gillard
authors.forename: Florence
authors.initials: F
authors.lastname: Lebon
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lengelé
authors.forename: Luc
authors.initials: L
authors.lastname: Quéré
authors.forename: BerendJan
authors.initials: B
authors.lastname: van Keulen
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D011743:Pyrimidines; D043587:Receptor, Muscarinic M3; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4