First dual M3 antagonists-PDE4 inhibitors: synthesis and SAR of 4,6-diaminopyrimidine derivatives.
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.
Provins
Laurent
L
Global Chemistry, UCB, R&D, Chemin du Foriest, B-1420 Braine-L'Alleud, Belgium. laurent.provins@ucb-group.com
Christophe
Bernard
B
Danhaive
Pierre
P
Dulieu
Jacques
J
Durieu
Véronique
V
Gillard
Michel
M
Lebon
Florence
F
Lengelé
Sébastien
S
Quéré
Luc
L
van Keulen
BerendJan
B
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
D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D011743:Pyrimidines; D043587:Receptor, Muscarinic M3; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4