Dual M3 antagonists-PDE4 inhibitors. Part 2: Synthesis and SAR of 3-substituted azetidinyl derivatives.
Introduction of 3-substituted azetidinyl substituents onto the 4,6-diaminopyrimidine scaffold allowed the improvement of PDE4 inhibiting activities. Preliminary in vivo activity in pulmonary inflammation models is reported.
Provins
Laurent
L
UCB Pharma S.A., 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
Gillard
Michel
M
Quéré
Luc
L
Stebbins
Karin
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001384:Azetidines / Q000737:chemistry*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001384:Azetidines; D011743:Pyrimidines; D043587:Receptor, Muscarinic M3; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4