Dual M3 antagonists-PDE4 inhibitors. Part 2: Synthesis and SAR of 3-substituted azetidinyl derivatives

Laurent Provins; Bernard Christophe; Pierre Danhaive; Jacques Dulieu; Michel Gillard; Luc Quéré; Karin Stebbins

doi:10.1016/j.bmcl.2007.03.047

Dual M3 antagonists-PDE4 inhibitors. Part 2: Synthesis and SAR of 3-substituted azetidinyl derivatives

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3077-80. doi: 10.1016/j.bmcl.2007.03.047. Epub 2007 Mar 19.

Authors

Laurent Provins¹, Bernard Christophe, Pierre Danhaive, Jacques Dulieu, Michel Gillard, Luc Quéré, Karin Stebbins

Affiliation

¹ UCB Pharma S.A., R&D, Chemin du Foriest, B-1420 Braine-L'Alleud, Belgium. [email protected]

PMID: 17398090
DOI: 10.1016/j.bmcl.2007.03.047

Abstract

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.

MeSH terms

3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
Animals
Azetidines / chemistry*
Cyclic Nucleotide Phosphodiesterases, Type 4
Female
Guinea Pigs
Humans
Mice
Mice, Inbred BALB C
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology*
Receptor, Muscarinic M3 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Azetidines
Pyrimidines
Receptor, Muscarinic M3
3',5'-Cyclic-AMP Phosphodiesterases
Cyclic Nucleotide Phosphodiesterases, Type 4