306759-94-4

Upstream product

• 544710-37-4 4-{1-Carbethoxy-2-[3,4-bis(difluoromethoxy)phenyl]-2-(6-bromo-pyridin-3-yl)ethyl}pyridine 
• 303165-20-0 (+/-)-[3,4-bis(difluoromethoxy)phenyl]-(2-bromopyridin-5-yl)methanol 
• 544710-36-3 [3,4-Bis(difluoromethoxy)phenyl]-(6-bromo-pyridin-3-yl)chloromethane 
• 127842-54-0 3,4-bis-(difluoromethoxy)-benzaldehyde 
• 624-28-2 2,5-dibromopyridine 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 
• 303165-22-2 (+/-)-4-{2-[3,4-bis(difluoromethoxy)phenyl]-2-[5-(2-bromo)pyridyl]ethyl}pyridine 

Relevant academic research and scientific papers

Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors

The synthesis and the biological evaluation of new potent phosphodiesterase type 4 (PDE4) inhibitors are presented. This new series was elaborated by replacement of the metabolically resistant phenyl hexafluorocarbinol of L-791,943 (1) by a substituted aminopyridine residue. The structure-activity relationship of N-substitution on 3 led to the identification of (-)-3n which exhibited a good PDE4 inhibitor activity (HWB-TNFα=0.12 μM) and an improved pharmacokinetic profile over L-791,943 (rat t1/2=2 h). (-)-3n was well tolerated in ferret with an emetic threshold of 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig (54%, 0.1 mg/kg, ip) as well as the ascaris-induced bronchoconstriction model in sheep (64%/97%, early/late, 0.5 mg/kg, iv).