Phosphodiesterase inhibitory properties of losartan. Design and synthesis of new lead compounds.
A 4-centre PDE4 pharmacophore search has been carried out in several 3D-databases containing compounds belonging to different therapeutic areas. Losartan, an angiotensin-II antagonist, has been identified as a new lead compound for developing PDE4 inhibitors. New families of compounds derived from losartan has been synthesized and their PDE inhibition has been measured.
Segarra
V
V
Almirall Prodesfarma Research Center, Barcelona, Spain.
Crespo
M I
MI
Pujol
F
F
Beleta
J
J
Doménech
T
T
Miralpeix
M
M
Palacios
J M
JM
Castro
A
A
Martinez
A
A
D000818:Animals; D015195:Drug Design; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D019808:Losartan / Q000737:chemistry / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D010726:Phosphodiesterase Inhibitors; D019808:Losartan