Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 2: (3-Substituted-5-halo-2-pyridinyl)guanidines.
Based on previous modeling predictions, a series of (3-substituted-5-chloro-2-pyridinyl)guanidines have been designed with good potency and selectivity for urokinase-type plasminogen activator (uPA). Compound 36 has a K(i) of 0.17 microM and greater than 300-fold selectivity with respect to tPA and plasmin.
Barber
Christopher G
CG
Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK. christopher_barber@sandwich.pfizer.com
Dickinson
Roger P
RP
D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D006146:Guanidines; D011725:Pyridines; D014568:Urokinase-Type Plasminogen Activator; C023666:pyridine