Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 1: SAR exploration and effective bioisosteric replacement of a phenyl substituent.
Novel substituted 2-anilino- and 2-cycloalkylaminoquinoxalines have been found to be useful and selective inhibitors of PDGF-R autophosphorylation. Replacement of an anilino-substituent with substituted cyclohexylamino- or norbornylamino substituents led to significant improvements in the pharmacokinetic profile of these analogues.
Myers
Michael R
MR
Aventis Pharmaceuticals, Route 202/206, Bridgewater, NJ 08807, USA. myers_michael_r@lilly.com
He
Wei
W
Hanney
Barbara
B
Setzer
Natalie
N
Maguire
Martin P
MP
Zulli
Allison
A
Bilder
Glenda
G
Galzcinski
Helen
H
Amin
Dilip
D
Needle
Saul
S
Spada
Alfred P
AP
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D023903:Coronary Restenosis / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011810:Quinoxalines; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor