Substituted 5,7-diphenyl-pyrrolo[2,3d]pyrimidines: potent inhibitors of the tyrosine kinase c-Src.
5,7-Diphenyl-pyrrolo[2,3d]pyrimidines represent a new class of highly potent inhibitors of the tyrosine kinase c-Src (IC50 < 50 nM) with specificity against a panel of different tyrosine kinases. The substitution pattern on the two phenyl rings determines potency and specificity and provides a means to modulate cellular activity.
Missbach
M
M
Novartis Pharma AG, Therapeutic Areas Arthritis & Bone Metabolism, Basel, Switzerland. martin.missbach@pharma.novartis.com
Altmann
E
E
Widler
L
L
Susa
M
M
Buchdunger
E
E
Mett
H
H
Meyer
T
T
Green
J
J
D000818:Animals; D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D002645:Chickens; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D019061:src-Family Kinases
D004791:Enzyme Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases