N(7)-substituted-5-aryl-pyrrolo[2,3-d]pyrimidines represent a versatile class of potent inhibitors of the tyrosine kinase c-Src.
5-Aryl-pyrrolo[2,3-d]pyrimidines incorporating different N(7)-substituents have been prepared and evaluated for their inhibitory potency towards the tyrosine kinase c-Src. Optimization of these compounds resulted in highly potent c-Src inhibitors, some (e.g. 4g, 6g, 7h, 8l) with excellent specificity towards other receptor and nonreceptor tyrosine kinases. In addition compounds 4g, 5b and 5c are characterized by a good pharmacokinetic profile.
Altmann
Eva
E
Novartis Pharma AG, Therapeutic Area Arthritis and Bone Metabolism, Basel, CH-4002, Switzerland.
Widler
Leo
L
Missbach
Martin
M
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D006801:Humans; D020128:Inhibitory Concentration 50; D010024:Osteoporosis / Q000188:drug therapy; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019061:src-Family Kinases
D011743:Pyrimidines; D011758:Pyrroles; C450639:Pyrrolo(2,3-d)pyrimidine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human