Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck II.
Pyrrolo[2,3-d]pyrimidines containing a 5-(4-phenoxyphenyl) substituent are novel, potent and selective inhibitors of lck in vitro. Exploration of C-6 position of the pyrrolo[2,3-d]pyrimidine and the terminal phenyl group structure-activity relationship (SAR) is detailed. Compound 1 is orally active in animal models.
Burchat
A F
AF
BASF Bioresearch Corporation, Worcester, MA 01605-5314, USA.
Calderwood
D J
DJ
Hirst
G C
GC
Holman
N J
NJ
Johnston
D N
DN
Munschauer
R
R
Rafferty
P
P
Tometzki
G B
GB
D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042787:Receptor, TIE-2; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor
D004791:Enzyme Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016392:Proto-Oncogene Proteins pp60(c-src)