Pyrrolo[2,3- d]pyrimidines Containing an Extended 5-Substituent as Potent and Selective Inhibitors of lck II

• Published in: Bioorganic & medicinal chemistry letters Vol. 10; no. 19; pp. 2171 - 2174
• Main Authors: Burchat, Andrew F, Calderwood, David J, Hirst, Gavin C, Holman, Nicholas J, Johnston, David N, Munschauer, Rainer, Rafferty, Paul, Tometzki, Gerald B
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02.10.2000; Elsevier
• Subjects: Animals; Biological and medical sciences; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Immunomodulators; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - antagonists & inhibitors; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - chemistry; Medical sciences; Mice; Molecular Structure; Pharmacology. Drug treatments; Proto-Oncogene Proteins pp60(c-src) - antagonists & inhibitors; Proto-Oncogene Proteins pp60(c-src) - metabolism; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Pyrroles - chemical synthesis; Pyrroles - chemistry; Pyrroles - pharmacology; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Receptor Protein-Tyrosine Kinases - metabolism; Receptor, TIE-2; Receptors, Growth Factor - antagonists & inhibitors; Receptors, Growth Factor - metabolism; Receptors, Vascular Endothelial Growth Factor; Intraperitoneal administration; Nitrogen heterocycle; Selectivity; Signal transduction; Interleukin 2; Structure activity relation; T-Lymphocyte; Bicyclic compound; Inhibition; Chemical synthesis; Protein-tyrosine kinase; Biological receptor; Ether; Enzyme; Transferases; Rodentia; Cytokine; Oral administration; Enzyme inhibitor; In vitro; Immunomodulator; Vertebrata; Mammalia; Mouse; Animal; Benzenic compound; Immunosuppressive agent; Cyclopentane derivatives; Gamma interferon
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00442-X

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.