Pyrrolo[2,3-d]pyrimidines containing diverse N-7 substituents as potent inhibitors of Lck.
A series of pyrrolo[2,3-d]pyrimidines was synthesized and evaluated as inhibitors of Lck. Lck accommodates a diverse set of substituents at N-7. Altering the substituent at N-7 provided compound 13, an orally available lck inhibitor which inhibited TCR mediated IL-2 production after oral dosing.
Calderwood
David J
DJ
Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605-5314, USA. david.calderwood@abbott.com
Johnston
David N
DN
Munschauer
Rainer
R
Rafferty
Paul
P
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000032:analysis*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011743:Pyrimidines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)