David N. Johnston

Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I

Pyrrolo[2,3-d]pyrimidines containing a 5-(4-phenoxyphenyl) substituent are potent and selective inhibitors of Ick in vitro; some compounds are selective for lck over src. Data are shown for two compounds demonstrating that they are potent and selective inhibitors of IL2 production in cells.

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.