Author/Authors :
Paul Bamborough، نويسنده , , Richard M. Angell، نويسنده , , Inder Bhamra، نويسنده , , David Brown، نويسنده , , James Bull، نويسنده , , John A. Christopher، نويسنده , , Anthony W.J. Cooper، نويسنده , , Lynsey H. Fazal، نويسنده , , Ilaria Giordano، نويسنده , , S. Lucy Hind، نويسنده , , Vipulkumar K. Patel، نويسنده , , Lisa E. Ranshaw، نويسنده , , Martin J. Sims، نويسنده , , Philip A. Skone، نويسنده , , Kathryn J. Smith، نويسنده , , Emma Vickerstaff، نويسنده , , Melanie Washington، نويسنده ,
Abstract :
2,4-Dianilino pyrimidines are well-known inhibitors of tyrosine kinases including lymphocyte specific kinase (Lck). Structure–activity relationships at the 4-position are discussed and rationalised. Examples bearing a 2-methyl-5-hydroxyaniline substituent at the 4-position were especially potent but showed poor oral pharmacokinetics. Replacement of this substituent by 4-amino(5-methyl-1H-indazole) yielded compounds with comparable enzyme potency and improved pharmacokinetic properties.
Keywords :
2 , 4-Dianilino pyrimidines , p56Lck inhibitors , Lck inhibitors , Protein kinase inhibitors
