| Literature DB >> 17600705 |
Paul Bamborough1, Richard M Angell, Inder Bhamra, David Brown, James Bull, John A Christopher, Anthony W J Cooper, Lynsey H Fazal, Ilaria Giordano, Lucy Hind, Vipulkumar K Patel, Lisa E Ranshaw, Martin J Sims, Philip A Skone, Kathryn J Smith, Emma Vickerstaff, Melanie Washington.
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.Entities:
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Year: 2007 PMID： 17600705 DOI： 10.1016/j.bmcl.2007.04.029
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823