N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics.
Bioorg Med Chem Lett
; 17(15): 4363-8, 2007 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-17600705
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.
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Database:
MEDLINE
Main subject:
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
/
Enzyme Inhibitors
/
Indazoles
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2007
Type:
Article
Affiliation country:
United kingdom