title: Pyrazolo[3,4-d]pyrimidines containing an extended 3-substituent as potent inhibitors of Lck -- a selectivity insight.
abstract: A series of para-substituted 3-phenyl pyrazolopyrimidines was synthesized and evaluated as inhibitors of lck. The nature of the substitution affected enzyme selectivity and potency for lck, src, kdr, and tie-2. The para-phenoxyphenyl analogue 2 is an orally active lck inhibitor with a bioavailability of 69% and exhibits an extended duration of action in animal models of T cell inhibition.
authors.affiliation: Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605-5314, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Burchat
authors.forename: David J
authors.initials: DJ
authors.lastname: Calderwood
authors.forename: Michael M
authors.initials: MM
authors.lastname: Friedman
authors.forename: Gavin C
authors.initials: GC
authors.lastname: Hirst
authors.forename: Biqin
authors.initials: B
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: Rafferty
authors.forename: Kurt
authors.initials: K
authors.lastname: Ritter
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Skinner
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D008297:Male; D008958:Models, Molecular; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)