title: Synthesis and activity of novel 5-substituted pyrrolo[2,3-d]pyrimidine analogues as pp60(c-Src) tyrosine kinase inhibitors.
abstract: Therapy with receptor tyrosine kinase inhibitors provides an improved treatment option in a number of diseases such as cancer, myocardial infection, osteoporosis, stroke, and neurodegeneration. We have designed, synthesized, and evaluated a series of novel 2-amino-5-[(benzyl)imino]methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-one 7a and 2-amino-5-[(substituted-benzyl)imino]methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-one 7b-e derivatives as potential tyrosine kinase inhibitors. These compounds were synthesized by condensation reaction using 2-tritylamino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbaldehyde 5 and appropriate benzylamines followed by detritylation. Compounds were evaluated for their inhibitory activity toward tyrosine phosphorylation for the pp60c-Src tyrosine kinase. Compounds 7a, 7d, and 7e demonstrated potent inhibitory activities against pp60c-Src tyrosine kinase with IC50 values of 13.9, 34.5, and 78.4 microM, respectively. Dihalogenated compounds 7d and 7e have 3 to 7-times lower IC50 values than that of the parent compound 7a.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ankara, Tandogan-Ankara, Turkey. olgen@pharmacy.ankara.edu.tr
authors.forename: Süreyya
authors.initials: S
authors.lastname: Olgen
authors.forename: Yasemin G
authors.initials: YG
authors.lastname: Isgör
authors.forename: Tülay
authors.initials: T
authors.lastname: Coban
mesh_terms: D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; D016392:Proto-Oncogene Proteins pp60(c-src)