Synthesis and activity of novel 5-substituted pyrrolo[2,3-d]pyrimidine analogues as pp60(c-Src) tyrosine kinase inhibitors

Olgen S., İŞGÖR Y. G., ÇOBAN T.

ARCHIV DER PHARMAZIE, cilt.341, sa.2, ss.113-120, 2008 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 341 Sayı: 2
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1002/ardp.200700141
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Sayfa Sayıları: ss.113-120
  • Anahtar Kelimeler: cancer, pyrrolopyrimidine derivatives, Schiff bases, tyrosine kinase pp60c-Src, SELECTIVE INHIBITORS, POTENT INHIBITORS, SRC, RECEPTOR, TARGETS, DESIGN, CANCER, LCK
  • Ankara Üniversitesi Adresli: Evet

Özet

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 pp60(c-Src) tyrosine kinase. Compounds 7a, 7d, and 7e demonstrated potent inhibitory activities against pp60(c-Src) tyrosine kinase with IC50 values of 13.9, 34.5, and 78.4 mu M, respectively. Dilialogenated compounds 7d and 7e have 3 to 7-times lower IC50 values than that of the parent compound 7a.