Synthesis of 1-(2-chloro-2-phenylethyl)-6-methylthio-1H-pyrazolo[3,4-d]pyrimidines 4-amino substituted and their biological evaluation.
A new series of 4-amino-6-methylthio-1H-pyrazolo[3,4-d]pyrimidines (2a-m) bearing the 2-chloro-2-phenylethyl chain at the N1 position, has been synthesized. The affinity of these compounds for A1 adenosine receptor (A1AR) was measured. The compounds showed poor affinity. A more interesting result was obtained by 2a, 2d, 2g, which demonstrated inhibitory activity on cell proliferation of the A-431 cell line stimulated by epithelial growth factor (EGF) and on EGF receptor tyrosine kinase (EGFR-TK) phosphorylation.
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, viale Benedetto XV, 16132 Genoa, Italy. schensil@unige.it
Silvia
S
Schenone
Olga
O
Bruno
Francesco
F
Bondavalli
Angelo
A
Ranise
Luisa
L
Mosti
Giulia
G
Menozzi
Paola
P
Fossa
Fabrizio
F
Manetti
Lucia
L
Morbidelli
Letizia
L
Trincavelli
Claudia
C
Martini
Antonio
A
Lucacchini
D058916:Adenosine A1 Receptor Antagonists; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D015394:Molecular Structure; D010766:Phosphorylation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism
D058916:Adenosine A1 Receptor Antagonists; D011743:Pyrimidines; D043682:Receptor, Adenosine A1; D004815:Epidermal Growth Factor; D066246:ErbB Receptors