Starting from the appropriate azides (4-chlorobenzyl-, 2-thiophenemethyl-, 2-fluorobenzyl-, and 4-fluorobenzylazides) agreeing with the substituent determining four series of derivatives (a-d), some 4-amino-substituted 1,2,3-triazolo[4,5-d]pyridazines (4a-d) corresponding to previously prepared derivatives were obtained by a well experimented synthetic route. Other new derivatives (6c,e) which were different from 4a-d because a chlorine atom had substituted the hydroxyl or the tautomeric oxamido group in the 7 position of the triazolopyridazine ring, were prepared from the suitable azides (2-fluorobenzyl and 2-chlorobenzyl), which similarly determine the series c and e, respectively, via the 4,7-dichloro derivatives 5. The radioligand binding assays at bovine brain adenosine A1 and A(2A) receptors showed that some compounds 4 possessed high affinity and selectivity for the A1 receptor subtype whilst binding affinity decreased in compounds 6 indicating the importance of a hydrogen bond donor in the 7 position of the triazolopyridazine ring. It is worth noting that compounds bearing the new lipophilic substituents 2-fluorobenzyl and 2-thiophenemethyl in the 1 position of the triazolopyridazine ring were the most active in the series.
|Autori:||L. BETTI; G. BIAGI; GIORGI I; O. LIVI; C. MANERA; V. SCARTONI; G. GIANNACCINI; A. LUCACCHINI|
|Titolo:||1,2,3-TRIAZOLO[4,5-D]PYRIDAZINES. PART VI. NEW 1-SUBSTITUTED-4-AMINO DERIVATIVES AND THEIR AFFINITY TOWARDS A1 AND A2 ADENOSINE RECEPTORS|
|Anno del prodotto:||1999|
|Digital Object Identifier (DOI):||10.1016/S0014-827X(99)00072-5|
|Appare nelle tipologie:||1.1 Articolo in rivista|