8-substituted adenosine and theophylline-7-riboside analogues as potential partial agonists for the adenosine A1 receptor

摘要: A series of 8-substituted adenosine and theophylline-7-riboside analogues (28 9 compounds, respectively) was tested on A1 A2A receptors as an extensive exploration the C8-region. Alkylamino substituents at 8-position cause affinity decrease for analogues, but increase derivatives. The is probably due to a direct steric hindrance between C8-substituent binding site well electronic effects, not influence ribose moiety adopt anti conformation. 8-substituents by lipophilic site. intrinsic activity in vitro some determining GTP shift receptor studies inhibition adenylate cyclase culture rat thyroid FRTL-5 cells, vivo cardiovascular system 8-butylaminoadenosine. Thus, it shown that 8-ethyl-, 8-butyl-, 8-pentylamino substituted may be partial agonists vitro, 8-butylaminoadenosine agonist vivo.