RESUMO
For the eradication of the Helicobacter pylori infection, authors have tested 50 HP-positive subjects (28 females and 22 males; mean age 47 years): 21 duodenal ulcers and 29 gastritis. All patients received the following treatment: omeprazole 40 mg for 30 days, azithromycin 500 mg in a single daily dose for 3 days for 2 cycles and metronidazole 250 mgx4 for 14 days. One month after the end of therapy, patients have been controlled: the HP eradication rates have been 76% (35/46), duodenal ulcer was cured in 90% (18/20). No important side-effects were reported by patients during the treatment. In conclusion the new therapeutic scheme with azithromycin represents a semplificated alternative treatment in the eradication of Helicobacter pylori.
RESUMO
The activity of a series of 1,3-dipropyl-xanthines bearing C8-cycloalkyl substituents as antagonists at A1 and A2 adenosine receptors is examined. Pharmacological results showed that the size of the 8-substituent is an important feature for response in activity of such class of antagonists. Among compounds 3-8, the 2-norbornyl analog 6 showed the best A1/A2 selectivity. A new route for the synthesis of 8-alkyl-substituted xanthines is presented. This method, consisting of a direct alkylation of the imidazole moiety through a radical mechanism reaction, was shown to be a more convenient strategy in comparison with the commonly employed synthetic schemes.
Assuntos
Antagonistas de Receptores Purinérgicos P1 , Xantinas/síntese química , Xantinas/metabolismo , Animais , Córtex Cerebral/metabolismo , Ligantes , Espectroscopia de Ressonância Magnética , Neostriado/metabolismo , Ratos , Receptores Purinérgicos P1/metabolismo , Ovinos , Relação Estrutura-AtividadeRESUMO
The syntheses and A1 and A2a adenosine binding activities of some new 1-aryl-1,4-dihydro-3-methyl[1]benzopyrano[2,3-c]pyrazol-4-ones, 1-aryl-4,9-dihydro-3-methyl-1H-pyrazolo[3,4-b]-quinolin-4-ones, and 1-aryl-1H-imidazo[4,5-b]quinoxalines are reported. Some compounds show A1 adenosine receptor affinity and selectivity. Structure-activity relationships on these new classes of adenosine receptor ligands are defined.
Assuntos
Pirazóis/síntese química , Quinolonas/síntese química , Quinoxalinas/síntese química , Receptores Purinérgicos P1/metabolismo , Animais , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Ligação Proteica , Pirazóis/química , Pirazóis/metabolismo , Quinolonas/química , Quinolonas/metabolismo , Quinoxalinas/química , Quinoxalinas/metabolismo , Ratos , Relação Estrutura-AtividadeRESUMO
Comparison of the affinity towards adenosine receptors of 2-phenyl-8-azaadenosines, bearing a lipophilic substituent on N(6), with the corresponding 2-phenyl-8-azaadenines was carried out. The compounds have good A1 affinity and high A1 selectivity. The obtained Ki(rib)/Ki(benz) ratios for A1 receptors, which showed variable values depending on the structure of the N(6) substituent, confirmed that 2-phenyl-8-azaadenines are characterized by greater freedom inside A1 receptors. This situation may be a favourable test of the hypothesized double disposition of these exogenous molecules within A1 receptors.
Assuntos
Adenina/análogos & derivados , Adenosina/síntese química , Compostos Aza/síntese química , Receptores Purinérgicos P1/metabolismo , Adenina/síntese química , Adenina/metabolismo , Adenosina/metabolismo , Animais , Compostos Aza/metabolismo , Ovinos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
This paper reports the synthesis and biological evaluation towards A1 and A2 adenosine receptors of new 1,2,3-triazole[4,5-d]pyridazines bearing lipophilic substituents in the 1 position. Some 1-benzyl-4-substituted amino derivatives were prepared and the cyclohexylamino-, anilino- and p-toluidino- derivatives showed an interesting moderately selective activity on the A1 receptor.
Assuntos
Piridazinas/síntese química , Receptores Purinérgicos P1/efeitos dos fármacos , Animais , Córtex Cerebral/metabolismo , Cromatografia Gasosa , Cristalografia por Raios X , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Neostriado/metabolismo , Piridazinas/química , Piridazinas/farmacologia , Ratos , OvinosAssuntos
Adenina/análogos & derivados , Receptores Purinérgicos P1/metabolismo , Animais , Ligação Competitiva , Córtex Cerebral/metabolismo , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Neostriado/metabolismo , Ratos , Ovinos , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
The title compounds were prepared to evaluate their affinity towards adenosine A1 and A2 receptors. Some 2-phenyl-N(6)-substituted-8-azadenines showed good binding properties and good A1 selectivity. The biological results allow us to confirm the presence in A1 receptors of a third lipophilic pocket, able to receive the substituent on N(9), and to evince increased affinity when a phenyl group on C(2) substitutes an n-butyl group. These affinity differences between analogous 2-n-butyl and 2-phenyl derivatives indicate that they arrange themselves within A1 receptors in a similar manner and suggest that this receptor is able to arrange 8-azaadenines, bearing three lipophilic substituents, in two different ways.
Assuntos
Adenina/análogos & derivados , Receptores Purinérgicos P1/metabolismo , Animais , Ligação Competitiva , Córtex Cerebral/metabolismo , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Neostriado/metabolismo , Ratos , Ovinos , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
Several title compounds were assayed to determine their relative affinity towards the adenosine receptors. Selectivity ratios (SR) showed a prevalent A1 affinity. The comparison with the selectivity ratios of the corresponding 9-benzyl-8-azaadenines and the comparison between the affinity constant values (K1) for each receptor of the two series, were performed. The results led us to conclude that A1 receptors are characterized by more different arrangements which regard especially to 9-benzyl-8-azaadenines.
Assuntos
Adenina/metabolismo , Adenosina/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenina/análogos & derivados , Adenina/química , Adenosina/análogos & derivados , Adenosina/química , Animais , Córtex Cerebral/metabolismo , Técnicas In Vitro , Ligantes , Proteínas de Membrana/metabolismo , Ratos , Ovinos , Relação Estrutura-AtividadeAssuntos
Artrite Reumatoide/sangue , Neutrófilos/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina-5'-(N-etilcarboxamida) , Ligação Competitiva , Membrana Celular/metabolismo , Humanos , Cinética , Fenetilaminas/metabolismo , Ensaio Radioligante , Receptores Purinérgicos P1/análise , Valores de Referência , TrítioRESUMO
Several studies have shown that sera from patients with Hodgkin's disease contain factors capable of inhibiting polymorphonuclear functions, among them chemotaxis. In the present study, we investigated whether these sera, which were able to inhibit PMN chemotaxis in the agarose test, were also able to affect the 3H-NECA binding to PMN membrane obtained from healthy donors. Control experiments were carried out using PMN incubated with a pool of sera from healthy volunteers. No significant difference was found in the maximum number of binding sites; on the contrary, the equilibrium dissociation constant was significantly increased in the membrane preparation of PMN incubated with pathological serum.
Assuntos
Adenosina/análogos & derivados , Doença de Hodgkin/sangue , Soros Imunes/farmacologia , Neutrófilos/metabolismo , Adenosina/metabolismo , Adenosina-5'-(N-etilcarboxamida) , Adolescente , Adulto , Idoso , Membrana Celular/metabolismo , Quimiotaxia de Leucócito , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A series of 1,3-disubstituted[1]benzopyrano[2,3-c]pyrazol-4-ones were synthesized and tested in vitro as A1 and A2 adenosine receptor ligands. The binding results and a molecular modelling study indicated that the presence of a proton donor group in the N6-H region of adenosine and the 7-NH region of xanthine, respectively and occupancy of the A2 lipophilic area by a moiety endowed with an electrostatic effect are essential for receptor affinity and A2-selectivity.