Synthesis and structural characterization of some ring-open analogues of Prazosin containing either the guanidine substructure or urea-equivalent groups are described. The opening of the pyrimidine ring in Prazosin is very important as far as the affinity for alpha(1)-adrenoceptor is concerned. The PA(2) values of the ring-open derivatives are 10(4)-10(5) fold lower than that of the parent. It is probable that the affinity decrease principally reflects a negative influence of the conformational factors in the interaction with the alpha(1)-receptor. The derivative 5 containing the guanidine moiety, charged at physiological pH, is as active as the other derivatives containing the uncharged urea-equivalent groups. This behaviour indicates, in this class of compounds, the importance of H-bonding interactions with the receptor. When in the ring-open models the ethanediamino substructure is substituted for the piperazine ring additional decrease in activity occurs.

ALPHA(1)-ADRENOCEPTOR BLOCKING ACTIVITY OF SOME RING-OPEN ANALOGS OF PRAZOSIN

BOSCHI, Donatella;DI STILO, Antonella;FRUTTERO, Roberta;MEDANA, Claudio;SORBA, Giovanni;GASCO, Alberto
1994

Abstract

Synthesis and structural characterization of some ring-open analogues of Prazosin containing either the guanidine substructure or urea-equivalent groups are described. The opening of the pyrimidine ring in Prazosin is very important as far as the affinity for alpha(1)-adrenoceptor is concerned. The PA(2) values of the ring-open derivatives are 10(4)-10(5) fold lower than that of the parent. It is probable that the affinity decrease principally reflects a negative influence of the conformational factors in the interaction with the alpha(1)-receptor. The derivative 5 containing the guanidine moiety, charged at physiological pH, is as active as the other derivatives containing the uncharged urea-equivalent groups. This behaviour indicates, in this class of compounds, the importance of H-bonding interactions with the receptor. When in the ring-open models the ethanediamino substructure is substituted for the piperazine ring additional decrease in activity occurs.
327
661
667
D. BOSCHI; A. DI STILO; R. FRUTTERO; C. MEDANA; G. SORBA; A. GASCO
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/3408
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 13
social impact