1,3-Dioxolane-based compounds (2−14) were synthesized, and the pharmacological profiles at α1-adrenoceptor subtypes were assessed by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Compound 9, with a pA2 of 7.53, 7.36, and 8.65 at α1A, α1B, and α1D, respectively, is the most potent antagonist of the series, while compound 10 with a pA2 of 8.37 at α1D subtype and selectivity ratios of 162 (α1D/α1A) and 324 (α1D/α1B) is the most selective. Binding assays in CHO cell membranes expressing human cloned α1-adrenoceptor subtypes confirm the pharmacological profiles derived from functional experiments, although the selectivity values are somewhat lower. Therefore, it is concluded that 1,3-dioxolane-based ligands are a new class of α1-adrenoceptor antagonists.

1,3-Dioxolane-Based Ligands as a Novel Class of Alpha1-Adrenoceptor Antagonists / Brasili, Livio; Sorbi, Claudia; Franchini, Silvia; Manicardi, M.; Angeli, P.; Marucci, G.; Leonardi, A.; Poggesi, E.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 46:8(2003), pp. 1504-1511. [10.1021/jm021078o]

1,3-Dioxolane-Based Ligands as a Novel Class of Alpha1-Adrenoceptor Antagonists

BRASILI, Livio;SORBI, Claudia;FRANCHINI, Silvia;
2003

Abstract

1,3-Dioxolane-based compounds (2−14) were synthesized, and the pharmacological profiles at α1-adrenoceptor subtypes were assessed by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Compound 9, with a pA2 of 7.53, 7.36, and 8.65 at α1A, α1B, and α1D, respectively, is the most potent antagonist of the series, while compound 10 with a pA2 of 8.37 at α1D subtype and selectivity ratios of 162 (α1D/α1A) and 324 (α1D/α1B) is the most selective. Binding assays in CHO cell membranes expressing human cloned α1-adrenoceptor subtypes confirm the pharmacological profiles derived from functional experiments, although the selectivity values are somewhat lower. Therefore, it is concluded that 1,3-dioxolane-based ligands are a new class of α1-adrenoceptor antagonists.
46
8
1504
1511
1,3-Dioxolane-Based Ligands as a Novel Class of Alpha1-Adrenoceptor Antagonists / Brasili, Livio; Sorbi, Claudia; Franchini, Silvia; Manicardi, M.; Angeli, P.; Marucci, G.; Leonardi, A.; Poggesi, E.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 46:8(2003), pp. 1504-1511. [10.1021/jm021078o]
Brasili, Livio; Sorbi, Claudia; Franchini, Silvia; Manicardi, M.; Angeli, P.; Marucci, G.; Leonardi, A.; Poggesi, E.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/449021
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 32
social impact