Passaggi a nord-ovest Interventi di archeologia preventiva nell'area fiorentina (Mezzana-perfetti Ricasoli) tra preistoria ed età romana

La curatela del volume collettaneo rende conto delle raqgioni del volume legato a azioni di archeologia preventiva in area dfiorentin

Gli scavi lungo l'asse stradale Mezzana- Perfetti-Ricasoli

Le AA. rendono conto della strategia di intervento archeologico e danno una breve descrizione dei contesti stratigrafic

Grosseto. Città etrusca di Roselle: indagini non invasive e saggi di scavo nel settore orientale

Il contributo illustra in dettaglio il resoconto dell'attività condotta sull'area del Parco Archeologico di Roselle nell'anno 201

1,3-Dioxolane-based ligands as a novel class of alpha(1)-adrenoceptor antagonists

1,3-Dioxolane-based compounds (2-14) were synthesized, and the pharmacological profiles at R1-adrenoceptor subtypes were assessed by functional experiments in isolated rat vas deferens (R1A), spleen (R1B), and aorta (R1D). Compound 9, with a pA2 of 7.53, 7.36, and 8.65 at R1A, R1B, and R1D, respectively, is the most potent antagonist of the series, while compound 10 with a pA2 of 8.37 at R1D subtype and selectivity ratios of 162 (R1D/R1A) and 324 (R1D/R1B) is the most selective. Binding assays in CHO cell membranes expressing human cloned R1-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 R1-adrenoceptor antagonists

Structure-Activity Relationships in 1,4-Benzodioxan-Related Compounds. 6. Role of the Dioxane Unit on Selectivity for Alpha1-Adrenoreceptor Subtypes

WB 4101-related benzodioxans 3-9 were synthesized, and their biological profiles at alpha1-adrenoreceptor subtypes and 5-HT1A serotoninergic receptors were assessed by binding assays in CHO and HeLa cells membranes expressing the human cloned receptors. Furthermore, receptor selectivity of selected benzodioxan derivatives was further determined in functional experiments in isolated rat vas deferens (alpha1A) and aorta (alpha1D) and guinea pig spleen (alpha1B), in additional receptor binding assays in rat cortex membranes containing alpha2-adrenoreceptors and 5-HT2 serotoninergic receptors, and in rat striatum membranes containing D2 dopaminergic receptors. An analysis of the results of receptor binding experiments for benzodioxan-modified derivatives 3-9 showed high affinity and selectivity toward the alpha1a-adrenoreceptor subtype for compounds 3-5 and 7 and a reversed selectivity profile for 9, which was a selective alpha1d antagonist. Furthermore, the majority of structural modifications performed on the prototype 1 (WB 4101) led to a marked decrease in the affinity for 5-HT1A serotoninergic receptors, which may have relevance in the design of selective alpha1A-adrenoreceptor antagonists. The exception to these findings was the chromene derivative 8, which exhibited a 5-HT1A partial agonist profile

Searching for cyclazosin analogues as alfa1B-adrenoceptor antagonists

A series of quinazoline derivatives, 2-20, structurally related to the racemic a1-adrenoceptor antagonist cyclazosin (1), were synthesized and evaluated for their functional antagonism at a1- and a2-adrenoceptors and for their binding affinity at human cloned a1a-, a1b- and a1d-adrenoceptor subtypes. They displayed, like 1, preferential antagonism and selectivity for a1 versus a2-adrenoceptors. Compounds 10, 13, and 18 showed high potency at a1-adrenoceptors similar to that of 1 (pKB values 8.47-8.89 versus 8.67), whereas 13 and 15 were endowed with the highest a1-adrenoceptor selectivity, only 3- to 4-fold lower than that of 1. In binding experiments, all of the compounds displayed an affinity practically similar to that found for 1, with the exception of 19 and 20 that were definitely less potent. The s-triazine analogue 18 was the most potent of the series with pKi values of 10.15 ( a1a), 10.22 ( a1b) and 10.40 ( a1d), resulting 77-fold more potent than 1 at a1a-adrenoceptors. In addition, the majority of compounds, like prototype 1, showed the same trend of preferential affinity for a1d- and a1b-adrenoceptors that a1a-subtype. In conclusion, we identified compounds 2-5, 10, 12 and 13, bearing either an aliphatic- or an arylalkyl- or aryloxyalkyl-acyl function, with an interesting subtype-selectivity profile, which makes them suitable candidates for their resolution as enantiomers structurally related to (+)-cyclazosin

Synthesis and alpha1-adrenoceptor antagonist activity of derivatives and isosters of the furan portion of (+)-cyclazosin

Alpha1-adrenoceptor selective antagonists are crucial in investigating the role and biological functions of alpha1-adrenoceptor subtypes. We synthesized and studied the a1-adrenoceptor blocking properties of new molecules structurally related to the alpha1B-adrenoceptor selective antagonist (+)-cyclazosin, in an attempt to improve its receptor selectivity. In particular, we investigated the importance of substituents introduced at position 5 of the 2-furan moiety of (+)-cyclazosin and its replacement with classical isosteric rings. The 5-methylfuryl derivative (+)-3, [(+)-metcyclazosin], improved the pharmacological properties of the progenitor, displaying a competitive antagonism and an 11 fold increased selectivity for alpha1B over alpha1A, while maintaining a similar selectivity for the alpha1B-adrenoceptor relative to the alpha1D adrenoceptor. Compound (+)-3 may represent a useful tool for alpha1B adrenoceptor characterization in functional studies