- Scouting new sigma receptor ligands: Synthesis, pharmacological evaluation and molecular modeling of 1,3-dioxolane-based structures and derivatives
-
Herein we report the synthesis and biological activity of new sigma receptor (σR) ligands obtained by combining different substituted five-membered heterocyclic rings with appropriate σR pharmacophoric amines. Radioligand binding assay, performed on guine
- Franchini, Silvia,Battisti, Umberto Maria,Prandi, Adolfo,Tait, Annalisa,Borsari, Chiara,Cichero, Elena,Fossa, Paola,Cilia, Antonio,Prezzavento, Orazio,Ronsisvalle, Simone,Aricò, Giuseppina,Parenti, Carmela,Brasili, Livio
-
-
- 1,3-Dioxolane-based ligands as a novel class of α1-adrenoceptor antagonists
-
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.
- Brasili, Livio,Sorbi, Claudia,Franchini, Silvia,Manicardi, Massimo,Angeli, Piero,Marucci, Gabriella,Leonardi, Amedeo,Poggesi, Elena
-
p. 1504 - 1511
(2007/10/03)
-
- Enzymatic resolution of 2,2-disubstituted-1,3-dioxolane-4-methanol carboxylic esters
-
The enantioselectivity of enzymatic hydrolysis of carboxylic esters of various 1,2-ketals of glycerol has been investigated. The influence of the ketal group has been studied. A number of lipases and proteinases have been tested and the best enantioselectivity was obtained with proteinase from Aspergillus oryzae which gave an E-value of 9 with 2,2-dimethyl-1,3-dioxolane-4-methanol butanoate. Variations in the acyl part revealed that butanoyl was optimal. All hydrolysis products have been synthesised in homochiral forms from homochiral starting materials.
- Partali,Melbye,Alvik,Anthonsen
-
-