SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF CYCLIC AND OPENED THIOANALOGUES OF PIPEROXAN

Three piperoxan analogues, derived from the opening of the benzodioxane ring and/or replacement of the oxygen atom with the less polar sulfur, were synthesized. The decrease of the -blocking activity found for these compounds showed that the binding site of benzodioxane-like compounds does not accept the substitution with less polar groups

2-{[(2-(2,6-Dimethoxyphenoxy)ethyl]}-1,4-benzoxathiano:A New Antagonist With High Potency and Selectivity Toward alpha1-Adrenoreceptors.

These results emphasize the importance of the position 4 in both thebenzodioxan and benzoxathian nucleus for the interactionat a,-adrenoreceptors. Since sulfur cannot form a productivehydrogen bond, the position 4 of antagonists bearinga benzodioxan or a benzoxathian nucleus would interactwith the receptor, either increasing the electron densityof the phenyl ring by a way of an electron-releasing effector giving rise to a dipole-dipole interaction.In conclusion, compound 1 is a potent and selectivealpha1-adrenoreceptor antagonist that may represent a valuabletool in the characterization of a-adrenoreceptor subtypes

New 4-(4-methyl-phenyl)phthalazin-1(2H)-one derivatives and their effects on alpha(1)-receptors

Continuing our research aimed at obtaining new Compounds with high affinity and selectivity toward alpha(1)-AR, a new series of arylpiperazine derivatives was designed, synthesized, and biologically tested. The new Compounds 1-17 are characterized by a phenylphthalazin-1(2H)-one fragment connected through an alkyl chain to an arylpiperazine residue. The pharmacological profile of these compounds was evaluated for their affinity and selectivity toward alpha(1)-AR, alpha(2)-AR and toward 5HT(1A) serotoninergic receptor. A discussion on the structure-activity relationship (SAR) of these compounds is also reported

Structure-activity relationships in a series of 8-substituted xanthines as bronchodilator and A(1)-adenosine receptor antagonists

Four new derivatives of 8-piperazine ethyl xanthine were synthesized and their bronchospasmolytic activity and A(1)-adenosine affinity were studied. Their relaxant action in the tracheal muscle was lower than that of theophylline and that of theophylline derivatives substituted at the 7-position. Only compound 9, where the methyl group in the 1-position of the theophylline was substituted by an isobutyl group, shows a good affinity towards the A(1)-adenosine receptor

Synthesis of new pyridazinone derivatives and their affinity towards alpha(1)-alpha(2)-adrenoceptors

A series of 3(2H)-pyridazinone derivatives was evaluated for their affinity in vitro towards alpha(1)-alpha(2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha(1)-adrenoceptor (with K-i values in the subnanomolar range), and a gradual increase in affinity was observed by increasing the polymethylene chain length of this series up to a maximum of six and seven carbon atoms, when the fragment 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl is linked in 5 position of the 3(2H)-pyridazinone ring, while a slight decrease was found for the higher homologues. Increasing the chain length when the 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl group is linked in 6 position of the 3(2H)-pyridazinone ring, had a different effect: there is the highest affinity when the polymethylene chain is of four carbon atoms. The alkylic chain, a spacer between the two major constituents of the molecule, can influence the affinity and the selectivity. (C) 1999 Elsevier Science Ltd. All rights reserved

Synthesis of new piperazine-pyridazinone derivatives and thier binding affinity toward a1-, a2-adrenergic and 5-HT1A serotoninergic receptors.

We report the design and synthesis of a new class of piperazine-pyridazinone analogues. The arylpiperazine moiety, the length of the spacer, and the terminal molecular fragment were varied to evaluate their influence in determining the affinity of the new compounds toward the alpha(1)-adrenergic receptor (alpha(1)-AR), alpha(2)-adrenergic receptor (alpha(2)-AR), and the 5-HT1A serotoninergic receptor (5-HT1AR). Biological data showed that most of the compounds have an alpha(1)-AR affinity in the nanomolar or subnanomolar range, while affinity toward the other two receptors was lower in most cases. However, several of the tested compounds also showed very good (in the nanomolar range) or moderate affinity toward the 5-HT1AR subtype

Synthesis of new piperazine-pyridazinone derivatives and their binding affinity toward alpha1-, alpha2-adrenergic and 5-HT1A serotoninergic receptors.

We report the design and synthesis of a new class of piperazine-pyridazinone analogs. The arylpiperazine moiety, the length of the spacer, and the terminal mol. fragment were varied to evaluate their influence in detg. the affinity of the new compds. toward the \u3b11-adrenergic receptor (\u3b11-AR), \u3b12-adrenergic receptor (\u3b12-AR), and the 5-HT1A serotoninergic receptor (5-HT1AR). Biol. data showed that most of the compds. have an \u3b11-AR affinity in the nanomolar or subnanomolar range, while affinity toward the other two receptors was lower in most cases. However, several of the tested compds. also showed very good (in the nanomolar range) or moderate affinity toward the 5-HT1AR subtype