Synthesis and biological evaluation of 2-aryliminopyrrolidines as selective ligands for I1 imidazoline receptors: discovery of new sympatho-inhibitory hypotensive agents with potential beneficial effects in metabolic syndrome.

New 2-aryliminopyrrolidines (1-18) were synthesized and tested for their binding properties on I1 imidazoline receptors vs α2-adrenergic receptors and their blood pressure effects after both systemic and intracerebral administrations. The purposes of this study were: (i) to analyze structure-activity and affinity relationships on I1 imdazoline receptors and (ii) to propose some leader compounds for the development of new sympatho-inhibitory drugs with potential applications in hypertension and/or metabolic syndrome, i.e., a cluster of cardiovascular (hypertension) and metabolic disorders. Our study highlights decisive arguments of SAR concerning both the affinity for I1Rs and the hypotensive activity of 2-aryliminopyrrolidines. Binding assays showed high affinity and selectivity of some compounds for I1 imidazoline receptors over α2-adreergic receptors. Compound 13 (laboratory reference LNP599; Ki = 3.2 nM on I1imidazoline receptors) is the prototype for the development of new centrally acting agents targeting specifically I1imidazoline receptors to be used in the management of hypertension and/or metabolic syndrome.

Synthesis, radiolabelling and stability of radioiodinated m-iodobenzylguanidine, a review.

Since the introduction of radioiodinated m-iodobenzylguanidine in 1980, much research has been performed, both in the chemical field as well as in medical sciences. This paper reviews the synthesis, radiolabelling and stability of radioiodinated m-iodobenzylguanidine. Regarding the many radiolabelling procedures for m-iodobenzylguanidine, the Cu(1+)-assisted nucleophilic exchange radioiodination can be considered as the method of first choice. Quality control of the radiopharmaceutical product is discussed and attention is paid to recent studies regarding the radiochemical stability of iodine-131 labelled m-iodobenzylguanidine.

[Benzoxazolinone phenylethanolamine antagonists of adrenergic receptors. A chemical and pharmacodynamic study]. / Phényléthanolamines benzoxazolinoniques antagonistes des récepteurs adrénergiques. Etude chimique et pharmacodynamique.

Benzoxazolinone can be considered as a bioisosteric analogue of pyrocatechol. This concept has led to the synthesis of benzoxazolinonic phenylethanolamines. The pharmacological study shows that these compounds possess an affinity for adrenergic receptors. Compound (XXXIV), the most interesting, is a competitive alpha and beta adrenergic antagonist which has been studied for antihypertensive activity.

C-Alkylpiperazines structurally related to piribedil. XI.

The synthesis of a new series of 1-alkoxybenzyl-4-(2-pyrimidyl)piperazines 2-methyl or 2,6-dimethyl substituted, related to piribedil, is described. Besides compounds (IV)-(IX a, b), the isomer (XI) of (V) was also prepared. Central dopaminergic and alpha-blocking activities both in vitro and in vivo were determined for all compounds. Derivatives (IV), (VII), (XI) were also studied for peripheral vasodilator and sympatholytic activities.

Synthesis and adrenergic blocking effects of 2-(alkylamino)-3,4-dihydroquinazolines.

Based on the known biological activity of a variety of guanidine-containing agents, several N-substituted 3,4-dihydroquinazolines were synthesized. These compounds can be considered to be rigid analogues of phenylguanidines. In anesthetized rats the compounds decreased blood pressure and were antagonists of the pressor response to norepinephrine.

Ergoline derivatives with oral, prolonged, alpha-adrenolytic activity.

The alpha-adrenolytic activity of 1-methyl-10-methoxydihydrolysergol 2-(3,5-dimethyl)pyrrolcarboxylate (XV, formula II) is, both in vitro and parenterally, quite similar to that of dihydroergotamine. By oral route the new compound is more active, and longer lasting than dihydroergotamine.

2,6-dialkylpiperazines. VIII (1)-N1-arylalkyl-N4-(2'-pyridyl)-2,6-dimethylpiperazines as adrenolytic and vasodilator agents.

A series of cis and trans N1-arylalkyl-N4-(2'-pyridyl)-2'6-dimethylpiperazines were synthetized and tested as adrenolytic and vasodilator agents. The N1-substitution with the 3,4-dimethoxyphenethyl group seems the most promising with regard to pharmacological activity, which was found to reside mainly in the trans isomer (3-II b). The adrenolytic activity of (3-II b) is comparable with that of the related 2-methyl derivative (1-III), while it is higher than that of (IV) in which the piperazine nucleus is C-unsubstituted.