G. Primofiore

Synthesis of pyrrolo[3,4-c]pyridine derivatives possessing an acid group and their in vitro and in vivo evaluation as aldose reductase inhibitors

Abstract Derivatives of [pyrrolo[3,4- c ]pyridin-1,3(2 H )-dion-2-yl] alkanoic acids were prepared and their in vitro aldose reductase inhibitory activity was tested on rat lens enzyme. The acetic derivatives 2, 5 and 15a–d proved to be much more potent inhibitors than the propionic derivatives, 7 and 16a–d , and the iso-propionic derivatives, 3 and 6 . The presence of a second planar aromatic area in the benzoyl derivatives 15a–d did not result in any increase in activity. Two of the most active compounds in vitro ( 2 and 5 ) were also evaluated in vivo as inhibitors of glutathione lens depletion in galactosemic rats. None of the compounds was found to be active in maintaining the rat lens glutathione level, suggesting possible problems of ocular bioavailability and metabolism. The aldose reductase inhibitory activity of compounds 2 and 15d was also discussed by taking into account their conformational and electronic characteristics evaluated by means of theoretical calculations.

Synthesis and β-blocking activity of (E)- and (Z)-iminoethers of 1,8-naphthyridine. Potential antihypertensive agents. 4

Abstract A series of substituted (E)-and (Z)-iminoethers of 1,8-naphthyridine was synthesized from corresponding ketones. The pharmacological activity of these compounds was evaluated on isolated preparations to assess the eventual interaction with α and β adrenoceptors. All the compounds exhibited β2 stimulating and β1 blocking properties, while on α receptors neither stimulating nor blocking activity was observed.

1-substituted 2-benzylaminobenzimidazole derivatives: compounds with H1-antihistaminic activity

Abstract The preparation of 1-substituted 2-benzylaminobenzimidazole derivatives 13–24 is described. Although these compounds have a different structure from the general structure I of antihistamines, they showed some antihistaminic activity (pA2: 5–7) when tested in vitro on guinea pig ileum. The introduction of an additional basic centre as in the Mannich bases 25–27 did not cause any improvement of activity. All the compounds tested proved to be inactive in in vivo induced passive cutaneous anaphylaxis (PCA) and cutaneous vasopermeability in rats.

Isosteric replacement of the indole nucleus by benzothiophene and benzofuran in a series of indolylglyoxylylamine derivatives with partial agonist activity at the benzodiazepine receptor

Summary A number of benzothienyl- and benzofurylglyoxylylamine derivatives, which are analogues of previously described indolylglyoxylylamines with a partial agonist activity, are reported in this paper. They were synthesized and tested to verify the importance of the presence of the indole NH group in the interaction of this class of compounds with the benzodiazepine agonist receptor site, since it was reported in literature that a hydrogen bond donor group such as NH was not necessary to elicit an agonist response. Several thienylglyoxylylamine derivatives were also prepared and tested. None of the compounds showed a high affinity at the BzR, demonstrating that the indole NH plays a decisive role in the interaction of the agonist glyoxylylamine ligands with the receptor site.

Indole Derivatives as Probes to Study the Benzodiazepine Binding Site in Gaba Receptor Complex

γ-Aminobutyric acid (GABA), one of the most ubiquitous inhibitory neurotrasmitter in the central nervous system (CNS), binds to its recognition sites, GABA receptor, and decreases neuronal excitability by increasing membrane chloride conductance. GABAA receptors are supermolecular receptor-chloride channel complexes of multiple subunits (α, β and γ) with distinct but interacting recognition sites for the neurotrasmitter, for convulsants (such as picrotoxin and bicyclophosphorothionates), and for depressants (such as benzodiazepines, barbiturates and neurosteroids) (MacDonald and Olsen, 1994).

BROMO DERIVATIVES OF GRAMINES. PREPARATION AND PHARMACOLOGICAL PROPERTIES

Bromieten von Gramin (I) ergibt ein nicht trennbares Gemisch des 5-Bromderivates (II) mit demo-Bromderivat (III), das durch Mannich-Reaktion aus 6-Bromindol (IV) rein . erhalten wird.