Synthesis and antibacterial activity of pyridazino[4,3-b]indole-4-carboxylic acids carrying different substituents at N-2.

The synthesis and the in vitro evaluation of antibacterial activity of new pyridazino[4,3-b]indole-4-carboxylic acids 2-4, 6 against some selected representative of Gram-positive and Gram-negative bacteria are reported. The role of the lipophilicity in the modulation of the antibacterial activity of the tested compounds is discussed. All the synthesized compounds appear quite weak against Gram-positive bacteria, whereas have no significant activity against Gram-negative bacteria.

Synthesis and antibacterial activity of 2-aryl-2,5-dihydro-3(3H)-oxo-pyridazino[4,3-b]indole-4-carboxylic acids.

The in vitro antibacterial and antifungal activities of a series of pyridazinoindolonic acids II against some selected representative of Gram-positive, Gram-negative bacteria and fungi have been investigated. Some interesting observations among the structural features necessary for high antibacterial activity are presented and discussed.

X-ray crystal structure, partitioning behavior, and molecular modeling study of piracetam-type nootropics: insights into the pharmacophore.

To detect possible molecular determinants of amnesia-reverting activity, the conformational properties of a number of rigid and flexible piracetam-type cognition enhancers have been assessed by X-ray diffraction, NMR spectroscopy, and ab initio and high-temperature-quenched molecular dynamics (QMD) calculations. The structures of the preferred conformers in solution derived from 1H-NMR spectral analysis were in good agreement with those found by QMD calculations. Interestingly, the calculation of the average molecular lipophilicity potential on the water-accessible surface of the selected conformers was helpful in interpreting the partitioning behavior observed by measuring octanol-water partition coefficients and capacity factors in reversed-phase high-performance liquid chromatography.

Linear solvation energy relationships in reversed-phase liquid chromatography. Examination of RP-8 stationary phases for measuring lipophilicity parameters.

Molecular lipophilicity can be expressed by log P or more conveniently by log kw, determined by the so-called "shake-flask" (SF) technique or by reversed-phase high-performance liquid chromatography (RP-HPLC), respectively. In the present study, the lipophilicity of a large set of solutes was measured by RP-HPLC on a silanol-deactivated octylsilane (OS) reversed phase, namely Inertsil OS (IN). IN lipophilicity parameters were found to be fairly well correlated with log P.

Synthesis and structure-antimicrobial activity relationships of quaternary ammonium derivatives of perhydropyrrolo-[3,4-c]pyridine.

A large homologous series of quaternary ammonium derivatives of perhydropyrrolo[3,4-c]pyridine 5 was synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria. Compounds 5 proved to be always more potent than benzalkonium chloride, taken as reference. Antibacterial activity, expressed as log 1/MIC, was found linearly related to lipophilicity up to C13-C14 homologs, where a break in the linear relationship was observed.

Synthesis and pharmacological evaluation of perhydropyrrolo [3,4-c]pyridine derivatives.

Several N,N'-bis-alkyl-perhydropyrrolo[3,4-c]pyridines 4 and the corresponding bis-quaternary derivatives 5 have been prepared through standard methods starting from the bicyclic dilactam 2. Compounds 4 and 5 were evaluated for their inhibitory properties against acetylcholine (ACh), 1,1-dimethylphenyl piperazinium iodide (DMPP), 5-hydroxytryptamine (5-HT) and histamine (H1), and the guinea pig isolated ileum. Pharmacological data indicated that the strongest anticholinergic activity was shown by the dibenzyl amine 4 g, which among the tested molecules presented also a rather potent effect at the ganglia level, resulting about three times more potent than hexamethonium as ganglionic blocking agent.

Synthesis and cognition activating properties of some mono- and bicyclic lactam derivatives.

Upon reductive cyclization cyano esters 2, 3, and 9 yielded piperidones and perhydropyrrolo[3,4-c]pyridine lactams, generally as a mixture of diasteromeric cis-trans forms. X-ray crystallographic analyses were carried out on bicyclic dilactam derivatives 6 and 10, and a cis configuration at the ring junction was determined in both cases. A series of neuropsychopharmacological tests performed on the title compounds indicated that they are generally nontoxic even at high doses (up to 1000 mg/kg ip).

Synthesis of 12-mono- and di-substituted 8-aza-11-oxasteroids.

The synthesis of unsaturated derivatives of 8-aza-11-oxa-17-oxo-gonane and D-homo-gonane carrying one or two functional substituents at C-12 is reported. The key step for the construction of the heterosteroid skeleton was the cyclocondensation reaction of aldol adducts 1, derived from 1,3-cycloalkanediones and diethyl 2-oxo-malonate, with tosyl chloride and isoquinoline.

[Theophylline and theobromine derivatives of nitrogen heterocyclic compounds].

7-Theophylline derivatives with 4,6-dihydroxy-5-pyrimidinyl-, 3-oxopiperazinylmethyl- and 4-methyl-3,5-dioxopiperazinylmethyl substituents are described: they can be viewed as structural analogues of a nucleic base pair in the Hoogsteen arrangement; theobromine could be converted into the 1-(3,5-dioxo-4-pyrazolidinyl) derivative, similarly analogous to a base pair in the Watson-Crick arrangement.

[Phthalimide derivatives of pyrimidine and thiazole heterocyclics].

The synthesis of some phthalimido-derivatives of the pyrimidine and thiazole ring systems is described. The functional groups have been suitably selected to enhance structural analogy with the pairs of pyrimidine and purine bases present in nucleic acids. In preliminary tests some of these compounds have shown inhibitory activity towards RNA polymerase reaction in vitro.

[Salts and betaines with quaternary ammonium function derived from sulfanilamide and from p-aminobenzoic and p-aminosalicylic acids].

The preparation of quaternary ammonium derivatives of sulfanilamide and of tertiary amines containing an aliphatic chain up to c-18 is described. Some members of this series show greater antimicrobial activity than the parent substances. This is found also in comparison with other analogous series which have been prepared.