Synthesis of 1,4-disubstituted-piperazines as potential antihypertensive agents

A new series of 1,4-disubstituted piperazines was synthesized. The pharmacological screening of some of the synthesized compounds revealed that compound III displayed a potent hypotenisve activity with rapid onset and prolonged duration of action, that was not accompanied by compensatory tachycardia. Moreover, compound III was found to be a competitive alpha-adrenergic blocker as well as a preferential beta 1- blocker. Compounds that block alpha adrenoreceptors do not show a great deal of structural similarity. Thus among the diverse structures which possess potent alpha- adrenergic blocking activity there are the 1,4-disubstituted piperazines Prazocin, which belongs to the latter class is now being used in clinical practice as an antihypertensive agent [12]. Consequently, a new series of 1-arylpiperazine derivatives were synthesized for evaluation as potential adrenergic blockers

Synthesis and biological activity of certain nicotinic acid derivations

A simple procedure for the synthesis of 3-ethoxy-carbonyl-4, 6- dimethyl-2-pyridine I is described. The reaction of I with NAOC2H5 affords the corresponding sodic derivative II, which reacts readily with certain alkyl and acyl halides to give the O-alkyl and O-acyl derivatives III. Structures of the reaction products were determined using both chemical and spectroscopic methods. Biological screening of some of the newly synthesized compounds revealed that they exhibit anti-hyperlipidaemic activity

novel approach to the interpretation of the properties and behaviour of heterocyclic n-oxides

In 1940, Linton reported that the dipole moment of pyridine 1-oxide [I] is 4-24 D, a value much lower than calculated for the group moment of the N-oxide function, and the moment of pyridine. In order to confirm the surprising stability of the N-oxide function, the electrochemical reduction potentials of [I] and quinoline 1-oxide [II] were determined polarographically. In acid solution the potentials of [I] and [II] were found much lower than those of ordinary 3 degree amine oxides. Comparing the heterocyclic N-oxides with the N-oxides of usual 3degree amines, several similarities and certain differences are found, some of which are outlined as follows: [a] Dipole moments: the usual amine oxides have very high dipole moments. The dipole moment of the heterocyclic N-oxides are significantly lower, [b] Boiling and melting points: amine oxides of the usual 3 degree amines have very high m.p. The m.p. of amine oxide of the type [I] and [II] are lower, and therefore they can be distilled at reduced pressure. [c]Solubility: the usual 3 degree amine oxides dissolve readily in water, and do not dissolve in fat solvents: the heterocyclic N-oxides tend to have the same solubility behaviour in water but contrary to 3 degree amine oxides, they can dissolve very readily in non polar solvents. [d] Susceptibility to reduction: while the common 3 degree amine oxides are readily reduced by common reducing agents viz. H2SO3 and acidified potassium iodide, the heterocyclic N-oxides are remarkably resistant to such reduction. From the foregoing, E Ochiai considered the heterocyclic N-oxides as a distinct class of compounds while Colonna has chosen to consider them as aldonitrones

Synthesis of pyrazolo [3,4-b] pyridine derivatives

The reaction of 3-amino-5-pyrazolones with 1, 3-dicarbonyl compounds has been shown to give either pyrazolo[l,5-a] pyrimidine or pyrazolo [3,4-b] pyridines depending on the conditions employed. The pyrazolo [3,4-b] pyridines were reported to be valuable from both the pharmacological and antimicrobial view points. Consequently, the present work comprised the investigation of the reaction of l-phenyl-3-amino-5-pyrazolone [I] with ethyl acetylpyruvate [II] aiming to synthesise pyrazolo [3,4-b] pyridine derivatives of biological interest