Biomedical subjects

J Sapa

Publications and source records attributed to J Sapa.

10 recordsLinked to original sources

PubMed2005

Synthesis, analgesic activity and computational study of new isothiazolopyridines of Mannich base type.

A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (3 and 4) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED50, was found to be 2-10 times more potent than that of acetylsalicylic acid and 1.5-10 times weaker than that of morphine, these being used as standards. The toxicities (LD50) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.

Analgesics↗

PubMed2004

Synthesis and analgesic action of N-(substituted-ethyl)pyrrole-3,4-dicarboximides.

We prepared a series of new N-[2-(4-substitutedpiperazin-1-yl)ethyl]-1-(n-butyl or phenyl)-2,5-dimethyl-3,4-pyrroledicarboximides 3 and the related products 4 and 5, nine representatives of which were evaluated as potential analgesic agents in an animal model (mice). The new pyrroledicarboximides were not toxic (LD50 > or = 1466 mg/kg) and eight of them displayed analgesic activity approximately 1.5-5 times superior to that of ASA in the writhing test. However, the compounds were found to be unstable in methanol solution and in dilute bases (methanol/NaOMe). The S-A relationship is discussed.

Analgesia↗

PubMed2004

Synthesis and properties of N-methyl and N-phenyl derivatives of 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines.

2-Methoxy- and 2-ethoxy-6-methyl-3,4-pyridinedicarboximides (XI, XII) reacted with N-methylhydrazine giving 2- and 3-methyl derivatives of the appropriate 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines (XV, XIII and XVI, XIV). In both cases 3-methyl isomer (XIII, XIV) was formed in higher yield than 2-methyl derivative (XV, XVI). Reaction of the imide XII with N-phenylhydrazine gave the salts of the suitable N-phenyldihydropyrido[3,4d]pyridazines with NH2-NHC6H5 (XXI and XXII) which transformed into N-phenylaminoimide (XXIII) during the boiling in 80% CH3COOH. Imide XXIII isomerized to the appropriate 2-phenyl and 3-phenylpyrido[3,4-d]pyridazines (XXIV - main reaction product and XXV) under the influence of heating in ethanolic solution of C2H5ONa. Some of N-phenylpiperazinylhydroxyalkyl(alkyl) derivatives of compound XXIV (XXVII, XXVIII) were pharmacologically active.

Analgesics, Non-Narcotic↗

PubMed2002

Preparation of novel derivatives of pyridothiazine-1,1-dioxide and their CNS and antioxidant properties.

Starting from isothiazolopyridine-1,1-dioxide (1), corresponding derivatives of 3-aryl-4-hydroxypyrido[3,2-e]-1,2-thiazine-1,1-dioxide (6) possessing the 3-[4-(substituted-phenyl)piperazinyl]propyl or 3-(4-substituted-piperidinyl)propyl side chain by the nitrogen atom of the thiazine ring were prepared. Under pharmacological central nervous system (CNS) screening in animal models (mice), all of the six pyridothiazines 6 tested exhibited analgesic action as the predominant profile of their activity ('writhing' test 12.5-50 mg/kg). Moreover, the radical scavenging activity against peroxyl radicals of the representative pyridothiazines 6 was evaluated in vitro in water environment and some of them proved to be moderate antioxidants.

Analgesics↗

PubMed2001

Synthesis and properties of 2-(4-substituted)butyl derivatives of some 2,3-dihydro-1,3-dioxo-1H-pyrrolo[3,4-c]pyridines.

The synthesis of 2-(4-substituted)butyl derivatives of 4-alkoxy-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (10-15) and the results of preliminary pharmacological screening are described in this paper. All the compounds tested showed a strong analgesic action, suppressed spontaneous locomotor activity and prolonged barbiturate sleep. Except 10, all significantly decreased systolic and diastolic blood pressure.

Analgesics, Non-Narcotic↗

PubMed1997

Search for new antiarrhythmic and hypotensive compounds. Synthesis, antiarrhythmic, antihypertensive, and alpha-adrenoceptor blocking activity of novel 1-[(2-hydroxy-3-amino)]-propylpyrrolidin-2-one derivatives.

A series of the derivatives of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl])propyl]-pyrrolidin-2- one (MG-1) was synthesized and tested for electrocardiographic, antiarrhythmic, and antihypertensive activity as well as for alpha 1- and alpha 2-adrenoceptors binding affinities. Some of the compounds of this series slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Only compound 7 (1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidine) possesses potent antiarrhythmic and a slight hypotensive properties, and affinity for alpha 1- and alpha 2-adrenoceptor. The results suggest that the antiarrhythmic and hypotensive effect of compound 7 and MG-1 is related to their adrenolytic properties, and that those properties depend on the presence of a phenylpiperazine moiety.

Adrenergic alpha-Antagonists↗

PubMed1995

Individual differences in docility in Limousin cattle.

Docility tests were performed over 3 yr on 906 Limousin heifers sired by 34 males. The heifers were tested individually when they were 10 to 11 mo old in a pen with a handler who had 2 min to lead the animal to a corner, keep it there for 30 consecutive seconds, and then to stroke it. Behaviours of the animals were recorded and scores calculated. The first score (docility score) was a continuous variable combining the greatest possible information. The second score (docility criterion) was a categorical trait with four classes. Tests were performed by seven different handlers. The effects of handler, year, birth period, dam parity, birth region, husbandry system, and sire were estimated. Handlers, birth period, husbandry system, and sire had significant effects. In particular, animals that were managed indoors were more docile than those reared out-of-doors at least part of the time. Heritability estimates of the docility score (.22) and docility criterion (.18) seem sufficient to select for docility traits.

Aggression↗

PubMedDate not supplied

Effect of monoterpene derivative KP-19 on the pressor activity of catecholamines in rats.

The present study investigated the influence of KP-19, the propranolol analogue, bearing natural monoterpene moiety in its structure, on the blood pressure and respiration, the effect on the isolated heart rhythm disturbances induced by occlusion and reperfusion and on the pressor activity of catecholamines in normotensive rats.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Synthesis and properties of tetra(hexa)hydropyrazolo [1,2-a]pyrido[3,4-d]pyridazine derivatives.

The synthesis of tetra(hexa)hydropyrazolo[1,2-a]pyrido[3,4-d]pyridazine derivatives (14-21) and the results of pharmacological screening are described in this paper. All compounds tested were non-toxic and showed a significant analgesic action. The analgesic effects were associated with the suppression of the spontaneous locomotor activity. Furthermore most of the synthesized compounds displayed a weak antimycobacterial action in the preliminary screening.

Analgesics, Non-Narcotic↗

PubMedDate not supplied

Synthesis and properties of some aminoalkanolic derivatives of xanthone.

A series of appropriate aminoalkanolic derivatives of xanthone III-VIII was synthesized and evaluated as potential antiarrhythmic agents. They were also tested for the effect on the cardiovascular system. The structure of the synthesized compounds was verified by IR 1H NMR, 13C NMR and mass spectral data.

Animals↗