Antitumor effect of Pt(II) amine phosphonate complexes on sarcoma sa-180 in mice. Crystal structure of cis-dichlorobis(diethyl-4-pyridylmethylphosphonate-kappaN)platinum(II) hydrate, cis-[PtCl2(4-pmpe)2].H20.

The cisplatin analogoues platinum (II) complexes of the general formula cis-[PtL2Cl2], where L is monodentate diethyl 2-, 3- or 4-pyridylmethylphosphonate (2-, 3- or 4-pmpe) ligand, have been synthesized and characterized by means of IR and NMR (1H, 31P, 195Pt) spectroscopy. The crystal and molecular structure of cis-[Pt(4-pmpe)2 Cl2].H2O (A3) shows a square planar geometry of PtL2Cl2, with two organic molecules and two chloride leaving ligands in a cis configuration. The antitumor activity of the platinum (II) complexes was examined against Sarcoma Sa-180 in mice. The obtained results indicate a marked anticancer effect of platinum phosphonate complexes, and moderate nephrotoxicity evaluated in the BUN and creatinine levels in comparison with cisplatin (CDDP).

Influence of mianserin on the antinociceptive effect of morphine, metamizol and indomethacin in mice.

The influence of mianserin (5 or 3.6mgkg(-1)) on antinociceptive effect of morphine (10mgkg(-1)), metamizol (500mgkg(-1)) and indomethacin (10 or 1.4mgkg(-1)) was investigated in a mouse model using the tail-flick and hot-plate tests. All drugs were injected intraperitoneally (i.p.). Mianserin was administered to mice 30min before applying the analgesic drugs. Measurement of nociception was performed within 2h after mianserin administration. The study was further conducted for 14 days with multiple drug doses. The results indicate that mianserin in a single dose increased the antinociceptive effect of metamizol (in the hot-plate and tail-flick tests) and indomethacin (only in the tail-flick test). Mianserin administered for 14 days together with metamizol increased the analgesic effect of the latter drug (in the hot-plate and tail-flick tests). Mianserin applied for 14 days increased the antinociceptive effect of indomethacin (in the tail-flick test).

Effect of citalopram and buspirone on the antinociceptive action of analgesic drugs.

The influence of citalopram (20 mg/kg i.p.) and buspirone (3 mg/kg i.p.) on analgesic effects of morphine (10 mg/kg i.p.), metamizole (500 mg/kg i.p.) and indomethacin (10 mg/kg) was studied with tail-flick and hot-plate tests on mice. The research studies were further conducted with multiple (14 days) drug dosage. The results indicate that citalopram and buspirone decrease analgesic effects of morphine, metamizole and indomethacin. This mode of action is more pronounced in case of a single dose than after multiple doses.

Comparison of pharmacophore cinnoline and quinoline systems on the basis of computer calculation and pharmacological screening of their condensed systems.

A series of new pyrimido[5,4-c]quinoline derivatives were prepared to compare the pharmacophore systems of cinnoline and quinoline. These compounds were obtained by the cyclocondensation of appropriately substituted 4-amino-3-quinolinecarboxylic acids 3 with acetic anhydride to the respective 2-methyl-1,3-oxazino[5,4-c]quinolin-4(3 H)-ones 4. These derivatives reacted with amines and gave N-3 substituted 2-methylpyrimido[5,4-c]quinolin-4(3 H)-ones 6. 4-Amino-3-quinolinecarboxamide 2 reacted with diethyl carbonate to give 1,2,3,4-tetrahydropyrimido[5,4-c]quinolin-2,4-diones 5. The SAR parameters of the derivatives obtained were analysed with the HyperChem 5.1/ChemPlus 2.0 computer program. The compounds synthesized were screened for their effect on the CNS.

Synthesis and action on the central nervous system of 8-substituted 6,7,8,9-tetrahydro-5H-1,2,4-triazolo[4,3-a]-diazepine derivatives.

Selected 8-substituted 6,7,8,9-tetrahydro-5H-1,2,4-triazolo[4,3-a] diazepine derivatives were synthesised and tested for their action on the central nervous system. The obtained results showed that the examined compounds type IV have sedative activity. The strongest effect was exerted by compound IV-f.

Effect of diazepam and midazolam on the antinociceptive effect of morphine, metamizol and indomethacin in mice.

The influence of midazolam and diazepam on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg) was investigated in a mouse model using the tail-flick and hot-plate tests. All drugs were injected intraperitoneally. Benzodiazepines were administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after benzodiazepine administration. Diazepam at doses of 0.25 mg/kg and 2.5 mg/kg injected with morphine was found to decrease the antinociceptive effect of morphine. Similarly, diazepam decreased the antinociceptive effect of metamizol (only in the tail-flick test) and indomethacin. Midazolam used at doses of 1.25 mg/kg and 2.5 mg/kg decreased the antinociceptive effect of morphine, metamizol (only in the tail-flick test) and indomethacin.

Irritation of gastrointestinal mucosa by new glycosyl derivative of diclofenac in comparison with diclofenac in rats.

We have obtained new glycosyl derivative of diclofenac 3 and studied its ulcerogenic effect in the gastrointestinal system. Diclofenac as free acid 1 and its derivative 3 were administered to rats per os in a single dose 20 mg/kg and in 5 doses of 5 mg/kg. Single dose of derivative 3 caused less irritation than 1; after multiple administration no irritating effect of derivative 3 was seen.

Synthesis and biological activity of some 4-amino-3-cinnoline carboxylic acid derivatives. Part 4: 2,4-Dioxo-1,2,3,4-tetrahydropyrimido[5,4-c]cinnolines.

A series of new 2,4-dioxo-1,2,3,4-tetrahydropyrimido[5,4-c]cinnolines and their 3-substituted derivatives were prepared. These compounds were obtained by cyclocondensation of the appropriate substituted 4-amino-3-cinnolinecarboxylic acid with urea or 4-amino-3-cinnolinecarboxamides with N,N'-carbonyldiimidazole (DCl), oxalyl chloride or diethyl carbonate. Most of these compounds showed a high sedative action in low doses.

Synthesis and biological activity of some 4-amino-3-cinnolinecarboxylic acid derivatives. Part 5: Pyrimido[5,4-c]cinnolines and triazepino[7,6-c]cinnoline.

A series of substituted 3-aminopyrimido[5,4-c]cinnolines 3, 7 was prepared. 6,7-Substituted 4-amino-3-cinnolinecarboxylic acid 1 were condensed with acetic anhydride to give the respective 1,3-oxazino[5,4-c]cinnolines 2. The obtained derivatives reacted with hydrazines and gave 3-aminopyrimido[5,4-c]cinnolines. Reaction of the esters 5 with hydrazines produced hydrazides 6, which upon treatment with N,N-dimethylformamide dimethyl acetal gave 3-aminopyrimido[5,4-c]cinnolines 7. Treatment of 6b with bromocyan produced 2-amino-3,4-dihydro-3,10-dimethyl-5 H-1,3,4-triazepino[7,6-c]cinnolin-5-on (8b). Some of the synthesized compounds were screened for their effect on the CNS.

Synthesis, structures and biological activity of some 4-amino-3-cinnoline-carboxylic acid derivatives. Part 3: 1,3-Oxazino[5,4-c]cinnolines and pyrimido[5,4-c]cinnolines.

6,7,8-Substituted 4-amino-3-cinnolinecarboxylic acids 1 were condensed with acid anhydrides to corresponding 1,3-oxazino[5,4-c]cinnolines 2. The reactions of 1,3-oxazino[5,4-c]cinnolines 2 with amines, hydrazine, hydroxylamine, alanine ethyl ester provided pyrimido[5,4-c]cinnolines 3, 4. Selected 3-substituted 2-methylpyrimido[5,4-c]cinnolin-4(3 H)-ones have been screened for CNS activity.

Synthesis and action on the central nervous system of 3-substituted 2-phenyl-2,3-dihydro-4H-1,3,2-benzoxazaphosphorin-4-one 2-oxide and 2-sulfide derivatives.

The synthesis of 3-substituted 2-phenyl-2,3-dihydro-4H-1,3,2-benzoxazaphosphorin-4-one 2-sulfide derivatives is described. The action of a series 2-oxide (1-6) and 2-sulfide (7-12) derivatives on the central nervous system has been evaluated. Compounds 1-4, 6, 7-10 exhibit neuroleptic activity. Derivatives of sulfide series act as antiserotoninergic drugs.

Synthesis, structures and biological activity of some 4-amino-3-cinnolinecarboxylic acid derivatives. Part 2.

6,7,8-Substituted 4-amino-3-cinnolinecarboxylic acids 1 were condensed with amines to the corresponding 4-amino-3-cinnolinecarboxamides 7, 8. A variety of pharmacological tests showed a significant CNS activity of some new amides. Decarboxylation of 4-amino-3-cinnolinecarboxylic acids 1 yielded the corresponding 4-aminocinnolines 4 and alkaline hydrolysis of 1 gave 4-oxo-3-cinnolinecarboxylic acids 2. The acids 1 were converted into pyrimido[5,4-c]cinnolines 6 on two ways of synthesis.

Synthesis, structures and biological activity of some N1-substituted 4-oxocinnolines.

The method of preparation of N1-substituted 4-hydroxycinnolines is described, by alkylation with methyl bromopropionate of the corresponding 4-hydroxycinnolines. The obtained esters were further converted into amides and hydrazides. The effect of several synthesized derivatives on central nervous system was studied. The structure of some of them was confirmed by the X-ray analysis.

Synthesis, structures and biological activity of some 4-amino-3-cinnolinecarboxylic acid derivatives, Part 1.

This work describes the synthesis of 4-amino-3-cinnolinecarboxamides, which were then hydrolyzed to corresponding 4-amino-3-cinnolinecarboxylic acids. Several compounds were tested for their antibacterial and antifungal activity, and for the central nervous system effect.

Synthesis and pharmacological investigations of new 6-oxo-1,2,3,4-tetrahydro-6H-pyrimido[2,1-b]quinazoline derivatives.

The synthesis and biological activity of a series of 6-oxo-1,2,3,4-tetrahydro-6H-pyrimido[2,1-b]quinazoline is reported. Pharmacological investigations have shown that the compounds exert depressive action on the central nervous system and exhibit neuroleptic activity.

Synthesis and action on the central nervous system of some N2-substituted cinnoline derivatives.

Alkylation of 4-hydroxycinnolines using ethyl bromoacetate resulted in N2-substituted acetic acids. These acids were converted to esters and amides. Some of the obtained acids were reduced with zinc dust to give 4-oxo-1,2,3,4-tetrahydro-2-cinnolineacetic acids. Several of the compounds were tested for their effect on central nervous system.

Synthesis and action on the central nervous system of 9,10-dihydropyrrolo [3,4-b][1,4]benzoxazepine derivatives.

The synthesis of tricyclic system ring, 9,10-dihydropyrrolo[3,4-b] [1,4]benzoxazepine, and its derivatives is described. Some of the chemical and pharmacological properties of these compounds are also reported.

Diazepinoquinazolines. Part II. Synthesis and pharmacological activity of some derivatives of 1,4-diazepino[2,1-b]quinazoline.

New derivatives of 1,4-diazepino[2,1-b]quinazoline were obtained. The diazepino quinazoline [IV] was obtained by the condensation of 2,5,6,7-tetrahydro-3-(methylthio)-1-phenyl-1H-1,4-diazepine with 5-chloroantranilic acid. Compounds was preparated in two steps from 2,3,4,5-tetrahydro-1,4-diazepino[2,1-b]quinazolin-7(1H)-one. The derivatives [II-IV], [VII], [VIII] were screened for their psychotropic activity.

[Influence of benzyl penicillin on cytotoxicity and level of metabolic activity of cyclophosphamide in mice]. / Wplyw benzylopenicyliny na cytotoksycznosc i poziom aktywnych metabolitów cyklofosfamidu u myszy.

The influence of benzylpenicillin on cytotoxicity of cyclophosphamide (CF) against leukaemia L 1210 was studied. The level of CF metabolites in mouse serum was traced. The benzylpenicillin appeared to enhance cytotoxic activity of CF and leads to increase of active metabolites when CF applied in high doses (300 mg/kg).