Substituted quinazolones as potent anticonvulsants and enzyme inhibitors.

A series of 6,8-disubstituted 3-[5- [[2-hydroxy-3-[(substituted phenyl)amino]propyl]thio]-1,3,4-thiadizol-2-yl] 2-methyl-4(3)- quinazolinones were synthesized whose structures were confirmed by elemental analyses, IR, NMR and mass spectral studies. All these compounds were evaluated in vivo for anticonvulsant and analgesic activities and in vitro for monoamine oxidase and succinate dehydrogenase enzyme inhibitory activities using rat brain homogenate as a source of enzyme at final concentration of 1 x 10(-4) mol/l. ALD50 values indicated their relatively nontoxic nature.

Monoamine oxidase inhibitory and anticonvulsant studies of substituted 1,4-benzodiazepines.

Sixteen new 2,3-dihydro-N-(substituted phenyl)-spiro (benzo [b] cyclopenta [e][1,4] diazepine-10(1H), 1'-cyclopentane)-9(10aH)-ethanamines, whose structures were confirmed by correct elemental analyses, IR, NMR and mass spectral studies, were synthesized and evaluated for anticonvulsant and analgesic activity in vivo and monoamine oxidase (MAO) inhibitory activities in vitro. The compounds exhibiting significant anticonvulsant and analgesic activity also showed marked inhibition of the enzyme MAO. The low toxicity of these compounds was reflected by their high approximate LD50 values.

Antiparkinsonian activity and dopamine receptor binding studies of imidazolone derivatives.

Mannich bases and styryl derivatives of imidazolones were evaluated for their antiparkinsonian activity. Two compounds showed potent antiparkinsonian activity. These active compounds also showed binding with dopamine receptors in striatal membrane preparation of rat brain.

Anti-inflammatory activity of quinazolinoformazans.

Eight substituted quinazolonoformazans were synthesized and evaluated for anti-inflammatory activity. The degree of protection provided by seven of these compounds, at a dose of 100 mg/kg, po, against carrageenin-induced edema in rat paw ranged from 26 to 57%. The four active substituted quinazolonoformazans (1, 2, 6, 8), on further evaluation for antiwrithmogenic activity, provided 10-80% protection against the aconitine-induced writhing response in mice. The ulcerogenic liabilities of two of the most active compounds were also determined. The doses producing ulcers in 50% of the treated rats (UD50) were 155 and 260 mg/kg, ip, for 2 and 8, respectively. The low toxicities possessed by these substituted quinazolonoformazans were indicated by their LD50 values which ranged from 600 to 1300 mg/kg, ip, in mice.

Anti-inflammatory and analgesic activities of 5-(4-[aryl(aryl azo)methyleneamino]phenyl)-1,3,4-oxadiazole-2(3H)-thiones.

Various new formazans of substituted oxadiazole 2(3H)-thiones were tested for their anti-inflammatory activity against carrageenin-induced paw oedema in albino rats. Among these, two most potent derivatives were evaluated in detail using cotton pellet implantation methods in albino rats of either sex. These two active analogues were also tested for their analgesic activity in albino mice and ulcerogenic liability in albino rats. The toxicity of the compounds was assessed by determination of their approximate LD50 value in albino mice. An attempt has also been made to establish the structure-activity relationship.

Novel formazans as potent anti-inflammatory and analgesic agents.

Various new substituted formazans were synthesized and characterized by elemental analyses, IR and mass spectral data. The compounds were evaluated for their ability to protect against inflammation by carrageenin-induced paw edema in albino rats of either sex. The active derivatives of the present series were also tested for their analgesic activity against aconitine-induced writhing in albino mice and ulcerogenic activity in albino rats. The toxicity of the compounds was assessed by determination of their approximate LD50 on albino mice. An attempt has also been made to establish a structure-activity relationship.

Monoamine oxidase inhibitory and anticonvulsant properties of some newer indolylimidazolones.

Newly synthesized indolylimidazolones were tested for their in vitro monoamine oxidase (MAO) inhibitory activity. These compounds were found to possess analgesic activity and anticonvulsant activity against maximal electroshock-induced convulsions in mice. The low toxicity of these compounds was reflected by their high approximate LD50 values.

Inhibition of rat brain monoamine oxidase and succinic dehydrogenase by anticonvulsant pyrazolines.

Substituted 1,5-diaryl-3(4-chlorophenyl)-delta 2-pyrazolines were synthesized and evaluated for anticonvulsant activity. Most pyrazolines (100 mg/kg) provided 20-80% protection against pentylenetetrazol-induced convulsions in mice. All compounds inhibited rat brain mitochondrial monoamine oxidase (MAO) and succinic dehydrogenase (SDH) and exhibited low toxicity as reflected by approximate LD50 values (500 to greater than 1000 mg/kg) in mice.

Tetrazoles as potent anti-inflammatory agents.

Various new tetrazoles were tested for their anti-inflammatory activity against carrageenin-induced paw oedema in albino rats. Among these, two most potent derivatives were evaluated in detail using cotton pellet implantation methods in albino rats of either sex. These two active analogues were also tested for their analgesic activity in albino mice and ulcerogenic liability in albino rats. All derivatives of the present series were evaluated for their antiproteolytic activity. The toxicity of the compounds was assessed by determination of their approximate LD50 in albino mice. An attempt has also been made to establish the structure activity relationship.

Novel thiazolidinones as potent anti-inflammatory and analgesic agents.

Various new butyridenyl-2-hydroxybenzylidenyl-1,3-thiazolidinones were synthesized and characterized by elemental analyses, IR and PMR spectral data. The compounds were evaluated for their ability to afford protection against inflammation by carrageenin-induced oedema and cotton pellet implantation in albino rats of either sex. The active derivatives of the present series were also tested for their analgesic activity against aconitine-induced writhing in albino mice and ulcerogenic activity in albino rats. The toxicity of the compounds was reflected by determination of their approximate LD50 in albino mice. An attempt has also been made to correlate their structure-activity relationship.

Substituted triazoles as anti-inflammatory agents.

Newly synthesized triazoles were evaluated for their anti-inflammatory and antiproteolytic activities. These derivatives possessed potent anti-inflammatory and antiproteolytic activities. In addition, these compounds were relatively less toxic.

Synthesis of some substituted benzodiazepines as possible CNS depressant drugs.

A new series of 2,3-cyclopentano-3,4-dihydro-4-spirocyclopentano-1,5-benzodi azepine which are substituted in 5-position with beta-N-heterocycloethyl or gamma-N-heterocyclo-n-propyl groups have been synthesized and evaluated for their CNS depressant activity including anticonvulsant, analgesic and pentobarbital induced hypnosis. These compounds were also investigated for their ability to inhibit in vitro succinate dehydrogenase (SDH). In most of the compounds an appreciable CNS depressant activity has been found to be associated with the compounds possessing good SDH inhibitory activity. Low toxicity of these compounds was reflected by their high approximate LD50 values.

Newer indolyl imidazolones as anti-inflammatory agents.

Sixteen new 1,2-disubstituted-4-(indol-3'-yl)methylene imidazol-5-ones were synthesized by the condensation of oxazolone with different aryl amines and evaluated as to their anti-inflammatory and antiproteolytic activities. These derivatives showed 2-38% protection against carrageenin-induced paw oedema in albino rats at a dose of 100 mg/kg p.o. All compounds showed antiproteolytic activity. The degree of inhibition against trypsin-induced hydrolysis of casein ranged from 10 to 75% at a concentration of 4 X 10(-4) mol/l. Furthermore, active compounds of the series were also screened for their analgesic activity against aconitine-induced writhing in albino mice. The toxicity of the compounds was reflected by their approximate LD50 values.

Role of catecholamines in the central actions of medroxyprogesterone acetate.

The role of catecholamines in the mechanism of antiovulatory and other central effects of medroxyprogesterone acetate (MPA) has been studied in adult healthy, non-pregnant female albino rats. It has been observed that a single dose of MPA (100 mg/kg) given intramuscularly did not cause any significant change in brain catecholamine levels after 7 days of treatment. However, there was a significant reduction in brain dopamine levels after 15 days of MPA administration. This reduction in brain dopamine levels may be responsible for the anti-ovulatory activity of MPA. Certain side effects of MPA such as amenorrhoea, galactorrhoea, breast tenderness, breast tumors, inactivity and depression may also be due to decrease in brain dopamine levels.

Role of monoamine oxidase-B in medroxyprogesterone acetate (17-acetoxy-6 alpha-methyl-4-pregnene-3, 20-dione) induced changes in brain dopamine levels of rats.

The effect of medroxyprogesterone acetate (MPA) on brain monoamine levels and monoamine oxidase (MAO) activity was studied in adult, healthy, non-pregnant female rats. MpA was injected in a single dose of 100 mg/kg i.m. Dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT) levels and MAO activity were estimated fluorometrically in rat brian. No change in DA, NA, 5-HT or MAO activity was observed after 7 days of MPA treatment while a significant decrease in DA levels along with a significant increase in MAO activity was observed after 21 days of MPA treatment. However, there was no change in NA and 5-HT levels after 21 days of MPA administration. The selective reduction of DA by MPA could be due to an increase in MAO-B activity. MPA does not appear to increase MAO-A activity because neither of the specific substrates (NA and 5-HT) of MAO-A was found to be decreased inspite of the increase in MAO activity as estimated by the kynuramine method. These findings suggest the importance of MAO-B also in DA metabolism in rat brain.

Anti-inflammatory, analgesic and antiproteolytic activities of some novel thiadiazoles.

Eighteen novel acetyl salicyloyl/butyroyl mercapto 1,3,4-thiadiazoles have been synthesized and characterized by their elemental analyses, IR and PMR spectral studies. Their efficacy against carrageenin induced paw oedema was tested in albino rats of either sex at a dose of 100 mg/kg p.o. In vitro antiproteolytic activity of the compounds was assessed by determining their ability to inhibit trypsin induced hydrolysis of bovine serum albumin. Active anti-inflammatory compounds were tested for their analgesic activity against aconitine induced writhing in albino mice. Approximate LD50 values were also determined in albino mice.