Synthesis and CVS activity of 1-(2,3, 2,5, 2,6 dichlorophenyl)-3-morpholinophenyl-5-substituted benzylidene-thiobarbituric acids (3-17).

Fifteen new thiobarbituric acids have been prepared by the Knoevenagel condensation of appropriate aldehydes with 1-(2,3, 2,5, 2,6 dichlorophenyl)-3-morpholinophenyl thiobarbituric acids. Five compounds of this series were found to be biphasic in nature whereas some compounds showed appreciable hypotensive activity of varying magnitude and duration.

Macrophage transmission of suppressor signal for suppression of delayed hypersensitivity and humoral response in JEV-infected mice.

Japanese encephalitis virus (JEV) infection induces suppressor T-cells (Ts1) which suppress both the humoral (Ts-PFC) and cell mediated (Ts-DTH) immune response by producing soluble suppressor factors. This study shows that in the JEV model, both TS-PFC and Ts-DTH mediate suppression by recruiting a second subpopulation of suppressor T-cells, the Ts2-PFC and Ts2-DTH. The signal between Ts1 and Ts2 is transmitted by macrophages (M phi). The suppressor factors are adsorbed by peritoneal or splenic M phi. Both heat-killed and live M phi are capable of adsorbing suppressor factors but only live M phi are capable of presenting the signal to T-cells. Thus these are at least two generations of suppressor T-cells in the JEV-specific suppressor pathway and the presence of M phi is obligatory for transmission of the signal.

CNS, anthelmintic and antiinflammatory activities of some 1-[2/3-(2-phenyl benzimidazole)]2-methyl/phenyl-4-(3,4-disubstituted benzylidene)5-oxo-imidazoles.

Twelve title compounds were synthesised by condensing 2-(2/3 amino phenyl)benzimidazoles with appropriate 2-methyl/phenyl 4(3,4-disubstituted benzylidene)oxazolin 5-ones in dry pyridine and screened for toxicity gross CNS, anthelmintic and anti-inflammatory activities. In their lethal test, all the compounds were found to be non-toxic, and CNS depressants and hypothermic in their neuropharmacological testings. They showed valuable results against N. brasiliensis, whereas, were inactive against H. nana in their in vivo anthelmintic screening. Most of them showed remarkable anti-inflammatory activity against carrageenin induced oedema.

Search for new antiamebic agents. I. Synthesis and bioassay of new Schiff bases of 1-phenyl-2-morpholinoethylidene-1-urea.

As potential agents against E. histolytica 19 new Schiff bases of 1-phenyl-2-morpholinoethylidene-1-urea were synthesized by the condensation of the parent compounds with various carbonyl compounds. Thirteen of them were tested against the axenic culture of E. histolytica at concentration 125 microgram/cm3 but no significant amoebicidal activity was observed.

Search for potential anticonvulsant agents. Synthesis of 2-phenyl/methyl-3-[o-, m- or p-(benzimidazol-2'-yl)phenyl]-6 or 6,8-substituted/unsubstituted quinazolin(3H)-4-ones.

Sixteen new quinazolones were synthesized by the condensation of substituted 4-oxo-3,1-benzoxazines and 2-(o-, m- or p-aminophenyl)benzimidazoles. All the sixteen compounds were tested for anticonvulsant activity in mice against pentylenetetrazole induced convulsions. Except for five compounds in which there was no protection, the others showed protection ranging from 20 to 80%.

Synthesis of some newer formazans and tetrazolium salts and their effect on Ranikhet disease virus and the vaccinia virus.

Synthesis and biological evaluation of a series of formazans and their corresponding tetrazolium salts are described. Several 1,3,5-trisubstituted formazans were prepared by condensing 4-acetoxy-3-methoxybenzaldehydephenylhydrazone and 2,4-dinitrophenylhydrazone of 2-benzimidazolecarboxaldehyde, with an appropriate phenyldiazonium salt. The formazans derived from 4-acetoxy-3-methoxybenzaldehydephenylhydrazone were further oxidized to their corresponding cyclization products, 2,3,5-trisubstituted tetrazolium salts. Oxidation of 1-aryl-3-(2'-benzimidazolyl)-5-(5-(2',4'-dinitrophenyl) formazans to their corresponding tetrazolium salt did not meet with success. Both the highly coloured formazans and water-soluble tetrazolium salts were screened for their antiviral, activity against vaccinia virus and Ranikhet disease virus in a stationary culture of chorioallantoic membrane of chick embryo. Two of the compounds were found to exhibit significant activity (87% and 83%) against the Ranikhet disease virus. However no activity against vaccinia virus could be observed.

Synthesis of N-aryl-N'-[2-phenyl-3-quinazoline(3H)-4-one] acylthiourea derivatives as anticonvulsants.

By the reaction of [2-phenyl-3-quinazolineo (3H)-4-one] acyl isothiocynates and appropriate aryl amines in acetone, 24 new compounds, having a substituted thiourea grouping at the 3-position of the quianozolone moiety, were prepared. All compounds, except two, showed different degree of protection against pentetrazol induced seizures test in albino mice. While studying the effect of structural variation no definite pattern could be observed due to variations in 1-aryl moiety, but it was noticed that generally the branching or lengthening of 3-acyl chain either diminishes or does not effect the activity.

Synthesis of some newer formazans and tetrazolium salts as antiviral agents.

Thirteen new formazans were prepared by the condensation of the phenylhydrazone of 3.4-dimethoxy-6-nitro-veratraldehyde with the appropriate phenyl diazonium salts. Attempts were made to oxidize these highly coloured formazans with various oxidizing agents to their corresponding tetrazolium salts. The most suitable oxidizing agent was found to be H2O2/Fe2+. Both the formazans and tetrazolium salts were screened for their antiviral activity against the Ranikhet disease virus and vaccinia virus in a stationary culture of chorioallantoic membrane of chick embryo. Among the 15 compounds tested one of the compounds namely 1-o-carboxyphenyl-3[3'.4'-dimethoxy-6'-nitrophenyl]-5-phenylformazan evinced 100% protection against the Ranikhet disease virus. Rest of the compounds showed significant protection ranging from 83 to 20%. An attempt has also been made to arrive at some structure-activity relationship.

Synthesis of some 2,3-disubstituted quinazolones as possible anticonvulsants.

By the condensation of 2-phenyl-3-acylchloride quinazolin (3H)-4-one with N-phenyl- and N-methyl piperazines or piperidine, 15 new 2-phenyl-3-piperidino/substituted piperazino acyl-quinazolin (3H)-4-ones 1--3 have been prepared. All the compounds barring one exhibited at the 100 mg/kg dose level significant activity against pentylenetetrazol induced seizures but these compounds did not afford any protection against electroshock induced seizures.

Search for potential anticonvulsant drugs: part I. Synthesis of 2-phenyl-3-benzimidazolyl/-alkyl (alkyl-aryl)--quinazolin (3H) -4-one.

By the condensation of 2-phenyl-3-carboxy alkyl/aryl-quinazolin (3H)-4-one and substituted (unsubstituted o-phenylenediamine, fifteen new 2-phenyl-3-benzimidazolyl(-alkyl/alkyl-aryl) -quinazolin (3H)-4-ones were prepared. All the fifteen compounds were tested for anticonvulsant activity in mice against pentylenetetrazol. A good protection was obtained by most of the compounds.

Search for potential amoebicides. Part V. N-substituted 2-nitro-4,5-dimethoxybenzamides and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids.

The authors in all have synthesised 28 new N-substituted 2-nitro, 4,5-dimethoxy-benzamides, and anils of 2-amino-3-methoxy and 2-amino-4,5-dimethoxybenzoic acids with a view to obtain potent amoebicides. Their work is based on the observation that a large number of dimethoxyphenyl substituted derivatives occupy an important place as antiamobic agents. Fourteen belonging to different series subjected to in vitro screening for amoebicidal activity against E. histolytica failed to show any significant activity.

Search for potential amoebicides. Part IV. Some hydrazones derivatives of 2-nitro-4-5-dimethoxybenzhydrazide and of 1-4-bis-[alpha(o-acetylhydrazino) phenethyl] piperazine.

By the condensation of 2-nitro-4-5-dimethoxybenzhydrazide and of 1,4-bis[alpha(O-acetylhydrazino) phenethyl] piperazine with various carbonyl compounds 42 hydrozones were synthesissed. Out of them 26 compounds were tested against the axenic-culture of E. histolytica at conc. of 125 mug/ml but no significant amoebicidal activity was observed.