Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants.

A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N-diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug.

Diphenamid photodegradation using Fe(III) impregnated N-doped TiO2/sulfite/visible LED process: Influence of wastewater matrix, kinetic modeling, and toxicity evaluation.

Sulfite-based photocatalysis has been recently employed as a promising technology for the treatment of organic pollutants via the generation of reactive radicals. In this contribution, the effect of wastewater matrix constituents and toxicity evaluation were systematically investigated in the FeIII impregnated N-doped TiO2 (FeN-TiO2)/sulfite/visible LED (Vis LED) process in the presence of diphenamid (DPA) as a model organic pollutant. The results showed that the presence of HCO3-, SO42-, NO3-, and F- had no detrimental effect on DPA degradation. Conversely, the presence of Cr(VI), NO2-, Cl-, and Br- caused a stronger retardation effect. The effect of natural organic matter such as humic acid (HA) was inert at normal concentrations. Interestingly, the retardation effect of inorganic ions can be quantified at any given ion concentration based on the linear correlations between the DPA decay (first-order kinetic constants) and concentration of ion species. Toxicity tests on Synechocystis sp., Microcystis flos-aquae, and Nostoc sp. algae revealed that higher toxicity was noticed at 240 min treatment time accompanied by lower toxicity with prolonging the treatment time for all selected algae except for Microcystis flos-aquae. In addition, novel two-phase mathematical models were successfully proposed to predict the accumulation of intermediates depending on their evolution profile.

Condensed bridgehead nitrogen heterocyclic system: synthesis and pharmacological activities of 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives of ibuprofen and biphenyl-4-yloxy acetic acid.

Several 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles were prepared by condensation of 4-amino-5-substituted-3-mercapto-(4H)-1,2,4-triazoles (3a,b) with various substituted aromatic acids and aryl/alkyl isothiocyanates through a one-pot reaction. These compounds were investigated for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, antibacterial and antifungal activities. Some of the synthesized compounds showed potent anti-inflammatory activity along with minimal ulcerogenic effect and lipid peroxidation, compared to those of ibuprofen and flurbiprofen. Some of the tested compounds also showed moderate antimicrobial activity against tested bacterial and fungal strains.

[Toxicologic characteristics of several pesticides and standards for them in water]. / Toksikologichna kharakteristika na niakoi pestitsidi i normiraneto im vuv vodite.

The progressive increase of production and application of chemicals for plant protection transmuted the problem of protection of water cleanliness into an international and national problem. The cases with incidental pesticide pollution of water-reservoirs became more numerous. A necessity arose of the supplement of our sanitary legislation with hygienic standards (MAC) for the water for the newly implemented chemicals for plant protection in the country. During the last several years, some of the most frequently used and formulated in our country pesticides were experimentally studied: Afalon and Patoran (from chemical group of carbamates and dithiocarbamates) and amide herbicide: Dimid, Ramrod, Lasso, Treflan. Complex hygienic-toxicological studies were carried out in order to study the toxicological effect of the pesticides mentioned and to elaborate hygienic norms (MAC) of the same in the water. The effect on the organoleptic qualities of water was determined as well as on the sanitary regime of waterreservoirs (according to BON5, sanitary-indictory microflora and toxicity for fishes). Toxicological studies were performed under the conditions of acute, subacute and chronic experiment. The results obtained allowed the hygienic-toxicological characteristics and the proposal of hygienic standards (MAC) for the pesticides studied in water.

A comparison of the acute toxicity, neuropathology, and electrophysiology of N,N-diethyl-m-toluamide and N,N-dimethyl-2,2-diphenylacetamide in rats.

The insect repellent DEET and the structurally related herbicide diphenamid both cause ataxia associated with a spongiform myelinopathy largely confined to the cerebellar roof nuclei. This local myelinopathy was accompanied by the formation of neuronal cytoplasmic clefts and was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide (DEET). These dose levels also produced a severe and often fatal prostration and clear electrophysiological signs of prolonged suppressed seizure activity. Diphenamid produced an identical myelinopathy after doses of 0.8 to 1.5 g/kg but without the severe prostration, suppressed seizures, or neuronal clefts. The effects of diphenamid were shown to be reversible over 3 to 7 days by neuropathological, motor, and auditory evoked response indices. Both compounds caused characteristic changes in auditory evoked response which may be useful in clinical diagnosis. Six other alkyl amides, two of which produce signs of CNS excitation, failed to produce myelinopathy at the maximum tolerated doses. Our findings show close parallels with a number of human cases of DEET poisoning and indicate that other amides, like diphenamid, also pose a potential hazard.