Reactions of phthalimides with 1-methylethylamine: analgesic and anti-inflammatory properties of resulting carboxamides.

The reaction of phthalimide derivatives (1a-c) with 1-methylethylamine in dimethylformamide (DMF) at room temperature afforded benzamido-N-prop-2-ynyl-2-(2-methylethyl)-carboxamide (3a), benzamido-N-cyclopentyl-2-(2-methylethyl)-car-boxamide (3b) and benzamido-N-benzyl-2-(2-methylethyl)-carboxamide (3c), respectively. In the carrageenan induced paw oedema test for anti-inflammatory activity, 3a (50 mg/kg) decreased the inflammatory response by 55% after 3 hrs while 3b and 3c exhibited significant reduction in the oedema level. The compounds 3a, 3b and 3c exhibited analgesic activities with 3b producing 76% inhibition. The activities were dose - dependent.

Phytochemical and active column fractions of Pyrenacantha staudtii leaf extracts on isolated rat uterus.

Four methanolic leaf fraction extracts of Pyrenacantha staudtii obtained from accelerated gradient chromatography (AGC) were tested on the isolated rat uterus. Various fractions--M1, M2, M3 and M4 through bioassay guided isolation were obtained. Fractions M(2) and M(4), containing saponins and alkaloids respectively, significantly (P<0.05) exerted high smooth muscle relaxant activity on the uterus. Fractions M(1) and M(3) containing fatty acids and tannins respectively did not exhibit significant effect on the isolated rat uterus. The results indicate the presence of active principles in the leaf extracts of P. staudtii which may be responsible for some of the applications in traditional medicines as remedy against threatened abortion and dysmenorrheal.

Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids.

In order to study the influence of the length of the amino acid chain of N,N-phthaloyl-amino acid amides as analogues of the former anticonvulsant taltrimide on the seizure-antagonizing activity glycine, beta-alanine and gamma-aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine-derived amides showed a higher activity than the beta-alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine derivatives. The N,N-phthaloyl-glycine amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylene-tetrazole. The ED50 of N,N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal administration to mice was 19.1 mg/kg. On a molar basis this activity is comparable to the activity of phenytoin with little toxicity in the rotorod test. In conclusion, N,N-phthaloyl-glycine amides might represent promising antiepileptic drugs.

Anticonvulsant activity of reaction products of 5,5-diphenylhydantoin with substituted methylene bromides.

Some derivatives of 5,5-diphenylhydantoin (phenytoin) were synthesized by the alkylation of phenytoin with substituted methylene bromides. The hydantoins were evaluated for possible anticonvulsant activity in the maximal electroshock (MES)- and subcutaneous pentylenetetrazole (ScMet)-induced seizures and for neurotoxicity in the rotorod test in mice and rats.

Synthesis and anticonvulsant activity of acetylenic quinazolinone derivatives.

Acetylenic derivatives of quinazolinones and quinazolinediones were synthesized and evaluated for their anticonvulsant activity. Most compounds displayed seizure-antagonizing activity in the maximal electroschock test (MES test) in most cases associated with little or no acute neurotoxicity determined in the rotorod test. Only three compounds exhibited significant activity in the seizure threshold test with subcutaneous pentylenetetrazole (scMet test). Based on the ED50 in the MES test, 1,3-bis-(prop-2-ynyl)-quinazoline-2,4-(1H,3H)-dione(9a) was about ten-fold less active than phenytoin or carbamazepine but about as active as mesuximide.