Synthesis and pharmacological screening of certain N-substituted amides structurally related to some local anesthetics.

Diphenylacetyl chloride and pivaloyl chloride have been condensed with a wide variety of amines. Some of the resulting amides showed local anesthetic properties higher than those of procaine hydrochloride.

Synthesis of certain 4-oxo-1.2.3.4-tetrahydroquinoline and benzazocine derivatives likely to possess analgesic activity.

Cyanoethylation of anthranilic acid afforded the N-cyanoethyl derivative which on treatment with ethanolic and methanolic hydrogen chloride yielded the corresponding diethyl and dimethyl esters respectively. Application of the Dieckmann's conditions to the N-acetyl derivatives of the two esters using sodium hydride and sodium ethoxide afforded different products. With the former, the expected products were obtained, while with the latter catalyst both esters furnished one and the same compound which was shown to be a benzazocine trione. The structure of the azocine was inferred from elemental analysis, spectroscopic data and formation of derivatives.

Synthesis of certain benzo- and pyridodiazepines likely to possess tranquilizing effect.

The synthesis of certain 1.5-benzodiazepinediones, some of their oxygen-free analogues and a number of the 7-nitro derivatives is described. Condensation of 3.4-diaminopyridine with diethylmalonate instead of affording the expected pyridodiazepine, yielded an imidazopyridine, the structure of which was inferred from spectral data Nevertheless, the pyridodiazepine was obtained by condensing the diamino-heterocycle with malonyl dichloride.

Synthesis and pharmacological screening of certain spiro compounds.

The synthesis of certain azaspirodione, azaspirane and bis-azaspirodione derivatives is described. Fusing equimolecular amounts of 3-oxaspiro[5.5]undecane-2.4-dione with certain amino compounds afforded the corresponding N-substituted azaspirodiones. Reduction of the N-harolaryl azaspirodiones gave the oxygen-free analogues. Reacting 3-azaspiro[5.5]undecane-2.4-dione with certain secondary amines under the Mannich conditions yielded the expected bases. Reacting one equivalent of ethylene-diamine with two equivalents of 2-oxaspiro[4.4]nonane-1.3-dione and the next higher homologues, viz, the decane and undecane afforded the respective ethylene bis-azaspirodiones. Likewise, on applying the Mannich conditions to the nitrogen analogues of the before-mentioned oxaspirodiones using piperazine as the secondary amine, bis-azaspirodions were obtained. The result of the pharmacological screening of some of the synthesized spiro compounds is included.

Effects of metaraminol, insulin and trasylol on the responses to haemorrhage in dogs.

The effect of addition of metaraminol, insulin and trasylol to fluid replacement with glucose-saline, on the responses to haemorrhage (30% of blood volume) in dogs, was investigated. Addition of metaraminol significantly increased the blood sugar and lactate responses to haemorrhage; the lactate-pyruvate (L/P) ratio, plasma phosphate and free fatty acid (FFA) levels were also significantly increased. A delayed hypotension was observed. Responses to haemorrhage during infusion of glucos-saline + insulin showed reduced blood sugar, blood lactate, pyruvate, and L/P ratios, plasma inorganic phosphate and FFA were diminished while, mean arterial blood pressure (MABP) changes were significantly higher than the glucose-saline group. Infusion of trasylol in glucose-saline did not significantly affect the blood sugar, lactate, and pyruvate resonses and the L/P ratio. Plasma phosphate response was also like the control group. The responses of plasma FFA and of MABP in this group were significantly higher than glucose-saline group. The mechanisms of these effects and the significance of thse results are discussed.

Synthesis of certain spiro compounds.

The synthesis of certain N-substituted azaspirodiones and azaspiranes is described. Fusing equimolecular amounts of 2-oxaspiro [4.4]nonane-1.3-dione with a number of amino compounds afforded the corresponding N-substituted azaspirodiones. However, with certain o-substituted anilines, no condensation took place. Reduction of the N-haloaryl azaspirodiones gave the corresponding oxygen free compounds. Other azaspiranes were isolated as the quaternary methiodides. Applying the Mannich conditions to 2-azaspiro[4.4]nonane-1.3-dione yielded the N-Mannich bases.

Synthesis of certain 3-aminoquinazolinone Schiff's bases structurally related to some biologically active compounds.

The condensation of 2-methyl-3-amino-4(3H)-quinazolinone and 2-phenyl-3-amino-4(3H)-quinazolinone with different aldehydes is described. Reacting equimolecular amounts of these two amino compounds with p-nitrobenzaldehyde, p-hydroxybenzaldehyde, cinnamaldehyde and 5-nitro-2-furfuraldehyde diacetate afforded the respective Schiff's bases. Condensation of benzaldehyde, anisaldehyde, p-dimethylaminobenzaldehyde and o-nitrobenzaldehyde with the former quinazolinone afforded the corresponding condensation products while with the latter no condensation took place. Furthermore, condensation of cinnamaldehyde with methylaminoquinazolinone in pyridine and in glacial acetic acid afforded the mono- and di-condensation products respectively while furfural, thiophenaldehyde, resorcinaldehyde, protocatechualdehyde, veratraldehyde, and salicylaldehyde, the condensation ended in failure.