N-aryl heterocycles via coupling reactions with arylboronic acids

Pentamidine is an effective antimicrobial agent. To increase its poor oral bioavailability due to the strong basic amidine functionality, the less basic O-acetylamidoxime prodrug, the diacetyldiamidoximeester, was used, which has greatly improved lipophilicity. The objectives of this investigation were the synthesis of all potential metabolites of the double prodrug, the conformational analysis of its structure, and to study the in vitro and in vivo biotransformation by ester cleavage and N-reduction to pentamidine via four intermediate metabolites. The biotransformation of diacetyldiamidoximeester to pentamidine involving the reduction of the amidoxime function and the ester cleavage could be demonstrated. The kinetic parameters were determined. Amidoximes were efficiently metabolized by several enzyme systems located in microsomes and mitochondria of different organs including the final formation of the active metabolite pentamidine. The formation of pentamidine after oral administration of the diacetyldiamidoximeester to rats could be demonstrated as well.

Diacetyldiamidoximeester of Pentamidine, a Prodrug for Treatment of Protozoal Diseases: Synthesis, in vitro and in vivo Biotransformation

Hydrazinium Monoformate: A New Hydrogen Donor. Selective Reduction of Nitrocompounds Catalyzed by Commercial Zinc Dust

Benzamidoximes: structural, conformational and spectroscopic studies. I

The effect of heat on arylamidoximes, la-g, has been examined. When acetic acid was used as solvent, amidoximes, la-g, provided three products, viz., 3,5-bis-aryl-1,2,4-oxadiazoles, 2a-g, 3-aryl-5-methyl-1,2,4-oxadiazoles, 3a-g, and a small quantity of an unknown polar compound. Heating arylamidoximes at controlled temperature without acetic acid furnished bis-aryloxadiazoles, 2a-g. An insight has been obtained about the mechanism of formation of 2 from 1.

Thermal Reactions of Arylamidoximes

Synthesis and spectroscopic studies of 5-methyl-3-phenyl- and 5-methyl-3-(o-, m-, and p-tolyl)-1,2,4-oxadiazoles

Synthesis of O-carbanilinobenzamidoximes

Etude de la conformation et de la configuration par des calculs MO semi-empiriques utilisant les methodes CNDO/2 et INDO

R. M. Srivastava

Papers

Synthesis and spectroscopic studies of 5-methyl-3-phenyl- and 5-methyl-3-(o-, m-, and p-tolyl)-1,2,4-oxadiazoles

Synthesis of O-carbanilinobenzamidoximes

Configuration and comformation of benzamide O-(anilinocarbonyl)oxime

Mass spectra of nitrones. Electron impact mass spectra of fluorenone nitrones

Mass spectra of nitrones. Electron impact mass spectra of fluorenone nitrones