Ultrasound-assisted improvement of drug solubility: a simple and useful method for the formation of salts from 4-hydroxy-6-methyl-3-nitropyridin-2(1H)-one

Autor: Diógenes Santiago Santos, Eduarda Ritter, Luiz Augusto Basso, Christiano Ev Neves, Anderson Jader dos Santos, Pablo Machado
Rok vydání: 2013
Předmět:
Zdroj: Monatshefte für Chemie - Chemical Monthly. 144:1165-1170
ISSN: 1434-4475
0026-9247
DOI: 10.1007/s00706-013-0948-0
Popis: The low aqueous solubility of drug-like compounds has been described as one of the main problems causing the failure of new chemical entities in medicinal chemistry programmes. This paper describes our efforts to overcome lack of solubility and to produce a novel template protocol for forming salts of poorly soluble compounds. We prepared a series of 4-hydroxy-6-methyl-3-nitropyridin-2(1H)-one amine salts by using ultrasound irradiation. The poorly water-soluble molecule 4-hydroxy-6-methyl-3-nitropyridin-2(1H)-one was recently described as an inhibitor of the Mycobacterium tuberculosis orotate phosphoribosyltransferase enzyme. Salts of this molecule were prepared in 88–98 % yield from a mixture of 4-hydroxy-6-methyl-3-nitropyridin-2(1H)-one with primary and secondary amines (dimethylamine, diethylamine, dipropylamine, ethanolamine, 2-amino-2-methyl-1,3-propanediol, d-threoninol, pyrrolidine and piperidine) after ultrasound irradiation. The main advantages of this method are a significant reduction in reaction times and the use of a renewable solvent as a reaction medium. Thus the compounds are obtained after irradiation for 8 min in ethanol.
Databáze: OpenAIRE
Externí odkaz: