4-Hydroxy-2-quinolones 173*. 1-R-3-(2-diethylamino- ethyl)-1H-quinazoline- 2,4-dione hydrochlorides as potential local anesthetic agents

Abstract

Local anesthetic agents are a distinct group of drugs which, upon direct contact, can reversibly lower or fully shut down feelings of pain in a limited region of mucous membrane, skin, or other tissues. About 40 preparations of this type are currently used in anesthetic practice [2,3]. Unfortunately none of these is without drawbacks, the most significant of which are high toxicity, inhibition of cardiac activity (up to cardiac arrest), and different kinds of allergic reaction. Hence the search for novel, efficient, and also safe local anesthetics is relevant at this time. The need to carry out an investigation of this type is also dictated by the fact that the last of these appeared in the pharmaceutical field all of 25 years ago (ropivacaine [4]) and is unfortunately still only an analog of the better known lidocaine and bupivacaine [2,3].The novel quinolone anesthetic chinoxicaine recently proposed [5] shows not only highly specific activity but also a series of other pharmacological properties useful for preparations of this type. However they

Synthesis of quinazolindionyl amino acid and dipeptide derivatives as possible antitumour agents

“…The key compound 1 was obtained from condensation of methyl benzoate carbamate derivative with ethanol amine according to the method described in literature. 21 In order to facilitate the introduction of the amino acid at N-1 of the quinazoline nucleus ethyl [3-(2-hydroxyethyl)-2,4-dioxo-(1H,3H)quinazolin-1-yl]acetate (2) was prepared by alkylation of 1 with ethyl chloroacetate in the presence of anhydrous potassium carbonate. Moreover, to investigate the effect of the length of the link between quinazoline nucleus and the amino acids on the anticancer activity some propionyl amino acid derivatives were also synthesized (Scheme 1).…”

“…The starting compound 3-(2-hydroxyethyl)-2,4-dioxo-(1H,3H)-quinazoline 1 was prepared according to the method described in literature. 21…”

Synthesis of quinazolindionyl amino acid derivatives as possible antitumour agents

“…The key compound 3-(2-hydroxyethyl)-2,4-dioxo(1H,3H)quinazoline 1 25 is a suitable scaffold for conjugation with amino acid derivatives at N-3 position via amide and ester bonds (Schemes 1-3). Prior to derivatization of 1, the reactive N-1 site was protected by alkylation with ethyl iodide to yield the N-1 ethyl derivative 2 to avoid the possible side-reactions that might occur.…”

“…The starting compounds 3-(2-hyd-roxyethyl)-2,4-di-oxo-(1H,3H)-quinazoline 1 and 1-ethyl-3-(2-hydroxyeth-yl)-2,4-dioxo-(1H,3H)-quinazoline 2 were prepared according to the described method in literature. 25 Potential cytotoxicity of the newly synthesized compounds was tested against human liver carcinoma cell line (HepG2) at pharmacology unit in cancer biology department at the National Cancer Institute, Cairo University, Cairo.…”