Quinolone antibacterials containing the new 7-[3-(1-aminoethyl)-1-pyrrolidinyl] side chain: the effects of the 1-aminoethyl moiety and its stereochemical configurations on potency and in vivo efficacy was written by Domagala, John M.;Hagen, Susan E.;Joannides, Themis;Kiely, John S.;Laborde, Edgardo;Schroeder, Mel C.;Sesnie, Josephine A.;Shapiro, Martin A.;Suto, Mark J.;Vanderroest, Steven. And the article was included in Journal of Medicinal Chemistry in 1993.Computed Properties of C10H8Cl2FNO3 This article mentions the following:
A series of stereochemically pure 7-[3-(1-aminoethyl)-1-pyrrolidinyl]-1,4-dihydro-4-oxoquinoline and 1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, were synthesized to study the effects of the 7-[3-(1-aminoethyl)-1-pyrrolidinyl] moiety on potency and in vivo efficacy relative to the known 7-[3-(aminomethyl)-1-pyrrolidinyl] derivatives The antibacterial efficacies of the target compounds and their relevant reference agents were determined in vitro using an assortment of Gram-neg. and Gram-pos. organisms and in vivo using Escherichia coli and Streptococcus pyogenes mouse infection models. The effects of the 7-[3-(1-aminoethyl)-1-pyrrolidinyl] moiety were also examined at the level of the target enzyme by employing a DNA-gyrase supercoiling inhibition assay. Selected compounds were further evaluated for potential phototoxic and clastogenic liabilities using a phototoxicity mouse model and an in vitro mammalian cell cytotoxicity assay. It was found that the differences in in vitro antibacterial activity between the stereoisomers were significantly greater than previously reported for other optically pure 3-substituted pyrrolidinyl side chains. Relative to their 7-[3-(aminomethyl)-1-pyrrolidinyl] analogs, the (3R,1S)-3-(1-aminoethyl)pyrrolidines generally conferred a 2-4-fold increase in Gram-pos. in vitro activity and an average of 10-fold improvement in oral efficacy. The level of phototoxicity and cytotoxicity of the product quinolones was ultimately determined by the combined influence of the 7-[3-(1-aminoethyl)-1-pyrrolidinyl] side chains and the other quinolone substituents. From this study, several compounds were identified with outstanding antibacterial activity and low degrees of phototoxicity and mammalian cell cytotoxicity. One such agent, R,S–I (PD 140248), showed the best overall blend of safety and efficacy. In the experiment, the researchers used many compounds, for example, Ethyl 3-(2,6-Dichloro-5-fluoro-3-pyridyl)-3-oxopropionate (cas: 96568-04-6Computed Properties of C10H8Cl2FNO3).
Ethyl 3-(2,6-Dichloro-5-fluoro-3-pyridyl)-3-oxopropionate (cas: 96568-04-6) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Computed Properties of C10H8Cl2FNO3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics