248282-10-2

Usage

Uses

Used in Pharmaceutical Industry:
ETHYL-5-CHLORO-1,2-DIHYDRO-4-HYDROXY-1-METHYL-2-OXO-3-QUINOLINE CARBOXYLATE is used as a chemical intermediate for the synthesis of drugs due to its unique molecular structure and functional groups. Its potential pharmaceutical properties make it a promising candidate for the development of new medications.
Used in Analytical Chemistry:
ETHYL-5-CHLORO-1,2-DIHYDRO-4-HYDROXY-1-METHYL-2-OXO-3-QUINOLINE CARBOXYLATE is used as a reference standard in analytical chemistry. Its distinct chemical properties allow it to serve as a benchmark for comparison and calibration in various analytical techniques, ensuring accurate measurements and results.

InChI:InChI=1/C13H12ClNO4/c1-3-19-13(18)10-11(16)9-7(14)5-4-6-8(9)15(2)12(10)17/h4-6,16H,3H2,1-2H3

Upstream product

• 40707-01-5 5-chloro-N-methylisatoic anhydride 
• 105-53-3 diethyl malonate 
• 64-17-5 ethanol 
• 248281-84-7 laquinimod 
• 20829-96-3 5-chloro-1H-benzo[d][1,3]oxazine-2,4-dione 
• 2148-56-3 2-chloro-6-aminobenzoic acid 
• 118-48-9 isatoic anhydride 
• 74-88-4 methyl iodide 

Downstream Products

• 248281-84-7 laquinimod 
• 1263357-57-8 5-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbohydrazide 
• 637027-41-9 1,2-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Synthesis, regioselectivity, and DFT analysis of new antioxidant pyrazolo[4,3-c]quinoline-3,4-diones

The condensation of hydrazine, N-methylhydrazine, and N-phenylhydrazine with ethyl 4-chloro-2-oxo- 1,2-dihydroquinoline-3-carboxylate derivatives has been investigated. As a result, 12 new antioxidant pyrazolo[4,3- c]quinolin-3,4-diones were obtained with good to high yields. When two cross-products could be possible, only one isomer bearing the methyl or the phenyl group at the N1 position is isolated and unequivocally characterized using 1D and 2D NMR techniques, FT-IR, and combustion analyses. DFT analysis of the reaction mechanism was carried out in the Pearson’s hard soft acid base framework, confirming the assigned structure to the observed pyrazolo[4,3-c]quinolin-3,4-diones. These calculations indicate a favored kinetic control for the synthesized pyrazolo[4,3- c]quinolin-3,4-diones compared to its possible regioisomer.

Synthesis, biological assessment and molecular modeling of new dihydroquinoline-3-carboxamides and dihydroquinoline-3-carbohydrazide derivatives as cholinesterase inhibitors, and Ca channel antagonists

The synthesis, biological evaluation, and molecular modeling of new 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides(4), 4-hydroxy-2-oxo-1,2- dihydroquinoline-3-carbohydrazide (6), and some hexahydropyrimido[5,4-c] quinoline-2,5-diones (9) produced earlier by our laboratory, as AChE/BuChE inhibitors, is described. From these analyses compound 4c resulted equipotent regarding the inhibition of cholinesterases'; inhibitors 6k, 9a, 9b were selective for AChE, whereas product 4d proved selective for BuChE. Docking analysis has been carry out in order to identify the binding mode in the active site, and to explain the observed selectivities. Only compound 9a has been shown to decrease K+-induced calcium signals in bovine chromaffin cells.

2-OXO-1,2-DIHYDRO-QUINOLINE MODULATORS OF IMMUNE FUNCTION

The present invention relates to new 2-oxo-1,2-dihydro-quinoline modulators of immune function, pharmaceutical compositions thereof, and methods of use thereof.

Synthesis and reactivity of laquinimod, a quinoline-3-carboxamide: Intramolecular transfer of the enol proton to a nitrogen atom as a plausible mechanism for ketene formation

5-Chloro-N-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-N-phenyl-3- quinolinecarboxamide (laquinimod, 2) is an oral drug in clinical trials for the treatment of multiple sclerosis. The final step in the synthesis of 2 is a high-yielding aminolysis reaction of ester 1 with N-ethylaniline. An equilibrium exists between 1 and 2, and removal of formed methanol during the reaction is a prerequisite for obtaining high yields of 2 from 1. The reactivity of 1 and 2 is explained by a mechanistic model that involves a transfer of the enol proton to the exocyclic carbonyl substituent with concomitant formation of ketene 3. This proton transfer is especially facilitated for 2 because the intramolecular hydrogen bond to the carbonyl oxygen is weakened due to steric interactions. Both 1 and 2 undergo solvolosis reactions that obey first-order reaction kinetics, further supporting the theory that these two molecules are able to decompose unimolecularly into ketene 3. The solvent-dependent spectroscopic features of 2 indicate that the molecule mainly resides in two conformations. One conformation is favored in nonpolar solvents and is likely the result of intramolecular hydrogen bonding. The other conformation is favored in polar solvents and probably exhibits less intramolecular hydrogen bonding.

Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders: Structure-Activity Relationship

Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).

Process for the manufacture of quinoline derivatives

A process for the preparation of the compounds of general formula (I) 1wherein R is selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and allyl; R5 is selected from the methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, methylthio, ethylthio, n-propylthio, methylsulphinyl, ethylsulphinyl, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy; wherein x=0?2, y=1?3 with the proviso that x+y=3; R6 is hydrogen; or R5 and R6 taken together are methylenedioxy; R′ is selected from methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy, wherein x=0?2, y=1?3 with the proviso that x+y=3; R″ is selected form hydrogen, fluoro and chloro, with the proviso that R″ is selected from fluoro and chloro only when R′ is selected from fluoro and chloro; by reacting a quinoline-3-carboxylic acid ester derivative of formula A with an aniline derivative of formula B 2in a solvent selected from straight or branched alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200° C.

QUINOLINE DERIVATIVES

The invention is related to compounds of general formula (I), wherein R is methyl, ethyl, n-propyl, iso-propyl, n-butyl or allyl; R' is methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, or OCHxFy, wherein x = O - 2, y = 1 - 3 with the proviso that x + y = 3; R'' is hydrogen, fluoro or chloro; with the proviso that R'' is fluoro or chloro only when R' is fluoro; R4 is hydrogen or pharmaceutically acceptable inorganic or organic cations; R5 is ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, trifluoromethyl, OCHxFy, or OCH2CHxFy wherein x = 0 - 2, y = 1 - 3 with the proviso that x + y = 3; R6 is hydrogen; or R5, and R6 taken together are methylenedioxy; and any tautomer thereof. The invention also relates to pharmaceutical compositions containing a compound of general formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of the compounds of formula (I), as well as methods for the treatment of mammals suffering from diseases resulting from autoimmunity and pathological inflammation by administering of a compound having formula (I) to said mammal.

PROCESS FOR THE MANUFACTURE OF QUINOLINE DERIVATIVES

A process for the preparation of the compounds of general formula (I); by reacting a quinoline-3-carboxylic acid ester derivative of formula A with an aniline derivative of formula B in a solvent selected from straight- or branch-chaineded alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200 C.

Quinoline derivatives

The invention is related to compounds of general formula (I) wherein R is methyl, ethyl, n-propyl, iso-propyl, n-butyl or allyl; R' is methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, or OCHxFy, wherein x=0-2, y=1-3 with the proviso that x+y=3, R'' is hydrogen, fluoro or chloro; with the proviso that R'' is fluoro or chloro only when R' is fluoro or chloro; R4 is hydrogen or pharmaceutically acceptable inorganic or organic cations; R5 is ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, trifluoromethyl, OCHxFy, or OCH2CHxFy wherein x=0-2, y=1-3 with the proviso that x+y=3; R6 is hydrogen; or R5 and R6 taken together are methylenedioxy; and any tautomer thereof. The invention also relates to pharmaceutical compositions containing a compound of the general formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of the compounds of formula (I), as well as methods for the treatment of mammals suffering from diseases resulting from autoimmunity and pathological inflammation by administering of a compound having the formula (I) to said mammal.

Quinoline derivatives

The invention relates to compounds of general formula (I) wherein R is selected from ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and allyl; R4 is selected from hydrogen and pharmaceutically acceptable inorganic and organic cations; R5 is selected from methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, CF3, and OCHxFy; wherein x=0-2, y=1-3 with the proviso that x+y=3; R6 is hydrogen; or R5 and R6 taken together are methylenedioxy; and any tautomer hereof. The invention also relates to pharmaceutical compositions containing a compound of the general formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of the compounds of formula (I), as well as methods of treating mammals suffering from diseases resulting from autoimmunity and pathological inflammation by administering a compound having the formula (I) to said mammal.