351892-49-4

Upstream product

• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 5345-54-0 3-chloro-4-methoxyaniline 

Downstream Products

• 1373767-27-1 ethyl 2-([1,1'-biphenyl]-3-yl)-7-chloro-6-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1373767-28-2 ethyl 7-chloro-6-methoxy-2-(3-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1373767-29-3 ethyl 7-chloro-6-methoxy-4-oxo-2-(3-phenoxyphenyl)-1,4-dihydroquinoline-3-carboxylate 
• 1445786-62-8 3-((3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)-6-isopropoxyquinolin-4-yl)amino)-5-cyclopentylbenzoic acid 
• 1445791-66-1 6-butoxy-7-chloro-4-(3-cyclopentyl-5-(hydroxymethyl)phenylamino)quinoline-3-sulfonamide 
• 1445788-22-6 6-butoxy-4-(3-cyclopentyl-5-(hydroxymethyl)phenylamino)-7-(2,4-dimethoxypyrimidin-5-yl)quinoline-3-sulfonamide 
• 1445791-12-7 methyl 3-((3-carbamoyl-6-(cyclohexylmethoxy)-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl)amino)-5-cyclopentylbenzoate 
• 1445791-10-5 methyl 3-(3-carbamoyl-7-chloro-6-(cyclohexylmethoxy)quinolin-4-ylamino)-5-cyclopentylbenzoate 
• 1445791-08-1 4-bromo-7-chloro-6-(cyclohexylmethoxy)quinoline-3-carboxamide 
• 1445787-64-3 3-((3-carbamoyl-6-(cyclohexylmethoxy)-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl)amino)-5-cyclopentylbenzoic acid 
• 1445790-42-0 methyl 3-((3-carbamoyl-6-(cyclopropylmethoxy)-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl)amino)-5-cyclopentylbenzoate 
• 1445790-40-8 methyl 3-(3-carbamoyl-7-chloro-6-(cyclopropylmethoxy)quinolin-4-ylamino)-5-cyclopentylbenzoate 
• 1445787-29-0 3-((3-carbamoyl-6-(cyclopropylmethoxy)-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl)amino)-5-cyclopentylbenzoic acid 
• 1445790-30-6 methyl 3-((3-carbamoyl-6-(cyclopentylmethoxy)-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl)amino)-5-cyclopentylbenzoate 

Relevant academic research and scientific papers

Fluorine walk: The impact of fluorine in quinolone amides on their activity against African sleeping sickness

Human African Trypanosomiasis, also known as African sleeping sickness, is caused by the parasitic protozoa of the genus Trypanosoma. If there is no pharmacological intervention, the parasites can cross the blood-brain barrier (BBB), inevitably leading to death of the patients. Previous investigation identified the quinolone amide GHQ168 as a promising lead compound having a nanomolar activity against T. b. brucei. Here, the role of a fluorine substitution at different positions was investigated in regard to toxicity, pharmacokinetics, and antitrypanosomal activity. This ‘fluorine walk’ led to new compounds with improved metabolic stability and consistent activity against T. b. brucei. The ability of the new quinolone amides to cross the BBB was confirmed using an 18F-labelled quinolone amide derivative by means of ex vivo autoradiography of a murine brain.

CHEMICAL COMPOUNDS

The invention is directed to substituted quinoline derivatives. Specifically, the invention is directed to compounds according to Formula (I): wherein R1, R2, R3; R4; and R5 are defined herein. The compounds of the invention are inhibitors of lactate dehydrogenase A and can be useful in the treatment of cancer and diseases associated with tumor cell metabolism, such as cancer, and more specifically cancers of the breast, colon, prostate and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting lactate dehydrogenase A activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Lead optimization of 3-carboxyl-4(1 H)-quinolones to deliver orally bioavailable antimalarials

Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.