190058-82-3

Upstream product

• 7745-91-7 3-bromo-4-methylaniline 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 

Downstream Products

• 1445786-82-2 3-((3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)-6-methylquinolin-4-yl)amino)-5-cyclopentylbenzoic acid 
• 1445789-90-1 methyl 3-((3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)-6-methylquinolin-4-yl)amino)-5-cyclopentylbenzoate 
• 1445786-60-6 3-((3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)-6-methylquinolin-4-yl)amino)benzoic acid 
• 1445789-02-5 ethyl 3-(3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)-6-methylquinolin-4-ylamino)benzoate 
• 1189105-59-6 7-bromo-4-chloro-6-methylquinoline 

Relevant academic research and scientific papers

Improvement of Aqueous Solubility of Lapatinib-Derived Analogues: Identification of a Quinolinimine Lead for Human African Trypanosomiasis Drug Development

Lapatinib, an approved epidermal growth factor receptor inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in 1 (NEU-1953), which was part of a series typically associated with poor aqueous solubility. In this report, we present various medicinal chemistry strategies that were used to increase the aqueous solubility and improve the physicochemical profile without sacrificing antitrypanosomal potency. To rank trypanocidal hits, a new assay (summarized in a cytocidal effective concentration (CEC50)) was established, as part of the lead selection process. Increasing the sp3 carbon content of 1 resulted in 10e (0.19 μM EC50 against T. brucei and 990 μM aqueous solubility). Further chemical exploration of 10e yielded 22a, a trypanocidal quinolinimine (EC50: 0.013 μM; aqueous solubility: 880 μM; and CEC50: 0.18 μM). Compound 22a reduced parasitemia 109 fold in trypanosome-infected mice; it is an advanced lead for HAT drug development.

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.