1190044-19-9

Upstream product

• 99-76-3 methyl 4-hydroxylbenzoate 
• 1284199-22-9 4-(cyclopropylmethoxy)benzoyl chloride 
• 1018856-62-6 4-(cyclopropylmethoxy)-N-(3-formyl-8-methylquinolin-7-yl)benzamide 
• 75-16-1 methylmagnesium bromide 
• 521074-55-5 7-amino-8-methylquinoline-3-carboxaldehyde 
• 355391-05-8 4-(cyclopropylmethoxy)benzoic acid 

Downstream Products

• 1190044-46-2 4-(cyclopropylmethoxy)-N-{3-[1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-8-methylquinolin-7-yl}benzamide 
• 1190044-20-2 N-[3-(1-chloroethyl)-8-methylquinolin-7-yl]-4-(cyclopropylmethoxy)benzamide hydrochloride 
• 1373823-33-6 3-bromo-N-[8-methyl-3-(1-pyrrolidin-1-ylethyl)quinolin-7-yl]benzamide 
• 1373823-34-7 4-(cyclopropylmethoxy)-N-{3-[(1S)-1-hydroxyethyl]-8-methylquinolin-7-yl}benzamide 
• 1373823-12-1 N-{3-[(1R)-1-azidoethyl]-8-methylquinolin-7-yl}-4-(cyclopropylmethoxy)benzamide 
• 1190044-49-5 N-{3-[(1R)-1-aminoethyl]-8-methylquinolin-7-yl}-4-(cyclopropylmethoxy)benzamide 
• 1373823-13-2 4-(cyclopropylmethoxy)-N-{8-methyl-3-[(1R)-1-{[(2-nitrophenyl)sulfonyl]amino}ethyl]quinolin-7-yl}benzamide 
• 1373823-14-3 N-{3-[(1R)-1-{(2-aminoethyl)[(2-nitrophenyl)sulfonyl]-amino}ethyl]-8-methylquinolin-7-yl}-4-(cyclopropylmethoxy)-benzamide 

Relevant academic research and scientific papers

Synthesis, structure-activity relationship, and pharmacological studies of novel melanin-concentrating hormone receptor 1 antagonists 3- aminomethylquinolines: Reducing human ether-a-go-go-related gene (hERG) associated liabilities

Recently, we discovered 3-aminomethylquinoline derivative 1, a selective, highly potent, centrally acting, and orally bioavailable human MCH receptor 1 (hMCHR1) antagonist, that inhibited food intake in F344 rats with diet-induced obesity (DIO). Subsequent investigation of 1 was discontinued because 1 showed potent hERG K+ channel inhibition in a patch-clamp study. To decrease hERG K+ channel inhibition, experiments with ligand-based drug designs based on 1 and a docking study were conducted. Replacement of the terminal p-fluorophenyl group with a cyclopropylmethoxy group, methyl group introduction on the benzylic carbon at the 3-position of the quinoline core, and employment of a [2-(acetylamino)ethyl]amino group as the amine portion eliminated hERG K+ channel inhibitory activity in a patch-clamp study, leading to the discovery of N-{3-[(1R)-1-{[2-(acetylamino)ethyl]amino} ethyl]-8-methylquinolin-7-yl}-4-(cyclopropylmethoxy)benzamide (R)-10h. The compound (R)-10h showed potent inhibitory activity against hMCHR1 and dose-dependently suppressed food intake in a 2-day study on DIO-F344 rats. Furthermore, practical chiral synthesis of (R)-10h was performed to determine the molecule's absolute configuration.

HETEROCYCLIC COMPOUND

The present invention provides to a compound having melanin-concentrating hormone receptor antagonistic action and low toxicity, and useful as a agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound re