1449763-35-2

Upstream product

• 58113-30-7 4-(3-chloropropoxy)-3-methoxyacetophenone 
• 1160707-44-7 1-[4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl]ethan-1-one 
• 1449763-02-3 1-(4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl)-3-(dimethylamino)propyl-2-en-1-one 
• 1394166-09-6 6-methyloxy-7-(4-(3-chloropropoxy))-4-4-hydroxyquinoline 
• 1436417-98-9 6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)-quinolin-4-ol 
• 1436417-99-0 4-chloro-6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)-quinoline 
• 1436418-01-7 4-(2-fluoro-4-nitrophenoxy)-6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinoline 
• 1290538-61-2 3-fluoro-4-{6-methoxy-7-[3-(4-methylpiperidin-1-yl)propoxy]quinolin-4-yloxy}phenylamine 
• 498-02-2 1-(3-methoxy-4-hydroxyphenyl)ethanone 
• 1449763-32-9 phenyl 3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperdine-1-yl)propoxy)quinolin-4-yloxy)phenylcarbamate 

Downstream Products

• 1449763-06-7 (E)-N¹-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-N⁴-(2-fluorobenzylidene)semicarbazide 
• 1428787-71-6 (E)-N⁴-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinoline-4-yloxy)phenyl)-N¹-(2,4-difluorobenzylidene)semicarbazide 
• 1428787-48-7 (E)-N⁴-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinoline-4-yloxy)phenyl)-N¹-(benzylidene)semicarbazide 
• 1491173-75-1 N¹-(3-fluoro-4-(6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-N⁴-(2,4-difluorobenzyl)semicarbazide 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel 4-phenoxy-6,7-disubstituted quinolines possessing (thio)semicarbazones as c-Met kinase inhibitors

In continuing our efforts to identify small molecules able to inhibit c-Met kinase, three series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives (23a-w, 26a-d and 30a-d) bearing (thio)semicarbazone scaffold were designed, synthesized and evaluated for their cytotoxicity. The biological data revealed that most compounds exhibited moderate-to-excellent activity against HT-29, MKN-45, A549 cancer cell lines and relative poor potency toward MDA-MB-231 cell as well as hardly any cytotoxicity in normal PBL cell. Eleven compounds were further examined for their inhibitory activity against c-Met kinase and three compounds (23h, 23n and 26a) demonstrated good inhibitory activity. This work resulted in the discovery of a potent c-Met inhibitor 23n, bearing 2-hydroxy-3-allylphenyl group at R2 moiety, as a valuable lead molecule, which possessed remarkable cytotoxicity and high selectivity against A549 and HT-29 cell lines with IC50 values of 11 nM and 27 nM. Besides, it displayed excellent c-Met kinase inhibition on a single-digital nanomolar level (IC50 = 1.54 nM). Meanwhile, the results from preliminarily in vivo study reflected that compound 23n showed promising overall PK profiles, consistent with the efficacy in both MKN-45 and HT-29 tumor xenograft mice model. These results clearly indicated that compound 23n is a potent and highly selective c-Met inhibitor and its favorable in vitro and in vivo profiles warrant further investigation.

Discovery and optimization of novel 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazones as c-Met kinase inhibitors

A novel series of N1-(3-fluoro-4-(6,7-disubstituted-quinolin-4- yloxy)phenyl)-N4-arylidenesemicarbazide derivatives were synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against A549, HT-29, MKN-45 and MDA-MB-231 cancer cell lines in vitro. Several potent compounds were further evaluated against three other cancer cell lines (U87MG, NCI-H460 and SMMC7721). Most of compounds tested exhibited moderate to excellent activity. The studies of SARs identified the most promising compound 28 (c-Met IC50 = 1.4 nM) as a c-Met kinase inhibitor. In this study, a promising compound 28 was identified, which displayed 2.1-, 3.3-, 48.4- and 3.6-fold increase against A549, HT-29, U87MG and NCI-H460 cell lines, respectively, compared with that of Foretinib.