125836-07-9

Upstream product

• 118-92-3 anthranilic acid 
• 152904-43-3 (E)-2-(2-nitrovinylamino)benzoic acid 
• 121845-92-9 2-<2-nitroethylideneamino>benzoic acid 

Downstream Products

• 81946-31-8 3-amino-1,4-dihydroquinoline-4-one 
• 125836-20-6 5-benzyloxycarbonyl-3,10-dioxo-1-methoxy-10a-nitro-octahydroacridine 
• 125836-20-6 5-benzyloxycarbonyl-3,10-dioxo-1-methoxy-10a-nitro-octahydroacridine 
• 1026441-72-4 N-(4-Amino-quinolin-3-yl)-4-chloro-benzamide 
• 110644-03-6 N-(4-Amino-quinolin-3-yl)-benzamide 
• 42606-33-7 3-nitro-4-aminoquinoline 
• 125836-11-5 1-benzyloxycarbonyl-3-nitro-1,4-dihydroquinolin-4-one 
• 39061-97-7 4-chloro-3-nitroquinoline 

Relevant academic research and scientific papers

Discovery of N -(2,4-Di- tert -butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a potent and orally bioavailable CFTR potentiator

Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screening in NIH-3T3 cells expressing the F508del-CFTR mutation. Extensive medicinal chemistry and iterative structure-activity relationship (SAR) studies to evaluate potency, selectivity, and pharmacokinetic properties resulted in the identification of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, 48, ivacaftor), an investigational drug candidate approved by the FDA for the treatment of CF patients 6 years of age and older carrying the G551D mutation.

CYCLOADDITION REACTIONS OF N-ALKOXYCARBONYL-4-QUINOLONES

3-Ethoxycarbonyl-4-1(H)-quinolone (2) and 3-nitro-4-1(H)-quinolone (3) reacted with a variety of chloroformates to give the N-acyl-3-ethoxycarbonyl-4-1(H)-quinolones (4a-d) and N-acyl-3-nitro-4-1(H)-quinolones (5a,b) respectively.Reaction of (4a,b,d) with 1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (6) gave the respective cycloadduct, 5,10a-diethoxycarbonyl-3,10-dioxo-1-methoxy-octahydroacridine (7a) and the analogues (7b,d).Treatment of (5a,b) with the above diene gave rise to two cycloadducts 3,10-dioxo-5-ethoxycarbonyl-1-methoxy-10a-nitro-octahydroacridines which had arisen from addition from the exo and endo transition states.The quinolones (4a,b) on reaction with Gesson's diene (12) and the ketene acetals (15) and (16), afforded Michael adducts 2--methyl-1-carboethoxy-4-methoxycyclohexa-1,3-diene (14a), and (14b), (17), (18) respectively.Base treatment of (14a,b) gave the aminoketone 7-(2'-aminobenzoyl)-8-hydroxy-3-methoxy-1,2-dihydronaphthalene (19) which was acetylated to afford (20).The latter could be selectively O-deacetylated to give 7-(2'-acetamidobenzoyl)-8-hydroxy-3-methoxy-1,2-dihydronaphthalene (21).