On April 1, 2004, Blanco-Pillado, Maria-Jesus; Chappell, Mark Donald; Garcia De la Torre, Marta; Diaz Buezo, Nuria; Fritz, James Erwin; Holloway, William Glen; Matt, James Edward, Jr.; Mitch, Charles Howard; Pedregal-Tercero, Concepcion; Quimby, Steven James; Siegel, Miles Goodman; Smith, Dana Rae; Stucky, Russell Dean; Takeuchi, Kumiko; Thomas, Elizabeth Marie; Wolfe, Chad Nolan published a patent.Reference of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one The title of the patent was Preparation of [[(aminoalkyl)aryl]oxy]nicotinamides and analogs as opioid receptor antagonist for treatment of obesity and related conditions. And the patent contained the following:
Title diaryl ethers I [wherein X1-X10 = independently C, CH, or N; provided that each of rings A or B has no more than 2 N atoms; E = O or NH; R1 and R2 = independently H or (un)substituted (cyclo)alkyl, alkenyl, alkynyl, (alkyl)aryl, (aryl)heterocyclyl, (cyclo)alkylheterocyclyl, (cyclo)alkanoylalkyl, aroylalkyl, aryloxyalkyl, benzhydryl, bicyclyl(alkyl), benzoyl(alkyl), alkoxyalkyl, alkoxycarbonyl, (aryl)alkylsulfonyl, heterocyclylalkylsulfonyl, cycloalkylalkyl, carboxyalkyl, carbamoylalkyl, etc.; R3 and R3′ = independently H, alkyl, alkenyl, alkynyl, (alkyl)aryl, or alkylcycloalkyl; R4 and R5 = independently H, (halo)alkyl, alkenyl, alkynyl, alkoxy(halo)alkyl, thioalkyl, halo, aryl(alkyl), alkanoyl, alkoxycarbonyl, aminoalkyl, cycloalkylalkyl, etc.; R6 and R7 = independently H, (cyclo)alkyl, alkenyl, alkynyl, alkanoyl, OH, alkoxy, (aryl)alkylsulfonyl, heterocyclylalkylsulfonyl, aryl(alkyl), carbamoyl(alkyl), etc.; m = 1-3; n = 0-3; p = 0-3; or pharmaceutically acceptable salts, solvates, enantiomers, racemates, diastereomers, or mixtures thereof] were prepared as μ-, κ-, and δ-opioid receptor antagonists. For example, reductive amination of 6-(2-fluoro-4-formylphenoxy)nicotinamide and 3-methylbutylamine provided II (99%). The latter inhibited ex vivo binding of [3H]-diprenorphine in rat striatum/nucleus accumbens by >65% at a concentration of 7 mg/kg. In an acute feeding rat obesity assay, II suppressed opioid receptors at a dose of 0.3 μg/kg. In addition, diet-induced obese rats achieved an energy balance (caloric intake minus utilization) of -81 kcal/kg/day upon administration of 0.3 mg/kg p.o. of II in an indirect calorimetry assay. Thus, I and their pharmaceutical compositions are useful for the treatment, prevention, or amelioration of obesity and related diseases. The experimental process involved the reaction of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one(cas: 74904-29-3).Reference of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one
The Article related to aryloxy nicotinamide preparation opioid receptor antagonist antiobesity, aryl heteroaryl ether preparation opioid receptor antagonist antiobesity, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Reference of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem