Preparation of aromatic amine derivatives as stearoyl-CoA desaturase (SCD) inhibitors.

Abstract

N-aryl- or N-heterocyclylheterocyclecarboxamide and -benzamide derivs. [I; wherein the ring A represents an arom. ring which may be substituted; the ring B represents a ring which may be substituted; the ring C represents an arom. ring which may be substituted; R represents a hydrogen atom, a hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted; and X represents a spacer having a main chain composed of 1 to 5 atoms.], salts thereof, or prodrugs of the compds. or the salts are prepd. These compds. are useful for the prevention and/or treatment of hyperlipidemia, diabetes, or obesity or improving serum lipids. Thus, a soln. of 2-[(2,5-dichlorophenoxy)methyl]isonicotinic acid, 4-(1H-pyrazol-1-ylmethyl)aniline, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, and hydroxybenzotriazole in DMF was stirred at room temp. overnight to give 2-[(2,5-dichlorophenoxy)methyl]-N-[4-(1H-pyrazol-1-ylmethyl)phenyl]isonicotinamide (II). II at 10 μM inhibited 100% stearoyl-CoA desaturase (SCD) in microsome. Pharmaceutical formulations, e.g. a capsule contg. 3-[(2,5-dichlorophenoxy)methyl]-N-[4-(1H-pyrazol-1-ylmethyl)phenyl]benzamide (III), were described. [on SciFinder(R)]