Preparation of 2H-benzo[b][1,4]oxazin-3(4H)-ones as stearoyl CoA desaturase inhibitors.

Abstract

Title compds. [I; R1 = H, (substituted) alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, heterocyclyl, aryl, heteroaryl; R2 = (substituted) alkyl, heterocyclyl, aryl, heteroaryl; R3, R4 = H, (substituted) alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl; X1 = O2C, NR'CO, O, S, SO2NR', etc.; R' = H, alkyl; L1, L2 = bond, (substituted) alkyleneoxy, alkylenethio, alkyleneimino; W = O, S], were prepd. Thus, N-[2-[6-(3,4-dichlorobenzylamino)-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl]ethyl]-2-hydroxyacetamide hydrochloride (multistep prepn. from 2-amino-4-nitrophenol, chloroacetyl chloride, ethanolamine, acetoxyacetic acid, and 3,4-dichlorobenzaldehyde given) inhibited stearoyl CoA desaturase with IC50 = 0.00139 μM. [on SciFinder(R)]