The effect of bromine scanning around the phenyl group of 4-phenyl-quinolone derivatives

Three quinolone compounds were synthesized and crystallized in an effort to study the structure-activity relationship of these calcium-channel antagonists. In all three quinolones, viz. ethyl 4-(4-bromo-phenyl)-2,7,7-trimethyl-5-oxo-1, 4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, (I), ethyl 4-(3-bromo-phenyl)-2, 7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-car-box-yl-ate, (II), and ethyl 4-(2-bromo-phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro- quinoline-3-carboxyl-ate, (III), all C21H24BrNO3, common structural features such as a flat boat conformation of the 1,4-di-hydro-pyridine (1,4-DHP) ring, an envelope conformation of the fused cyclo-hexa-none ring and a bromo-phenyl ring at the pseudo-axial position and orthogonal to the 1,4-DHP ring are retained. However, due to the different packing inter-actions in each compound, halogen bonds are observed in (I) and (III). Compound (III) crystallizes with two molecules in the asymmetric unit. All of the prepared derivatives satisfy the basic structural requirements to possess moderate activity as calcium-channel antagonists.