Structure of 1,4-dihydro-1-ethyl-4-iminecinnoline-3-carboxylic acids, classical isosters of quinolone antibacterials: Crystal structures of hydrochlorides of 7-chloro and 7-methyl derivatives

Crystal structures of hydrochlorides of 7-chloro- and 7-methyl-4-iminecinno line analogs of antibacterial quinolones have been determined by X-ray diff raction methods. The cell parameters for the 7-chloro (1) analog in the spa ce group P2(1)/c are a = 9.061(1), b = 19.062(1), c = 7.310(1)Angstrom, bet a = 104.92(1)degrees, Z = 4, and D-calc = 1.569 g/cm(3) and for the 7-methy l (2) analog in the space group P (1) over bar are a = 7.277(5), b = 9.080( 5), c = 10.058(5) Angstrom, alpha = 106.10(1), beta = 102.38(1), gamma = 90 .18(1)degrees, Z = 2, and D-calc = 1.429 g/cm(3). Despite geometrical equiv alency of methyl and chlorine and some resemblance of their packings, the c rystal structures are not isostructural. Each compound forms a strong intra molecular hydrogen bond between protonated 4-imine (a donor) and 3-carboxyl ic tan acceptor) groups. Compounds with a similar bond, but with reversed f unctionality and orientation of the 3-carboxylic group, form common quinolo nes, being mostly 4-oxoquinoline-3-carboxylic acids. The difference should exclude chemical affinity of 4-imine analogs to the guanine base of a bacte rial DNA in DNA-gyrase complex, as proposed by Shen et al.(2) for 4-oxoquin oline-3-carboxylic acids showing antibacterial activity. Also the free acid ic function of a carboxyl group may significantly lower permeability of 4-i mine-3-carboxylic analogs of quinolones. Surprisingly, they have demonstrat ed antibacterial activity comparable with that of nalidixic acid.