Structures of three N-pyridyl-2-phenylsuccinimides and structural evidence for substituent effects on anticonvulsant properties

Abstract

T = 295 K, Mo Ka with .lambda. = 0.70930 .ANG.. Compound (I-6): C15H12N2O2, Mr = 252.26, monoclinic, P21/c, a = 8.441 (3), b = 15.269 (1), c = 9.745 (2) .ANG., .beta. = 92.34 (2).degree., V = 1254.9 (19) .ANG.3, Z = 4, Dx = 1.335 g cm-3, .mu. = 0.85 cm-1, F(000) = 528, R = 0.0345 for 1682 observed reflections. Compound (I-10): C16H14N2O2, Mr 266.30, monoclinic, P21/n, a = 11.637 (1), b = 5.793 (1), c = 20.778 (2) .ANG., .beta. = 105.26 (1).degree., V = 1351.3 (25) .ANG.3, Z = 4, Dx = 1.309 g cm-3, .mu. = 0.82 cm-1, F(000) = 560, R, = 0.0379 for 1840 observed reflections. Compound (I-11): C16H13ClN2O2, Mr = 300.74, triclinic, P.hivin.1, a = 9.076 (3), b = 9.366 (1), c = 10.477 (3) .ANG., .alpha. = 118.27 (2), .beta. = 93.85 (2), .gamma. = 105.26 (1).degree., V = 737.2 (15) .ANG.3, Z = 2, Dx = 1.350 g cm-3, .mu. = 2.61 cm-1, F(000) = 312, R = 0.0528 for 2018 observed reflections. The three N-pyridyl-2-phenylsuccinimides [N-(3-methyl-2-pyridyl)-2-p-chlorophenylsuccinimide (I-11); N-(3-methyl-2-pyridyl)-2-phenylsuccinimide (I-10) and N-(3-pyridyl)-2-phenylsuccinimide (I-6)], examined by means of X-ray structure analysis, have been previously subjected to extensive pharmacological screening, with regard to their anticonvulsive activity. Pharamacological properties of the compounds examined are clearly connected with the conformation of the molecules. The conformation of the molecules of biologically active derivatives (I-10) and (I-11) differs from the conformation of the inactive molecule of (I-6). This difference involves relative positioning of the pyridyl ring and the succinimide moiety. The Cl atom in (I-11) has only a minor effect on the conformation and geometry of the molecule in comparison with (I-10).