Stereochemical basis for activity in thiadiazole anticonvulsants: 1-[5-(biphenyl-2-yl)-1,3,4-thiadiazol-2-yl]methanaminium chloride and two inactive analogues, 2-(biphenyl-4-yl)-5-[2-(1-methylethylidene)hydrazino]-1,3,4-thiadiazole and the methanol solvate of its hydrochloride salt.
In 1-[5-(biphenyl-2-yl)-1,3,4-thiadiazol-2-yl]methanaminium chloride, C15H14N3S+.Cl-, the protonation occurs at the amine N atom. The outer phenyl ring makes an angle of 88.0 (2) degrees with the plane through the inner benzene ring, and the planes of the thiadiazole ring and the attached benzene ring intersect at an angle of 165.5 (4) degrees . In addition to classical N-H...N and N-H...Cl(-) hydrogen bonds producing chains parallel to the c axis, there are weak C-H...N and C-H...Cl- hydrogen bonds. The hydrogen bonds and packing interactions result in hydrophilic and hydrophobic planar areas in the crystal, perpendicular to the a axis. Stereochemical comparison with phenytoin shows that the two compounds may utilize similar mechanisms of action. 2-(Biphenyl-4-yl)-5-[2-(1-methylethylidene)hydrazino]-1,3,4-thiadiazole, C17H16N4S, where Z' = 2, and the methanol solvate of its hydrochloride salt, 5-(biphenyl-4-yl)-2-[2-(1-methylethylidene)hydrazino]-1,3,4-thiadiazol-3-ium chloride methanol solvate, C17H17N4S+.Cl-.CH3OH, adopt linear almost planar molecular conformations. The para position of the outer phenyl ring in these compounds precludes adoption of the phenytoin anticonvulsant stereochemistry.
Camerman
Arthur
A
Ardono Research, 341 101st Avenue SE, Bellevue, WA 98004, USA.
Hempel
Andrew
A
Mastropaolo
Donald
D
Camerman
Norman
N
D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D000432:Methanol / Q000737:chemistry*; D008958:Models, Molecular; D013237:Stereoisomerism; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology*
D000927:Anticonvulsants; D013830:Thiadiazoles; D000432:Methanol