title: X-ray crystallographic and theoretical studies of an anticonvulsant enaminone: methyl 4-(4'-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate.
abstract: OBJECTIVE
  The aims of this study were to establish the structure of the potent anticonvulsant enaminone methyl 4-(4'-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E139), and to determine the energetically preferred conformation of the molecule, which is responsible for the biological activity.
  
  
  METHODS
  The structure of the molecule was determined by X-ray crystallography. Theoretical ab initio calculations with different basis sets were used to compare the energies of the different enantiomers and to other structurally related compounds.
  
  
  RESULTS
  The X-ray crystal structure revealed two independent molecules of E139, both with absolute configuration C11(S), C12(R), and their inverse. Ab initio calculations with the 6-31G, 3-21G and STO-3G basis sets confirmed that the C11(S), C12(R) enantiomer with both substituents equatorial had the lowest energy. Compared to relevant crystal structures, the geometry of the theoretical structures shows a longer C-N and shorter C=O distance with more cyclohexene ring puckering in the isolated molecule.
  
  
  CONCLUSIONS
  Based on a pharmacophoric model it is suggested that the enaminone system HN-C=C-C=O and the 4-bromophenyl group in E139 are necessary to confer anticonvulsant property that could lead to the design of new and improved anticonvulsant agents.
authors.affiliation: Faculty of Pharmacy, Kuwait University, Safat, Kuwait. ivanoe@hsc.kuniv.edu.kw
authors.forename: I O
authors.initials: IO
authors.lastname: Edafiogho
authors.forename: B J
authors.initials: BJ
authors.lastname: Denny
authors.forename: C H
authors.initials: CH
authors.lastname: Schwalbe
authors.forename: P R
authors.initials: PR
authors.lastname: Lowe
mesh_terms: D000927:Anticonvulsants / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003510:Cyclohexanes / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000927:Anticonvulsants; D003510:Cyclohexanes; C482385:E139 compound