Enaminones 11. An examination of some ethyl ester enaminone derivatives as anticonvulsant agents.

In this paper, we investigated the previously synthesized anticonvulsant enaminone ethyl ester analogs using the computational gaussian 03 programs. The significant chemical features of the enaminone compounds that lead to positive anticonvulsant activity were identified. From our analyses, we believe that the neutrality of the phenyl ring may be important for binding in the hydrophobic pocket of the active site and that the binding of the phenyl substituent is the main reason why some analogs are active and others are inactive.

3-(4-Chloro-benzene-sulfonamido)-5-methyl-cyclo-hex-2-en-1-one.

For the title compound, C(13)H(14)ClNO(3)S, geometrical parameters, determined using X-ray diffraction techniques, are compared with those calculated by density functional theory (DFT), using hybrid exchange-correlation functional, B3LYP methods. The dihedral angle between the benzene ring and the conjugated part of the cyclo-hexene ring is 87.47 (5)°. The cyclo-hexene ring and its substituents are disordered over two conformations, with occupancies of 0.786 (3) and 0.214 (3). In the crystal, mol-ecules are linked into chains in the c-axis direction by inter-molecular N-H⋯O(C=O) hydrogen bonds. C-H⋯O inter-actions are also observed.

tert-Butyl 4-(4-chloro-anilino)-6-methyl-2-oxocyclo-hex-3-ene-carboxyl-ate.

In the title compound, C(18)H(22)ClNO(3), the dihedral angle between the benzene ring and the conjugated part of the enaminone ring is 55.19 (9)°. The ester substituent makes a dihedral angle of 81.0 (2)° with this latter moiety. The crystal structure features N-H⋯O and weak C-H⋯O inter-molecular inter-actions.

tert-Butyl 6-methyl-2-oxo-4-[4-(trifluoro-meth-oxy)anilino]cyclo-hex-3-ene-1-carboxyl-ate.

In the title compound, C(19)H(22)F(3)NO(4), the dihedral angle between the benzene ring and the conjugated part of the enaminone ring is 42.5 (1)°. The ester substituent makes a dihedral angle of 81.3 (2)° with this latter moiety. The crystal structure is held together by strong N-H⋯O and weak C-H⋯O inter-molecular inter-actions. The enaminone ring is disordered over two orientations with relative occupancies of 0.794 (4) and 0.206 (4).

Enaminones: Exploring additional therapeutic activities.

Enaminones, enamines of beta-dicarbonyl compounds, have been known for many years. Their early use has been relegated to serving as synthetic intermediates in organic synthesis and of late, in pharmaceutical development. Recently, the therapeutic potential of these entities has been realized. This review provides the background and current research in this area with emphasis of these agents as potential anticonvulsants, their proposed mechanisms of action, and as potential modulators of multidrug resistance (MDR).