A crystal-state, solution and theoretical study of the preferred conformation of linear C alpha, alpha-diphenylglycine derivatives and dipeptides with potential anticonvulsant activity.
Several linear molecules containing the C alpha, alpha-diphenylglycine residue were prepared as potential anticonvulsants. The conformational preferences of the C alpha, alpha-diphenylglycine residue were assessed in these synthetic derivatives and dipeptides by X-ray diffraction, FTIR absorption and 1H NMR techniques, and by conformational energy computations. Five (out of six) derivatives adopt the fully extended C5 conformation in the crystal state. This intramolecularly H-bonded form is largely populated in chloroform solution in all the derivatives investigated. Conformational energy computations in vacuo support the view that the intramolecularly H-bonded C7-ring form is the most stable structure for these compounds. Only one linear derivative exhibits a (modest) anticonvulsant activity.
Department of Organic Chemistry, University of Padova, Italy.
C
C
Toniolo
M
M
Crisma
N
N
Fabiano
P
P
Melchiorri
L
L
Negri
J A
JA
Krause
D S
DS
Eggleston
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives*; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D012640:Seizures / Q000188:drug therapy
D000927:Anticonvulsants; D004151:Dipeptides; D005998:Glycine