Synthesis and CLOGP correlation of imidooxy anticonvulsants.
J Med Chem
; 36(23): 3517-25, 1993 Nov 12.
Article
en En
| MEDLINE
| ID: mdl-8246220
ABSTRACT
Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of > 4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss structure activity and the Craig plot analytical approaches as well as a semiempirical method. CLOG P analysis was also applied to this series after experimentally determining the NOR fragment. All compounds were minimized and these physicochemical parameters correlated to anticonvulsant activity. Several interesting substituted benzyloxy compounds emerged from this study the 2',4'-dichloro (2b), 4'-(trifluoromethyl) (2c), 2'-bromo (2d), 3'-chloro (2o), 2'-chloro (2r), 2'-fluoro (2p), and 3'-fluoro (2w) analogs, all of which had comparable, or better activity than the parent unsubstituted analog (2a). X-ray crystal analysis of the active 2a versus inactive N-benzyl-2-azaspiro[4.4]nonane-1,3-dione (10) is discussed.
Buscar en Google
Banco de datos:
MEDLINE
Asunto principal:
Pirrolidinonas
/
Compuestos de Espiro
/
Anticonvulsivantes
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Año:
1993
Tipo del documento:
Article