A novel access to arylated and heteroarylated beta-carboline based PDE5 inhibitors.
Med Chem
; 6(6): 374-87, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-21054274
ABSTRACT
Starting from a previously reported lead compound GR30040X (a hydantoin tetrahydro-ß-carboline derivative with a 4- pyridinyl ring at C- 5), a series of structurally related tetrahydro-ß-carboline derivatives were prepared. The tetrahydro-ß-carboline skeleton was fused either to a hydantoin or to a piperazindione ring, the pendant aryl group attached to C-5 or C-6 was changed to a 3, 4-dimethoxyphenyl or a 3-pyridinyl ring; different N-substituents on the terminal ring were introduced, a straight chain ethyl group, a branched tert. butyl and P-chlorophenyl group rather than n-butyl group of the lead compound. All four possible diastereomers of target tetrahydro-ß-carboline derivatives were prepared, separated by column chromatography and the significance of these stereochemical manipulations were studied. Synthesized compounds were evaluated for their inhibitory effect versus PDE5. Seven hits were obtained with appreciable inhibitory activity versus PDE5 with IC50s 0.14 - 4.99 µM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carbolinas
/
Inibidores da Fosfodiesterase 5
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article