| Autor: |
Baron, B. M., Cregge, R. J., Farr, R. A., Friedrich, D., Gross, R. S., Harrison, B. L., Janowick, D. A., Matthews, D., McCloskey, T. C., Meikrantz, S., Nyce, P. L., Vaz, R., Metz, W. A. |
| Zdroj: |
Journal of Medicinal Chemistry; February 2005, Vol. 48 Issue: 4 p995-1018, 24p |
| Abstrakt: |
(E)-3-(2-Carboxy-2-phenylvinyl)-4,6-dichloro-1H-indole-2-carboxylic acid, 1, is a potent and selective antagonist of the glycine site of the N-methyl-d-aspartate (NMDA) receptor. Using 3D comparative molecular field analysis (CoMFA) to guide the synthetic effort, a series of aryl diacid analogues of 1 were synthesized to optimize in vivo potency, duration of action, and binding activity. It was found that the incorporation of a substituted aromatic with an electron withdrawing group or a heterocyclic group at the 2-position of the 3-propenyl moiety of 1 gave compounds with better affinity and potency in the murine stroke model. Ultimately this led to the discovery of 3-[2-(3-aminophenyl)-2-carboxyvinyl]-4,6-dichloro-1H-indole-2-carboxylic acid, 19, as a new potent selective glycine-site NMDA receptor antagonist. |
| Databáze: |
Supplemental Index |
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