Start small and stay small. Minimizing attrition in the clinic with a focus on CNS therapeutics.
Curr Top Med Chem
; 9(18): 1688-704, 2009.
Article
en En
| MEDLINE
| ID: mdl-19929834
Diseases of the central nervous system are among the most devastating to patients and their families. Despite this, treatments for these diseases have lagged behind other therapeutic areas. Although social and economic factors may be partly responsible for the paucity of therapeutic agents, a particularly daunting challenge for CNS drug discovery is the need for compounds to cross the blood brain barrier. Recent analyses of successful drugs have shown that their chemical properties have not changed substantially over the past 40 years while the properties of compounds entering the clinic have become inflated. This property inflation has only exacerbated the challenges of CNS drug discovery as the requirements for delivery to the brain are even more stringent than those for other tissues. New approaches are needed to meet these challenges. In this review, we discuss the merits of fragment based lead discovery and how it may be used to address the challenges of CNS drug discovery. We also summarize compounds discovered by high-throughput screening, substrate evolution and fragment-based lead discovery for well known CNS targets. The results indicate that FBLD may be a key method for discovery of brain penetrable CNS therapeutics.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fármacos del Sistema Nervioso Central
/
Enfermedades del Sistema Nervioso Central
/
Descubrimiento de Drogas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Curr Top Med Chem
Asunto de la revista:
QUIMICA
Año:
2009
Tipo del documento:
Article
Pais de publicación:
Emiratos Árabes Unidos