Complex target-oriented total synthesis in the drug discovery process: the discovery of a highly promising family of second generation epothilones.
J Am Chem Soc
; 125(10): 2899-901, 2003 Mar 12.
Article
em En
| MEDLINE
| ID: mdl-12617656
ABSTRACT
The total synthesis of a family of (E)-9,10-dehydro derivatives of epothilone D (i.e., 12,13-desoxyepothilone B) is described. The route is particularly concise and amenable to production of new congeners. Furthermore, the chemistry described herein constitutes a major simplification in the total synthesis of EpoD, which is in human clinical trials. This new family of epothilones shows major advantages in terms of their potency and pharmacostability relative to the wild-type saturated analogues in the D series. From the perspective of compound availability through synthesis, potency, and pharmacokinetic properties, these compounds could well warrant advancement to clinical evaluation in humans.
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Base de dados:
MEDLINE
Assunto principal:
Epotilonas
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article