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Design and synthesis of dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole oximes as potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases.
Dandu, Reddeppareddy; Zulli, Allison L; Bacon, Edward R; Underiner, Ted; Robinson, Candy; Chang, Hong; Miknyoczki, Sheila; Grobelny, Jennifer; Ruggeri, Bruce A; Yang, Shi; Albom, Mark S; Angeles, Thelma S; Aimone, Lisa D; Hudkins, Robert L.
Afiliação
  • Dandu R; Department of Medicinal Chemistry, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. dreddy@cephalon.com
Bioorg Med Chem Lett ; 18(6): 1916-21, 2008 Mar 15.
Article em En | MEDLINE | ID: mdl-18308565
Fused dihydroindazolopyrrolocarbazole oximes have been identified as low nanomolar, potent dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors with excellent cellular potency. Development of the structure-activity relationships (SAR) led to identification of compounds 35 and 40 as potent, selective dual TIE-2/VEGF-R2 inhibitors with favorable pharmacokinetic properties. Compound 35 was orally active in tumor models with no observed toxicity.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2008 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2008 Tipo de documento: Article