Discovery of orally active, pyrrolidinone-based progesterone receptor partial agonists.

Washburn, David G; Hoang, Tram H; Frazee, James S; Johnson, Latisha; Hammond, Marlys; Manns, Sharada; Madauss, Kevin P; Williams, Shawn P; Duraiswami, Chaya; Tran, Thuy B; Stewart, Eugene L; Grygielko, Eugene T; Glace, Lindsay E; Trizna, Walter; Nagilla, Rakesh; Bray, Jeffrey D; Thompson, Scott K

Washburn, David G; Hoang, Tram H; Frazee, James S; Johnson, Latisha; Hammond, Marlys; Manns, Sharada; Madauss, Kevin P; Williams, Shawn P; Duraiswami, Chaya; Tran, Thuy B; Stewart, Eugene L; Grygielko, Eugene T; Glace, Lindsay E; Trizna, Walter; Nagilla, Rakesh; Bray, Jeffrey D; Thompson, Scott K.

Afiliação

Washburn DG; Department of Chemistry, Metabolic Pathways Centre for Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA 19406, USA. dave.g.washburn@gsk.com

Bioorg Med Chem Lett ; 19(16): 4664-8, 2009 Aug 15.

Article em En | MEDLINE | ID: mdl-19616429

ABSTRACT

ABSTRACT

We have designed and synthesized a novel series of pyrrolidinones as progesterone receptor partial agonists. Compounds from this series had improved AR selectivity, rat pharmacokinetic properties, and in vivo potency compared to the lead compound. In addition, these compounds had improved selectivity against hERG channel inhibition.

Assuntos

Pirrolidinonas/química; Receptores de Progesterona/agonistas; Administração Oral; Animais; Sítios de Ligação; Descoberta de Drogas; Canais de Potássio Éter-A-Go-Go/metabolismo; Haplorrinos; Humanos; Pirrolidinonas/síntese química; Pirrolidinonas/farmacocinética; Ratos; Receptores de Progesterona/metabolismo; Relação Estrutura-Atividade

Texto completo

Imprimir

XML

PubMed Links

Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirrolidinonas / Receptores de Progesterona Limite: Animals / Humans Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo

Imprimir

XML

PubMed Links

Buscar no Google