RESUMO
2,7-Diamino-thiazolo[4,5-d]pyrimidine analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities and inhibited in vitro cellular proliferation in EGFR-overexpressing human tumor cells. The synthesis and preliminary biological, physical, and pharmacokinetic evaluation of these thiazolopyrimidine compounds are reported.
Assuntos
Antineoplásicos/síntese química , Receptores ErbB/antagonistas & inibidores , Inibidores de Proteínas Quinases/análogos & derivados , Inibidores de Proteínas Quinases/síntese química , Pirimidinas/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologiaRESUMO
A series of 1,3-disubstituted cyclohexylmethyl urea and amide derivatives were synthesized as motilin receptor antagonists. Starting from known motilin antagonists, 1a and 1b, the cyclopentene scaffold was replaced and the four recognition elements optimized to arrive at a potent novel series.
Assuntos
Amidas/síntese química , Amidas/farmacologia , Cicloexanos/química , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores , Receptores de Neuropeptídeos/antagonistas & inibidores , Ureia/síntese química , Ureia/farmacologia , Amidas/química , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Ureia/químicaRESUMO
A series of glucose conjugates was synthesized and tested for inhibition of SGLT1 and SGLT2. The core structure was derived from compound 1a. Modification of the benzofuran moiety and 4'-substituent of the phenyl ring in compound 1a improved selectivity at SGLT2. Select compounds were compared to 1a in metabolic stability and in vivo efficacy studies.
