RESUMEN
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.
Asunto(s)
Antineoplásicos/síntesis química , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/análogos & derivados , Inhibidores de Proteínas Quinasas/síntesis química , Pirimidinas/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacologíaRESUMEN
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.
Asunto(s)
Amidas/síntesis química , Amidas/farmacología , Ciclohexanos/química , Receptores de la Hormona Gastrointestinal/antagonistas & inhibidores , Receptores de Neuropéptido/antagonistas & inhibidores , Urea/síntesis química , Urea/farmacología , Amidas/química , Línea Celular , Evaluación Preclínica de Medicamentos , Humanos , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad , Urea/químicaRESUMEN
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.