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1-aryl-3-(4-(7-methylthieno[3,2-d]pyrimidin-4-yloxy)phenyl)ureas: synthesis and molecular modelling studies using VEGFR-2

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Resumo:The development of anticancer drugs inhibiting angiogenesis has been an area of extensive research in the past decade. Angiogenesis is a requirement for tumor growth and metastasis and occurs through several signalling pathways. One key pathway that initiates proliferation and migration of endothelial cells is signalling through the vascular endothelial growth factor receptor-2 (VEGFR-2).1 Therefore, small molecules that block this signalling pathway through inhibition of VEGFR-2 tyrosine kinase activity could potentially inhibit angiogenesis and tumor growth. Recently works describing thienopyrimidine2 and thienopyrimidine 1,3-diarylureas3 as VEGFR-2 inhibitors have emerged in the literature. Here we present the synthesis of new 1-aryl-3-(4-(7-methylthieno[3,2-d]pyrimidin-4-yloxy)phenyl)ureas 2 in high yields by reaction of 4-[(7-methylthieno[3,2-d]pyridin-4-yl)oxy]aniline 1 with arylisocyanates. The former was prepared by regioselective nucleophilic substitution of 4-chloro-7-methylthieno[3,2-d]pyrimidine with 4-aminophenol
Autores principais:Soares, Pedro
Outros Autores:Froufe, Hugo J.C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Borges, Fernanda; Queiroz, Maria João R.P.
Ano:2011
País:Portugal
Tipo de documento:documento de conferência
Tipo de acesso:acesso aberto
Instituição associada:Instituto Politécnico de Bragança
Idioma:inglês
Origem:Biblioteca Digital do IPB
Descrição
Resumo:The development of anticancer drugs inhibiting angiogenesis has been an area of extensive research in the past decade. Angiogenesis is a requirement for tumor growth and metastasis and occurs through several signalling pathways. One key pathway that initiates proliferation and migration of endothelial cells is signalling through the vascular endothelial growth factor receptor-2 (VEGFR-2).1 Therefore, small molecules that block this signalling pathway through inhibition of VEGFR-2 tyrosine kinase activity could potentially inhibit angiogenesis and tumor growth. Recently works describing thienopyrimidine2 and thienopyrimidine 1,3-diarylureas3 as VEGFR-2 inhibitors have emerged in the literature. Here we present the synthesis of new 1-aryl-3-(4-(7-methylthieno[3,2-d]pyrimidin-4-yloxy)phenyl)ureas 2 in high yields by reaction of 4-[(7-methylthieno[3,2-d]pyridin-4-yl)oxy]aniline 1 with arylisocyanates. The former was prepared by regioselective nucleophilic substitution of 4-chloro-7-methylthieno[3,2-d]pyrimidine with 4-aminophenol