RESUMO
Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization. The structure-activity relationships related to stereo- and regio-chemical effects of substituents on the aromatic ring in the A segment were studied. Analogs, which carry a meta-substituted phenyl ring in the A segment show comparable activity for inhibition of tubulin polymerization to 2, as well as in the cell proliferation assay using KB cells containing P-glycoprotein, compared to those of 1 and 2.
Assuntos
Antineoplásicos/síntese química , Oligopeptídeos/síntese química , Moduladores de Tubulina , Tubulina (Proteína)/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Biopolímeros , Proliferação de Células/efeitos dos fármacos , Humanos , Células KB , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Nus , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A series of highly potent thiourea inhibitors of cytomegalovirus (CMV) with improved stability properties was prepared and evaluated. Compound 29 inhibited the virus in cultured HFF cells with IC50 of 0.2 nM.
Assuntos
Antivirais/síntese química , Citomegalovirus/efeitos dos fármacos , Herpesviridae/efeitos dos fármacos , Tioureia/análogos & derivados , Antivirais/farmacologia , Células Cultivadas , Resistência Microbiana a Medicamentos , Humanos , Concentração Inibidora 50 , Relação Estrutura-Atividade , Tioureia/farmacologiaRESUMO
Bis-(aryl)thioureas were found to be potent and selective inhibitors of cytomegalovirus (CMV) in cultured HFF cells. Of these, the thiazole analogue 38 was investigated as a potential development candidate.
Assuntos
Antivirais/química , Antivirais/farmacologia , Citomegalovirus/efeitos dos fármacos , Tioureia/análogos & derivados , Tioureia/farmacologia , Acilação , Derivados de Benzeno/química , Derivados de Benzeno/farmacologia , Linhagem Celular , Herpesviridae/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Relação Estrutura-AtividadeRESUMO
[reaction: see text] Aldol reactions using bis-(chiral alpha-methylbenzyl)glycine esters with aldehydes gave excellent diastereoselectivity. Thus, an enantiopure ribosylglycine was prepared for the synthesis of analogues of the natural antibiotics muraymycin. This method was extended for formation of beta-hydroxyamino esters.
