RESUMO
A set of 4-(R2-imino)-3-mercapto-5-(R1)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.
Assuntos
Antineoplásicos/farmacologia , Inibidores do Crescimento/farmacologia , Iminas/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Triazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores do Crescimento/síntese química , Inibidores do Crescimento/química , Iminas/síntese química , Iminas/química , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/químicaRESUMO
A Veratrum piperidine chiron was prepared over 11 steps (7.9% yield) from (-)-citronellal. Three methods for the installation of the propargylic side chain onto a cyclic enamide are presented.
Assuntos
Caprilatos/síntese química , Piperidinas/química , Piperidinas/síntese química , Sulfonamidas/química , Alcaloides de Veratrum/química , Alcaloides de Veratrum/síntese química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
Opening of representative epoxides with 1,2-amino alcohols delivered the amino diols. The product amino diols were then oxidized under Swern conditions. The amino diketones so prepared were not isolated, but were condensed directly with hydroxylamine to give the substituted pyrazines.
