RESUMO
A new asymmetric synthetic route to (+)- and (-)-limaspermidine was devised, starting with chirally resolved enantiomerically pure 2-pyrone Diels-Alder cycloadducts. This route utilizes intramolecular Pd-catalyzed aromatic C-H amidation and imino-Diels-Alder reactions to construct the key indoline and indolizidine subunits onto the central cyclohexane core, allowing the straightforward formal total syntheses of both (+)- and (-)-limaspermidine.
RESUMO
Inexpensive sodium sulfide trihydrate was found to promote unprecedented 6e-regio-predefined redox condensation of o-nitroanilines with α-tetralones to benzo[a]phenazines. The method was also successfully extended to acetophenones and higher homologs as reducing partners to provide 2-phenylquinoxalines. Compared to traditional approaches toward benzo[a]phenazine and quinoxaline cores starting with o-phenylenediamines, the present strategy could afford these heterocycles with well-defined regiochemistry based on the structure of starting o-nitroanilines.
RESUMO
In our efforts to discover novel multi-target agents having better antitumor activities than celecoxib, 21 new aryl-substituted pyrazole derivatives possessing cis-diphenylethylene scaffold were mostly synthesized by a one-pot approach to ethyl 1,4,5-triaryl-1H-pyrazole-3-carboxylates via an improved Claisen condensation - Knorr reaction sequence. The cytotoxic effects of these compounds against three human cancer cell lines HT-29, Hep-G2, MCF-7 as well as their inhibition of NO production were studied. Results showed that incorporation of the important pharmacophoric groups of two original molecules celecoxib and combretastatin A-4 in a single molecule plays an important role in determining a better biological activities of the new coxib-hybrided compounds.
Assuntos
Antineoplásicos/síntese química , Bibenzilas/química , Inibidores de Ciclo-Oxigenase 2/química , Desenho de Fármacos , Pirazóis/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Pirazóis/síntese química , Pirazóis/farmacologia , Células RAW 264.7RESUMO
A new series of vinca-alkaloids derivatives containing various α,ß-unsaturated aromatic side chains was synthesized. Four new vinca-alkaloids derivatives showed selective cytotoxicities against KB tumor cell lines with IC50 value below 0.1 µM, thus comparable with vinblastine.