7 research outputs found
Una nueva aproximaci贸n a la optimizaci贸n terap茅utica del diclofenaco
In an effort for obtaining compounds with lower gastric toxicity than diclofenac, five different N,Ndisubstitutedaminoethylester derivatives of diclofenac were synthesized and evaluated. These esterswere designed so as to satisfy the structural requirement for them to possess the anticholinergic activityin intact form before cleavage. Besides blocking the acidic carboxyl group by esterification this activitywas incorporated into the synthesized esters with an expected additional benefit of having reduced gastricacid secretion and thereby abolishing the local irritation by a dual mechanism. This report describes thesynthesis, hydrolysis kinetics and the biological activity of these esters. All the ester derivatives werefound to be stable in buffers (pH 2.0 and 7.4) for sufficient time period, assuring them to be absorbedintact and to successfully overcome the local gastric irritation of the parent drug. A fast enzymatichydrolysis was observed for all the derivatives in 80% pooled human serum. The synthesized esters werefound to possess the proposed anticholinergic activity. The anti-inflammatory activity for most of thecompounds was retained with a significant reduction in the ulcerogenic potential compared to diclofenac.Con objeto de obtener compuestos con menor toxicidad g谩strica que el diclofenaco, se sintetizaron yevaluaron cinco 茅steres derivados aminoet铆licos N,N-sustituidos derivados del diclofenaco. Estos 茅steresse dise帽aron para satisfacer el requisito estructural de disponer de una actividad anticolin茅rgica intactaantes de la separaci贸n. Adem谩s de bloquear el grupo carboxilo 谩cido mediante esterificaci贸n, estaactividad se incorpor贸 a los 茅steres sintetizados, con el beneficio adicional esperado de la reducci贸n dela secreci贸n de 谩cido g谩strico y la consecuente eliminaci贸n de la irritaci贸n local mediante un mecanismodual. En este estudio se describen la s铆ntesis, la cin茅tica de la hidr贸lisis y la actividad biol贸gica de estos茅steres. Todos los derivados de 茅ster permanecieron estables en tampones de pH 2,0 y 7,4 durante unper铆odo de tiempo suficiente, lo que asegur贸 su absorci贸n en estado intacto y la eliminaci贸n de lairritaci贸n g谩strica local producida por el f谩rmaco principal. Se observ贸 una r谩pida hidr贸lisis enzim谩ticade todos los derivados en un 80% de suero humano combinado. Se descubri贸 que los 茅steres sintetizadospose铆an la actividad anticolin茅rgica propuesta. Se mantuvo la actividad antiinflamatoria en la mayor铆a delos compuestos y se logr贸 una significativa reducci贸n del potencial ulcerog茅nico en comparaci贸n con eldiclofenaco
A novel approach towards therapeutic optimization of diclofenac
Con objeto de obtener compuestos con menor toxicidad g谩strica que el diclofenaco, se sintetizaron yevaluaron cinco 茅steres derivados aminoet铆licos N,N-sustituidos derivados del diclofenaco. Estos 茅steresse dise帽aron para satisfacer el requisito estructural de disponer de una actividad anticolin茅rgica intactaantes de la separaci贸n. Adem谩s de bloquear el grupo carboxilo 谩cido mediante esterificaci贸n, estaactividad se incorpor贸 a los 茅steres sintetizados, con el beneficio adicional esperado de la reducci贸n dela secreci贸n de 谩cido g谩strico y la consecuente eliminaci贸n de la irritaci贸n local mediante un mecanismodual. En este estudio se describen la s铆ntesis, la cin茅tica de la hidr贸lisis y la actividad biol贸gica de estos茅steres. Todos los derivados de 茅ster permanecieron estables en tampones de pH 2,0 y 7,4 durante unper铆odo de tiempo suficiente, lo que asegur贸 su absorci贸n en estado intacto y la eliminaci贸n de lairritaci贸n g谩strica local producida por el f谩rmaco principal. Se observ贸 una r谩pida hidr贸lisis enzim谩ticade todos los derivados en un 80% de suero humano combinado. Se descubri贸 que los 茅steres sintetizadospose铆an la actividad anticolin茅rgica propuesta. Se mantuvo la actividad antiinflamatoria en la mayor铆a delos compuestos y se logr贸 una significativa reducci贸n del potencial ulcerog茅nico en comparaci贸n con eldiclofenaco.In an effort for obtaining compounds with lower gastric toxicity than diclofenac, five different N,Ndisubstitutedaminoethylester derivatives of diclofenac were synthesized and evaluated. These esterswere designed so as to satisfy the structural requirement for them to possess the anticholinergic activityin intact form before cleavage. Besides blocking the acidic carboxyl group by esterification this activitywas incorporated into the synthesized esters with an expected additional benefit of having reduced gastricacid secretion and thereby abolishing the local irritation by a dual mechanism. This report describes thesynthesis, hydrolysis kinetics and the biological activity of these esters. All the ester derivatives werefound to be stable in buffers (pH 2.0 and 7.4) for sufficient time period, assuring them to be absorbedintact and to successfully overcome the local gastric irritation of the parent drug. A fast enzymatichydrolysis was observed for all the derivatives in 80% pooled human serum. The synthesized esters werefound to possess the proposed anticholinergic activity. The anti-inflammatory activity for most of thecompounds was retained with a significant reduction in the ulcerogenic potential compared to diclofenac
Synthesis, hydrolysis studies and phamacodynamic profiles of amide prodrugs of dexibuprofen with amino acids
Synthesis, anti-inflammatory activities and docking studies of amide derivatives of meclofenamic acid
Optimization of Hierarchical Modulation for Use of Scalable Media
This paper studies the Hierarchical Modulation, a transmission strategy of the approaching scalable multimedia over frequency-selective fading channel for improving the perceptible quality. An optimization strategy for Hierarchical Modulation and convolutional encoding, which can achieve the target bit error rates with minimum global signal-to-noise ratio in a single-user scenario, is suggested. This strategy allows applications to make a free choice of relationship between Higher Priority (HP) and Lower Priority (LP) stream delivery. The similar optimization can be used in multiuser scenario. An image transport task and a transport task of an H.264/MPEG4 AVC video embedding both QVGA and VGA resolutions are simulated as the implementation example of this optimization strategy, and demonstrate savings in SNR and improvement in Peak Signal-to-Noise Ratio (PSNR) for the particular examples shown