RESUMEN

A sensitive and specific high-performance liquid chromatography (HPLC) method for the separation and quantification of 3-(S)-quinuclidinol in 3-(R)-quinuclidinol, precursor for active pharmaceutical ingredients (solifenacin, revatropate and talsaclidine), has been developed and validated by precolumn derivatization. Several chiral columns were tested in a normal phase system. Excellent enantioseparation with the resolution more than 11.4 was achieved on Chiralpak IC column using isocratic mobile phase consisting of n-hexane, ethanol, 2-propanol and diethylamine (80:8:12:0.4, v/v). The detection was carried out using UV detector at 230 nm. The influence of mobile phase composition, namely organic modifiers, additives, aliphatic alkanes and water content in mobile phase, on retention and enantioseparation was studied. Validation of the developed method including specificity, system suitability, limit of detection, limit of quantification, linearity, repeatability, intermediate precision, accuracy and solution stability was performed according to the International Conference on Harmonization guidelines. The advantage of the method is a good HPLC enantioseparation by precolumn derivatization using reaction mixture as sample, simpler UV detection, short analysis time (<30 min), and therefore this method is suitable option for routine quantification of 3-(S)-quinuclidinol in 3-(R)-quinuclidinol.

RESUMEN

In the present study, fourteen derivatives comprising of 5-benzylidene-2-(phenylimino)-thiazolidin-4-one moiety were synthesized. The structures of synthesized compounds were established by elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data and tested for electrocardiographic, antiarrhythmic and antihypertensive activities. Compound 11 was found to be most potent in this series. The pharmacological results suggested that, the antiarrhythmic effects of these compounds were related to their Ca(++) ion channel antagonistic properties, which are believed to be due to the presence of 5-benzilidine-2-(phenylimino)-thiazolidin-4-one moiety. The antihypertensive effect of ß-blocker side chain is enhanced by the presence of less bulky aliphatic and heterocyclic tertiary amines.

Asunto(s)

Antihipertensivos/síntesis química , Antihipertensivos/farmacología , Tiazolidinas/síntesis química , Tiazolidinas/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratas , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

In the present study, we have synthesized novel dihydropyrimidines (1a-j), their dimethylated adducts (2a-j), and hydrazine derivatives (3a-j) of 2a-j and subsequently their pyrazole derivatives (4a-j). Elemental analysis, IR, 1H NMR and mass spectral data elucidated structure of newly synthesized compounds. Some of these novel derivatives showed moderate to potent in vitro antioxidant, anti-inflammatory, antibacterial, antifungal and anthelmintic activity.

Asunto(s)

Antihelmínticos/farmacología , Antiinfecciosos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Animales , Antihelmínticos/síntesis química , Antihelmínticos/química , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antioxidantes/síntesis química , Antioxidantes/química , Bacterias/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hongos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oligoquetos/efectos de los fármacos , Pirazoles/síntesis química , Pirazoles/química , Pirimidinas/síntesis química , Pirimidinas/química , Estereoisomerismo

RESUMEN

The core objective of nanoparticles is to control and manipulate biomacromolecular constructs and supramolecular assemblies that are critical to living cells in order to improve the quality of human health. By definition, these constructs and assemblies are nanoscale and include entities such as drugs, proteins, DNA/RNA, viruses, cellular lipid bilayers, cellular receptor sites and antibody variable regions critical for immunology and are involved in events of nanoscale proportions. The emergence of such nanotherapeutics/diagnostics will allow a deeper understanding of human longevity and human ills that include cancer, cardiovascular disease and genetic disorders. A technology platform that provides a wide range of synthetic nanostructures that may be controlled as a function of size, shape and surface chemistry and scale to these nanotechnical dimensions will be a critical first step in developing appropriate tools and a scientific basis for understanding nanoparticles.