RESUMEN
Tolterodine tartrate belongs to the family of muscarinic receptor antagonists and is indicated for the treatment of overactive urinary bladder syndrome. This chapter provides an overview of physical, analytical, and ADME profiles; highlights methods of chemical synthesis; and discusses stability of tolterodine as a free base and/or its l-tartrate salt in solution and in the solid state. The information presented in this chapter is based on the peer-reviewed literature, compendial reports (USP, EP), and authors' data. Patent literature is included only in a few instances.
Asunto(s)
Antagonistas Muscarínicos , Tartrato de Tolterodina , Estabilidad de Medicamentos , Humanos , Antagonistas Muscarínicos/química , Antagonistas Muscarínicos/farmacocinética , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/uso terapéutico , Tartrato de Tolterodina/química , Tartrato de Tolterodina/farmacocinética , Tartrato de Tolterodina/farmacología , Tartrato de Tolterodina/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológicoRESUMEN
This chapter is a review on physical and chemical properties, methods of preparation, analysis, as well as pharmacodynamics and pharmacokinetics of Alendronate sodium (4-amino-1-hydroxybutane-1,1-diphosphonic acid sodium salt), a bone metabolism regulator, indicated for the treatment of excessive bone resorption and osteoporosis.
Asunto(s)
Alendronato/química , Conservadores de la Densidad Ósea/química , Alendronato/análisis , Alendronato/síntesis química , Alendronato/farmacocinética , Animales , Cristalografía , Humanos , Solubilidad , Terminología como AsuntoRESUMEN
Multifrequency continuous wave (cw) and echo-detected (ED) electron paramagnetic resonance (EPR) was employed to study the mobility of nitroxides confined in nanocapsules. The complexes p-hexanoyl calix[4]arene with 4-methoxy-2,2,6,6-tetramethylpiperidine-N-oxyl (MT) and N-(2-methylpropyl)-N-(1-diethylphosphono-2,2-dimethylpropyl)-aminoxyl (DEPN) were studied by X-, W-band and 360 GHz cw EPR at temperatures between 90 and 370 K. Thereby we were able to extract the canonical values of the hyperfine and g-tensors of the encapsulated radicals as well as information on restricted orientational dynamics of the caged spin probes. Comparing cw and ED-EPR data obtained on MT@C6OH we found that between 90 and 200 K the caged nitroxide undergoes isotropic small-angle fluctuations (librations), whereas at higher temperatures restricted rotations of the radical with correlation times of 0.75 x 10(-10) s and 1.2 x 10(-10) s dominate at 325 and 300 K, respectively. The activation energy of the rotational motion of encapsulated MT radicals was evaluated as E(a) = 1.0 kcal mol(-1), which is comparable to the magnitude of van der Waals interactions. Compared to MT, the reorientational motion of DEPN was found to be slower and more isotropic.
Asunto(s)
Calixarenos/química , Nanocápsulas/química , Óxidos de Nitrógeno/química , Marcadores de Spin , Óxidos N-Cíclicos/química , Espectroscopía de Resonancia por Spin del Electrón , TemperaturaRESUMEN
We present an X-ray diffraction (XRD) and multi frequency electron spin resonance (ESR) study of the structure and dynamics of an inclusion complex of p-hexanoyl calix[4]arene (C6OH) with 4-methoxy-2,2,6,6-tetramethylpiperidine-N-oxyl (MT). The single crystal XRD experiments reveal that MT along with ethanol (solvent) molecules are entrapped in a capsular type crystalline lattice of the host C6OH material. ESR measurements were performed at 9.2 GHz/0.33 T (X-band) and at 360 GHz/14 T. In order to avoid ESR line broadening resulting from electron dipole-dipole interaction between nitroxides occupying neighbouring capsules in the crystal lattice, the capsules containing nitroxides were separated from each other by capsules containing diamagnetic dibenzylketone (DBK). Due to the extremely high g-tensor resolution of ESR at 360 GHz, we were able to distinguish, by shifts of their gxx component, between encapsulated nitroxide molecules forming a hydrogen bond between their O-(N) group and the OH group of an ethanol molecule occupying the same capsule and nitroxides missing this interaction. Temperature dependent ESR measurements revealed an orientational anisotropy in the motion of MT encapsulated in C6OH. Solid lipid nanoparticles (SLN) prepared from C6OH and loaded with the nitroxide retained the microcrystalline capsular structure of the pertinent inclusion complex. We found that encapsulated MT in SLNs becomes inaccessible to reducing agents such as sodium ascorbate.
RESUMEN
The para-acylcalix[n]arenes possess a very rich capacity to self-assemble into a wide variety of structures and sizes ranging from molecular assemblies through dimeric capsules, molecular sheets to nanoparticles. All these assemblies are capable of taking guest molecules and in the process of this inclusion discrete nanoscopic reaction vessels may be formed for photochemistry. Interestingly this uptake of quite large organic molecules occurs in the bulk in non-porous crystals without loss of crystallinity. At the air-water interface either as Langmuir monolayers or as colloidal suspensions the para-acylcalix[n]arenes show interaction with ionic species. The extension from para-acylcalix[4]arenes to para-acylcalix[8]arenes is in its infancy but already there is much promise for novel assemblies to be found.
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Calixarenos/química , Acilación , Calixarenos/síntesis química , Lípidos/química , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Nanoestructuras/químicaRESUMEN
The first capsular crystalline inclusion complex of para-hexanoyl calix[4]arene with stable nitroxyl radical DEPN has been isolated and showed a low mobility of the radical in the capsule.
Asunto(s)
Calixarenos/química , Óxido Nítrico/química , Rastreo Diferencial de Calorimetría , Cristalografía por Rayos X , Espectroscopía de Resonancia por Spin del Electrón , Enlace de Hidrógeno , Modelos Moleculares , Conformación Molecular , EstereoisomerismoRESUMEN
The thermal treatment of different inclusion complexes of para-octanoyl calix[4]arene leads to the formation of a guest-free van der Waals nanocapsular structure possessing a remarkable stability caused by the high mobility of alkanoyl arms.
RESUMEN
In an ethanol/water mixture, the nitroxyl radical TEMPO abstracts a hydrogen atom from a phenolic OH group of the amphiphilic para-hexanoylcalix[4]arene, and the hydroxylamine TEMPOH formed yields a stable inclusion complex with another molecule of the calixarene.
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Calixarenos/química , Hidroxilamina/química , Óxidos N-Cíclicos/química , Radicales Libres/química , Hexanoles/química , Hidrógeno/química , Enlace de Hidrógeno , Modelos Moleculares , Óxidos de Nitrógeno/química , Fenoles/química , TemperaturaRESUMEN
We have utilized para-hexanoylcalix[4]arene nanocapsules as hosts to carry out phototransformations of cis- and trans-stilbene. Single-crystal X-ray diffraction studies were performed to define precisely the location of encapsulated stilbenes inside the capsule and to analyze possible pathways of phototransformation. cis-Stilbene stacks as a pi-pi dimer located at the center of the capsule, whereas trans-stilbene does not form such a dimer. Irradiation of the crystalline inclusion complexes of each isomer of stilbene in the solid state leads to the appearance of the second isomer, and after prolonged photolysis, photodimerization also occurs. syn-Tetraphenylcyclobutane is formed as the major product of dimerization and its yield depends on the time and intensity of irradiation. In most cases, the single crystals of the complexes remain intact during irradiation; hence, the nanocapsules have the potential to serve as robust nanoreactors in the solid state. The confinement in the nanocapsules is sufficient to keep the reacting molecules together, although this is less restrictive than for trans-stilbene crystals, in which the molecules cannot achieve a favorable orientation for dimerization.
Asunto(s)
Nanocápsulas/química , Fotoquímica/métodos , Estilbenos/química , Calixarenos/química , Cristalización , Cristalografía por Rayos X , Dimerización , Fenoles/química , Estereoisomerismo , Estilbenos/efectos de la radiaciónRESUMEN
The thermal reactions of several TEMPO and DEPN (N-(2-methylpropan-2-yl)-N-(1-diethylphosphono-2,2-dimethylpropyl)-aminoxyl) based alkoxyamines were studied by means of (1)H and (31)P NMR spectroscopy aiming to distinguish the contributions of diastereoselective homolysis and coupling to the total equilibrium diastereomeric distribution. The TEMPO-based compounds reveal no diastereomeric excess while DEPN based compounds show a moderate excess both upon homolysis and coupling. The diastereomeric preference of homolysis for DEPN-(propionate-like) adducts does not depend on the ester group and it is mainly affected by the size of beta-substituents. The diastereoselective coupling is sensitive to the total recombination rate constant k(c) and diastereoselectivity increases with the decrease of k(c). Small diastereoselective coupling is found in the recombination of DEPN with sec-butyl isobutyrate radical, where no prochiral centers are formed upon cleavage of corresponding alkoxyamine.