RESUMEN
In this paper, we focus on critical issues directly related to the viability of carbon nanotube-based nanoelectromechanical switches, to perform their intended functionality as logic and memory elements, through assessment of typical performance parameters with reference to complementary metal-oxide-semiconductor devices. A detailed analysis of performance metrics regarding threshold voltage control, static and dynamic power dissipation, speed, and integration density is presented. Apart from packaging and reliability issues, these switches seem to be competitive in low power, particularly low-standby power, logic and memory applications.
RESUMEN
Interaction of ethyl 2-amino-4,5,6, 7-tetrahydrobenzo[b]thiophene-3-carboxylate 1 with 2-thiophene carbonyl chloride 2 afforded ethyl 2-(2-thenoylamino)-4, 5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 3 which upon cyclization yielded 2-(2-thienyl)-5,6,7, 8-tetrahydrobenzo[b]-thieno[2,3-d]-4H-3, 1-oxazin-4-one 4 and 2(2-thienyl)-3-amino-5, 6,7,8-tetrahydrobenzo-[b]thieno[2,3-d]-3,4-dihydropyrimidin-4-one 6. Some of the prepared compounds were screened for their antiinflammatory activity, compound 7c and 9b showed significant activity.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Pirimidinas/síntesis química , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/toxicidad , Femenino , Granuloma/tratamiento farmacológico , Granuloma/patología , Dosificación Letal Mediana , Masculino , Ratones , Pirimidinas/farmacología , Pirimidinas/toxicidad , RatasRESUMEN
sigma receptors may represent an exciting new approach for the development of novel psychotherapeutic agents. Unfortunately, many of the commonly used sigma ligands lack selectivity (e.g., many bind at phencyclidine or dopamine receptors) or suffer from other serious drawbacks. Recently, we described a series of 2-phenylaminoethanes that bind at sigma receptors with high affinity and selectivity. Because there is evidence that 1-phenylpiperazines can structurally mimic the 2-phenylaminoethane moiety, we prepared a series of 1-phenylpiperazines and related analogues and incorporated structural features already shown to enhance the sigma binding of the 2-phenylaminoethanes. Several of these derivatives bind at sigma receptors with high affinity (Ki = 1-10 nM) and lack appreciable affinity for phencyclidine and dopamine receptors. In as much as certain of these agents structurally resemble the high-affinity, but nonselective, sigma ligand haloperidol, and because they bind with 10 times the affinity of haloperidol, we have apparently identified what appears to be the primary sigma pharmacophore of that agent.
Asunto(s)
Piperazinas/metabolismo , Piperidinas/metabolismo , Receptores Opioides/metabolismo , Animales , Cobayas , Técnicas In Vitro , Ligandos , Piperazinas/síntesis química , Piperidinas/síntesis química , Ensayo de Unión Radioligante , Receptores Dopaminérgicos/metabolismo , Receptores de Neurotransmisores/metabolismo , Receptores de Fenciclidina , Receptores sigma , Relación Estructura-ActividadRESUMEN
Liquid chromatography with electrochemical detection (LC/ECD) and gas chromatography/mass spectrometry (GC/MS) were used to identify metabolites of N-methyl-3,4-methylenedioxyamphetamine (MDMA) in samples of rat plasma and urine. Several potential metabolites, based on what is known about the metabolism of the desmethyl analog (i.e., MDA), were synthesized as standards to aid in the identification of the MDMA metabolites. MDA and N-methyl-1-(4-hydroxy-3-methoxy-phenyl)-2-aminopropane (3b) were identified in urine by HPLC and confirmed by GC/MS. 1-(4-Hydroxy-3-methyoxyphenyl)2-aminopropane, (3a), N-methyl-1-(3-hydroxy-4-methoxyphenyl)-2-aminopropane (2b) and 1-(3,4-dihydroxyphenyl)-2-aminopropane (4a) were tentatively identified by LC/ECD but insufficient sample size precluded confirmation by mass spectrometry. MDA was also identified in brain and plasma extracts. Because MDA is a metabolite of MDMA in humans, and because it has been speculated that the neurotoxic effects of MDA and MDMA may be due to a metabolite, the results of the present study may ultimately aid our understanding of the neurotoxic mechanism of these drugs of abuse.
Asunto(s)
3,4-Metilenodioxianfetamina/análogos & derivados , Drogas de Diseño , 3,4-Metilenodioxianfetamina/farmacocinética , Animales , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Inactivación Metabólica/fisiología , Inyecciones Subcutáneas , Masculino , N-Metil-3,4-metilenodioxianfetamina , Ratas , Ratas EndogámicasRESUMEN
With [3H]ketanserin as the radioligand, structure-affinity relationships (SAFIRs) for binding at central 5-HT2 serotonin receptors (rat frontal cortex) were examined for a series of 27 4-substituted 1-(2,5-dimethoxyphenyl)-2-aminopropane derivatives (2,5-DMAs). The affinity (Ki values) ranged over a span of several orders of magnitude. It appears that the lipophilic character of the 4-position substituent plays a major role in determining the affinity of these agents for 5-HT2 receptors, 2,5-DMAs with polar 4-substituents (e.g. OH, NH2, COOH) display a very low affinity (Ki greater than 25,000 nM) for these receptors, whereas those with lipophilic functions display a significantly higher affinity. The results of these studies prompted us to synthesize and evaluate examples of newer lipophilic derivatives and several of these (e.g. n-hexyl, n-octyl) bind with very high (Ki values = 2.5 and 3 nM, respectively) affinities at central 5-HT2 sites. Although, 2,5-DMAs are generally considered to be 5-HT2 agonists, preliminary studies with isolated rat thoracic aorta suggest that some of the more lipophilic derivatives (e.g. the n-hexyl and n-octyl derivatives) are 5-HT2 antagonists.
Asunto(s)
Anfetaminas/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas de la Serotonina/metabolismo , Animales , Técnicas In Vitro , Ketanserina/metabolismo , Masculino , Ratas , Ratas Endogámicas , Antagonistas de la Serotonina/síntesis química , Solubilidad , Relación Estructura-ActividadRESUMEN
A convenient route is reported for the synthesis of 1,2,3-selenadiazole, 1,2,3-thiadiazole, 1,2,4-triazolo[4,3-a]pyrimidine, tetrazolo[4,5-a]pyrimidine, benzimidazolo[1,2-a]pyrimidine and pyrazolo[3,4-b]pyridine derivatives in which the naphthyl nucleus is incorporated. The preliminary results of antifungal testing are reported.
Asunto(s)
Antifúngicos/síntesis química , Azoles/síntesis química , Naftalenos/síntesis química , Piridinas/síntesis química , Pirimidinas/síntesis química , Tiadiazoles/síntesis química , Azoles/farmacología , Bencimidazoles/síntesis química , Bencimidazoles/farmacología , Fenómenos Químicos , Química , Hongos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Naftalenos/farmacología , Pirazoles/síntesis química , Pirazoles/farmacología , Piridinas/farmacología , Pirimidinas/farmacología , Selenio/farmacología , Tetrazoles/síntesis química , Tetrazoles/farmacología , Tiadiazoles/farmacología , Triazoles/síntesis química , Triazoles/farmacologíaRESUMEN
A method for the determination of the enantiomeric content of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in microsamples (200 microliters) of whole blood is described. The method involves liquid-liquid extraction of MDA and MDMA from blood and derivatization with the chiral reagent N-trifluoroacetyl-L-prolyl chloride. Separation, identification and quantitation of diastereomeric derivatives is by gas chromatography-mass spectrometry. The analytical range of the assay is from 0.12 ng to 48 ng injected on-column. Details for the synthesis of the enantiomers of MDMA are also provided.