Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
1.
J Appl Microbiol ; 135(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38609348

RESUMEN

AIM: Evaluate the efficacy of sponge wipe sampling at recovering potential bacterial surrogates for Category A and B non-spore-forming bacterial bioterrorism agents from hard, nonporous surfaces. METHODS: A literature survey identified seven nonpathogenic bacteria as potential surrogates for selected Category A and B non-spore-forming bacterial agents. Small (2 × 4 cm) and large (35.6 × 35.6 cm) coupons made from either stainless steel, plastic, or glass, were inoculated and utilized to assess persistence and surface sampling efficiency, respectively. Three commercially available premoistened sponge wipes (3M™, Sani-Stick®, and Solar-Cult®) were evaluated. RESULTS: Mean recoveries from persistence testing indicated that three microorganisms (Yersinia ruckeri, Escherichia coli, and Serratia marcescens) demonstrated sufficient persistence across all tested material types. Sampling of large inoculated (≥107 CFU per sample) coupons resulted in mean recoveries ranging from 6.6 to 3.4 Log10 CFU per sample. Mean recoveries for the Solar-Cult®, 3M™ sponge wipes, and Sani-Sticks® across all test organisms and all material types were ≥5.7, ≥3.7, and ≥3.4 Log10 CFU per sample, respectively. Mean recoveries for glass, stainless steel, and ABS plastic across all test organisms and all sponge types were ≥3.8, ≥3.7, and ≥3.4 Log10 CFU per sample, respectively. CONCLUSIONS: Recovery results suggest that sponge wipe sampling can effectively be used to recover non-spore-forming bacterial cells from hard, nonporous surfaces such as stainless steel, ABS plastic, and glass.


Asunto(s)
Bioterrorismo , Acero Inoxidable , Bacterias/aislamiento & purificación , Plásticos , Escherichia coli/aislamiento & purificación , Serratia marcescens/aislamiento & purificación , Vidrio , Recuento de Colonia Microbiana , Armas Biológicas
2.
Front Chem ; 9: 700562, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34195176

RESUMEN

Motivated by their importance in chemistry, physics, astronomy and materials science, we investigate routes to the formation of large polycyclic aromatic hydrocarbon (PAH) molecules and the fullerene C60 from specific smaller PAH building blocks. The behaviour of selected PAH molecules under electron (using transmission electron microscopy, TEM) and laser irradiation is examined, where four specific PAHs-anthracene, pyrene, perylene and coronene-are assembling into larger structures and fullerenes. This contrasts with earlier TEM studies in which large graphene flakes were shown to transform into fullerenes via a top-down route. A new combined approach is presented in which spectrometric and microscopic experimental techniques exploit the stabilisation of adsorbed molecules through supramolecular interactions with a graphene substrate and enable the molecules to be characterised and irradiated sequentially. Thereby allowing initiation of transformation and characterisation of the resultant species by both mass spectrometry and direct-space imaging. We investigate the types of large PAH molecule that can form from smaller PAHs, and discuss the potential of a "bottom-up" followed by "top-down" mechanism for forming C60.

3.
Nanoscale ; 10(16): 7639-7648, 2018 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-29645046

RESUMEN

Carbon nanomaterials such as polyaromatic hydrocarbons (PAHs), graphene, fullerenes and nanotubes are on the frontline of materials research due to their excellent physical properties, which in recent years, have started to compete with conventional inorganic materials in charge transfer based applications. Recently, a variety of new structures such as single-walled carbon nanobelts (SWCNBs) have been conceived, however, to date only one 'all-phenyl' example has been synthesised, due to problems with their stability and the challenging synthetic methodologies required. This study introduces a new class of phenacene-based SWCNBs and their chalcogenide derivatives, forming the new sub-class of single-walled heterocyclic carbon nanobelts (SWHNBs) which are expected to be both more stable and easier to synthesise than the all carbon analogues. Subsequent theoretical examination of the structure-property relationships found that unlike the small-molecule acene homologues (tetracene, pentacene etc.) which become more reactive with addition of oxygen, an increase in the molecular size of the SWCNBs actually stabilises the HOMO energy level, in correlation with the increasingly negative nuclear independent chemical shift (NICS) calculations of their cylindrical aromaticities. The FMO energies of the phenacene SWCNBs are similar to that of the nanobelt reported by Itami and co-workers, but those of the SWHNBs are deeper and thus more stable. The sulfur derivative of one SWHNB was found to give hole-charge transfer mobilities as high as 1.12 cm2 V-1 s-1, which is three orders of magnitude larger than the corresponding unsubstituted SWCNB (3 × 10-3 cm2 V-1 s-1). These findings suggest the candidates are air-stable and potentially high-performing organic semiconductors for organic thin film transistor (OTFT) devices, while the structure-property relationships uncovered here will aid the design and synthesis of future three-dimensional organic nanomaterials.

4.
Nanoscale ; 9(38): 14385-14394, 2017 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-28948268

RESUMEN

The preparation of inorganic nanomaterials with a desired structure and specific properties requires the ability to strictly control their size, shape and composition. A series of chemical reactions with platinum compounds carried out within the 1.5 nm wide channel of single-walled carbon nanotubes (SWNTs) have demonstrated the ability of SWNTs to act as both a very effective reaction vessel and a template for the formation of nanocrystals of platinum di-iodide and platinum di-sulphide, materials that are difficult to synthesise in the form of nanoparticles by traditional synthetic methods. The stepwise synthesis inside nanotubes has enabled the formation of Pt compounds to be monitored at each step of the reaction by aberration-corrected high resolution transmission electron microscopy (AC-HRTEM), verifying the atomic structures of the products, and by an innovative combination of fluorescence-detected X-ray absorption spectroscopy (FD-XAS) and Raman spectroscopy, monitoring the oxidation states of the platinum guest-compounds within the nanotube and the vibrational properties of the host-SWNT, respectively. This coupling of complementary spectroscopies reveals that electron transfer between the guest-compound and the host-SWNT can occur in either direction depending on the composition and structure of the guest. A new approach for nanoscale synthesis in nanotubes developed in this study utilises the versatile coordination chemistry of Pt which has enabled the insertion of the required chemical elements (e.g. metal and halogens or chalcogens) into the nanoreactor in the correct proportions for the controlled formation of PtI2 and PtS2 with the correct stoichiometry.

5.
Chem Commun (Camb) ; 51(4): 648-51, 2015 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-25415311

RESUMEN

The encapsulation of trityl-functionalised C60 molecules inside carbon nanotubes drastically affects the intermolecular interactions for this species. Whilst the orientations of molecules in the crystal are often controlled by thermodynamics, the molecular orientations in nanotubes are a result of kinetic control imposed by the mechanism of entry into and encapsulation within the nanotube.

6.
Nat Mater ; 10(9): 687-92, 2011 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-21822259

RESUMEN

The ability to tune the properties of graphene nanoribbons (GNRs) through modification of the nanoribbon's width and edge structure widens the potential applications of graphene in electronic devices. Although assembly of GNRs has been recently possible, current methods suffer from limited control of their atomic structure, or require the careful organization of precursors on atomically flat surfaces under ultra-high vacuum conditions. Here we demonstrate that a GNR can self-assemble from a random mixture of molecular precursors within a single-walled carbon nanotube, which ensures propagation of the nanoribbon in one dimension and determines its width. The sulphur-terminated dangling bonds of the GNR make these otherwise unstable nanoribbons thermodynamically viable over other forms of carbon. Electron microscopy reveals elliptical distortion of the nanotube, as well as helical twist and screw-like motion of the nanoribbon. These effects suggest novel ways of controlling the properties of these nanomaterials, such as the electronic band gap and the concentration of charge carriers.

7.
J Dent Educ ; 69(11): 1222-37, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16275685

RESUMEN

The purpose of this study was to examine the use of personality measures to predict the success of dental students (N = 87) in clinical and academic courses and to compare their personality profiles to those of dental practitioners (N = 130). A second purpose of the study was to develop a new criterion measure, the Student Professionalism Scale, based on competencies previously identified as necessary for professional success. The Canadian Dental Aptitude Test (DAT) predicted first-year, preclinical academic success; the DAT Reading Comprehension component predicted third-year clinical performance; and Perceptual Ability, the ability to deal with two- and three-dimensional objects, predicted student professionalism. Results from the personality measure indicated that Conscientiousness and Neuroticism, and to a lesser extent Agreeableness, were significant predictors of both first-year academic performance and professional behavior. In comparing the personality profiles of dental students to dental practitioners, students who were more similar to the dentists did better in their first year of coursework. Implications of the findings are discussed in the context of the dental admissions process.


Asunto(s)
Personalidad , Rol Profesional , Criterios de Admisión Escolar , Estudiantes de Odontología/psicología , Canadá , Odontólogos/psicología , Evaluación Educacional , Femenino , Predicción , Humanos , Relaciones Interpersonales , Masculino , Modelos Psicológicos , Inventario de Personalidad , Facultades de Odontología
8.
Arch Virol ; 149(11): 2215-33, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15503208

RESUMEN

Increase in systemic levels of lipopolysaccharide (LPS) contributes to the pathogenesis of distant organ injury after burn. Stress signals elicited from burn influence transcriptional activities of mouse endogenous retroviruses (MuERVs) in various distant organs. The involvement of LPS pathways in the burn-mediated regulation of MuERVs in the spleen was investigated in this study. Spleen harbors substantial numbers of tissue macrophages, a key responder to LPS stimulation. Spleen tissues collected from CD14 (LPS receptor) knockout (KO) and wild type (WT) mice after burn were subjected to RT-PCR analysis of MuERV expression. There was a substantial induction of 2 bands and a marked downregulation of a band in CD14 KO mice compared to WT mice after burn. Sequence analysis of these CD14- and burn-dependent bands identified 3 new alternatively spliced and 2 defective env transcripts of MuERVs as well as novel splicing signals. Chromosomal loci of putative MuERVs sharing the unique U3 sequences of these transcripts were mapped by surveying the entire genome of C57BL/6J mice. In addition, coding potentials, transcriptional regulatory elements, and adjacent cellular genes of these putative MuERVs were analyzed. The results from these studies suggest that injury-triggered LPS/CD14 signaling events play roles in the transcriptional regulation of certain MuERVs carrying unique U3 promoter sequences.


Asunto(s)
Quemaduras/virología , Retrovirus Endógenos/genética , Receptores de Lipopolisacáridos/fisiología , Transcripción Genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Femenino , Regulación Viral de la Expresión Génica , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Regiones Promotoras Genéticas , Empalme del ARN , Bazo/virología
9.
Aust Vet J ; 80(10): 636-41, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12465817

RESUMEN

OBJECTIVE: To examine the susceptibility of the grey-headed flying fox (Pteropus poliocephalus) to Australian bat lyssavirus (ABL), and to provide preliminary observations on the pathogenesis of the disease in flying foxes. PROCEDURE: Ten flying foxes were inoculated intramuscularly with ABL, and four with a bat-associated rabies virus. Inoculated animals were observed daily, and clinical samples collected every 9 to 14 days. Animals with abnormal clinical signs were euthanased, and samples collected for histological, serological, virological and immunohistological examinations. At 3 months post inoculation (PI), all survivors were euthanased, and each submitted to a similar examination. RESULTS: Three ABL-inoculated flying foxes, and two rabies-inoculated animals developed abnormal clinical signs between 15 and 24 days PI. All three ABL-inoculated animals had histological lesions consistent with a lyssavirus infection, and lyssaviral antigen was identified in the central nervous system (CNS) of each. Virus was isolated from the brain of two affected animals. Of the rabies-inoculated flying foxes, both had histological lesions and viral antigen in the CNS. Virus was recovered from the brain of only one. None of the five affected flying foxes developed anti-lyssavirus antibodies, but, by 3 months PI, five of the seven ABL-inoculated survivors, and one of the two rabies virus-inoculated survivors, had seroconverted. The dynamics of the immune responses were quite variable. CONCLUSIONS: The response of flying foxes to ABL, administered by a peripheral route of inoculation, was similar to that of bats inoculated peripherally with bat-derived rabies viruses.


Asunto(s)
Anticuerpos Antivirales/sangre , Quirópteros/inmunología , Quirópteros/virología , Lyssavirus/patogenicidad , Infecciones por Rhabdoviridae/veterinaria , Animales , Encéfalo/virología , Lyssavirus/genética , Lyssavirus/inmunología , Lyssavirus/aislamiento & purificación , Ratones , Pruebas de Neutralización/veterinaria , Reacción en Cadena de la Polimerasa/veterinaria , ARN Viral/sangre , Virus de la Rabia/patogenicidad , Infecciones por Rhabdoviridae/virología
10.
J Exp Biol ; 204(Pt 14): 2491-8, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11511664

RESUMEN

It is well established that ultraviolet sensitivity plays an important role in the visually guided behaviour of birds. From a foraging perspective, evidence now exists that ultraviolet wavelengths are used by birds when foraging for insects, berries, seeds and mammals. Here, we present the results of two laboratory experiments that test the effect of removing (i) ultraviolet wavelengths and (ii) wavebands in the human-visible region on the frequency-dependent seed preferences of zebra finches (Taeniopygia guttata). Although the seeds and backgrounds used in our experiments reflected mainly at long wavelengths, we found that removal of ultraviolet wavelengths significantly changed the strength and direction of frequency dependence compared with full-spectrum illumination. We also found that the removal of ultraviolet wavelengths (300-400 nm) did not affect the strength of frequency dependence compared with the removal of short wavelengths (approximately 400-500 nm), medium wavelengths (approximately 500-600 nm) or long wavelengths (approximately 600-700 nm). Since frequency-dependent selection has direct consequences for the stability of prey populations and the spectral quality of ambient light is known to vary considerably with climate, time of day and local habitat geometry, our results suggest that ultraviolet wavelengths might play an important role in the dynamics of plant populations. However, we urge caution about overestimating the importance of ultraviolet wavelengths compared with wavelengths in the human-visible spectrum.


Asunto(s)
Alimentación Animal , Conducta de Elección , Preferencias Alimentarias , Semillas , Pájaros Cantores/fisiología , Rayos Ultravioleta , Visión Ocular/fisiología , Animales , Masculino , Dispersión de Radiación
11.
Int J Periodontics Restorative Dent ; 20(5): 486-97, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11203586

RESUMEN

The role of polypeptide growth factors in periodontal regeneration has been documented through animal and human studies. Human platelets contain platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) in their alpha granules. PDGF has been shown to play a role in periodontal regeneration. It has been demonstrated that TGF-beta has a very potent effect on cells associated with bone. The case reports presented demonstrate a new biotechnology in which platelet gel is used in combination with demineralized freeze-dried bone allografts for the treatment of periodontal osseous defects. The treated teeth presented with severe bone loss and a guarded prognosis. Platelet gel biotechnology was used as a novel treatment modality. A significant reduction in probing depths was noted, and radiographically significant amounts of new bone were visible as early as 2 months postoperative. Results up to 2 years postoperative are presented.


Asunto(s)
Pérdida de Hueso Alveolar/cirugía , Regeneración Tisular Guiada Periodontal/métodos , Factor de Crecimiento Derivado de Plaquetas/uso terapéutico , Factor de Crecimiento Transformador beta/uso terapéutico , Adulto , Pérdida de Hueso Alveolar/diagnóstico por imagen , Proceso Alveolar/diagnóstico por imagen , Biotecnología , Plaquetas , Trasplante Óseo , Colágeno , Técnica de Descalcificación , Femenino , Estudios de Seguimiento , Liofilización , Geles , Humanos , Masculino , Membranas Artificiales , Persona de Mediana Edad , Bolsa Periodontal/cirugía , Factor de Crecimiento Derivado de Plaquetas/administración & dosificación , Pronóstico , Radiografía , Conservación de Tejido , Factor de Crecimiento Transformador beta/administración & dosificación , Trasplante Autólogo , Trasplante Homólogo , Cicatrización de Heridas
12.
Gen Dent ; 48(3): 299-302, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11199596

RESUMEN

The effect of a mandibular intraosseous injection of 2% lidocaine with 1:100,000 epinephrine on the heart rate and blood pressure of 20 volunteer patients was examined. Changes in blood pressure from preoperative levels were minimal and did not vary significantly at any time of measurement. The only statistically significant change in heart rate occurred immediately after the intraosseous injection (an increase of 12 beats per minute). In young healthy adults, the intraosseous injection of 1.5 mL of 2% lidocaine with 1:100,000 epinephrine resulted in a slight transient elevation in heart rate but had no significant effect on systolic or diastolic blood pressure.


Asunto(s)
Anestesia Dental/métodos , Anestésicos Locales/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Infusiones Intraóseas , Adulto , Análisis de Varianza , Epinefrina/administración & dosificación , Humanos , Inyecciones , Lidocaína/administración & dosificación , Mandíbula , Estadísticas no Paramétricas , Vasoconstrictores/administración & dosificación
14.
Virus Res ; 47(1): 7-17, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9037732

RESUMEN

The complete nucleotide sequence of the Czech strain of rabbit haemorrhagic disease virus (RHDV) was determined to be 7437 nucleotides in length with a 5-terminal non-coding region of 9 nucleotides and a 3'-terminal non-coding region of 59 nucleotides. Two open reading frames (ORFs) were found within this sequence coding for polypeptides of 2344 (nucleotides 10-7044) and 117 amino acids (nucleotides 7025-7378). The sequence of this isolate was approximately 1% different from that reported by Meyers et al., having 78 nucleotide changes which resulted in 30 amino acid differences, the majority of these clustering in the N-terminus of the large ORF and the middle of the viral coat protein. Only a single conservative amino acid change was seen in the smaller 3'-terminal ORF. Since the virus cannot at present be propagated in tissue culture, but isolated only after replication in rabbits, the reported sequence must be considered as a consensus sequence from the viral population. To gain some understanding of the possible sequence diversity within this virus population, 97 clones were sequenced from a polymerase chain reaction (PCR) fragment to determine the sequence diversity of the virus population. Four major classes of variant were described with mutations generally in the third base position of codons. A nested reverse transcriptase (RT) PCR (using sequence derived for the coat protein of RHDV) was used to determine the presence or absence of RHDV inoculated into non-host animal species. No replication of the virus was detected in 28 different vertebrate species other than rabbits. PCR tests on both mosquitoes and fleas feeding on RHDV infected rabbits were positive. The RT-PCR test was more sensitive when compared with an antigen capture ELISA to detect the presence of genomic RNA/or virus in infected rabbits.


Asunto(s)
Infecciones por Caliciviridae/veterinaria , Variación Genética , Genoma Viral , Virus de la Enfermedad Hemorrágica del Conejo/genética , Reacción en Cadena de la Polimerasa , Secuencia de Aminoácidos , Animales , Antígenos Virales/análisis , Australia , Secuencia de Bases , Infecciones por Caliciviridae/virología , ADN Viral , Virus de la Enfermedad Hemorrágica del Conejo/aislamiento & purificación , Virus de la Enfermedad Hemorrágica del Conejo/fisiología , Datos de Secuencia Molecular , Conejos , Vertebrados/virología , Replicación Viral
15.
J Med Chem ; 39(1): 253-66, 1996 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-8568815

RESUMEN

A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4-disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the 6-phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity. Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.


Asunto(s)
Antiinflamatorios no Esteroideos/química , Inhibidores de la Ciclooxigenasa/síntesis química , Compuestos de Espiro/síntesis química , Sulfonamidas/síntesis química , Sulfonas/síntesis química , Analgésicos/síntesis química , Analgésicos/farmacología , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/farmacología , Artritis Experimental/tratamiento farmacológico , Carragenina/farmacología , Inhibidores de la Ciclooxigenasa/farmacocinética , Inhibidores de la Ciclooxigenasa/farmacología , Edema/tratamiento farmacológico , Humanos , Intestinos/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Compuestos de Espiro/química , Compuestos de Espiro/farmacocinética , Compuestos de Espiro/farmacología , Estómago/efectos de los fármacos , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacocinética , Sulfonamidas/farmacología , Sulfonas/química , Sulfonas/farmacocinética , Sulfonas/farmacología
16.
Ann Pharmacother ; 29(7-8): 671-5, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-8520078

RESUMEN

OBJECTIVE: To determine the frequency of diagnosis of peripheral vascular disease (PVD) and selected related conditions in patients in a nursing facility, to determine the frequency of patients with risk factor(s) for or clinical evidence of PVD but without a diagnosis of PVD or a related condition, and to determine the frequency with which patients with and without a diagnosis of PVD or a related condition were treated with drug and nondrug therapies. DESIGN: A multicenter, disease-based, retrospective evaluation. SETTING: 41 nursing facilities in 6 regions of the US. PATIENTS: 4038 patients in a nursing facility: 827 patients with a PVD or related diagnosis; 2719 patients without a PVD or related diagnosis but with risk factor(s) for or clinical evidence of PVD; and 492 patients without a PVD or related diagnosis, risk factor(s), and clinical evidence. MAIN OUTCOME MEASURES: Evidence of disease and drug therapy for PVD. RESULTS: PVD was documented in 21% of patients; another 67% had risk factor(s) for or clinical evidence of PVD but no diagnosis of PVD or a related condition. Pentoxifylline was prescribed for 3% of the total sample and 12% of patients with PVD or a related condition. CONCLUSIONS: PVD appears to be inadequately evaluated in patients in a nursing facility. Disease treatment strategies should be developed and implemented to educate healthcare professionals and the general public about the need to acknowledge, assess, and treat PVD and related conditions.


Asunto(s)
Enfermedades Vasculares Periféricas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Casas de Salud/estadística & datos numéricos , Pentoxifilina/uso terapéutico , Enfermedades Vasculares Periféricas/diagnóstico , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Vasodilatadores/uso terapéutico
18.
J Med Chem ; 36(15): 2172-81, 1993 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-8340920

RESUMEN

2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4' - yl]methyl]-3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Tetrazoles/síntesis química , Tetrazoles/farmacología , Triazoles/síntesis química , Triazoles/farmacología , Animales , Sitios de Unión , Femenino , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Conejos , Ratas , Relación Estructura-Actividad , Tetrazoles/metabolismo , Triazoles/metabolismo , Útero/efectos de los fármacos , Útero/metabolismo
19.
J Med Chem ; 36(1): 101-10, 1993 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-8421274

RESUMEN

A series of 5-[1-[4-[(4,5-disubstituted-1H-imidazol-1-yl)methyl]- substituted]-1H-pyrrol-2-yl]-1H-tetrazoles and 5-[1-[4-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-substituted]- 1H-pyrrol-2-yl]-1H-tetrazoles were investigated as novel AT1-selective angiotensin II receptor antagonists. Computer-assisted modeling techniques were used to evaluate structural parameters in comparison to the related biphenyl system. New synthetic procedures have been developed to prepare the novel compounds. The best antagonists in this series had IC50 values (rat uterine membrane receptor binding) in the 10(-8) M range and corresponding pA2 in isolated organ assay (rabbit aorta rings). Structure-activity relationships indicate some similarities with the finding in the biphenyl system. Substitution on the pyrrole ring modulates activity. Compound 5 antagonized angiotensin-induced blood pressure increase when administered to conscious rat at 30 mg/kg per os.


Asunto(s)
Angiotensina II/antagonistas & inhibidores , Antagonistas de Receptores de Angiotensina , Pirroles/síntesis química , Animales , Sitios de Unión/efectos de los fármacos , Femenino , Masculino , Músculo Liso Vascular/efectos de los fármacos , Pirroles/metabolismo , Pirroles/farmacología , Conejos , Ratas , Ratas Sprague-Dawley , Receptores de Angiotensina/metabolismo , Relación Estructura-Actividad , Útero/efectos de los fármacos , Útero/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...