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1.
Bioorg Med Chem ; 111: 117864, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39116711

RESUMEN

As a step toward the development of novel small-molecule positive allosteric modulators (PAMs) of glucagon-like peptide 1 receptor (GLP-1R) for the treatment of type 2 diabetes, obesity, and heart diseases, we discovered a novel 2-amino-thiophene (2-AT) based lead compound bearing an ethyl 3-carboxylate appendage. In this work, we report the syntheses and biological studies of more than forty 2-AT analogs, that have revealed a 2-aminothiophene-3-arylketone analogue 7 (MW 299) showing approximately a 2-fold increase in insulin secretion at 5 µM when combined with the GLP-1 peptide at 10 nM. In vivo studies using CD1 mice at a dose of 10 mg/kg, clearly demonstrated that the blood plasma glucose level was lowered by 50% after 60 min. Co-treatment of 7 with sitagliptin, an inhibitor of GLP-1 degrading enzyme Dipeptidyl Peptidase IV, further confirmed 7 to be an effective PAM of GLP-1R. The small molecular weight and demonstrated allosteric modulating properties of these compound series, show the potential of these scaffolds for future drug development.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón , Tiofenos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Animales , Tiofenos/farmacología , Tiofenos/química , Tiofenos/síntesis química , Regulación Alostérica/efectos de los fármacos , Ratones , Humanos , Relación Estructura-Actividad , Estructura Molecular , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Relación Dosis-Respuesta a Droga , Insulina/metabolismo , Fosfato de Sitagliptina/farmacología , Fosfato de Sitagliptina/síntesis química , Fosfato de Sitagliptina/química
2.
Nanotechnology ; 34(38)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37321202

RESUMEN

Control over the distribution of dopants in nanowires is essential for regulating their electronic properties, but perturbations in nanowire microstructure may affect doping. Conversely, dopants may be used to control nanowire microstructure including the generation of twinning superlattices (TSLs)-periodic arrays of twin planes. Here the spatial distribution of Be dopants in a GaAs nanowire with a TSL is investigated using atom probe tomography. Homogeneous dopant distributions in both the radial and axial directions are observed, indicating a decoupling of the dopant distribution from the nanowire microstructure. Although the dopant distribution is microscopically homogenous, radial distribution function analysis discovered that 1% of the Be atoms occur in substitutional-interstitial pairs. The pairing confirms theoretical predictions based on the low defect formation energy. These findings indicate that using dopants to engineer microstructure does not necessarily imply that the dopant distribution is non-uniform.


Asunto(s)
Arsenicales , Nanocables , Nanocables/química , Nanotecnología/métodos , Propiedades de Superficie , Arsenicales/química
4.
Sci Adv ; 10(31): eado8272, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39083609

RESUMEN

The growth of layered 2D compounds is a key ingredient in finding new phenomena in quantum materials, optoelectronics, and energy conversion. Here, we report SnP2Se6, a van der Waals chiral (R3 space group) semiconductor with an indirect bandgap of 1.36 to 1.41 electron volts. Exfoliated SnP2Se6 flakes are integrated into high-performance field-effect transistors with electron mobilities >100 cm2/Vs and on/off ratios >106 at room temperature. Upon excitation at a wavelength of 515.6 nanometer, SnP2Se6 phototransistors show high gain (>4 × 104) at low intensity (≈10-6 W/cm2) and fast photoresponse (< 5 microsecond) with concurrent gain of ≈52.9 at high intensity (≈56.6 mW/cm2) at a gate voltage of 60 V across 300-nm-thick SiO2 dielectric layer. The combination of high carrier mobility and the non-centrosymmetric crystal structure results in a strong intrinsic bulk photovoltaic effect; under local excitation at normal incidence at 532 nm, short circuit currents exceed 8 mA/cm2 at 20.6 W/cm2.

5.
ACS Appl Mater Interfaces ; 15(48): 56150-56157, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38011316

RESUMEN

Tin monosulfide (SnS) is a two-dimensional layered semiconductor that exhibits in-plane ferroelectric order at very small thicknesses and is of interest in highly scaled devices. Here we report the epitaxial growth of SnS on hexagonal boron nitride (hBN) using a pulsed metal-organic chemical vapor deposition process. Lattice matching is observed between the SnS(100) and hBN{11̅0} planes, with no evidence of strain. Atomic force microscopy reveals superlubricity along the commensurate direction of the SnS/hBN interface, and first-principles calculations suggest that friction is controlled by the edges of the SnS islands, rather than interface interactions. Differential phase contrast imaging detects remnant polarization in SnS islands with domains that are not dictated by step-edges in the SnS. The growth of ferroelectric SnS on high quality hBN substrates is a promising step toward electrically switchable ferroelectric semiconducting devices.

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