RESUMO
The interiors of giant planets remain poorly understood. Even for the planets in the Solar System, difficulties in observation lead to large uncertainties in the properties of planetary cores. Exoplanets that have undergone rare evolutionary processes provide a route to understanding planetary interiors. Planets found in and near the typically barren hot-Neptune 'desert'1,2 (a region in mass-radius space that contains few planets) have proved to be particularly valuable in this regard. These planets include HD149026b3, which is thought to have an unusually massive core, and recent discoveries such as LTT9779b4 and NGTS-4b5, on which photoevaporation has removed a substantial part of their outer atmospheres. Here we report observations of the planet TOI-849b, which has a radius smaller than Neptune's but an anomalously large mass of [Formula: see text] Earth masses and a density of [Formula: see text] grams per cubic centimetre, similar to Earth's. Interior-structure models suggest that any gaseous envelope of pure hydrogen and helium consists of no more than [Formula: see text] per cent of the total planetary mass. The planet could have been a gas giant before undergoing extreme mass loss via thermal self-disruption or giant planet collisions, or it could have avoided substantial gas accretion, perhaps through gap opening or late formation6. Although photoevaporation rates cannot account for the mass loss required to reduce a Jupiter-like gas giant, they can remove a small (a few Earth masses) hydrogen and helium envelope on timescales of several billion years, implying that any remaining atmosphere on TOI-849b is likely to be enriched by water or other volatiles from the planetary interior. We conclude that TOI-849b is the remnant core of a giant planet.
RESUMO
We present the results of a thermodynamics and kinetics study of the adsorption of neon and carbon dioxide on aggregates of chemically opened carbon nanohorns. Both the equilibrium adsorption characteristics, as well as the dependence of the kinetic behavior on sorbent loading, are different for these two adsorbates. For neon the adsorption isotherms display two steps before reaching the saturated vapor pressure, corresponding to adsorption on strong and on weak binding sites; the isosteric heat of adsorption is a decreasing function of sorbent loading (this quantity varies by about a factor of 2 on the range of loadings studied), and the speed of the adsorption kinetics increases with increasing loading. By contrast, for carbon dioxide there are no substeps in the adsorption isotherms; the isosteric heat is a nonmonotonic function of loading, the value of the isosteric heat never differs from the bulk heat of sublimation by more than 15%, and the kinetic behavior is opposite to that of neon, with equilibration times increasing for higher sorbent loadings. We explain the difference in the equilibrium properties observed for neon and carbon dioxide in terms of differences in the relative strengths of adsorbate-adsorbate to adsorbate-sorbent interaction for these species.
RESUMO
The discovery of heteroaryl-phenyl-substituted pyrazole derivatives as canine selective COX-2 inhibitors is described. Structure-activity relationship (SAR) studies of this class of compounds led to the identification of compound 1 which demonstrated a canine whole blood COX-2 inhibitory IC50 of 12 nM and selectivity ratio of COX-1/COX-2 greater than 4000-fold.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Inibidores de Ciclo-Oxigenase 2/síntese química , Pirazóis/síntese química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Cães , Concentração Inibidora 50 , Pirazóis/farmacologia , Relação Estrutura-AtividadeRESUMO
Structure-activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alkyl(thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood (CWB) COX-2 assay.
Assuntos
Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Éteres/química , Pirazóis/química , Compostos de Sulfidrila/química , Alquilação , Animais , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacocinética , Cães , Concentração Inibidora 50 , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Structure-activity relationship (SAR) studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO(2)Me)/sulfamoyl (SO(2)NH(2))-pyridine derivatives for canine COX enzymes are described. The studies led to the identification of 2e as lead with potent in vitro activity, selectivity, and in vivo activity in dogs and cats.
Assuntos
Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2/efeitos dos fármacos , Pirazóis , Administração Oral , Animais , Gatos , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacocinética , Modelos Animais de Doenças , Cães , Avaliação Pré-Clínica de Medicamentos , Técnicas In Vitro , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacocinética , Relação Estrutura-AtividadeRESUMO
Aryl and hetero aryl substituted 3,6-ketals of 15-membered azalide analogues were synthesized and were found to have potent in vitro antibacterial activity against veterinary pathogens, including Staphylococcus aureus and Pasteurella multocida.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/farmacologia , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Feminino , Hormônio Liberador de Gonadotropina/síntese química , Mastite Bovina/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Pasteurella multocida/efeitos dos fármacos , Pasteurelose Pneumônica/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria.
Assuntos
Antibacterianos/síntese química , Azitromicina/análogos & derivados , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Feminino , Mastite/tratamento farmacológico , Camundongos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted.