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1.
Anesthesiology ; 141(1): 100-115, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38537025

RESUMO

BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) 150 mmHg or greater were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (less than 140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function, and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101 of 161, 62.7% vs. 66 of 166, 39.8%; difference, 23.2%; 95% CI, 12.4 to 34.1%; P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP 150 mmHg or greater, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Hemorragia Cerebral , Dexmedetomidina , Remifentanil , Humanos , Dexmedetomidina/uso terapêutico , Dexmedetomidina/administração & dosagem , Remifentanil/administração & dosagem , Remifentanil/uso terapêutico , Masculino , Feminino , Estudos Prospectivos , Hemorragia Cerebral/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Método Simples-Cego , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Resultado do Tratamento , Hipnóticos e Sedativos/uso terapêutico
2.
Org Biomol Chem ; 20(20): 4086-4090, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35545885

RESUMO

In this paper, a palladium-catalyzed [4 + 2] cycloaddition of 5-methylene-1,3-oxazinan-2-ones with 4-arylidene-2,4-dihydro-3H-pyrazol-3-ones has been developed to produce spiropyrazolones in high yields with excellent diastereoselectivities in nearly all cases. The cycloaddition reaction was scaled-up without significant loss of yield, and its synthetic utility has been demonstrated by further transformations of the products. The reaction type of N-Ts cyclic carbamates under palladium catalysis was extended to include [4 + 2] cycloaddition for the first time.


Assuntos
Alcenos , Paládio , Carbamatos , Catálise , Reação de Cicloadição , Estereoisomerismo
3.
Mol Divers ; 26(4): 2149-2158, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34585322

RESUMO

A series of compounds containing trifluoroacetyl groups were synthesized, and their insecticidal activity against Nilaparvata lugens and Aphis craccivora was evaluated. The compound structure was identified by NMR, HRMS, and single-crystal diffraction. The bioassay results indicated that compound 4-1 (R1 is chloropyridine, R2 is H), 4-2 (R1 is chlorothiazole, R2 is H) and 4-19 (R1 is benzyl, R2 is isopropyl) had the best activity against Nilaparvata lugens (93.5%, 94.1% and 95.5%) at 100 mg/L concentration. The effect of different substituents of R1 or R2 on the activity was studied through the structure-activity relationship. Molecular docking of compounds 4-1 and 4-2 was discussed.


Assuntos
Afídeos , Inseticidas , Animais , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/farmacologia
4.
Mol Divers ; 26(2): 801-813, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33548013

RESUMO

To discover novel strobilurin fungicides, a series of methyl (E)-1-(2-((E)-2-methoxy-1-(methoxy-imino)-2-oxoethyl)benzyl)-2-(1-arylidene)hydrazine-1-carboxylates were designed based on the principle of biologically active splicing and the receptor target structure. The fungicidal activity results show that this class of compounds has excellent fungicidal activity, especially against S. sclerotiorum (Lib.) deBary, wheat white powder and puccinia polysora. The result of structure-activity relationship implied that the introduction of t-butyl in the side chain facilitates the hydrophobic interaction between the compound and the active site. The electrostatic effect of the substituents on the benzene ring is also a key factor affecting such activities. Among them, the compound I-1 not only showed a fungicidal effect comparable to that of kresoxim-methyl in vivo, but also had an excellent inhibitory effect on spore germination of P. oryzae Cav in vitro, which indicated that it could be used as a potential commercial fungicide for plant disease control.


Assuntos
Fungicidas Industriais , Hidrazinas , Relação Estrutura-Atividade
5.
Org Biomol Chem ; 18(34): 6724-6731, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32832951

RESUMO

A copper-catalysed cascade ester amidation/radical cyclization of 2-amino-1,4-naphthoquinones with α-bromocarboxylates to afford benzo[f]indole-2,4,9(3H)-triones is described, and the reaction has a broad substrate scope and the desired products are obtained in mostly moderate to good yields. Mechanism-probing experiments indicate that the otherwise challenging radical coupling reaction of α-bromocarboxylates with 2-amino-1,4-naphthoquinones is facilitated by a 5-endo radical cyclization.

6.
Mol Divers ; 24(1): 119-130, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30852722

RESUMO

Methyl and phenyl esters of 2',3'-PhABA and iso-2',3'-PhABA were prepared for the biological investigation and development of practical applications. These esters exhibited excellent activity in most plant growth inhibitory assays. And, three esters were more efficient than ABA in stomatal closure. The 2',3'-PhABA analogs and their methyl esters have good stability in hydrolysis assay, and the different lipid solubility and permeability of different esters may be one of the origins of their active selectivity for different plants and physiological processes. Furthermore, in the study of drought tolerance, all four esters had comparable activity to ABA. These results suggest that these esters were potent plant growth regulator (PGR) candidates for anti-drought. The finding that different esters have different selective bioactivity and biophysical properties indicates that these esters not only function as ABA-like PGRs but also have the possibility as potential selective pro-hormone. 2',3'-BenzoABA esters as PGR candidates with prolonged and selective bioactivity.


Assuntos
Técnicas de Química Sintética , Éteres Fenílicos/síntese química , Éteres Fenílicos/farmacologia , Reguladores de Crescimento de Plantas/síntese química , Reguladores de Crescimento de Plantas/farmacologia , Cromatografia Líquida de Alta Pressão , Secas , Hidrólise , Estrutura Molecular , Fenótipo , Desenvolvimento Vegetal/efeitos dos fármacos , Estresse Fisiológico
7.
Molecules ; 25(24)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322288

RESUMO

A series of novel 1,2,4-triazole derivatives containing oxime ether and phenoxy pyridine moiety were designed and synthesized. The new compounds were identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). Compound (Z)-1-(6-(4-nitrophenoxy)pyridin-3-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one O-methyl oxime (5a18) was further confirmed by X-ray single crystal diffraction. Their antifungal activities were evaluated against eight phytopathogens. The in vitro bioassays indicated that most of the title compounds displayed moderate to high fungicidal activities. Compound (Z)-1-(6-(4-bromo-2-chlorophenoxy)pyridin-3-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one O-methyl oxime (5a4) exhibited a broad-spectrum antifungal activities with the EC50 values of 1.59, 0.46, 0.27 and 11.39 mg/L against S. sclerotiorum, P. infestans, R. solani and B. cinerea, respectively. Compound (Z)-1-(6-(2-chlorophenoxy)pyridin-3-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one O-benzyl oxime (5b2) provided the lowest EC50 value of 0.12 mg/L against S. sclerotiorum, which were comparable to the commercialized difenoconazole. Moreover, homologous modeling and molecular docking disclosed possible binding modes of compounds 5a4 and 5b2 with CYP51. This work provided useful guidance for the discovery of new 1,2,4-triazole fungicides.


Assuntos
Antifúngicos/química , Oximas/química , Triazóis/química , Ascomicetos , Sítios de Ligação , Bioensaio , Botrytis , Isótopos de Carbono , Domínio Catalítico , Dioxolanos , Desenho de Fármacos , Éter , Fungicidas Industriais/química , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Estrutura Molecular , Phytophthora infestans , Ligação Proteica , Rhizoctonia , Esterol 14-Desmetilase/química , Relação Estrutura-Atividade
8.
J Org Chem ; 84(17): 10649-10657, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31356065

RESUMO

A copper-catalyzed three-component difunctionalization of aromatic alkenes to access 1,4-naphthoquinone derivatives with diverse structures is described. Experiments show that the difunctionalization reaction is accompanied by ester exchange reaction with the solvent. In this method, α-bromocarboxylates are used as radical precursors and 2-amino-1,4-naphthoquinones as radical trapping reagents. The substrate scope is broad because various aromatic alkenes, 2-amino-1,4-naphthoquinones, and α-bromocarboxylates are employed in the reaction, and corresponding products are obtained in moderate to good yields.

9.
J Org Chem ; 84(2): 679-686, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30582323

RESUMO

Phosphine-catalyzed [3+2] annulation of ß-sulfonamido-substituted enones and sulfamate-derived cyclic imines has been developed, giving a series of imidazoline derivatives in moderate to excellent yields with good to excellent diastereoselectivities. A scale-up reaction worked well under mild reaction conditions. A possible mechanism was proposed on the basis of the results obtained.

10.
J Org Chem ; 84(2): 1006-1014, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30592606

RESUMO

A silver-catalyzed three-component difunctionalization of alkenes by using 2-amino- and 2-hydroxy-1,4-naphthoquinone derivatives as the radical-trapping reagents is reported. Various alkenes and 2-amino- or 2-hydroxy-1,4-naphthoquinones with diverse structures and electronic properties are applied to the reaction. The methodology provides an alternative method to access CF3-functionalized alkyl-substituted quinone derivatives which are prevalent structures in bioactive molecules. Furthermore, a plausible radical pathway for the reaction is proposed based on results from primary control experiments.

11.
Mol Divers ; 23(3): 809-820, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30519778

RESUMO

1,1-Diaryl compounds are a series of compounds which possess two aryl groups attached to a central carbon atom. This special structure made it as a very important module in bioactive molecules, and compounds of this type are numerous. 1,1-Diaryl derivatives can be used as catalysts in chemical synthesis, chemical probes and biologically active molecules for medicines and pesticides. In this review, we focus on the application of these compounds in pesticides, such as insecticides and fungicides. The generic structure of the 1,1-diaryl compounds is discussed in this review.


Assuntos
Hidrocarbonetos Aromáticos/química , Praguicidas/química , Hidrocarbonetos Aromáticos/farmacologia , Praguicidas/farmacologia , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/farmacologia
12.
Org Biomol Chem ; 16(26): 4881-4887, 2018 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-29931027

RESUMO

The palladium-catalyzed diastereoselective [3 + 2] cycloaddition reaction of vinylcyclopropanes with sulfamate-derived cyclic imines worked efficiently under mild reaction conditions, providing 2,3-dihydrobenzo[e]pyrrolo[1,2-c][1,2,3]oxathiazine 5,5-dioxide derivatives in good to excellent yields.

13.
J Biol Chem ; 291(48): 25019-25031, 2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27758861

RESUMO

Complex III or the cytochrome (cyt) bc1 complex constitutes an integral part of the respiratory chain of most aerobic organisms and of the photosynthetic apparatus of anoxygenic purple bacteria. The function of cyt bc1 is to couple the reaction of electron transfer from ubiquinol to cytochrome c to proton pumping across the membrane. Mechanistically, the electron transfer reaction requires docking of its Rieske iron-sulfur protein (ISP) subunit to the quinol oxidation site (QP) of the complex. Formation of an H-bond between the ISP and the bound substrate was proposed to mediate the docking. Here we show that the binding of oxazolidinedione-type inhibitors famoxadone, jg144, and fenamidone induces docking of the ISP to the QP site in the absence of the H-bond formation both in mitochondrial and bacterial cyt bc1 complexes, demonstrating that ISP docking is independent of the proposed direct ISP-inhibitor interaction. The binding of oxazolidinedione-type inhibitors to cyt bc1 of different species reveals a toxophore that appears to interact optimally with residues in the QP site. The effect of modifications or additions to the toxophore on the binding to cyt bc1 from different species could not be predicted from structure-based sequence alignments, as demonstrated by the altered binding mode of famoxadone to bacterial cyt bc1.


Assuntos
Proteínas de Bactérias/química , Complexo III da Cadeia de Transporte de Elétrons/química , Hidroquinonas/química , Ligação de Hidrogênio , Imidazolinas/química , Metacrilatos/química , Oxazóis/química , Oxirredução , Estrobilurinas
14.
J Org Chem ; 82(1): 633-641, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-27991792

RESUMO

A bifunctional phosphine-catalyzed highly enantioselective [2+4] cycloaddition of α-substituted allenoates with (E)-1-benzyl-4-olefinicpyrrolidine-2,3-diones has been achieved, giving pyrrolidin-2-one fused dihydropyran derivatives in moderate to good yields with excellent enantioselectivities (up to 98% ee). This reaction provides a useful catalytic asymmetric access to dihydropyran structural motifs.

15.
Molecules ; 22(12)2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29244719

RESUMO

2',3'-iso-Benzoabscisic acid (iso-PhABA), an excellent selective abscisic acid (ABA) analog, was developed in our previous work. In order to find its more structure-activity information, some structural modifications were completed in this paper, including the substitution of phenyl ring and replacing the ring with heterocycles. Thus, 16 novel analogs of iso-PhABA were synthesized and screened with three bioassays, Arabidopsis and lettuce seed germination and rice seedling elongation. Some of them, i.e., 2',3'-iso-pyridoabscisic acid (iso-PyABA) and 2',3'-iso-franoabscisic acid (iso-FrABA), displayed good bioactivities that closed to iso-PhABA and natural (+)-ABA. Some others, for instance, substituted-iso-PhABA, exhibited certain selectivity to different physiological process when compared to iso-PhABA or (+)-ABA. These analogs not only provided new candidates of ABA-like synthetic plant growth regulators (PGRs) for practical application, but also new potential selective agonist/antagonist for probing the specific function of ABA receptors.


Assuntos
Ácido Abscísico/análogos & derivados , Ácido Abscísico/síntese química , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Germinação , Lactuca/metabolismo , Estrutura Molecular , Oryza/metabolismo , Reguladores de Crescimento de Plantas/síntese química , Reguladores de Crescimento de Plantas/metabolismo , Plântula/metabolismo , Sementes/metabolismo
16.
Aldrichimica Acta ; 49(1): 3-13, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28077882

RESUMO

Recent advances in chiral-phosphine-catalyzed asymmetric annulation reactions; including annulations of allenes, alkynes, Morita-Baylis-Hillman (MBH) carbonates, and ketenes; and their applications in the synthesis of bioactive molecules and natural products are reviewed.

17.
Bioorg Med Chem Lett ; 26(24): 5936-5942, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27838182

RESUMO

A series of 1,1-diaryl tertiary alcohols and some of their dehydration derivatives were designed, synthesized and evaluated for their antifungal activities. Some compounds exhibited moderate inhibitory activities against seven plant pathogens at 50µg/mL in vitro, compounds 5g and 7c displayed nearly the same or higher fungicidal activities against some certain plant pathogens compared with the lead compound pyrimorph. A qualitative structure-activity relationship (SAR) analysis revealed that the Cl substituent and its position at the pyridine ring were crucial for the compounds' activities. Specially, several compounds displayed 100% protection effect against wheat powdery mildew or cucumber anthrax at 400mg/mL in vivo, which suggested that these compounds might be potential fungicidal candidates for certain plant diseases.


Assuntos
Álcoois/farmacologia , Antraz/tratamento farmacológico , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Álcoois/síntese química , Álcoois/química , Animais , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Doenças das Plantas , Relação Estrutura-Atividade
18.
J Mater Sci Mater Med ; 27(1): 5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26610928

RESUMO

The influences of steam sterilization on the physicochemical properties of calcium phosphate (Ca-P) porous bioceramics, including ß-tricalcium phosphate (ß-TCP), biphasic calcium phosphate (BCP) and hydroxyapatite (HA) are investigated. After being steam sterilized in an autoclave (121 °C for 40 min), the porous bioceramics are dried and characterized. The steam sterilization has no obvious effects on the phase composition, thermal stability, pH value and dissolubility of ß-TCP porous bioceramic, but changes its morphology and mechanical strength. Meanwhile, the steam sterilization leads to the significant changes of the morphology, phase composition, pH value and dissolubility of BCP porous bioceramic. The increase of dissolubility and mechanical strength, the decrease of pH value of the immersed solution and partial oriented growth of crystals are also observed in HA porous bioceramic after steam sterilization. These results indicate that the steam sterilization can result in different influences on the physicochemical properties of ß-TCP, BCP and HA porous bioceramics, thus the application of the steam sterilization on the three kinds of Ca-P porous bioceramics should be considered carefully based on the above changed properties.


Assuntos
Materiais Biocompatíveis , Fosfatos de Cálcio/química , Cerâmica , Vapor , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Solubilidade
19.
J Am Chem Soc ; 137(13): 4316-9, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25799312

RESUMO

The first phosphine-catalyzed highly enantioselective [3 + 3] cycloaddition of Morita-Baylis-Hillman carbonates with C,N-cyclic azomethine imines is described. Using a spirocyclic chiral phosphine as the catalyst, a novel class of pharmaceutically interesting 4,6,7,11b-tetrahydro-1H-pyridazino[6,1-a]iso-quinoline derivatives were obtained in high yields with good to excellent diastereoselectivities and extremely excellent enantioselectivities (98->99% ee).


Assuntos
Compostos Azo/química , Carbonatos/química , Iminas/química , Fosfinas/química , Tiossemicarbazonas/química , Catálise , Reação de Cicloadição , Estereoisomerismo
20.
Bioorg Med Chem Lett ; 25(11): 2438-41, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25913114

RESUMO

2',3'-Benzoabscisic acid 4a is significantly more active than (±)-ABA and can be potentially used as a plant growth regulator for agriculture. In this study, six 4a analogs were designed and synthesized. Bioassay showed that 4a displayed greater activity than (±)-ABA and the six analogs produced less inhibition than 4a itself. Specially, some analogs displayed markedly different activities to different physiological and biochemical process, which were largely different from ABA and 4a. Compared to (±)-ABA, 4b and 4c were more effective germination inhibitors for lettuce, but less effective inhibitors for rice elongation. Five-membered analog 5 was higher or slightly weaker in inhibiting Arabidopsis seed germination and rice elongation, respectively, but at least 10 times less effective than (±)-ABA in lettuce seed germination. Dual acid 6 and alkyne acid 20 nearly produced no inhibitory activity for Arabidopsis seed germination, but displayed excellent activity in inhibiting rice seedling growth. The preference of the analogs to different physiology process indicated that they might provide a strategy to develop novel ABA agonists or antagonist and be used as probe to investigate the function of different ABA receptors.


Assuntos
Ácido Abscísico/análogos & derivados , Ácido Abscísico/síntese química , Naftalenos/síntese química , Ácido Abscísico/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Bioensaio , Germinação/efeitos dos fármacos , Lactuca/efeitos dos fármacos , Lactuca/crescimento & desenvolvimento , Estrutura Molecular , Naftalenos/farmacologia , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento
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