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1.
Nanomaterials (Basel) ; 13(17)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37686953

RESUMO

Quantum-dot cellular automata (QCA) are a promising nanoscale computing technology that exploits the quantum mechanical tunneling of electrons between quantum dots in a cell and electrostatic interaction between dots in neighboring cells. QCA can achieve higher speed, lower power, and smaller areas than conventional, complementary metal-oxide semiconductor (CMOS) technology. Developing QCA circuits in a logically and physically reversible manner can provide exceptional reductions in energy dissipation. The main challenge is to maintain reversibility down to the physical level. A crucial component of a computer's central processing unit (CPU) is the arithmetic logic unit (ALU), which executes multiple logical and arithmetic functions on the data processed by the CPU. Current QCA ALU designs are either irreversible or logically reversible; however, they lack physical reversibility, a crucial requirement to increase energy efficiency. This paper shows a new multilayer design for a QCA ALU that can carry out 16 different operations and is both logically and physically reversible. The design is based on reversible majority gates, which are the key building blocks. We use QCADesigner-E software to simulate and evaluate energy dissipation. The proposed logically and physically reversible QCA ALU offers an improvement of 88.8% in energy efficiency. Compared to the next most efficient 16-operation QCA ALU, this ALU uses 51% fewer QCA cells and 47% less area.

2.
J Med Chem ; 59(5): 1711-26, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26861551

RESUMO

Induction of IFNα in the upper airways via activation of TLR7 represents a novel immunomodulatory approach to the treatment of allergic asthma. Exploration of 8-oxoadenine derivatives bearing saturated oxygen or nitrogen heterocycles in the N-9 substituent has revealed a remarkable selective enhancement in IFNα inducing potency in the nitrogen series. Further potency enhancement was achieved with the novel (S)-pentyloxy substitution at C-2 leading to the selection of GSK2245035 (32) as an intranasal development candidate. In human cell cultures, compound 32 resulted in suppression of Th2 cytokine responses to allergens, while in vivo intranasal administration at very low doses led to local upregulation of TLR7-mediated cytokines (IP-10). Target engagement was confirmed in humans following single intranasal doses of 32 of ≥20 ng, and reproducible pharmacological response was demonstrated following repeat intranasal dosing at weekly intervals.


Assuntos
Adenina/análogos & derivados , Asma/tratamento farmacológico , Descoberta de Drogas , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Receptor 7 Toll-Like/agonistas , Adenina/administração & dosagem , Adenina/química , Adenina/farmacologia , Administração Intranasal , Asma/metabolismo , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Piperidinas/química , Relação Estrutura-Atividade
3.
Bioorg Med Chem Lett ; 21(10): 3037-40, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21482467

RESUMO

Heteroalicyclic carboxamidines were synthesised and evaluated as inhibitors of nitric oxide synthases. (2R)-2-Pyrrolidinecarboxamidine, in particular, was shown to be a highly potent in vitro (IC(50)=0.12 µM) and selective iNOS inhibitor (>100-fold vs both eNOS and nNOS), with probable binding to the key anchoring glutamate residue and co-ordination to the haem iron.


Assuntos
Amidinas/síntese química , Amidinas/farmacologia , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Heme/antagonistas & inibidores , Compostos Heterocíclicos/síntese química , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Prolina/análogos & derivados , Amidinas/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Estrutura Molecular , Prolina/síntese química , Prolina/química , Prolina/farmacologia
4.
Bioorg Med Chem Lett ; 19(15): 4504-8, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19520573

RESUMO

A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyrimidine (47), a member of the 2-pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic profile, high brain penetration and good efficacy in rat models of hypersensitivity.


Assuntos
Aminas/síntese química , Inibidores de Ciclo-Oxigenase 2/síntese química , Éteres/síntese química , Pirimidinas/síntese química , Sulfonas/síntese química , Aminas/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Química Farmacêutica/métodos , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Modelos Animais de Doenças , Desenho de Fármacos , Éteres/farmacologia , Humanos , Inflamação , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Pirimidinas/farmacologia , Ratos , Sulfonas/farmacologia
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