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1.
Acta Pharmaceutica Sinica ; (12): 731-740, 2022.
Artigo em Chinês | WPRIM | ID: wpr-922893

RESUMO

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by 1H NMR, 13C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC50 = 0.26 μmol·L-1) was 6.7 times than the lead compound A (IC50 = 1.73 μmol·L-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

2.
Acta Pharmaceutica Sinica ; (12): 96-105, 2020.
Artigo em Chinês | WPRIM | ID: wpr-780572

RESUMO

Based on the structure of inhibitors XL765 and WR23, the quinoxaline scaffold was selected as an attractive structure for drug design. In this protocol, the 2-position of quinoxaline was modified with a substituted phenoxy fragment. Meanwhile, the linking chain at the 3-position was changed to a sulfonyl hydrazine or was removed. A series of substituent groups were added at the 6-position of the quinoxaline scaffold. Twenty-two quinoline derivatives were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, and ESI-MS. All compounds were screened for anti-tumor activity in vitro in A549, MCF-7, HCT-116 and HepG2 cancer cells. The results showed that P6b was effective, P6e and P6f had better activity against HCT116 (IC50 = 3.24, 4.78 and 4.50 μmol·L-1), and P6d had strong inhibitory effect on MCF-7 (IC50 = 0.228 7 μmol·L-1).

3.
Chinese Traditional and Herbal Drugs ; (24): 2935-2938, 2014.
Artigo em Chinês | WPRIM | ID: wpr-854819

RESUMO

Objective: To establish a method of reversal phase-high performance liquid chromatography (RP-HPLC) for determining the mass concentration of oxalate in human plasma and urine and to monitor the variation of mass concentration of oxalate in the patients with primary hyperoxaluria (PH) before and after combined liver-kidney transplantation. Methods: Agilent XDBC18 (150 mm × 4.6 mm, 5 μm) column and Agilent Zorbax extend-C18 (12.5 mm × 4.6 mm, 5 μm) guard column were used. Methyl alcohol and aqueous solution containing 0.1 mol/L ammoniom acetate (15∶85) were used as mobile phase. The flow rate was at 1.2 mL/min, ultraviolent determination wavelength was 314 nm, column temperature was at 26.3 ℃, and injection volume was 50 μL. o-phenylenediamine was used as derivating agent, reacted with oxalate in human plasma and urine so as to obtain the compound with better ultraviolet absorption-2, 3-dyhydroxy quinoxaline. Results: The detection limit in human plasma was 0.3 mg/L, the linear range was 1.953-125 mg/L, the average recovery was 94.89%, and its RSD was 4.1%; The detection limit in urine was 0.5 mg/L, the linear range was 1.953-125 mg/L, the average recovery was 94.31%, and its RSD was 3.2%. Conclusion: The method is believable for determining the mass concentration of oxalate with its simplicity, sensibility, repeatability, and better recovery rate.

4.
Mem. Inst. Oswaldo Cruz ; 103(8): 778-780, Dec. 2008. tab
Artigo em Inglês | LILACS | ID: lil-502297

RESUMO

A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl)-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.


Assuntos
Animais , Feminino , Camundongos , Antiprotozoários/química , Óxidos N-Cíclicos/química , Leishmania mexicana/efeitos dos fármacos , Quinoxalinas/química , Antiprotozoários/farmacologia , Antiprotozoários/toxicidade , Óxidos N-Cíclicos/farmacologia , Óxidos N-Cíclicos/toxicidade , Camundongos Endogâmicos BALB C , Macrófagos/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Quinoxalinas/farmacologia , Quinoxalinas/toxicidade , Relação Estrutura-Atividade
5.
Journal of Korean Medical Science ; : 307-312, 2005.
Artigo em Inglês | WPRIM | ID: wpr-84035

RESUMO

Antagonists for spinal N-methyl-D-aspartate (NMDA) and amino-hydroxy-methtyl-isoxazolepropionate (AMPA) receptors are effective in attenuating acute nociception or injury-induced hyperalgesia. The antinociception of spinal gabapentin is developed in injury-induced hyperalgesia without affecting acute nociception. The authors evaluated the effects of intrathecal gabapentin, NMDA antagonist (MK801) and AMPA antagonist (NBQX) in the formalin test which shows injury-induced hyperalgesia as well as acute pain. We further assessed the interactions between gabapentin and either MK801 or NBQX. Male Sprague-Dawley rats were implanted with intrathecal catheters. To evoke pain, 50 microliter of 5% formalin solution was injected into the hindpaw. The interaction was investigated by a fixed dose analysis or an isobolographic analysis. MK801 and NBQX suppressed flinching responses during phase 1 of the formalin test, while gabapentin had little effect on phase 1. All three agents decreased the phase 2 flinching response. A fixed dose analysis in phase 1 showed that gabapentin potentiated the antinociceptive effect of MK801 and NBQX. Isobolographic analysis in phase 2 revealed a synergistic interaction after coadministration of gabapentin-MK801 or gabapentin-NBQX. Correspondingly, spinal gabapentin with NMDA or AMPA antagonist may be useful in managing acute pain and injury-induced hyperalgesia.


Assuntos
Animais , Masculino , Ratos , Aminas/administração & dosagem , Analgésicos/farmacologia , Ácidos Cicloexanocarboxílicos/administração & dosagem , Maleato de Dizocilpina/farmacologia , Interações Medicamentosas , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hiperalgesia/tratamento farmacológico , Injeções Espinhais , Quinoxalinas/farmacologia , Ratos Sprague-Dawley , Receptores de AMPA/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Ácido gama-Aminobutírico/administração & dosagem
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