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| 1 | Design,synthesis,and anti-inflammatory evaluation of a series of novel amino acid-binding 1,5-diarylpyrazole derivatives显示文摘Aim: To design and synthesize a series of novel amino acid-binding 1,5-diarylpyrazole derivatives, which are intended to act as prodrugs with better aqueous solubility than celecoxib, and which will exert potent anti-inflammatory activi-ties after being converted to their parent compounds in vivo. Methods: To introduce an amino acid, celecoxib analogs containing amino or methylamino group were synthesized first through multi-step chemical reactions. All the synthesized compounds were screened in an intact cell-based assay in vitro and in carrageenan-induced mouse paw edema in vivo. Some active compounds were selected for further evaluation in a carrageenan-induced rat paw edema model. The preliminary pharmacokinetics experiments were conducted using high performance liquid chromatography/mass spectrometry (HPLC/MS). Results: Celecoxib, 6 of the 1,5-diarylpyrazole class of celecoxib analogs, and their amino acid derivatives (hydrochloride salts) were synthesized. In vitro screening, the hydrochloride salts showed decreased inhibitory effects on cyclooxygenase (COX)- 1 and COX-2 compared with their parent compounds, but some exhibited potent anti-inflammatory activity in vivo. Compound 4a was selected for further evaluation, and its anti-inflammatory effect was equivalent to that of celecoxib after oral administration in the carrageenan-induced rat paw edema model. At three doses (25 mg/kg, 50 mg/kg, and 100 mg/kg) the percentage inhibition on edema was 20.7%, 52.6%, and 62.6% (for compound 4a) and 27.8%, 38.4%, and 40.1% (for celecoxib), respectively. Preliminary pharmacokinetic evaluations support the hypothesis that compound 4a was actually converted to its parent compound, compound 4. Conclusion: The compound bound with amino acid acts like prodrug, which can exert anti-inflammatory effect similar to celecoxib after being converted to its parent compound. This finding will be of great benefit in carrying out structural modifications of prodrug-like selective COX-2 inhibitors. | Li MH Yin LL Cai MJ Zhang WY Huang Y Wang X Zhu XZ Shen JK | 2005 | Acta Pharmacologica Sinica2005，26，7： | 2 |
| 2 | The effect of glucose during ischemia on brain ATP,lactate,and glutamate in piglets显示文摘 | Le Blanc MH Qian XB Cai ZW | 1997 | Biol Neonate1997，72，1： | 1 |
| 3 | Microbiotas and environments of the Nansha Islands and adjacent sea显示文摘IN the past 12 years, the Multidisciplinary Oceanographic Expedition Team to Nansha Islandsorganized by the Chinese Academy of Sciences has carried out many investigations and ob-tained a lot of scientific research results. In the present study, 177 surface sediments and 7core specimens were used for analyzing foraminifers, ostracods, radiolarians, bryozoans, gas-tropods, bivalves, diatoms, dinonagellates, sporopollen and calcareous nannoplankton, con- | Chen, MH Cai, HM Tu, X Lu, LH | 1997 | Chinese Science Bulletin1997，42，20： | 1 |
| 4 | Effect of hypoxia on blood glucose and insulin receptor function in newborn calves显示文摘 | Cheng NL Cai WJ Jiang MH | 1997 | Pediatr Res1997，41，4： | 1 |
| 5 | The effect of glucose during ischemia on brain ATP, lactate, and glutamate in piglets显示文摘 | LeBlanc MH Qian X Cai Zw | 1997 | Biol Neonate1997，72，4： | 1 |
| 6 | The effect of glucose during ischemia on brain ATP , lactate, and glutamate in piglets显示文摘 | LeBlanc MH Qian X Cai ZW | 1997 | Biol Neonate1997，72，4： | 1 |
| 7 | Statistical optimization of medium composition for aspergiolide A production by marinederived fungus Aspergillus glaucus显示文摘 | Cai MH Zhou XS Sun XQ | | 0，，： | 1 |
| 8 | The effect of glucose during ischemia on briain ATP, lactate and glutamate in piglets显示文摘 | LeBlanc MH Qian XB Cai ZW | 1997 | Biol Neonate1997，72，1： | 1 |
| 9 | The influence of CYP2D6 activity on the kinetics of propafenone enantiomers in Chinese subjects显示文摘 | Cai WM Chen B Cai MH | 1999 | Br J Clin Pharmacol1999，47，5： | 1 |
| 10 | Inhibition of cell proliferation,vascular endothelial growth factor and tumor growth by albendazole显示文摘 | Pourgholami MH Cai ZY Wang L | 2009 | Cancer Invest2009，27，2： | 1 |
| 11 | The effect of glucose during ischemia on brain ATP,lactate,and glutamate in piglets显示文摘 | Le Blanc MH Qian XB Cai ZW | 1997 | Biol Neonate1997，72，1： | 1 |
| 12 | Potent inhibition of tumoral hypoxia-inducible factor 1 alpaha by albendazole显示文摘 | Pourgholami MH Cai ZY Badar S | 2010 | BMC Cancer2010，10，7： | 1 |
| 13 | Polybrominated diphenyl ethers in fish and sediment from river polluted by electronic waste 显示文摘 | Luo Q Cai ZW Wong MH | 2007 | Sci Total Environ2007，383，： | 1 |
| 14 | Potent inhibition of tumoral hypoxia-inducible factor 1 alpha by albendazole显示文摘 | Pourgholami MH Cai ZY Badar S | | 0，，01： | 1 |
| 15 | Suppression of lung tumor metastasis in mice by recombinant adeno-associated virus-mediated expression of vasostatin显示文摘 | Cai K Tam P Xu RA Shan MH | 2008 | Clin Cancer Res2008，14，3： | 1 |
| 16 | Inhibition of cell pro- liferation, vascular endothelial growth factor and tumor growth by albendazole 显示文摘 | Pourgholami MH Cai ZY Wang L | 2009 | Cancer Invest2009，27，2： | 1 |
| 17 | Aberrant expression and demethylation of γ-synuclein in colorectal cancer,correlated with progression of the disease显示文摘 | Ye Q Zheng MH Cai Q | | 0，，10： | 1 |
| 18 | Environmental contamination from electronic waste recycling at Guiyu, Southeast China显示文摘 | Leung A Cai ZW Wong MH | 2006 | J Mater Cycles Waste Manage2006，8，： | 1 |
| 19 | Effect of hypoxia on blood glucose显示文摘 | Cheng NL Cai WJ Jiang MH | 1997 | hormones and insulin receptor function in newborn culves Pediatr Res1997，41，： | 1 |
| 20 | Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults, a large-scale, randomised, double-blind placebo- controlled, phase 3 trial 显示文摘 | Zhu FC Zhang J Zhang XF Zhou C Wang ZZ Huang SJ Wang H Yang CL Jiang HM Cai JP Wang YJ Ai X Hu YM Tang Q Yao X Yan Q Xian YL Wu T Li YM Miao J Ng MH Shih JW Xia NS | 2010 | Lancet2010，376，： | 1 |
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