- Novel L-arginine derivatives as aminopeptidase N inhibitors: design, chemistry, and pharmacological evaluation
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Considering the important roles played in tumor, aminopeptidase N has been an appealing target for anti-tumor drug development. Here, a serial of novel aminopeptidase N inhibitors with L-arginine scaffold were designed, synthesized and evaluated for aminopeptidase N inhibitory activities. The preliminary anti-enzyme activity assay demonstrated that compounds 5e, 5h, 11e, 11g, and 11h showed comparable activities with the positive control bestatin, an approved aminopeptidase N inhibitor. In vitro anti-proliferation assay, compound 5f showed excellent activities against four kinds of tumor cells which overexpress aminopeptidase N. In vivo anti-metastasis assay, compounds 5f and 11g exhibited better activities than bestatin. So 5f and 11g should be lead compounds as novel aminopeptidase N inhibitors for further development.
- Mou, Jiajia,Luan, Yepeng,Chen, Danghui,Wang, Qiang
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p. 3015 - 3025
(2017/10/06)
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- A class of novel Schiff's bases: Synthesis, therapeutic action for chronic pain, anti-inflammation and 3D QSAR analysis
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To discover analgesics for treating chronic pain 17 novel Schiff's bases, N,N′-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 μmol/kg of these Schiff's bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 μmol/kg of these Schiff's bases exhibited desirable anti-inflammation. Thus the present Schiff's bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff's bases on the analgesic activity was explained with 3D QSAR.
- Zhou, Yinjian,Zhao, Ming,Wu, Yingting,Li, Chunyu,Wu, Jianhui,Zheng, Meiqing,Peng, Li,Peng, Shiqi
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experimental part
p. 2165 - 2172
(2010/05/18)
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- Design, synthesis and primary activity assay of bi- or tri-peptide analogues with the scaffold l-arginine as amino-peptidase N/CD13 inhibitors
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A series of bi- or tri-peptide analogues with the scaffold l-arginine were designed, synthesized and evaluated for their inhibitory activities against amino-peptidase N (APN) and metalloproteinase-2 (MMP-2). The primary activity assay showed that all the compounds exhibited higher inhibitory activities against APN than MMP-2. Within this series, compounds C6 and C7 (IC50 = 4.2 and 4.3 μM) showed comparable APN inhibitory activities with the positive control bestatin (IC50 = 3.8 μM).
- Mou, Jiajia,Fang, Hao,Liu, Yingzi,Shang, Luqing,Wang, Qiang,Zhang, Lei,Xu, Wenfang
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scheme or table
p. 887 - 895
(2010/05/02)
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- Design, synthesis and primary activity evaluation of l-arginine derivatives as amino-peptidase N/CD13 inhibitors
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A series of l-arginine derivatives were designed, synthesized and assayed for their activities against amino-peptidase N (APN)/CD13 and metalloproteinase-2 (MMP-2). The results showed that most compounds exhibited high inhibitory activities against APN and low activities against MMP-2. Within this series, two compounds 5q and 5s (IC50 = 5.3 and 5.1 μM) showed similar inhibitory activities compared with bestatin (IC50 = 3.8 μM), which could be used as novel lead compounds for the future APN inhibitors development as anticancer agents.
- Mou, Jiajia,Fang, Hao,Jing, Fanbo,Wang, Qiang,Liu, Yingzi,Zhu, Huawei,Shang, Luqing,Wang, Xuejian,Xu, Wenfang
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scheme or table
p. 4666 - 4673
(2009/12/01)
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- AZIRIDINE ALDEHYDES, AZIRIDINE-CONJUGATED AMMO DERIVATIVES, AZIRIDINE-CONJUGATED BIOMOLECULES AND PROCESSES FOR THEIR PREPARATION
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The present invention relates to unprotected amino aldehydes and applications for same. More particularly, the present invention relates to novel aziridine aldehydes and processes for preparing these novel compounds. The invention also relates to aziridine-conjugated amino derivatives, and processes for preparing the same. Pentacyclic compounds may be prepared using the aziridine aldehydes of the present invention, and the invention relates to these compounds and the processes by which they are made. The invention also relates to aziridine-conjugated bioactive molecules, such as amino acids and peptides, and processes for preparing such compounds.
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Page/Page column 62; 109; 110
(2008/12/05)
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- Inhibitory effects of L-arginine derivatives on endothelium-dependent vasorelaxing response to acetylcholine of the rat aorta
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Nω-nitro-L-arginine alkyl esters (A-1-A-B) and L-arginine alkyl esters (E-1-E-B) were synthesized, and the vasorelaxing effects of acetylcholine were studied in the absence or presence of these compounds in rat aortic rings with intact endothelium that was precontracted with phenylephrine. These compounds revealed that the nitro group is an essential inhibiting group of these inhibitors, and that hydrophobic functional groups can fine-tune the binding effects. Among them, A-3 is the most potent inhibitor.
- Wang, Guei-Jane,Lai, Tzi-Chung,Chen, Chinpiao
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p. 611 - 617
(2007/10/03)
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