145757-48-8Relevant academic research and scientific papers
NOVEL COMPOUND WITH EFFECTS OF THROMBOLYSIS, FREE RADICAL SCAVENGING AND THROMBUS-TARGETING AS WELL AS PREPARATION METHOD AND USE THEREOF
-
, (2015/11/03)
The present invention discloses a novel compound with effects of thrombolysis, free radical scavenging and thrombus-targeting, as well as a preparation method and use thereof. The compound is a ternary conjugate formed by conjugating a thrombolytic peptide, a free radical scavenger and a thrombus-targeting/antithrombotic peptide together via a linking arm. The present invention also discloses a pharmaceutical composition containing the compounds, wherein the compounds form a nanospherical structure.
A class of novel nitronyl nitroxide labeling basic and acidic amino acids: Synthesis, application for preparing ESR optionally labeling peptides, and bioactivity investigations
Zhang, Jianwei,Zhao, Ming,Cui, Guohui,Peng, Shiqi
, p. 4019 - 4028 (2008/12/22)
Aimed at optional ESR label 2-(4′-hydroxyl)phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl was introduced into the guanido of l-Arg-OH, the ω-amino group of l-Lys-OH with methylcarboxyl as a linker, and into the β-carboxyl of l-Asp-OH and the γ-carboxyl of l-Glu-OH with ethylamino as a linker. It was explored that the synthetic 30 novel ESR labeling amino acid derivatives were stable enough to the reaction conditions of peptide synthesis. Their incorporation led to 12 novel ESR optionally labeling PAK, RGDS, RGDV, and ECG. A series of NO related chemical tests, the in vitro and in vivo assays of these peptides confirmed that this strategy was practical.
Protective effect of nitronyl nitroxide-amino acid conjugates on liver ischemia-reperfusion induced injury in rats
Bi, Wei,Cai, Jianhui,Xue, Ping,Zhang, Yanrong,Liu, Sanguang,Gao, Xiang,Li, Meng,Wang, Zhibo,Baudy-Floc'h, Michele,Green, Sarah A.,Bi, Lanrong
, p. 1788 - 1794 (2008/12/20)
Stable nitroxides are potential antioxidant drugs. In this study, we have linked nitroxide to natural amino acids with the aim to improve therapeutic activity. The radical scavenging activities of two nitronyl nitroxide-amino acid conjugates (NNR and NNK) were evaluated in PC 12 cell survival assays. The NO scavenging activities of these compounds were confirmed in the acetylcholine-induced vasorelaxation assay. In addition, the protective effect of NNR was demonstrated in an in vivo rat model of hepatic ischemia-reperfusion (I/R) induced injury and oxidative change. Because NNR reduced hepatic I/R injury by minimizing oxidative stress, it might be possible to develop it into a possible therapeutic agent for hepatic I/R injury.
Novel 2-substituted nitronyl nitroxides as free radical scavengers: Synthesis, biological evaluation and structure-activity relationship
Wu, Yihui,Bi, Lanrong,Bi, Wei,Li, Zeng,Zhao, Ming,Wang, Chao,Ju, Jingfang,Peng, Shiqi
, p. 5711 - 5720 (2007/10/03)
To develop more potent small molecules with enhanced free radical scavenger properties, we designed and synthesized a series of nitronyl nitroxide derivatives 4a-h. A lead compound 4f was discovered based on Ach-induced vascorelaxation assay. Further chemical modification based on this scaffold provided a new series of 2-substituted phenylnitronyl nitroxide derivatives 6a-s. The newly synthesized compounds 6a-s possess improved radical scavenger's activity based on PC12 cell survival assay. Compounds 6g,n,o, and s are some of the most potent compounds in terms of NO, H2O2, and OH scavenging ability. 2-Substitued phenylnitronyl nitroxides had a higher radical scavenging activity with the electron-donating group (EDG). In contrast, the introduction of electron-withdrawing group (EWG) to the aromatic ring led to a dramatic decrease in its radical scavenging activity. These results suggest that the electron-donating group (EDG) of the aromatic ring may be an important factor influencing the radical scavenging behavior of these compounds, and the potency of free radical scavenging activity largely depended on the position and electronic properties of the phenyl ring substituents. The enhanced radical scavenging capacities of the novel 2-substituted nitronyl nitroxides may be potential drug leads against the deleterious action of ROS (reactive oxygen species)/RNS (reactive nitrogen species).
Synthesis and biological activity of nitronyl nitroxide containing peptides
Zhao, Ming,Liu, Junling,Wang, Chao,Wang, Lili,Liu, Hu,Peng, Shiqi
, p. 4285 - 4292 (2007/10/03)
[1-(1′,3′-Dioxyl-4′,4′,5′, 5′-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1′,3′-dioxyl- 4′,4′,5′,5′-tetramethyldihydroimidazol-2-yl) -phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9c was evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.
Synthesis and bioactivities of nitronyl nitroxide and RGD containing pseudopeptides
Liu, Junling,Zhao, Ming,Wang, Chao,Peng, Shiqi
, p. 4065 - 4069 (2007/10/03)
1-(1′,3′-dioxyl-4′,4′,5′,5′- tetramethyldihydroimidazol-2′-yl)-phenyl-4-yloxylacetic acid (3), and 1-(1′,3′-dioxyl-4′,4′,5′,5′- tetramethyldihydroimidazol-2′-yl)-phenyl-4-yloxylacetyl-RGDS (13), -RGDV (14), -RGDF (15) were synthesized. The ESR measurement gave the same spectroscopy for 3 and 13-15. The NO scavenging tests in vitro, anti-platelet aggregation tests in vitro and the anti-thrombosis assay in vivo indicated that introducing 3 into the N-terminal of RGDS, RGDV and RGDF the corresponding bioactivities for both of 3 and RGD peptides can be remained completely. The present combinations provided a beneficial strategy for simultaneous scavenging NO and anti-thrombosis, and for the use of spin label of RGD peptides in the conformational researches.
Treatment of diseases of the central nervous system using uric acid as a scavenger of peroxynitrite
-
, (2008/06/13)
The process of treating a disease of the central nervous system with an agent from one or more of the following three classes of agents: (1) nitric oxide scavengers, (2) peroxynitrite scavengers, and (3) agents that either interfere with the synthesis of iNOS in the cell or the enzymatic activity of iNOS in the cell.
2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide derivatives and their use as therapeutic agents for maintaining blood pressure
-
, (2008/06/13)
(1) The imidazoline derivative represented by the following general formula (1) STR1 where R1 is a substituent endowed with water solubility or fat solubility, particularly carboxyl group or carboxymethoxy group or a pharmaceutically acceptable salt thereof, (2) The method for producing the above-mentioned compound, and (3) A therapeutic agent containing as its active ingredient the above-mentioned imidazoline derivative or an imidazoline derivative wherein R1 indicated in the formula (1) is hydrogen atom. The imidazoline derivative set forth under (1) above is a novel substance; and this compound itself and its derivative having R1 as indicated in the general formula (1) is hydrogen atom are useful as a therapeutic agent for treatment of shock from the fall in blood pressure by virtue of their ability to remove excess NO which is the vascular endothelium-derived relaxing factor (EDRF).
