Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors
摘要:
p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-alpha production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. (c) 2012 Elsevier Masson SAS. All rights reserved.
Facile and Efficient Synthesis of 2-Aminoquinoline-3-carboxylic Acid Derivatives via Reductive Cyclization of Nitro and Cyano Groups Induced by Low-valent Titanium
Samarium(II) iodide induced reductive coupling of nitriles with nitro compounds
作者:Longhu Zhou、Yongmin Zhang
DOI:10.1039/a803077d
日期:——
The intermolecular and intramolecular reductive coupling of a cyano group with a nitro group induced by SmI2 was studied. Amidines and 2-aminoquinoline derivatives are prepared in good yields under neutral and mild conditions respectively.
Low-Valent Titanium Induced Reductive Coupling of Nitriles with Nitro Compounds
作者:Longhu Zhou、Yongmin Zhang
DOI:10.1080/00397919808004430
日期:1998.9
Abstract The intermolecular and intramolecular reductivecoupling of a cyano group with a nitro group induced by a low-valenttitanium reagent prepared from TiCl4/Sm was studied. Amidines and 2-aminoquinolines derivatives are preparied in good yields under mild conditions respectively.
Expedious and practical synthesis of the bioactive alkaloids rutaecarpine, euxylophoricine A, deoxyvasicinone and their heterocyclic homologues
作者:Abdulkareem Hamid、Abdelhakim Elomri、Adam Daïch
DOI:10.1016/j.tetlet.2006.01.031
日期:2006.3
deoxyvasicinone (3), is reported from suitable aromatic amino acids 7 or corresponding aromatic amino esters 8 and imino-thioethers 5 or 6 in a one-step sequence in moderate to good yields. The key step of this methodology is based on an intramolecular aza-displacement of a methylthio group followed by spontaneous cyclodehydration. Furthermore, when aromatic amino esters 8 were used instead of amino acids