TY - JOUR ID - 4883 TI - Synthesis and Evaluation of Pyridinyltriazoles as Inhibitors of p38 MAP Kinase JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Moallem, Seyed Adel AU - Hadizadeh, Farzin AU - Abdol Abadi, Fatemeh AU - Shahraki, Mahmoud AU - Shamsara, Jamal AD - Pharmaceutical Sciences Research Centre, Mashhad University of Medical sciences Mashhad, Iran AD - Biotechnology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran AD - Medical Toxicology Research Centre, Mashhad University of Medical Sciences Mashhad, Iran AD - School of Pharmacy, Mashhad University of Medical Sciences Mashhad, Iran Y1 - 2012 PY - 2012 VL - 15 IS - 4 SP - 945 EP - 950 KW - Inhibitors KW - p38 MAP kinase KW - Pyridinylimidazoles DO - 10.22038/ijbms.2012.4883 N2 - Objective(s) Inhibitors of p38 MAP kinase are considered as suitable target in the treatment of inflammatory diseases such as rheumatoid arthritis and bowel inflammatory diseases. The development of 5-alkylthio-1-aryl-2-(4-pyridinyl) triazoles as inhibitors of p38 MAP kinase is described. These are analogues of 4- pyridinyl imidazole p38 MAP kinase inhibitor reported by Merck Research Laboratories, in which imidazole ring has been replaced with triazole. Materials and Methods Reaction of pyridine-4-carboxylic acid hydrazide 1 and arylisothiocyanate (2a, b) gave the intermediate thiourea derivative 3a, b (Figure 2). Refluxing  of the latter in aqueous saturated sodium carbonate gave 1-aryl-5-mercapto-2-(4-pyridinyl) triazoles 4a, b. Treatment of 4a, b with alkyl iodide afforded the desired 5-alkylthio-1-aryl-2-(4-pyridinyl) triazoles (5a-d). P38 MAP kinase inhibitory activity of the synthesized compounds was evaluated in vitro by ELISA method and also by molecular docking. Results Compound 5c at 1 µM concentration and compound 5d at 1 µM and 10 µM significantly inhibited the p38 phosphorylation. These inhibitory effects are equal to those of standard compound SB202190 and no significant differences were observed. Conclusion We demonstrated that both tested compounds have inhibitory effect on p38 MAP kinase and we did not find significant difference between their inhibitory effects and those of standard inhibitor SB202190. UR - https://ijbms.mums.ac.ir/article_4883.html L1 - https://ijbms.mums.ac.ir/article_4883_8448715e49720b590c57f7fc3a1035d8.pdf ER -