Synthesis of new series of pyrimido[4,5-b][1,4] benzothiazines as 15-lipoxygenase inhibitors and study of their inhibitory mechanism

Medicinal Chemistry Research

Volumn 22, Issue 10, 2013, Pages 5036-5043

  Nikpour, Mohsen ^a   Mousavian, Mina ^b   Davoodnejad, Mahdieh ^c   Alimardani, Maliheh ^c   Sadeghian, Hamid ^c,d  

^a ISLAMIC AZAD UNIVERSITY   (Iran)

^b ISLAMIC AZAD UNIVERSITY   (Iran)

^c MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^d MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

DMAB; Docking; DPPH; Radical scavenging; SAR

Indexed keywords

1,1 DIPHENYL 2 PICRYLHYDRAZYL; 2 (4 METHYL PIPERAZINYL); 2 (4 METHYLPIPERAZIN 1 YL) 4 PROPYL 5H PYRIMIDO[4,5B][1,4]BENZOTHIAZINE; 2 (4 METHYLPIPERIDIN 1 YL) 4 PROPYL 5H PYRIMIDO[4,5B][1,4]BENZOTHIAZINE; 2 (4 PHENYLPIPERAZIN 1 YL) 4 PROPYLPYRIMIDO[4,5B][1,4]BENZOTHIAZINE; 2 (MORFOLIN 4 YL) 4 PROPYL 5H PYRIMIDO[4,5B][1,4]BENZOTHIAZINE; 2 (PIPERIDIN 1 YL) 4 PROPYL 5H PYRIMIDO[4,5B][1,4]BENZOTHIAZINE; 2 [(5 BROMO 2 CHLORO 6 PROPYLPYRIMIDIN 4YL)SULFANYL]ANILINE; 4 ALKYL PYRIMIDO[4,5 B ]BENZOTHIAZINE; 4 PROPYL 2 (PYRROLIDIN 1 YL) 5H PYRIMIDO[4,5B][1,4]BENZOTHIAZINE; ANTIOXIDANT; ARACHIDONATE 15 LIPOXYGENASE; BENZOTHIAZINE DERIVATIVE; ENZYME INHIBITOR; LINOLEIC ACID; LIPOXYGENASE; PYRIMIDO[4,5 B ][1,4] BENZOTHIAZINE; UNCLASSIFIED DRUG; UNSATURATED FATTY ACID;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIOXIDANT ACTIVITY; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; MOLECULAR DOCKING; MOLECULAR MODEL; MOUSE; NONHUMAN; PEROXIDATION; SOYBEAN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

EID: 84883448357     PISSN: 10542523     EISSN: 15548120     Source Type: Journal    
DOI: 10.1007/s00044-013-0506-7     Document Type: Article

References (19)

1. Bakavoli M, Nikpour M, Rahimizadeh M, Saberi MR, Sadeghian H (2007) Design and synthesis of pyrimido[4,5-e][1,3,4]thiadiazine derivatives as potent 15-lipoxygenase inhibitors. Bioorg Med Chem 15:2120-2126
2. Bakavoli M, Sadeghian H, Tabatabaei Z, Rahimizadeh M, Nikpour M (2008) SAR comparative studies on pyrimido[4,5-b][1,4]benzothiazine derivatives as 15-lipoxygenase inhibitors using ab initio calculations. J Mol Model 14:471-478
3. Charlier C, Michaux C (2003) Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new start to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem 38:645-659
4. Cyrus T, Witztum JL, Rader DJ, Tangirala R, Fazio S, Linton MF, Funk CD (1999) Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. J Clin Invest 103:1597-1604
5. Feltenmark S, Gautam N, Brunnström A, Griffiths W, Backman L, Edenius C, Lindbom L, Björkholm M, Claesson H (2008) Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells. Proc Natl Acad Sci USA 105:680-685
6. Harats D, Shaish A, George J, Mulkins M, Kurihara H, Levkovitz H, Sigal E (2002) Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL reseptor-deficient mice. Arterioscler Thromb Vasc Biol 20:2100-2105
7. Huey R, Morris GM. AutoDock Tools; a tutorial, 2006, 10550 North Torrey pines Road, CA 92037-1000, USA
8. Iranshahi M, Jabbari A, Orafaie A, Mehri R, Zeraatkar S, Ahmadi T, Alimardani M, Sadeghian H (2012) Synthesis and SAR studies of mono O-prenylated coumarins as potent 15-lipoxygenase inhibitors. Eur J Med Chem 57:134-142
9. Jabbari A, Davoodnejad M, Alimardani M, Assadieskandar A, Sadeghian A, Safdari H, Movaffagh J, Sadeghian H (2012) Synthesis and SAR Studies of 3-allyl-4-prenyloxyaniline amides as potent 15-lipoxygenase inhibitors. Bioorg Med Chem 20:5518-5526
10. Jeon SG, Moon HG, Kim YS, Choi JP, Shin TS, Hong SW, Tae YM, Kim SH, Zhu Z, Gho YS, Kim YK (2009) 15-lipoxygenase metabolites play an important role in the development of a T-helper type 1 allergic inflammation induced by double-stranded RNA. Clin Exp Allergy 39:908-917
11. Kelavkar U, Glasgow W, Eling TE (2002) The effect of 15-lipoxygenase-1 expression on cancer cells. Curr Urol Rep 3:207-214
12. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639-1662
13. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785-2791
14. Nikpour M, Sadeghian H, Saberi MR, Shafiee Nick R, Seyedi SM, Hosseini A, Parsaee H (2010) Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors. Bioorg Med Chem 18:855-862
15. Nikpour M, Zarinabadi S, Saberi S (2012) Efficient synthesis of novel azo compounds based on pyrimido[4,5-e][1,3,4]thiadiazine. Bull Chem Soc Ethiop 26:115-120
16. Pooryaghoobi M, Bakavoli M, Alimardani M, Bazzazan T, Sadeghian H (2013) New insight into the SAR of pyrimido[4,5-b][1,4] benzothiazines as 15-lipoxygenase inhibitors. Iran J Basic Med Sci (in press)
17. Sadeghian H, Seyedi SM, Saberi MR, Arghiani Z (2008) Design and synthesis of eugenol derivatives, as potent 15-lipoxygenase inhibitors. Bioorg Med Chem 16:890-901
18. Sadeghian H, Attaran N, Jafari Z, Saberi MR, Pordel M, Riazi M (2009) Design and synthesis of 4-methoxyphenylacetic acid esters as 15-lipoxygenase inhibitors and SAR comparative studies of them. Bioorg Med Chem 17:2327-2335
19. Seyedi SM, Jafari Z, Attaran N, Sadeghian H, Saberi MR, Riazi MM (2009) Design, synthesis and SAR studies of 4-allyoxyaniline amides as potent 15-lipoxygenase inhibitors. Bioorg Med Chem 17:1614-1622