Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives

Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.

[1]  R. Bansal,et al.  Synthesis of new pyridazinone derivatives as platelet aggregation inhibitors , 2010, Medicinal Chemistry Research.

[2]  A. Rauk,et al.  Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d]pyridazin-4(5H)-ones. , 2010, European journal of medicinal chemistry.

[3]  M. Dąbrowska-Szponar,et al.  Synthesis, Fungicidal and Antibacterial Activity of New Pyridazine Derivatives. , 2009 .

[4]  N. N. Smolyar,et al.  Synthesis of 4-amino-6-(hetaryl)pyridazin-3-ones as analogs of pyridazine-based cardiotonic agents , 2009, Pharmaceutical Chemistry Journal.

[5]  S. Ahamad,et al.  Synthesis and in-vitro antifungal activity of 6-substituted-phenyl-2- {[(4'-substituted phenyl-5'-thioxo)-1,2,4-triazol-3-yl]-methyl}-2,3,4,5-tetrahydropyridazin-3-one derivatives. , 2008, Acta poloniae pharmaceutica.

[6]  S. Archan,et al.  Levosimendan: current status and future prospects , 2008, Current opinion in anaesthesiology.

[7]  A. Karaburun,et al.  Some pyrrole substituted aryl pyridazinone and phthalazinone derivatives and their antihypertensive activities. , 2004, European journal of medicinal chemistry.

[8]  E. Sotelo,et al.  Pyridazines. Part 34: Retro-ene-assisted palladium-catalyzed synthesis of 4,5-disubstituted-3(2H)-pyridazinones , 2003 .

[9]  E. Sotelo,et al.  Pyridazines. Part XXIX: synthesis and platelet aggregation inhibition activity of 5-substituted-6-phenyl-3(2H)-pyridazinones. Novel aspects of their biological actions. , 2002, Bioorganic & medicinal chemistry.

[10]  W. Foye,et al.  Foye's Principles of Medicinal Chemistry , 2002 .

[11]  J. Bourguignon,et al.  Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic antineuroinflammatory compound. , 2002, Journal of medicinal chemistry.

[12]  T. Kinoshita,et al.  Discovery of 6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)- pyridazinebutanoic acid (FK 838): a novel non-xanthine adenosine A1 receptor antagonist with potent diuretic activity. , 1999, Journal of medicinal chemistry.

[13]  D. Shinde,et al.  Synthesis of 2,4‐Diarylamino‐6‐(3′,5′,6′‐trichloropyridin‐2′‐yl)oxy Triazine and Its Herbicidal Activity. , 1998 .

[14]  M. Hann,et al.  Synthesis and anti-HIV-1 activity of a series of imidazo[1,5-b]pyridazines. , 1993, Journal of medicinal chemistry.

[15]  F. Schade,et al.  The specific type III and IV phosphodiesterase inhibitor zardaverine suppresses formation of tumor necrosis factor by macrophages. , 1993, European journal of pharmacology.

[16]  A. Monge,et al.  Selective Thromboxane Synthetase Inhibitors and Antihypertensive Agents. New Derivatives of 4-Hydrazino-5H-pyridazino(4,5-b)indole, 4-Hydrazinopyridazino(4,5-a)indole, and Related Compounds. , 1987 .

[17]  A. Monge,et al.  Selective thromboxane synthetase inhibitors and antihypertensive agents. New derivatives of 4-hydrazino-5H-pyridazino[4,5-b]indole, 4-hydrazinopyridazino[4,5-a]indole, and related compounds. , 1987, Journal of medicinal chemistry.

[18]  J. Krushinski,et al.  Molecular structure of the dihydropyridazinone cardiotonic 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-pyridazinyl)- 2H-indol-2-one, a potent inhibitor of cyclic AMP phosphodiesterase. , 1987, Journal of medicinal chemistry.

[19]  D. B. Evans,et al.  Cardiotonic agents. 1. 4,5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3 (2H)-pyridazinones: novel positive inotropic agents for the treatment of congestive heart failure. , 1984, Journal of medicinal chemistry.

[20]  L. Krakoff,et al.  Effect of methylprednisolone upon arterial pressure and the renin angiotensin system in the rat. , 1975, The American journal of physiology.

[21]  Steve Berry,et al.  Yield!! #!*&%! , 2004, JEMS : a journal of emergency medical services.

[22]  R. Falotico,et al.  6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents. , 1990, Journal of medicinal chemistry.

[23]  C. Barnes,et al.  Drug dosage in laboratory animals : a handbook , 1964 .