Synthesis and antihypertensive activity of novel 3-hydrazino-5-phenyl-1,2,4-triazines

Abstract

In an effort to develop antihypertensive agents with peripheral vasodilator activity, a series of 40 novel 3-hydrazino-5-phenyl-1,2,4-triazines (II) were synthesized and evaluated in the spontaneously hypertensive rat assay (SHR assay). Based on the performance of the structurally related standard, hydralazine (I), 15 triazines were active. Thirteen of these hypotensive triazines possessed LD50 values in the mouse greater than I (LD50 = 100 mg/kg); only one active triazine had an LD50 value greater than 300 mg/kg (11d). Four asymmetric triazines had moderate antihypertensive activity and LD50 values greater than 300 mg/kg (6b, 7c, 8f, and 9g). Based on the relationship between toxicity and antihypertensive activity, three triazines (8f, 9g, and 11d) were chosen for dose-responses studies in the SHR assay. None were as efficacious as I, but all three were less toxic, resulting in similar therapeutic indices relative to I.

Solvent-free synthesis of triazines using N-halosulfonamides

“…[23][24][25][26][27] Therefore, the mechanism shown in Scheme 2 may be suggested for the conversion of the various doctrines, acid hydrazides and ammonium acetate to trisubstituted triazines. 28 95 5,6-Bis(4-methoxyphenyl)-3-(p-tolyl)-1,2,4-triazine ( 10 3-Phenyl-5,6-di(p-tolyl)-1,2,4-triazine ( 25 5,6-Diphenyl-3-(pyridin-4-yl)-1,2,4-triazine ( 3-(Pyridin-4-yl)-5,6-di(p-tolyl)-1,2,4-triazine ( …”

Synthesis and Anti-Inflammatory Evaluation of 3-Methylthio-1,2,4-Triazines, 3-Alkoxy-1,2,4-Triazines, and 3-Aryloxy-1,2,4-Triazines

“…The 3-methylthio intermediates were synthesized according to the method of Paudler and Chen (13) with modifications by Heilman et al (14). Melting points and recrystallization solvents are shown in Tables 1-111.…”

“…3-Methoxy-5-substituted-1,2,4-triazines (IIIa-111 v)-In a 1-liter round-bottom flask equipped with condenser and magnetic stirrer was placed the appropriate 3-methylthio-S-substituted-1,2,4-triazine (IIa-1Iu) (13,14) dissolved in methanol (500 ml). T o this stirred solution was added a molar excess of sodium methoxide, and the mixture was refluxed for 10 hr.…”

Potent anticancer and antimicrobial activities of pyrazole, oxazole and pyridine derivatives containing 1,2,4-triazine moiety

“…1,2,4-Triazines and their derivatives have been widely studied in terms of their synthetic methodologies and reactivity, since some of these derivatives were reported to have promising biological activities and used as a drugs in medicinal chemistry (Nyffenegger et al, 2007), including antifungal (Sztanke et al, 2005;Holla et al, 2001), anti-HIV (El-Barbary et al, 2005;Makk et al, 2014), anticancer (Abdel-Monem, 2004;El-Gendy et al, 2003), antiinflammatory (Kumar et al, 2014;Mullick et al, 2009), analgesic (Makhlouf and Maklad, 2004), antiamebic activity (Singh et al, 2005), antimicrobial activity (ElBarbary et al;Hegde et al, 2008;Bishnoi et al, 2014), antiasthma agents (Paul et al, 1985) and diuretic and antihypertensive activities (Abdel-Monem, 2004;Paul et al, 1985;Heilman et al, 1979;Ibrahim et al, 2008;Abd-El-All et al, 2013).…”

“…On the other hand, cyclization of chalcone derivatives 6, 7 with hydrazine hydrate in ethanol and a few drops of hydrochloric acid formed the corresponding new pyrazoline hydrazine derivatives 8, 9 (Heilman et al, 1979;Shawali and Gomha, 2002;Ismail, 2001). Under the same reaction conditions, chalcone derivatives 6, 7 react with phenyl hydrazine or hydroxylamine hydrochloride to afford the corresponding new N-phenyl pyrazoline 10, 11 and oxazole derivatives 12, 13, while aminocyanopyridine derivatives 14, 15 were synthesized by refluxing chalcone derivatives 6, 7 with malononitrile in the presence of ammonium acetate in ethanol solution (Scheme 2).…”