5-(1-Piperazinyl)-1H-1,2,4-triazol-3-amines as antihypertensive agents

Abstract

A series of 5-(1-piperazinyl)-1H-1,2,4-triazol-3-amines was synthesized and screened for antihypertensive and diuretic activity in spontaneously hypertensive rats (SHR). One compound, 5-[4-[(3-chlorophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-am ine (8), was selected to define the mechanism of its antihypertensive activity. Studies in SHR suggest ganglionic blocking activity. Short-lived antihypertensive activity was observed in conscious renal hypertensive dogs.

The role of 5-arylalkylamino- and 5-piperazino- moieties on the 7-aminopyrazolo[4,3-d]pyrimidine core in affecting adenosine A1 and A2A receptor affinity and selectivity profiles

“…The not commercially available 1-substituted piperazines were prepared as reported below ( 60 ) or as previously described ( 59 , 61 ) 35 , 36 .…”

“…Instead, microwave-assisted reaction of the 5-chloro derivative 56 with the N-substituted piperazines 57 – 63 , in N-methylpyrrolidone and in the presence of diisopropylethylamine, proceeded to completion, thus giving the desired pyrazolopyrimidine derivatives 15 – 20 with good yields (48–85%). The piperazine derivatives 57, 58, 62 and 63 were commercially available, while derivatives 59 and 61 were prepared as previously described 35 , 36 . The piperazine derivative 60 was synthesized starting from the reductive alkylation of N-Boc-piperazine 63 with 2,4,6-trifluorobenzaldeyde and triacetoxy sodium borohydride.…”

Synthesis of triazole Schiff bases: Novel inhibitors of nucleotide pyrophosphatase/phosphodiesterase-1

“…Compounds 10, 13, and 22 were found to be most potent inhibitors against PDE1/NPP1 enzymes with IC 50 values 132.20 ± 2.89, 152.83 ± 2.39, and 251.0 ± 6.64 lM, respectively, better than the standard EDTA (IC 50 = 277.69 ± 2.52 lM). Compounds 23,21, and 20 were found to be weakly active with IC 50 values between 404 and 1164 lM. Nonetheless, all other derivatives were found to be inactive.…”

“…1,2,4-Triazoles are cyclic hydrazones with Hatom (or substitution) on either hydrazide N-atom or an amide N-atom. According to the literature, 1H-1,2,4-triazoles and their analogues have diverse biological activities, such as antiasthamatic, 1,2 antiviral, 3 antifungal, 4 antibacterial, 5 hypnotic, 6 pesticidal, 7 breast cancer preventive, 8,9 anticonvulsant, anticancer, antiinflammatory, [10][11][12][13][14][15][16][17][18][19] CNS depressant, 20 and antihypertensive 21,22 activities. 1,2,4-Triazole derivatives have been used as mimics and isosteres.…”

Methyl 4-tert-butoxycarbonyl-N-cyanopiperazine-1-carboximidothioate

“…The title compound, (I), may prove to be an intermediate for antihypertensive agents, potential antimalarials (Meyer et al, 1989;Johnson & Werbel, 1983) and molecular rectification materials.…”