Synthesis and positive inotropic evaluation of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted piperazine moieties

Centroid⋯centroid and hydrogen bond interactions as robust supramolecular units for crystal engineering: X-ray crystallographic, computational and urease inhibitory investigations of 1,2,4-triazolo[3,4-a]phthalazines

“…Subsequent hydrazination in ethanol at 80 °C gave 1-chloro-4-hydrazineylphthalazine 4 which was cyclized to 6-chloro-3-methyl-[1,2,4]triazolo[3,4- a ]phthalazine 5 and 6-chloro-[1,2,4]triazolo[3,4- a ]phthalazine 6 by reacting with acetyl chloride and triethyl orthoformate in 1,4-dioxane at 110 °C, respectively. 32 The structure of compound 5 shows the incorporation of a methyl group at 2.81 and 9.96 ppm in 1 H and 13 C NMR spectra, respectively, confirming the smooth cyclization of 4 into 5 . Similarly, a distinct singlet at 9.62 ppm attributable to C sp2 –H of triazole ring confirmed the formation of compound 6 .…”

“…2,3-Dihydrophthalazine-1,4-dione 2 was obtained as a white solid (5.95 g, 92%). 32 1 H NMR (400 MHz, DMSO-d 6 ) δ H : 11.56 (br s, 2H, NH), 8.09–8.05 (m, 2H, ArH), 7.89–7.85 (m, 2H, ArH); 13 C{ 1 H} NMR (101 MHz, DMSO-d 6 ) δ C : 154.7, 132.7, 127.2, 125.2.…”

“…1-Chloro-4-hydrazineylphthalazine 4 was obtained as a yellow solid (1.25 g, 64%) and used as such without further purification. 32…”

“…The combined organics were dried over MgSO 4 , filtered, and concentrated in vacuo to give 5 as a light yellow solid (770 mg, 55%). 32 1 H NMR (400 MHz, CDCl 3 ) δ H : 8.67 (d, 1H, J = 7.9 Hz, ArH), 8.26 (d, 1H, J = 8.2 Hz, ArH), 8.01–7.97 (m, 1H, ArH), 7.88–7.84 (m, 1H, ArH), 2.81 (s, 3H, CH 3 ); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ C : 149.9, 147.9, 142.5, 134.9, 131.3, 127.6, 124.2, 123.7, 122.2, 10.0.…”

“…29 Moreover, [1,2,4]triazolo[3,4- a ]phthalazines have been reported as inhibitors of bromodomains 30 in addition to anticancer 31 and positive inotropic activities. 32 Fig. 1 demonstrates some selective examples of drug molecules encompassing phthalazine nucleus.…”