Discovery of novel pyrazolopyrimidinone analogs as potent inhibitors of phosphodiesterase type-5

Direct N-heterocyclization of hydrazines to access styrylated pyrazoles: synthesis of 1,3,5-trisubstituted pyrazoles and dihydropyrazoles

“…The present protocol was applied in some complex molecules to elaborate the commercial importance in late stage modifications. In continuation to our ongoing project for the synthesis of selective PDE5 inhibitors, 17 the pyrazole-bearing analogue with different heterocyclic moiety in the native structure of sildenafil ( Fig. 1 ) was prepared only to show the utility of method in late stage modifications of important drug scaffolds.…”

Innovative trends and perspectives for erectile dysfunction treatment: A systematic review

“…Sawant et al (2015) [34] stated that a novel pyrazolopyrimidinone analogue (compound-4a) may act as new alternative and as potent inhibitor of PDE5 compared with the classic PDE5Is sildenafil, vardenafil, tadalafil, and avanafil. They found that the new compound had better in vivo efficacy and good physicochemical properties.…”

Synthesis and Antiviral Activity of Sulfonohydrazide and 1,3,4-Oxadiazole Derivatives of 6,6-Dimethyl-9-Oxo-4,5,6,7,8,9-Hexahydropyrazolo[5,1-b] Quinazoline

“…The solid obtained was collected by filtration and washed with water (35 mL) to afford the desired product compound 8 as: Off-white solid; yield 74%; 1 H NMR (400 MHz, DMSO-d 6 ): δ 0.97 (s, 6H), 1.28-1.32 (t, 2H, J 1 = 7.2 Hz, J 2 = 7.2 Hz), 1.47-1.51 (t, 2H, J 1 = 6.4 Hz, J 2 = 6. 6,5,6,7,8,…”

“…), and then dried over anhydrous sodium sulfate and concentrated completely to obtain the desired products 2a-c as solids. N'- (6,5,6,7,8,] quinazoline-3-carbonyl)-2-fluorobenzenesulfonohydrazide (2a): Offwhite solid; yield 78%; 1 H NMR (400 MHz, DMSO-d 6 ): δ 0.94 (s, 6H), 1.22 (s, 4H), 1.46 (s, 4H), 7.3-7.34 (m, 1H), 7.39-7.44 (m, 1H), 7.68-7.7 (m, 1H), 7.78-7.82 (m, 1H), 8.29 (s, 1H), 10.12 (s, 1H), 10.39 (s, 1H); 13 (6 ,6 -dimethyl-9 -oxo-4,5,6 ,7,8 ,9 -hexahydropyrazolo [5,1-b]quinazoline-3-carbonyl)benzenesulfonohydrazide (2b): Off-white solid; yield 85%; 1 H NMR (400 MHz, DMSO-d 6 ): δ 0.97 (s, 6H), 1.44-1.47 (t, 2H, J 1 = 6.4 Hz, J 2 = 6.4 Hz), 2.41-2.44 (t, 2H, J 1 = 6.0 Hz, J 2 = 6.0 Hz), 3.16 (s, 2H) 4 -Chloro-N'- (6 ,6 -dimethyl-9 -oxo-4,5,6 ,7,8 ,9 -hexahydropyrazolo [5,1-b]quinazoline-3-carbonyl)benzenesulfonohydrazide (2c): Off-white solid; yield 76%; 1 H NMR (400 MHz, DMSO-d 6 ): δ 0.99 (s, 6H), 1.44-1.48 (t, 2H, J 1 = 6.4 Hz, J 2 = 6.8 Hz), 2.41-2.45 (t, 2H, J 1 = 6.0 Hz, J 2 = 6.0 Hz), 3.28 (s, 2H)…”

“…3 These compounds act as a kinase inhibitor with unexpected anti-proliferative activity against cells, including tumour cells in xenograft tumour models; hence, pyrazolopyrimidinone or a suitable salt or pro-drug is useful for the treatment of individuals suffering from a cancer or other proliferative disorder or disease. [4][5][6] Pyrazolopyrimidinone derivatives are also used to inhibit a guanosine 3′,5′-cyclic phosphate phosphodiesterase in the treatment of sexual dysfunction and in the treatment of cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis. 7 Sulfonohydrazide derivatives are pharmaceutically active compounds that show inhibitory activity of the JNK (Jun-Kinase) function and are hence used in the treatment or prevention of disorders of the autoimmune and neuronal systems.…”