Identification and experimental confirmation of novel cGMP efflux inhibitors by virtual ligand screening of vardenafil-analogues was written by Kashgari, Farzane Kuresh;Ravna, Aina;Sager, Georg;Lysaa, Roy;Enyedy, Istvan;Dietrichs, Erik Sveberg. And the article was included in Biomedicine & Pharmacotherapy in 2020.Formula: C23H32N6O4S This article mentions the following:
Background: Clin. studies have reported overexpression of PDE5 and elevation of intracellular cyclic GMP in various types of cancer cells. ABCC5 transports cGMP out of the cells with high affinity. PDE5 inhibitors prevent both cellular metabolism and cGMP efflux by inhibiting ABCC5 as well as PDE5. Increasing intracellular cGMP is hypothesized to promote apoptosis and growth restriction in tumor cells and also has potential for clin. use in treatment of cardiovascular disease and erectile dysfunction. Vardenafil is a potent inhibitor of both PDE5 and ABCC5-mediated cGMP cellular efflux. Nineteen novel vardenafil analogs that have been predicted as potent inhibitors by VLS were chosen for tests of their ability to inhibit ATP- dependent transport of cGMP by measuring the accumulation of cyclic GMP in inside-out vesicles. Aim: In this study, we investigated the ability of nineteen new compounds to inhibit ABCC5- mediated cGMP transport. We also determined the Ki values of the six most potent compounds Methods: Preparation of human erythrocyte inside out vesicles and transport assay. Results: Ki values for six of nineteen compounds that showed more than 50% inhibition of cGMP transport in the screening test were determined and ranged from 1.1 to 23.1渭M. One compound was significantly more potent than the pos. control, sildenafil. Conclusion: Our findings show that computational screening correctly identified vardenafil-analogs that potently inhibit cGMP efflux-pumps from cytosol and could have substantial clin. potential in treatment of patients with diverse disorders. In the experiment, the researchers used many compounds, for example, 2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (cas: 224785-90-4Formula: C23H32N6O4S).
2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (cas: 224785-90-4) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Formula: C23H32N6O4S
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics