457914-32-8

Upstream product

• 51859-98-4 (2-fluorobenzyl)hydrazine 
• 141-46-8 Glycolaldehyde 
• 428854-24-4 2-(1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidine-4,5,6- triamine 
• 370879-49-5 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-phenyldiazen-1-yl]pyrimidine-4,6-diamine 
• 256376-59-7 ethyl 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate 
• 256376-68-8 please input 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-formamidine 
• 304874-06-4 methyl 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbimidate 
• 256376-62-2 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide 
• 256504-39-9 ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate 
• 256376-65-5 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile 
• 370879-47-3 N'-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidine-4,5,6-triamine 

Relevant academic research and scientific papers

Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-Activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.

Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase.

The pyrazolopyridine stimulators of soluble guanylate cyclase BAY 41-2272 and 41-8543 were oxidised in rats and dogs at their 5-pyrimidinyl-cyclopropyl and -morpholino residue. These metabolites activate the soluble guanylate cyclase, induce vasoelaxation and thereby may contribute to the in vivo activity of BAY 41-2272 and BAY 41-8543.