Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C20H17FN6 |
| Molecular Weight | 360.3876 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC(=NC=C1C2CC2)C3=NN(CC4=CC=CC=C4F)C5=NC=CC=C35
InChI
InChIKey=ATOAHNRJAXSBOR-UHFFFAOYSA-N
InChI=1S/C20H17FN6/c21-16-6-2-1-4-13(16)11-27-20-14(5-3-9-23-20)17(26-27)19-24-10-15(12-7-8-12)18(22)25-19/h1-6,9-10,12H,7-8,11H2,(H2,22,24,25)
BAY-41-2272 is a direct and NO-independent soluble guanylate cyclase (sGC) stimulator. It sensitizes sGC to nitric oxide (NO), its physiological stimulator, and contains antiplatelet activity. BAY-41-2272 is an inhibitor of GCS. BAY-41-2272 inhibits platelet aggregation (IC50 = 36 nM) and phenylephrine-induced contractions of rabbit aorta (IC50 = 0.30 uM). BAY-41-2272 also reduces vascular smooth muscle growth through cAMP- and cGMP-dependent PKA and PKG pathways. BAY-41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. BAY-41-2272 may provide a novel therapeutic compound for treating chronic hypoxic pulmonary hypertension.
Originator
Sources: http://adisinsight.springer.com/drugs/800016537 | https://www.ncbi.nlm.nih.gov/pubmed/19263460
Curator's Comment: # Bayer
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| NO-independent regulatory site of direct sGC stimulators like YC-1 and BAY 41-2272. | 2001 |
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| BAY 41-2272 activates two isoforms of nitric oxide-sensitive guanylyl cyclase. | 2002 Apr 12 |
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| Pharmacological actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vitro studies. | 2002 Jan |
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| BAY41-2272, a novel nitric oxide independent soluble guanylate cyclase activator, relaxes human and rabbit corpus cavernosum in vitro. | 2003 Feb |
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| Cardiorenal and humoral properties of a novel direct soluble guanylate cyclase stimulator BAY 41-2272 in experimental congestive heart failure. | 2003 Feb 11 |
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| The Rho-kinase inhibitor Y-27632 and the soluble guanylyl cyclase activator BAY41-2272 relax rabbit vaginal wall and clitoral corpus cavernosum. | 2003 Jan |
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| Residues stabilizing the heme moiety of the nitric oxide sensor soluble guanylate cyclase. | 2005 Apr 18 |
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| Resonance Raman and infrared spectroscopic studies of high-output forms of human soluble guanylyl cyclase. | 2005 Apr 6 |
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| Inhibitory effects on human eosinophil chemotaxis in vitro by BAY 41-2272, an activator of nitric oxide-independent site of soluble guanylate cyclase. | 2005 Mar 15 |
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| Molecular mechanisms underlying rat mesenteric artery vasorelaxation induced by the nitric oxide-independent soluble guanylyl cyclase stimulators BAY 41-2272 [5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-4-ylamine] and YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl Indazole]. | 2006 Apr |
|
| Protective effects of BAY 41-2272 (sGC stimulator) on hypertension, heart, and cardiomyocyte hypertrophy induced by chronic L-NAME treatment in rats. | 2006 Mar |
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| Soluble guanylate cyclase stimulation on cardiovascular remodeling in angiotensin II-induced hypertensive rats. | 2006 Nov |
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| A cell-based nitric oxide reporter assay useful for the identification and characterization of modulators of the nitric oxide/guanosine 3',5'-cyclic monophosphate pathway. | 2007 Apr 15 |
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| Effect of BAY 41-2272 in the pulmonary hypertension induced by heparin-protamine complex in anaesthetized dogs. | 2007 Jan-Feb |
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| Differential sensitivity of excitatory and inhibitory synaptic transmission to modulation by nitric oxide in rat nucleus tractus solitarii. | 2007 Mar |
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| Protective effect of prior physical conditioning on relaxing response of corpus cavernosum from rats made hypertensive by nitric oxide inhibition. | 2007 Mar-Apr |
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| Nitric oxide-independent stimulation of soluble guanylate cyclase with BAY 41-2272 in cardiovascular disease. | 2007 Spring |
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| Binding of YC-1 or BAY 41-2272 to soluble guanylyl cyclase induces a geminate phase in CO photolysis. | 2008 Nov 26 |
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| Novel therapies for cyclic GMP control of vascular smooth muscle growth. | 2008 Nov-Dec |
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| Antigrowth properties of BAY 41-2272 in vascular smooth muscle cells. | 2009 Feb |
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| YC-1 stimulates the expression of gaseous monoxide-generating enzymes in vascular smooth muscle cells. | 2009 Jan |
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| Distinct molecular requirements for activation or stabilization of soluble guanylyl cyclase upon haem oxidation-induced degradation. | 2009 Jul |
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| Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart. | 2009 Jul |
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| Soluble guanylate cyclase: not a dull enzyme. | 2009 Jun 2 |
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| Novel soluble guanylyl cyclase stimulator BAY 41-2272 attenuates ischemia-reperfusion-induced lung injury. | 2009 Mar |
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| NO-independent activators of soluble guanylate cyclase: therapeutic potential. | 2009 May |
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| Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension. | 2009 May |
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| Oxidative stress impairs vasorelaxation induced by the soluble guanylyl cyclase activator BAY 41-2272 in spontaneously hypertensive rats. | 2009 May |
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| Soluble guanylate cyclase agonists inhibit expression and procoagulant activity of tissue factor. | 2009 Oct |
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| Investigation of relaxant effects of new agents affecting nitric oxide/cyclic guanosine monophosphate pathway on sheep oddi sphincter. | 2010 Aug |
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| Role of soluble guanylyl cyclase-cyclic GMP signaling in tumor cell proliferation. | 2010 Jan 1 |
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| Effects of sex and estrogen on chicken ductus arteriosus reactivity. | 2010 May |
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| The anti-aggregating effect of BAY 41-2272, a stimulator of soluble guanylyl cyclase, requires the presence of nitric oxide. | 2010 Nov |
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| BAY 41-2272 inhibits the development of chronic hypoxic pulmonary hypertension in rats. | 2010 Nov 25 |
|
| Andrographolide inhibits tumor angiogenesis via blocking VEGFA/VEGFR2-MAPKs signaling cascade. | 2014 Jul 25 |
Sample Use Guides
Rats: Eight-week-old male Wistar rats with hypertension induced by angiotensin II infused subcutaneously at 250 ng/kg per minute were treated orally with a low ([L] 2 mg/kg per day) or high ([H] 10 mg/kg per day) dose of BAY-41-2272 for 14 days. BAY-41-2272-H partially suppressed the rise in blood pressure and reduced the heart weight (4.20+/-0.34 versus 3.68+/-0.20 mg/g; P<0.01), whereas BAY-41-2272-L had no effect.
Route of Administration:
Oral
In vitro, BAY-41-2272 results in concentration dependent relaxation of human and rabbit cavernosum with EC50 of 489.1 nM and 406.3 nM, respectively. BAY-41-2272 at subthreshold concentrations of 30 to 50 nM potentiated nitrergic responses. Moreover, the inhibition of nitrergic responses by L-NAME was reversed by 0.3 to 3 uM BAY-41-2272.
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DTXSID90180320
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142435
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9798973
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34A162J6WB
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256376-24-6
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ACTIVE MOIETY
