BAY-41-2272

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

Structure Search

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)

HIDE SMILES / InChI

Molecular Formula	C20H17FN6
Molecular Weight	360.3876
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21825001 | https://www.ncbi.nlm.nih.gov/pubmed/11242081 | https://www.ncbi.nlm.nih.gov/pubmed/20828552 | https://www.ncbi.nlm.nih.gov/pubmed/15066950

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Soluble guanylate cyclase 34 Target ID: CHEMBL2111348 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11242081 \| https://www.ncbi.nlm.nih.gov/pubmed/12544359	Activator 1430		0.3 µM [EC50]
Phosphodiesterase 5A 30 Target ID: CHEMBL1827 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15066950	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Heart failure 103 Sources: http://adisinsight.springer.com/drugs/800016537 https://www.ncbi.nlm.nih.gov/pubmed/17445086	Primary		Preclinical	Unknown Approved Use Unknown
Hypertension 567 Sources: http://adisinsight.springer.com/drugs/800016537 https://www.ncbi.nlm.nih.gov/pubmed/16982964 https://www.ncbi.nlm.nih.gov/pubmed/27895434	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Functional characterization of nitric oxide and YC-1 activation of soluble guanylyl cyclase: structural implication for the YC-1 binding site?	2004 Mar 23	15023055
Soluble guanylate cyclase activator reverses acute pulmonary hypertension and augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs.	2004 Oct 12	15466650
Effects of the sGC stimulator BAY 41-2272 are not mediated by phosphodiesterase 5 inhibition.	2004 Sep 21	15381669
Effects of BAY 41-2272, a soluble guanylate cyclase activator, on pulmonary vascular reactivity in the ovine fetus.	2005 Apr	15608146
Residues stabilizing the heme moiety of the nitric oxide sensor soluble guanylate cyclase.	2005 Apr 18	15878710
Resonance Raman and infrared spectroscopic studies of high-output forms of human soluble guanylyl cyclase.	2005 Apr 6	15796527
BAY 41-2272, a potent activator of soluble guanylyl cyclase, stimulates calcium elevation and calcium-activated potassium current in pituitary GH cells.	2005 Dec	16445574
Characterization of the first potent and selective PDE9 inhibitor using a cGMP reporter cell line.	2005 Dec	16150925
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	15748699
Mechanisms underlying relaxation of rabbit aorta by BAY 41-2272, a nitric oxide-independent soluble guanylate cyclase activator.	2005 Sep	16173929
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	16352702
Hydrogen peroxide restrains endothelium-derived nitric oxide bioactivity -- role for iron-dependent oxidative stress.	2006 Aug 15	16864001
Enhancing cGMP in experimental progressive renal fibrosis: soluble guanylate cyclase stimulation vs. phosphodiesterase inhibition.	2006 Jan	16048904
Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: interaction with nitric oxide.	2006 Jan 13	16371226
Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling.	2006 Jan 17	16391154
Protective effects of BAY 41-2272 (sGC stimulator) on hypertension, heart, and cardiomyocyte hypertrophy induced by chronic L-NAME treatment in rats.	2006 Mar	16633081
Vasorelaxing effect of BAY 41-2272 in rat basilar artery: involvement of cGMP-dependent and independent mechanisms.	2006 Mar	16391173
Soluble guanylate cyclase stimulation on cardiovascular remodeling in angiotensin II-induced hypertensive rats.	2006 Nov	16982964
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	17336915
Elevated pressure selectively blunts flow-evoked vasodilatation in rat mesenteric small arteries.	2007 Jan	17128286
Effect of BAY 41-2272 in the pulmonary hypertension induced by heparin-protamine complex in anaesthetized dogs.	2007 Jan-Feb	17201729
Effects of BAY 41-2272, an activator of nitric oxide-independent site of soluble guanylate cyclase, on human NADPH oxidase system from THP-1 cells.	2007 Jul 12	17499238
Differential sensitivity of excitatory and inhibitory synaptic transmission to modulation by nitric oxide in rat nucleus tractus solitarii.	2007 Mar	17138620
Protective effect of prior physical conditioning on relaxing response of corpus cavernosum from rats made hypertensive by nitric oxide inhibition.	2007 Mar-Apr	16915305
Gastric motility in soluble guanylate cyclase alpha 1 knock-out mice.	2007 Nov 1	17717014
Effects of 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272) on smooth muscle tone, soluble guanylyl cyclase activity, and NADPH oxidase activity/expression in corpus cavernosum from wild-type, neuronal, and endothelial nitric-oxide synthase null mice.	2007 Sep	17596536
Nitric oxide-independent stimulation of soluble guanylate cyclase with BAY 41-2272 in cardiovascular disease.	2007 Spring	17445086
Gender-specific hypertension and responsiveness to nitric oxide in sGCalpha1 knockout mice.	2008 Jul 1	18339647
Binding of YC-1 or BAY 41-2272 to soluble guanylyl cyclase induces a geminate phase in CO photolysis.	2008 Nov 26	18980304
Novel therapies for cyclic GMP control of vascular smooth muscle growth.	2008 Nov-Dec	19127140
Antigrowth properties of BAY 41-2272 in vascular smooth muscle cells.	2009 Feb	19188837
Activation of BKCa channels by nitric oxide prevents coronary artery endothelial dysfunction in ouabain-induced hypertensive rats.	2009 Jan	19145772
YC-1 stimulates the expression of gaseous monoxide-generating enzymes in vascular smooth muscle cells.	2009 Jan	18923065
Distinct molecular requirements for activation or stabilization of soluble guanylyl cyclase upon haem oxidation-induced degradation.	2009 Jul	19466990
Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart.	2009 Jul	19424280
Soluble guanylate cyclase: not a dull enzyme.	2009 Jun 2	19451346
Novel soluble guanylyl cyclase stimulator BAY 41-2272 attenuates ischemia-reperfusion-induced lung injury.	2009 Mar	19074557
NO-independent activators of soluble guanylate cyclase: therapeutic potential.	2009 May	19387430
Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension.	2009 May	19263460
Oxidative stress impairs vasorelaxation induced by the soluble guanylyl cyclase activator BAY 41-2272 in spontaneously hypertensive rats.	2009 May	19247264
Soluble guanylate cyclase agonists inhibit expression and procoagulant activity of tissue factor.	2009 Oct	19592462
Investigation of relaxant effects of new agents affecting nitric oxide/cyclic guanosine monophosphate pathway on sheep oddi sphincter.	2010 Aug	20697210
Role of soluble guanylyl cyclase-cyclic GMP signaling in tumor cell proliferation.	2010 Jan 1	19948239
Effects of sex and estrogen on chicken ductus arteriosus reactivity.	2010 May	20164203
Nitric oxide stimulates interleukin-6 production in skeletal myotubes.	2010 May	20035621
The anti-aggregating effect of BAY 41-2272, a stimulator of soluble guanylyl cyclase, requires the presence of nitric oxide.	2010 Nov	20977455
BAY 41-2272 inhibits the development of chronic hypoxic pulmonary hypertension in rats.	2010 Nov 25	20828552
Heme oxygenase-1 deficiency leads to alteration of soluble guanylate cyclase redox regulation.	2010 Oct	20605906
Mechanisms of relaxant activity of the nitric oxide-independent soluble guanylyl cyclase stimulator BAY 41-2272 in rat tracheal smooth muscle.	2010 Oct 25	20670622
Andrographolide inhibits tumor angiogenesis via blocking VEGFA/VEGFR2-MAPKs signaling cascade.	2014 Jul 25	24814888

Patents

Sample Use Guides

In Vivo Use Guide

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 Use Guide

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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:17:45 GMT 2023` Edited by `admin` on `Sat Dec 16 09:17:45 GMT 2023`
Record UNII	34A162J6WB
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BAY-41-2272

Common Name

English

4-PYRIMIDINAMINE, 5-CYCLOPROPYL-2-(1-((2-FLUOROPHENYL)METHYL)-1H-PYRAZOLO(3,4-B)PYRIDIN-3-YL)-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID90180320