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Chemistry

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Also known as: 1350653-20-1, Verquvo, Methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate, Mk-1242, Vericiguat [inn], Bay-1021189
Molecular Formula
C19H16F2N8O2
Molecular Weight
426.4  g/mol
InChI Key
QZFHIXARHDBPBY-UHFFFAOYSA-N
FDA UNII
LV66ADM269

Vericiguat
Vericiguat is a direct stimulator of soluble guanylate cyclase (sGC) used in the management of systolic heart failure to reduce mortality and hospitalizations. A key component of the NO-sGC-cGMP signaling pathway that helps to regulate the cardiovascular system, sGC enzymes are intracellular enzymes found in vascular smooth muscle cells (amongst other cell types) that catalyze the synthesis of cyclic guanosine monophosphate (cGMP) in response to activation by nitric oxide (NO). Cyclic GMP acts as a second messenger, activating a number of downstream signaling cascades that elicit a broad variety of effects, and these diverse cellular effects have implicated deficiencies in its production (primarily due to insufficient NO bioavailability) in the pathogenesis of various cardiovascular diseases. As a direct stimulator of sGC, vericiguat mitigates the need for a functional NO-sGC-cGMP axis and thereby helps to prevent the myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Vericiguat was approved by the FDA in January 2021 - developed by Merck under the brand name Verquvo - for use in certain patients with systolic heart failure. Although not the first sGC stimulator to be granted FDA approval ([riociguat] was approved in 2013 for use in pulmonary hypertension), vericiguat is unique amongst its peers in that modifications to its structure have dramatically decreased its susceptibility to oxidative metabolism, resulting in a relatively long half-life and allowing for once-daily dosing.
Vericiguat is a Soluble Guanylate Cyclase Stimulator. The mechanism of action of vericiguat is as a Guanylate Cyclase Stimulator.
1 2D Structure

Vericiguat

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
methyl N-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate
2.1.2 InChI
InChI=1S/C19H16F2N8O2/c1-31-19(30)25-14-15(22)26-17(27-16(14)23)13-11-6-10(20)7-24-18(11)29(28-13)8-9-4-2-3-5-12(9)21/h2-7H,8H2,1H3,(H,25,30)(H4,22,23,26,27)
2.1.3 InChI Key
QZFHIXARHDBPBY-UHFFFAOYSA-N
2.1.4 Canonical SMILES
COC(=O)NC1=C(N=C(N=C1N)C2=NN(C3=C2C=C(C=N3)F)CC4=CC=CC=C4F)N
2.2 Other Identifiers
2.2.1 UNII
LV66ADM269
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Bay 1021189

2. Verquvo

2.3.2 Depositor-Supplied Synonyms

1. 1350653-20-1

2. Verquvo

3. Methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate

4. Mk-1242

5. Vericiguat [inn]

6. Bay-1021189

7. Bay 1021189

8. Vericiguat [usan]

9. Bay1021189

10. Lv66adm269

11. Methyl N-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate

12. Methyl (4,6-diamino-2-(5-fluoro-1-((2-fluorophenyl)methyl)-1h-pyrazolo(3,4-b)pyridin-3-yl(pyrimidin-5-yl)carbamate

13. Methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)pyrimidin-5-yl)carbamate

14. Methyl N-(4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo(3,4-b)pyridin-3-yl)pyrimidin-5-yl)carbamate

15. Unii-lv66adm269

16. Methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate

17. Vericiguatum

18. Vericiguat [jan]

19. Vericiguat [usan:inn]

20. Vericiguat [who-dd]

21. Bay1021189; Verquvo

22. Schembl429958

23. Vericiguat (jan/usan/inn)

24. Chembl4066936

25. Vericiguat [orange Book]

26. Gtpl10010

27. Chebi:142432

28. Dtxsid001318361

29. Bcp18886

30. Ex-a4694

31. Who 9805

32. Mfcd28502029

33. S9693

34. Zinc72318626

35. Cs-6981

36. Db15456

37. Sb16806

38. Ac-36737

39. Hy-16774

40. Bay1021189bay1021189

41. J3.590.750e

42. D11051

43. P14957

44. A887763

45. Q27283201

46. Bay1021189; Bay 1021189; Bay-1021189; Bay10-21189; Bay-10-21189; Bay 10-21189

47. Methyl 4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-ylcarbamate

48. Methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate

2.4 Create Date
2011-12-26
3 Chemical and Physical Properties
Molecular Weight 426.4 g/mol
Molecular Formula C19H16F2N8O2
XLogP31.5
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count10
Rotatable Bond Count5
Exact Mass426.13642811 g/mol
Monoisotopic Mass426.13642811 g/mol
Topological Polar Surface Area147 Ų
Heavy Atom Count31
Formal Charge0
Complexity622
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Vericiguat is indicated in adults with symptomatic, chronic heart failure and an ejection fraction of <45% to reduce the risk of cardiovascular death and heart failure-related hospitalization following a hospitalization for heart failure or need for outpatient intravenous diuretics.


Treatment of symptomatic chronic heart failure


5 Pharmacology and Biochemistry
5.1 Pharmacology

By directly stimulating the increased production of intracellular cyclic guanosine monophosphate (cGMP), vericiguat causes the relaxation of vascular smooth muscle and vasodilation. Vericiguat has a relatively long half-life (~30h) that allows for once-daily dosing. Animal reproduction studies have demonstrated the potential for embryo-fetal toxicity when vericiguat is administered to pregnant females - defects in major vessel and heart formation, as well as spontaneous abortions/resorptions, were observed when vericiguat was administered to pregnant rabbits during organogenesis. The possibility of pregnancy should be excluded prior to beginning therapy with vericiguat, and adequate contraception should be used throughout therapy and for one month following cessation of treatment.


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
VERICIGUAT
5.2.2 FDA UNII
LV66ADM269
5.2.3 Pharmacological Classes
Soluble Guanylate Cyclase Stimulator [EPC]; Guanylate Cyclase Stimulators [MoA]
5.3 ATC Code

C01


C - Cardiovascular system

C01 - Cardiac therapy

C01D - Vasodilators used in cardiac diseases

C01DX - Other vasodilators used in cardiac diseases

C01DX22 - Vericiguat


5.4 Absorption, Distribution and Excretion

Absorption

Following the administration of 10mg of vericiguat by mouth once daily, the average steady-state Cmax and AUC in patients with heart failure is 350 mcg/L and 6,680 mcgh/L, respectively, with a Tmax of 1 hour. The absolute bioavailability of orally-administered vericiguat is approximately 93% when taken with food - co-administration with meals has been shown to reduce pharmacokinetic variability, increase Tmax to roughly 4 hours, and increase Cmax and AUC by 41% and 44%, respectively.


Route of Elimination

Following the oral administration of radiolabeled vericiguat, approximately 53% of the administered radioactivity was recovered in the urine and 45% in the feces. A human mass balance study found that the portion recovered in the urine comprised approximately 40.8% N-glucuronide metabolite, 7.7% other metabolites, and 9% unchanged parent drug, while virtually the entire portion recovered in the feces comprised unchanged vericiguat.


Volume of Distribution

In healthy subjects the steady-state volume of distribution of vericiguat is approximately 44 liters.


Clearance

Vericiguat is a low-clearance drug, with an observed plasma clearance of 1.6 L/h in healthy volunteers and 1.3 L/h in patients with systolic heart failure.


5.5 Metabolism/Metabolites

Vericiguat is primarily metabolized via phase II conjugation reactions, with CYP-mediated oxidative metabolism comprising a small (<5%) portion of its overall biotransformation. The major inactive metabolite, vericiguat N-glucuronide (M1), is formed by UGT1A9 and, to a lesser extent, UGT1A1. Other identified metabolites include a denbenzylated compound and an M15 metabolite thought to be the result of oxidative metabolism, although these metabolites are poorly characterized.


5.6 Biological Half-Life

In patients with heart failure, the half-life of vericiguat is 30 hours.


5.7 Mechanism of Action

Heart failure (HF) involves, amongst other morphologic and physiologic changes, the impaired synthesis of nitric oxide (NO) and decreased activity of soluble guanylate cyclase (sGC). Functioning normally, NO binds to sGC and stimulates the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger involved in the maintenance of vascular tone, as well as cardiac contractility and remodeling. Defects in this pathway are thought to contribute to the myocardial and vascular dysfunction associated with heart failure and are therefore a desirable target in its treatment. Vericiguat directly stimulates sGC by binding to a target site on its beta-subunit, bypassing the need for NO-mediated activation, and in doing so causes an increase in the production of intracellular cGMP that results in vascular smooth muscle relaxation and vasodilation.


API Reference Price

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16-Feb-2023
26-Dec-2024
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Looking for 1350653-20-1 / Vericiguat API manufacturers, exporters & distributors?

Vericiguat manufacturers, exporters & distributors 1

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PharmaCompass offers a list of Vericiguat API manufacturers, exporters & distributors, which can be sorted by GMP, USDMF, JDMF, KDMF, CEP (COS), WC, Price,and more, enabling you to easily find the right Vericiguat manufacturer or Vericiguat supplier for your needs.

Send us enquiries for free, and we will assist you in establishing a direct connection with your preferred Vericiguat manufacturer or Vericiguat supplier.

PharmaCompass also assists you with knowing the Vericiguat API Price utilized in the formulation of products. Vericiguat API Price is not always fixed or binding as the Vericiguat Price is obtained through a variety of data sources. The Vericiguat Price can also vary due to multiple factors, including market conditions, regulatory modifications, or negotiated pricing deals.

API | Excipient name

Vericiguat

Synonyms

1350653-20-1, Verquvo, Methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)carbamate, Mk-1242, Vericiguat [inn], Bay-1021189

Cas Number

1350653-20-1

Unique Ingredient Identifier (UNII)

LV66ADM269

About Vericiguat

Vericiguat is a direct stimulator of soluble guanylate cyclase (sGC) used in the management of systolic heart failure to reduce mortality and hospitalizations. A key component of the NO-sGC-cGMP signaling pathway that helps to regulate the cardiovascular system, sGC enzymes are intracellular enzymes found in vascular smooth muscle cells (amongst other cell types) that catalyze the synthesis of cyclic guanosine monophosphate (cGMP) in response to activation by nitric oxide (NO). Cyclic GMP acts as a second messenger, activating a number of downstream signaling cascades that elicit a broad variety of effects, and these diverse cellular effects have implicated deficiencies in its production (primarily due to insufficient NO bioavailability) in the pathogenesis of various cardiovascular diseases. As a direct stimulator of sGC, vericiguat mitigates the need for a functional NO-sGC-cGMP axis and thereby helps to prevent the myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Vericiguat was approved by the FDA in January 2021 - developed by Merck under the brand name Verquvo - for use in certain patients with systolic heart failure. Although not the first sGC stimulator to be granted FDA approval ([riociguat] was approved in 2013 for use in pulmonary hypertension), vericiguat is unique amongst its peers in that modifications to its structure have dramatically decreased its susceptibility to oxidative metabolism, resulting in a relatively long half-life and allowing for once-daily dosing.

Vericiguat Manufacturers

A Vericiguat manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Vericiguat, including repackagers and relabelers. The FDA regulates Vericiguat manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Vericiguat API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Vericiguat manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Vericiguat Suppliers

A Vericiguat supplier is an individual or a company that provides Vericiguat active pharmaceutical ingredient (API) or Vericiguat finished formulations upon request. The Vericiguat suppliers may include Vericiguat API manufacturers, exporters, distributors and traders.

click here to find a list of Vericiguat suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Vericiguat USDMF

A Vericiguat DMF (Drug Master File) is a document detailing the whole manufacturing process of Vericiguat active pharmaceutical ingredient (API) in detail. Different forms of Vericiguat DMFs exist exist since differing nations have different regulations, such as Vericiguat USDMF, ASMF (EDMF), JDMF, CDMF, etc.

A Vericiguat DMF submitted to regulatory agencies in the US is known as a USDMF. Vericiguat USDMF includes data on Vericiguat's chemical properties, information on the facilities and procedures used, and details about packaging and storage. The Vericiguat USDMF is kept confidential to protect the manufacturer’s intellectual property.

click here to find a list of Vericiguat suppliers with USDMF on PharmaCompass.

Vericiguat NDC

National Drug Code is a comprehensive database maintained by the FDA that contains information on all drugs marketed in the US. This directory includes information about finished drug products, unfinished drug products, and compounded drug products, including those containing Vericiguat as an active pharmaceutical ingredient (API).

Finished drug products

The FDA updates the NDC directory daily. The NDC numbers for Vericiguat API and other APIs are published in this directory by the FDA.

Unfinished drugs

The NDC unfinished drugs database includes product listing information submitted for all unfinished drugs, such as active pharmaceutical ingredients (APIs), drugs intended for further processing and bulk drug substances for compounding.

Pharmaceutical companies that manufacture Vericiguat as an active pharmaceutical ingredient (API) must furnish the FDA with an updated record of all drugs that they produce, prepare, propagate, compound, or process for commercial distribution in the US at their facilities.

Compounded drug products

The NDC directory also contains data on finished compounded human drug products that contain Vericiguat and are produced by outsourcing facilities. While these outsourcing facilities are not mandated to assign a Vericiguat NDC to their finished compounded human drug products, they may choose to do so.

click here to find a list of Vericiguat suppliers with NDC on PharmaCompass.

Vericiguat GMP

Vericiguat Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Vericiguat GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Vericiguat GMP manufacturer or Vericiguat GMP API supplier for your needs.

Vericiguat CoA

A Vericiguat CoA (Certificate of Analysis) is a formal document that attests to Vericiguat's compliance with Vericiguat specifications and serves as a tool for batch-level quality control.

Vericiguat CoA mostly includes findings from lab analyses of a specific batch. For each Vericiguat CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Vericiguat may be tested according to a variety of international standards, such as European Pharmacopoeia (Vericiguat EP), Vericiguat JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Vericiguat USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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