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Chemistry

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Also known as: 444805-28-1, Cmx001, Cmx 001, Hdp-cidofovir, Hexadecyloxypropyl-cidofovir, Hdp-cdv
Molecular Formula
C27H52N3O7P
Molecular Weight
561.7  g/mol
InChI Key
WXJFKKQWPMNTIM-VWLOTQADSA-N
FDA UNII
6794O900AX

Brincidofovir
Brincidofovir is an alkoxyalkyl ester prodrug containing the synthetic, acyclic nucleoside monophosphate analog cidofovir linked, through its phosphonate group, to a lipid, 3-hexadecyloxy-1-propanol, with antiviral activity against double-stranded DNA viruses. Upon oral administration, brincidofovir crosses the intestinal wall and penetrates target viral-infected cells before being cleaved to the free antiviral agent cidofovir. In turn, cidofovir is phosphorylated by pyruvate kinases to its active metabolite cidofovir diphosphate. Cidofovir diphosphate, bearing structural similarity to nucleotides, competes with deoxycytosine-5-triphosphate (dCTP) for viral DNA polymerase and gets incorporated into the growing viral DNA strands. As a result, it prevents further DNA polymerization and disrupts DNA replication of viruses. Compared to cidofovir, which is given intravenously, hexadecyloxypropyl-cidofovir shows better oral bioavailability, less toxicity and enhanced cellular penetration.
1 2D Structure

Brincidofovir

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
[(2S)-1-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxypropan-2-yl]oxymethyl-(3-hexadecoxypropoxy)phosphinic acid
2.1.2 InChI
InChI=1S/C27H52N3O7P/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-19-35-20-16-21-37-38(33,34)24-36-25(23-31)22-30-18-17-26(28)29-27(30)32/h17-18,25,31H,2-16,19-24H2,1H3,(H,33,34)(H2,28,29,32)/t25-/m0/s1
2.1.3 InChI Key
WXJFKKQWPMNTIM-VWLOTQADSA-N
2.1.4 Canonical SMILES
CCCCCCCCCCCCCCCCOCCCOP(=O)(COC(CN1C=CC(=NC1=O)N)CO)O
2.1.5 Isomeric SMILES
CCCCCCCCCCCCCCCCOCCCOP(=O)(CO[C@@H](CN1C=CC(=NC1=O)N)CO)O
2.2 Other Identifiers
2.2.1 UNII
6794O900AX
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Cidofovir Hexadecyloxypropyl Ester

2. Cmx 001

3. Cmx-001

4. Cmx001

5. Hdp-cdv

6. Hexadecyloxypropyl Cidofovir

7. Tembexa

2.3.2 Depositor-Supplied Synonyms

1. 444805-28-1

2. Cmx001

3. Cmx 001

4. Hdp-cidofovir

5. Hexadecyloxypropyl-cidofovir

6. Hdp-cdv

7. Cmx-001

8. Hexadecyloxypropyl Cidofovir

9. Tembexa

10. Brincidofovir [usan]

11. [(2s)-1-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxypropan-2-yl]oxymethyl-(3-hexadecoxypropoxy)phosphinic Acid

12. 6794o900ax

13. Brincidofovir (usan)

14. 3-(hexadecyloxy)propyl Hydrogen ((((s)-1-(4-amino-2-oxopyrimidin-1(2h)-yl)-3-hydroxypropan-2-yl)oxy)methyl)phosphonate

15. Phosphonic Acid, P-(((1s)-2-(4-amino-2-oxo-1(2h)-pyrimidinyl)-1-(hydroxymethyl)ethoxy)methyl)-, Mono(3-(hexadecyloxy)propyl) Ester

16. Cidofovir-hdp

17. Brincidofovir [usan:inn]

18. Hexadecyloxypropyl - Cidofovir

19. Cidofovir Prodrug

20. Unii-6794o900ax

21. Cidofovir Hexadecyloxypropyl Ester

22. Hdp-hpmpc

23. Brincidofovir; Cmx001

24. Hdp-cdvcmx001

25. Brincidofovir [inn]

26. Cmx001;hdp-cdv

27. Brincidofovir (cmx-001)

28. 1-o-hexadecylpropanediol-cdv

29. Schembl139922

30. Brincidofovir [who-dd]

31. Chembl203321

32. Gtpl11556

33. Dtxsid60196190

34. Brincidofovir [orange Book]

35. Bcp08580

36. Ex-a2366

37. Nsc783202

38. Zinc14141521

39. Db12151

40. Nsc-783202

41. Ncgc00686671-01

42. Ac-36043

43. A13326

44. D10547

45. Q15411004

46. C525733000

47. [(1s)-1-[(4-amino-2-oxo-pyrimidin-1-yl)methyl]-2-hydroxy-ethoxy]methyl-(3-hexadecoxypropoxy)phosphinic Acid

48. [[(s)-2-(4-amino-2-oxo-1,2-dihydropyrimidine-1-yl)-1-(hydroxymethyl)ethoxy]methyl]phosphonic Acid 3-(hexadecyloxy)propyl Ester

49. 3-((2s)-2-{[(3-hexadecyloxypropoxy)(hydroxyphosphoryl)]methoxy}-3-hydroxypropyl)-6-amino-3-hydropyrimidin-2-one

2.4 Create Date
2005-08-01
3 Chemical and Physical Properties
Molecular Weight 561.7 g/mol
Molecular Formula C27H52N3O7P
XLogP34.9
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count7
Rotatable Bond Count26
Exact Mass561.35428800 g/mol
Monoisotopic Mass561.35428800 g/mol
Topological Polar Surface Area144 Ų
Heavy Atom Count38
Formal Charge0
Complexity721
Isotope Atom Count0
Defined Atom Stereocenter Count1
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

Brincidofovir is indicated for the treatment of human smallpox disease in adult and pediatric patients.


Treatment of adenovirus in immunocompromised patients


Treatment of smallpox


5 Pharmacology and Biochemistry
5.1 Pharmacology

The pharmacologically active agent resulting from brincidofovir metabolism, cidofovir diphosphate, has an exceedingly long duration of action that allows for it to be dosed once weekly. The entirety of a brincidofovir smallpox treatment consists of only two doses, on days 1 and 8, which seemingly reduces the risk of adverse reactions. Regimens involving a longer duration of administration (i.e. more than a single dose on days 1 and 8) have been shown to increase mortality compared to placebo and should therefore be avoided. Brincidofovir is considered a potential human carcinogen and has demonstrated the potential to cause infertility - as such, its use should be restricted to situations in which it is absolutely necessary.


5.2 MeSH Pharmacological Classification

Antiviral Agents

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)


5.3 ATC Code

J - Antiinfectives for systemic use

J05 - Antivirals for systemic use

J05A - Direct acting antivirals

J05AB - Nucleosides and nucleotides excl. reverse transcriptase inhibitors

J05AB17 - Brincidofovir


5.4 Absorption, Distribution and Excretion

Absorption

The oral bioavailability of brincidofovir is 13.4% in its tablet formulation and 16.8% in its suspension formulation. Following oral administration, the Cmax and AUCtau of brincidofovir were 480 ng/mL and 3400 nghr/mL, respectively. The Cmax and AUCtau of the active metabolite, cidofovir diphosphate, were 9.7 pg/106 cells and 1200 pghr/106 cells, respectively. Maximum plasma concentrations (Tmax) of brincidofovir are reached at approximately 3 hours post-administration, while maximal plasma concentrations for cidofovir diphosphate are reached at approximately 47 hours post-administration.


Route of Elimination

Brincidofovir is eliminated as metabolites in both the urine (~51%) and feces (~40%).


Volume of Distribution

The apparent volume of distribution of brincidofovir is 1230 L.


Clearance

The apparent clearance of brincidofovir in healthy adult patients is 44.1 L/h.


5.5 Metabolism/Metabolites

Brincidofovir is a pro-drug of [cidofovir] and as such must undergo some basic metabolic reactions to become pharmacologically active. Upon entering the target cell, the phosphodiester bond of brincidofovir is hydrolyzed to generate cidofovir, which is then phosphorylated to generate the active agent: cidofovir diphosphate. The specific enzyme(s) responsible for this reaction have not been elucidated, but _in vitro_ findings suggest sphingomyelin phosphodiesterase plays a major role in the initial hydrolysis of brincidofovir. There are two major inactive metabolites of brincidofovir, CMX103 and CMX064, which are generated via carboxylation of the terminal carbon followed by several cycles of CYP-mediated oxidative reactions and fatty acid oxidation. These reactions are mediated, at least in part, by CYP4F2.


5.6 Biological Half-Life

The mean terminal half-lives of brincidofovir and its pharmacologically active metabolite, cidofovir diphosphate, are 19.3 hours and 113 hours, respectively.


5.7 Mechanism of Action

Brincidofovir is a pro-drug comprising [cidofovir] conjugated to a lipid molecule - the lipid component mimics an endogenous lipid, lysophosphatidylcholine, which allows the molecule to hijack endogenous lipid uptake pathways to enter infected cells. Following uptake, the lipid molecule is cleaved to generate cidofovir, which is then phosphorylated to generate the active antiviral compound, cidofovir disphosphate. The antiviral effects of cidofovir diphosphate appear to be the result of two distinct mechanisms. Mechanistic studies using recombinant vaccinia DNA polymerase suggest that it inhibits orthopoxvirus DNA polymerase-mediated DNA synthesis. In addition, cidofovir is an acyclic nucleotide analogue of deoxycytidine monophosphate - cidofovir diphosphate can therefore be incorporated into the growing viral DNA chain and consequently slow the rate of viral DNA synthesis.


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Looking for 444805-28-1 / Brincidofovir API manufacturers, exporters & distributors?

Brincidofovir manufacturers, exporters & distributors 1

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PharmaCompass offers a list of Brincidofovir 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 Brincidofovir manufacturer or Brincidofovir supplier for your needs.

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

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

API | Excipient name

Brincidofovir

Synonyms

444805-28-1, Cmx001, Cmx 001, Hdp-cidofovir, Hexadecyloxypropyl-cidofovir, Hdp-cdv

Cas Number

444805-28-1

Unique Ingredient Identifier (UNII)

6794O900AX

About Brincidofovir

Brincidofovir is an alkoxyalkyl ester prodrug containing the synthetic, acyclic nucleoside monophosphate analog cidofovir linked, through its phosphonate group, to a lipid, 3-hexadecyloxy-1-propanol, with antiviral activity against double-stranded DNA viruses. Upon oral administration, brincidofovir crosses the intestinal wall and penetrates target viral-infected cells before being cleaved to the free antiviral agent cidofovir. In turn, cidofovir is phosphorylated by pyruvate kinases to its active metabolite cidofovir diphosphate. Cidofovir diphosphate, bearing structural similarity to nucleotides, competes with deoxycytosine-5-triphosphate (dCTP) for viral DNA polymerase and gets incorporated into the growing viral DNA strands. As a result, it prevents further DNA polymerization and disrupts DNA replication of viruses. Compared to cidofovir, which is given intravenously, hexadecyloxypropyl-cidofovir shows better oral bioavailability, less toxicity and enhanced cellular penetration.

Brincidofovir Manufacturers

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

Brincidofovir Suppliers

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

Brincidofovir GMP

Brincidofovir 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 Brincidofovir 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 Brincidofovir GMP manufacturer or Brincidofovir GMP API supplier for your needs.

Brincidofovir CoA

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

Brincidofovir CoA mostly includes findings from lab analyses of a specific batch. For each Brincidofovir 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.

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