MARIBAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H19Cl2N3O4
Molecular Weight	376.235
Optical Activity	( - )
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)NC1=NC2=CC(Cl)=C(Cl)C=C2N1[C@H]3O[C@@H](CO)[C@H](O)[C@@H]3O

InChI

InChIKey=KJFBVJALEQWJBS-XUXIUFHCSA-N

InChI=1S/C15H19Cl2N3O4/c1-6(2)18-15-19-9-3-7(16)8(17)4-10(9)20(15)14-13(23)12(22)11(5-21)24-14/h3-4,6,11-14,21-23H,5H2,1-2H3,(H,18,19)/t11-,12-,13-,14-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C15H19Cl2N3O4
Molecular Weight	376.235
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20881959 | http://www.fiercebiotech.com/biotech/viropharma-terminates-maribavir-trial-after-failure | https://www.ncbi.nlm.nih.gov/pubmed/19759127

Maribavir (previously known as 1263W94) is a novel benzimidazole riboside compound. This drug was in phase III of clinical trial for the prevention of cytomegalovirus (CMV) infections in transplant patients, sponsored by ViroPharma. However, drug failed to demonstrate a higher efficacy rate than the placebo. Maribavir has activity against cytomegalovirus and Epstein-Barr virus (EBV), but not against other human herpesviruses. Maribavir’s mechanism of action is unique and is complex compared to the currently approved antivirals for CMV. Maribavir inhibits the viral UL97 kinase rather than the viral DNA polymerase. The UL97 kinase is important for viral DNA elongation, DNA packaging, and nuclear egress of encapsidated viral DNA. In addition, maribavir inhibits the EBV DNA polymerase processivity factor (BMRF1), reduces the level of certain EBV glycoproteins, and inhibits viral transcription. However, future work will be designed to address the interaction of MBV and BGLF4 and to evaluate the mechanisms through which maribavir downregulates viral transcripts. BGLF4 belongs to the family of conserved herpesvirus PKs, which includes HCMV UL97, HSV UL13, and HSV US3. Maribavir does need to be phosphorylated for its activity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine protein kinase UL97 1 Target ID: P16788\|\|\|Q91B49 Gene ID: NA Gene Symbol: UL97 Target Organism: Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12121906/	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cytomegalovirus infection 6 Sources: https://clinicaltrials.gov/ct2/show/NCT00411645	Preventing		Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Human cytomegalovirus: challenges, opportunities and new drug development.	1999 Sep	10574177
Synthesis and evaluation of a series of 2'-deoxy analogues of the antiviral agent 5,6-dichloro-2-isopropylamino-1-(beta-L-ribofuranosyl)-1H-benzimidazole (1263W94).	2000 Jan-Feb	10772705
Synthesis and antiviral evaluation of halogenated beta-D- and -L-erythrofuranosylbenzimidazoles.	2000 Jun 15	10882374
Activities of benzimidazole D- and L-ribonucleosides in animal models of cytomegalovirus infections.	2004 May	15105130
Mechanism of action of the ribopyranoside benzimidazole GW275175X against human cytomegalovirus.	2004 May	15105116
Inhibition of human cytomegalovirus replication by benzimidazole nucleosides involves three distinct mechanisms.	2004 Oct	15388453
In vitro activity and mechanism of action of methylenecyclopropane analogs of nucleosides against herpesvirus replication.	2005 Mar	15728900

Patents

Sample Use Guides

In Vivo Use Guide

100 mg twice daily for up to 12 weeks

Route of Administration: Oral

In Vitro Use Guide

Maribavir (MBV) may be linked to indirect effects on the transcription of Epstein-Barr virus (EBV) genes through the interaction of BGLF4 with multiple viral proteins. It was examined the effects of MBV and acyclovir (ACV) on the expression of the early (EA-D) and the late (gp125 and gp350) viral proteins by immunofluorescence staining. EA-D was detected in the nucleus, while both gp125 and gp350 were detected in the cytoplasm. MBV (20 μM) reduced the number of cells expressing EA-D by about 50% and almost eliminated the expression of gp125 and gp350 . It was revealed the potent inhibitory effect of MBV on the phosphorylation of EA-D during lytic infection and the lack of such an effect produced by ACV. Both drugs inhibited the expression of the two late viral glycoproteins, but MBV had a considerably greater effect, probably due to its greater antiviral potency.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:53:34 GMT 2023` Edited by `admin` on `Sat Dec 16 17:53:34 GMT 2023`
Record UNII	PTB4X93HE1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MARIBAVIR

Official Name

English

maribavir [INN]

Common Name

English

1H-BENZIMIDAZOL-2-AMINE, 5,6-DICHLORO-N-(1-METHYLETHYL)-1-.BETA.-L-RIBOFURANOSYL-

Systematic Name

English

1263-W-94

Code

English

MARIBAVIR [USAN]

Common Name

English

5,6-DICHLORO-N-(1-METHYLETHYL)-1-.BETA.-L-RIBOFURANOSYL-1H-BENZIMIDAZOL-2-AMINE

Common Name

English

Maribavir [WHO-DD]

Common Name

English

LIVTENCITY

Brand Name

English

BW-1263W94

Code

English

5,6-DICHLORO-2-(ISOPROPYLAMINO)-1-.BETA.-L-RIBOFURANOSYLBENZIMIDAZOLE

Common Name

English

1263W94

Code

English

GW-257406X

Code

English

Classification Tree Code System Code

WHO-VATC

QJ05AX10