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Details

Stereochemistry ABSOLUTE
Molecular Formula C29H28F4N4O4
Molecular Weight 572.5506
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LETERMOVIR

SMILES

COC1=CC=CC(=C1)N2CCN(CC2)C3=NC4=C(F)C=CC=C4[C@H](CC(O)=O)N3C5=CC(=CC=C5OC)C(F)(F)F

InChI

InChIKey=FWYSMLBETOMXAG-QHCPKHFHSA-N
InChI=1S/C29H28F4N4O4/c1-40-20-6-3-5-19(16-20)35-11-13-36(14-12-35)28-34-27-21(7-4-8-22(27)30)23(17-26(38)39)37(28)24-15-18(29(31,32)33)9-10-25(24)41-2/h3-10,15-16,23H,11-14,17H2,1-2H3,(H,38,39)/t23-/m0/s1

HIDE SMILES / InChI

Molecular Formula C29H28F4N4O4
Molecular Weight 572.5506
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Letermovir (AIC246 or MK-8228), a 3,4-dihydro-quinazoline- 4-yl-acetic acid derivative, is the prototype viral terminase complex inhibitor that is most advanced in its clinical development. The novel compound was initially developed by AiCuris. In April 2011, the drug was granted orphan drug designation for prevention of CMV disease by the European Commission. In August 2011, the US Food and Drug Administration granted it a fast track designation. In 2012, the results of Phase IIb clinical trials using letermovir in bone marrow transplant patients were presented at various international meetings, and the data were subsequently published in 2014.42 It`s continued clinical development is currently undertaken in agreement with Merck. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. It targets the UL56 subunit of the viral terminase complex. Letermovir is currently in Phase III development.

Originator

Approval Year

TargetsConditions
PubMed

PubMed

TitleDatePubMed
In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246.
2010 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Letermovir oral or intravenous (IV) formulation will be administered once daily for up to 14 weeks after transplant. The dose will be 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion will be administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
Route of Administration: oral or intravenous
In Vitro Use Guide
Letermovir revealed potent antiviral activity against 17 HCMV clinical isolates, with 50% effective concentrations (EC50s) in the low nanomolar range (0.8-3.1nM).
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:51:14 UTC 2019
Edited
by admin
on Mon Oct 21 20:51:14 UTC 2019
Record UNII
1H09Y5WO1F
Record Status Validated (UNII)
Record Version
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Name Type Language
LETERMOVIR
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
AIC246
Code English
LETERMOVIR [WHO-DD]
Common Name English
(4S)-2-(8-FLUORO-2-(4-(3-METHOXYPHENYL)PIPERAZIN-1-YL)-3-(2-METHOXY-5-(TRIFLUOROMETHYL)PHENYL)-3,4-DIHYDROQUINAZOLIN-4-YL)ACETIC ACID
Systematic Name English
4-QUINAZOLINEACETIC ACID, 8-FLUORO-3,4-DIHYDRO-2-(4-(3-METHOXYPHENYL)-1-PIPERAZINYL)-3-(2-METHOXY-5-(TRIFLUOROMETHYL)PHENYL)-, (4S)-
Common Name English
MK-8228
Code English
2-((4S)-8-FLUORO-2-(4-(3-METHOXYPHENYL)PIPERAZIN-1-YL)-3-(2-METHOXY-5-(TRIFLUOROMETHYL)PHENYL)-4H-QUINAZOLIN-4-YL)ACETIC ACID
Systematic Name English
AIC-246
Code English
LETERMOVIR [JAN]
Common Name English
LETERMOVIR [INN]
Common Name English
AIC 246
Code English
LETERMOVIR [USAN]
Common Name English
PREVYMIS
Brand Name English
Classification Tree Code System Code
WHO-ATC J05AX18
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
NCI_THESAURUS C281
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
EU-Orphan Drug EU/3/12/999
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
NDF-RT N0000193800
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
FDA ORPHAN DRUG 340211
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
Code System Code Type Description
EPA CompTox
917389-32-3
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
WIKIPEDIA
LETERMOVIR
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
CAS
917389-32-3
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
ChEMBL
CHEMBL1241951
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
EVMPD
SUB90389
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
PUBCHEM
45138674
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
NCI_THESAURUS
C115099
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
INN
9384
Created by admin on Mon Oct 21 20:51:14 UTC 2019 , Edited by admin on Mon Oct 21 20:51:14 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MINOR
TRANSPORTER -> SUBSTRATE
MINOR
TRANSPORTER -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INDUCER
TRANSPORTER -> INHIBITOR
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

DOSE

blood-to-plasma ratio PHARMACOKINETIC