Amenamevir Chemical Properties

Density 

1.360±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMF:PBS (pH 7.2) (1:20):0.04(Max Conc. mg/mL);0.08(Max Conc. mM)
DMF:2.0(Max Conc. mg/mL);4.14(Max Conc. mM)

form 

A solid

pka

12.60±0.70(Predicted)

color 

White to off-white

InChIKey

MNHNIVNAFBSLLX-UHFFFAOYSA-N

SMILES

C1S(=O)(=O)CCC(C(N(C2=C(C)C=CC=C2C)CC(NC2=CC=C(C3N=CON=3)C=C2)=O)=O)C1

Amenamevir Usage And Synthesis

Description

Amenamevir is an antiviral inhibitor of herpes simplex virus 1 (HSV-1) helicase-primase complex activity. It inhibits recombinant HSV-1 helicase with an IC₅₀ value of 0.078 μM and recombinant HSV-1 primase when used at concentrations greater than or equal to 0.03 μM. Amenamevir inhibits replication of varicella-zoster virus (VZV), HSV-1, and HSV-2 in human embryonic fibroblast (HEF) cells (EC₅₀s = 0.047, 0.036, and 0.028 μM, respectively) and is not cytotoxic to HEF cells with a 50% cytotoxic concentration (CC₅₀) of greater than 30 μM. Amenamevir also inhibits replication of clinical VZV isolates in HEF cells (EC₅₀s = 0.038-0.10 μM). In vivo, it increases survival of cutaneously HSV-1-infected mice in a zosteriform-spread model of progressive HSV-1 infection (ED₅₀ = 1.9 mg/kg twice per day).

Uses

Amenamevir is a helicase-primase inhibitor which has potent antiviral activity against HSVs with an EC50 of 14 ng/mL.

Synthesis

he industrial synthesis of Amenamevir was first released by Kontani in their patent from 2005 (Scheme 2).17 Aniline 2 first underwent alkylation with ethyl bromoacetate 5 to intermediate 6, the amidation of 6 with synthesized acid chloride 7 in pyridine formed compound 8. 8 was then saponified and followed by condensation with aniline 10 to yield Amenamevir. The synthesis employs chlorinated solvents (DCM, CHCl3) during five steps. Based on the synthetic method of kontani, xumeng developed a superior strategy.
Different from Kontani, Xumeng first reacted acid 1 with oxalyl chloride, then followed by the nucleophilic addition with aniline 2 to provide amide intermediate 11. Then 11 sequentially subjected to N-alkylation, ester hydrolysis and amidation reaction to obtain Amenamevir.^[2]

in vivo

IC 50

HSV-1: 7.7-20 ng/mL (IC₅₀); HSV-2: 15-58 ng/mL (IC₅₀)

References

[1] KOJI CHONO. ASP2151, a novel helicase-primase inhibitor, possesses antiviral activity against varicella-zoster virus and herpes simplex virus types 1 and 2.[J]. Journal of Antimicrobial Chemotherapy, 2010, 65 8: 1733-1741. DOI: 10.1093/jac/dkq198
[2] LI X, ZARGANES-TZITZIKAS T, KURPIEWSKA K, et al. Amenamevir by Ugi-4CR†[J]. Green Chemistry, 2023, 4: 1322-1325. DOI:10.1039/D2GC04869H.

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