| Identification | Back Directory | [Name]
ASP 2151 | [CAS]
841301-32-4 | [Synonyms]
CS-2753
ASP 2151
AMenaMevir
Amcnamevir
Amenamevir (ASP2151)
ASP 2151 (Amenamevir)
ASP2151;ASP 2151;ASP-2151
N-(2,6-Dimethylphenyl)-N-(2-{[4-(1,2,4-oxadiazol-3-yl)phenyl] amino}-2-oxoethyl)-1,1-dioxothiane-4-carboxamide
N-(2-((4-(1,2,4-Oxadiazol-3-yl)phenyl)amino)-2-oxoethyl)-N-(2,6-dimethylphenyl)tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide
N-(2,6-Dimethylphenyl)tetrahydro-N-[2-[[4-(1,2,4-oxadiazol-3-yl)phenyl]amino]-2-oxoethyl]-2H-thiopyran-4-carboxamide 1,1-dioxide
2H-Thiopyran-4-carboxamide, N-(2,6-dimethylphenyl)tetrahydro-N-[2-[[4-(1,2,4-oxadiazol-3-yl)phenyl]amino]-2-oxoethyl]-, 1,1-dioxide | [Molecular Formula]
C24H26N4O5S | [MDL Number]
MFCD19443709 | [MOL File]
841301-32-4.mol | [Molecular Weight]
482.55 |
| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [Description]
Amenamevir is an antiviral inhibitor of herpes simplex virus 1 (HSV-1) helicase-primase complex activity.1 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]
Amenamevir (ASP2151) administration accelerates the reduction in virus titer in a dose-dependent manner in the range of 3 to 30 mg/kg/day. Amenamevir treatment decreases both lesion scores and HSV-1 titers in a dose-dependent manner, irrespective of the dosing interval. Based on the correlation curves, the PK parameters at which HSV-1 growth is completely suppressed by oral administration of Amenamevir are estimated to be 10,000 ng/mL or higher for the maximum concentration of drug in serum (Cmax), 60 μg ? h/ml or higher for concentration-time curve over 24 h (AUC24h), and 21 to 24 h for T>100 . The mean concentration of Amenamevir in plasma at 5 days postinfection increases in a dose-dependent manner, with doses of 3 mg Amenamevir/g or higher significantly reducing the intradermal HSV-1 titer[1]. | [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 |
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