Amenamevir Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Amenamevir is an antiviral inhibitor of herpes simplex virus 1 (HSV-1) helicase-primase complex activity. It inhibits recombinant HSV-1 helicase with an IC
50 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 (EC
50s = 0.047, 0.036, and 0.028 μM, respectively) and is not cytotoxic to HEF cells with a 50% cytotoxic concentration (CC
50) of greater than 30 μM. Amenamevir also inhibits replication of clinical VZV isolates in HEF cells (EC
50s = 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 (ED
50 = 1.9 mg/kg twice per day).
Synthese
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]
Amenamevir Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
