176161-24-3 Usage
Description
BENZIMIDAVIR, also known as Maribavir, is an orally bioavailable benzimidazole L-riboside antiviral with a spectrum of activity primarily targeting human cytomegalovirus (CMV) and Epstein–Barr virus (EBV). It functions as an inhibitor of the CMV UL97 kinase and has demonstrated anti-CMV activity with an acceptable adverse effect profile in clinical trials.
Uses
Used in Antiviral Applications:
BENZIMIDAVIR is used as an antiviral agent for the treatment of cytomegalovirus infections. It specifically targets the CMV UL97 kinase, inhibiting the virus's ability to replicate and spread within the host.
Used in Transplant Recipients:
BENZIMIDAVIR was in phase III clinical trials for the prevention of CMV infection in transplant recipients at risk. The drug was being developed under the "fast track" status granted by the US Food and Drug Administration, aiming to provide a solution for patients undergoing transplantation procedures who are at a higher risk of developing CMV infections.
Mechanism of action
Maribavir inhibits the CMV UL97 kinase, an
enzyme which is required for the normal replication of the virus . In the absence of functioning UL97 kinase,
viral replication is severely impaired in vitro, with an abnormal cell
culture cytopathic effect characterized by the nuclear aggregation of
excess amorphous viral proteins, mainly the tegument protein pp65. Impaired UL97 function appears to cause a
defect in viral encapsidation and/or egress of viral
particles from the nucleus. In addition, viral DNA
synthesis may also be reduced.
CMV replication is not completely shut off in the absence of the UL97
kinase; the widely varying maribavir IC50s under different assay
conditions suggest that host cells can variably substitute for the normal
function of UL97, a factor that may affect the therapeutic potency of
maribavir in vivo.
Drug interactions
Since CYP3A4 appears to be the major maribavir-metabolizing
enzyme, there are potential drug interactions with CYP3A4 inhibitors,
such as azole antifungals, macrolide antibiotics, and HIV protease
inhibitors, or CYP3A4 inducers, such as rifampicin or efavirenz. There
are insufficient data to assess the clinical significance of this
interaction. Phase I clinical trials examined the pharmacokinetics of
maribavir in HIV-infected subjects, many of whom were concomitantly
using antifungals and protease inhibitors. Overall, the pharmacokinetic data were not significantly
different from those of healthy individuals not on these drugs. In
healthy adults, oral administration of ketoconazole, a potent CYP3A4
inhibitor, resulted in a 35% decrease in the clearance of maribavir, which is not expected to have adverse
consequences because of the low observed toxicity of maribavir.
Further studies are required to assess potential impairment of antiviral
activity by CYP3A4 inducers.
Maribavir may have some inhibitory effect on cytochrome P450
isozymes, CYP2C19 and CYP2D6, as assessed after administration of
multiple concurrently administered drug probes, including omeprazole
(2C19) and dextromethorphan (2D6).
Check Digit Verification of cas no
The CAS Registry Mumber 176161-24-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,7,6,1,6 and 1 respectively; the second part has 2 digits, 2 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 176161-24:
(8*1)+(7*7)+(6*6)+(5*1)+(4*6)+(3*1)+(2*2)+(1*4)=133
133 % 10 = 3
So 176161-24-3 is a valid CAS Registry Number.
InChI:InChI=1/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
176161-24-3Relevant articles and documents
Design, synthesis and antiviral activity of α-L-arabinofuranosyl derivatives of 2-substituted-5,6-dichlorobenzimidazoles
Girardet, Jean-Luc,Drach, John C.,Chamberlain, Stanley D.,Koszalka, George W.,Townsend, Leroy B.
, p. 2389 - 2401 (1998)
A number of 2.-s. have been prepared by condensation of 2-bromo-5,6- dichlorobenzimidazole or 2,5,6-trichlorobenzimidazole with tetra-O-acetyl-L- arabinofuranose. 2-Alkylamino derivatives were prepared by a substitution of the 2-chloro group with the appropriate amines. All target compounds were evaluated for activity against HCMV and HSV-1. The 2-chloro and 2-bromo derivatives showed moderate activity against HCMV at non-cytotoxic concentrations.
Lyxofuranosyl benzimidazoles as antiviral agents
-
, (2008/06/13)
The present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds. In one embodiment, the present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds selected from the group consisting of compounds having a formula selected from the following: wherein R2, R4, R5, R6, and R7are independently the same or different and independently selected from the group consisting of: —H, —F, —Cl, —Br, —I, —NO2, —N(R8)2, —OR8, —SR12, and —CF3, wherein R8is independently —H or an alkyl group having 1-6 carbon atoms and wherein R12is independently —H or a hydrocarbyl group having 1-10 carbon atoms; and, R9, R10and R11are independently the same or different and are H or a hydroxyl protecting group; anomeric and optical isomers thereof; and, pharmaceutically acceptable salts and prodrug derivatives thereof. The present invention also pertains to antiviral compositions using these compounds, methods of treating a viral infection using these compounds, and the use of these compounds in the preparation of a medicament for use in the treatment of a viral infection.
Form vi 5,6-dichloro-2-(isopropylamino)-1-(β-l-ribofuranosyl)-1h-bezimimidazole
-
, (2008/06/13)
The invention relates to Form VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole, pharmaceutical compositions comprising the same, and their use in medical therapy.
