198821-22-6 Usage
Description
Merimepodib is an inhibitor of inosine-5''-monophosphate dehydrogenase (IMPDH; Kis = 7 and 10 nM for IMPDH type I and type II, respectively) with antiviral and immunosuppressant activities. It reduces Ebola, Lassa, chikungunya, Junin, and Zika virus titers in vitro and inhibits Zika virus replication in Huh7 cells (EC50 = 0.6 μM). Merimepodib inhibits the proliferation of PHA-stimulated T cells and SPAS-stimulated B cells (IC50s = 104 and 132 nM, respectively), effects that can be reversed by guanosine but not adenosine . In vivo, merimepodib (50 and 100 mg/kg) increases allograft survival in a murine skin transplantation model and prevents development of graft versus host disease (GVHD) in splenocyte allografted mice.
Uses
Inhibition of inosine monophosphate dehydrogenase (IMPDH), which has potential
antiviral, antiproliferative, antiparasitic, and immunosuppressive activity.
in vitro
vx-497 (mw 452.5) inhibited the proliferation of primary human, rat, mouse, and dog lymphocytes at concentrations of approximately 100 nm. the inhibitory effect of vx-497 on lymphocytes was reversed in the presence of exogenous guanosine, but not in the presence of adenosine or uridine, confirming that the antilymphocytic activity of vx-497 was specifically due to inhibition of impdh[1]. vx-497 was most potent against the first group of viruses on virus replication, which included hbv, hcmv, emcv, and rsv, with ic50 values of 0.38, 0.80, 1.0, and 1.14 μm, respectively [3].
in vivo
oral administration of vx-497 dose-dependently inhibited the primary igm antibody response, with an ed50 value of approximately 30-35 mg/kg in mice. single daily dosing of vx-497 was as effective as twice-daily dosing in this model of immune activation [1].in the skin transplant study, trunk skin grafts from balb/c mice were grafted onto c57bl/6 mice. administration of vx-497 twice daily until day 10 significantly prolonged graft survival to 13.2 ± 1.2 (p < 0.001, kaplan meier log-rank test) days in the 50 mg/kg group and 13.9 ± 1.0 (p < 0.001) days in the 85 mg/kg group [4].
references
[1]. jain j1, almquist sj,shlyakhter d,harding mw. vx-497: a novel, selective impdh inhibitor and immunosuppressive agent.j pharm sci.2001 may;90(5):625-37.[2]. pimkin m1,markham gd. inosine 5'-monophosphate dehydrogenase.adv enzymol relat areas mol biol.2009;76:1-53.[3]. markland w1,mcquaid tj,jain j,kwong ad. broad-spectrum antiviral activity of the imp dehydrogenase inhibitor vx-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon.antimicrob agents chemother.2000 apr;44(4):859-66.[4]. decker cj1,heiser ad,chaturvedi pr,faust tj,ku g,moseley s,nimmesgern e. the novel impdh inhibitor vx-497 prolongs skin graft survival and improves graft versus host disease in mice.drugs exp clin res.2001;27(3):89-95.
Check Digit Verification of cas no
The CAS Registry Mumber 198821-22-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,9,8,8,2 and 1 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 198821-22:
(8*1)+(7*9)+(6*8)+(5*8)+(4*2)+(3*1)+(2*2)+(1*2)=176
176 % 10 = 6
So 198821-22-6 is a valid CAS Registry Number.
InChI:InChI=1/C23H24N4O6/c1-30-20-10-17(5-6-19(20)21-12-24-14-32-21)27-22(28)26-16-4-2-3-15(9-16)11-25-23(29)33-18-7-8-31-13-18/h2-6,9-10,12,14,18H,7-8,11,13H2,1H3,(H,25,29)(H2,26,27,28)/t18-/m0/s1
198821-22-6Relevant articles and documents
Polymorphic forms of (S). -tetrahydrofuran-3-yl-3- (3- (3-methoxy-4- (oxazol-5-yl) pheny1) ureido) benzylcarbamate
-
Page/Page column 11, (2008/06/13)
The present invention relates to polymorphic forms of (S)-tetrahydrofuran-3-yl 3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate, processes therein, pharmaceutical compositions thereof, and uses therewith.
Inhibitors of IMPDH enzyme
-
Page column 36, (2010/02/04)
The present invention relates to a novel class of compounds which are IMPDH inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.
