1163-36-6 Usage
Description
Clemizole hydrochloride is a chemical compound with a variety of pharmacological properties, including antihistamine, antiviral, and anticonvulsant activities. It is known for its ability to inhibit Hepatitis C RNA replication, block histamine 1 receptors, and suppress the function of the nonstructural protein 4B (NS4B) in the virus.
Uses
Used in Pharmaceutical Industry:
Clemizole hydrochloride is used as an antihistamine for treating allergic reactions due to its high nanomolar concentration in blocking histamine 1 receptors. This property makes it effective in alleviating symptoms associated with allergies.
Used in Antiviral Applications:
Clemizole hydrochloride is used as an antiviral agent for inhibiting Hepatitis C RNA replication in cell culture. It achieves this by suppressing the binding between the nonstructural protein 4B and the viral RNA genome, with minimal toxicity to the host cell. Additionally, it shows synergistic effects when combined with other antiviral drugs like boceprevir, enhancing the overall treatment efficacy.
Used in Neurological Applications:
Clemizole hydrochloride is used as an anticonvulsant in the treatment of seizures, as demonstrated in a zebrafish model of Dravet Syndrome. Its ability to inhibit seizures makes it a potential therapeutic option for patients suffering from epilepsy and other seizure-related disorders.
Used in Ion Channel Modulation:
Clemizole hydrochloride is used as a potent inhibitor of the transient receptor potential channel TRPC5 (IC50 = 1.0-1.3 μM). It selectively blocks TRPC5 over other TRP channels, which may have implications in various physiological and pathological processes involving ion channel regulation.
Originator
Allercur,Roerig,US,1960
Manufacturing Process
From 13.1 g of N-p-chlorobenzyl-2-nitroaniline (MP 110°C, obtained in the
form of orange-red needles, from o-nitrochlorobenzene and pchlorobenzylamine by reaction for 3 hours at 150°C) by reduction with Raneynickel and hydrogen, in which reaction the substance may be suspended in
methanol or dissolved in methanol-ethyl acetate at normal pressure and at
about 40°C with combination of the theoretical quantity of hydrogen, 12.2 g
are obtained of o-amino-N-p-chlorobenzylaniline, which after recrystallization
from aqueous methanol has a MP of 90°C.8 g of o-amino-N-p-chlorobenzylaniline and 2.8 g of pyridine are dissolved in
dry ether and reacted with an ethereal solution of 3.9 g of chloracetyl chloride
with cooling in a mixture of ice and common salt. 8 g of N-p-chlorobenzyl-N'-
chloracetyl-o-phenylene diamine are obtained which can be worked up in the
form of the crude product and, in the slightly colored form, has a MP of
130°C.7.6 g of this compound are boiled with 3.9 g of pyrrolidine in 70 cc of toluene
for some hours under reflux. After extraction by shaking with water and
treatment with hydrochloric acid the hydrochloride is produced of N-pchlorobenzyl-N'-pyrrolidylacetyl-o-phenylene diamine together with some 1-pchlorobenzyl-2-N-pyrrolidylmethyl-benzimidazole. The former, after
recrystallization from butanol, melts with foaming at 205°C, the latter, after
recrystallization from butanol melts at 239°C to 241°C, and is in the form of
white microscopic rods. Boiling in nitrobenzene converts the former compound
into the latter.
Therapeutic Function
Antihistaminic
Biological Activity
(ns4b)the ns4b protein is a key player in hcv replication. disrupting ns4b function thus represents an attractive new anti-hcv strategy. combining clemizole with other anti-hcv agents could increase the antiviral effect achieved with 1 active drug alone and decrease emergence of viral resistance.
in vitro
although significant, clemizole’s antiviral effect was moderate (50% effective concentration of 8 mm against a hcv genotype 2a clone). clemizole’s antiviral effect was highly synergistic with the hcv protease inhibitors vx950 and sch503034, without toxicity. in contrast, clemizole combinations with either interferon, ribavirin, or the nucleoside (nm283) and nonnucleoside (hcv796) hcv polymerase inhibitors were additive [1].
in vivo
clemizole had an unexpectedly short plasma half-life; it was very rapidly bio-transformed into a glucuronide (m14) and a dealkylated metabolite (m12) and into a variety of lesser metabolites in c57bl/6j mice [2].
IC 50
8 mm
references
[1] einav s, sobol hd, gehrig e, glenn js. the hepatitis c virus (hcv) ns4b rna binding inhibitor clemizole is highly synergistic with hcv protease inhibitors. j infect dis. 2010;202(1):65-74. [2] nishimura t, hu y, wu m, pham e, suemizu h, elazar m, liu m, idilman r, yurdaydin c, angus p, stedman c, murphy b, glenn j, nakamura m, nomura t, chen y, zheng m, fitch wl, peltz g. using chimeric mice with humanized livers to predict human drug metabolism and a drug-drug interaction. j pharmacol exp ther. 2013;344(2):388-96. doi: 10.1124/jpet.112.198697. epub 2012 nov 8.
Check Digit Verification of cas no
The CAS Registry Mumber 1163-36-6 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,1,6 and 3 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1163-36:
(6*1)+(5*1)+(4*6)+(3*3)+(2*3)+(1*6)=56
56 % 10 = 6
So 1163-36-6 is a valid CAS Registry Number.
InChI:InChI=1/C19H20ClN3.ClH/c20-16-9-7-15(8-10-16)13-23-18-6-2-1-5-17(18)21-19(23)14-22-11-3-4-12-22;/h1-2,5-10H,3-4,11-14H2;1H
1163-36-6Relevant articles and documents
BENZIMIDAZOLE MODULATORS OF H1 RECEPTOR AND/OR NS4B PROTEIN ACTIVITY
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Page/Page column 31, (2010/11/03)
The present invention relates to new benzimidazole modulators of H1 receptor activity and/or inhibitors of NS4B protein activity, pharmaceutical compositions thereof, and methods of use thereof formula (I).
