13392-28-4 Usage
Description
Rimantadine (Brand name: Flumadine) is a kind of RNA synthesis inhibitor that used as an orally administrated antiviral drug in the prophylaxis and for the treatment of influenza. It is capable of shortening the duration and alleviated the symptoms of influenza. However, it is now not recommended for the treatment of influenza any longer due to the emergence of resistance problem since 2009. Its mechanism of action is not fully understood. It is indicated that it take effects through inhibiting the viral replication through possibly inhibiting the uncoating process of the virus. The virus M2 protein (an ion channel) seems to play an important role in the susceptibility of influenza A virus to the treatment of Rimantadine.
References
https://www.drugbank.ca/drugs/DB00478
https://en.wikipedia.org/wiki/Rimantadine
Uses
Rimantadine act by blocking the M2 ion channel which is required for uptake of protons into the interior of the virus to permit acid-promoted viral uncoating (decapsidation).
Brand name
Flumadine (Forest).
General Description
Resistant variants of influenza type A have been recoveredfrom rimantadine-treated patients.Resistance with inhibitory concentrations increased morethan 100-fold have been associated with single nucleotidechanges that lead to amino acid substitutions in the transmembranedomain of M2. rimantadineshare cross-susceptibility and resistance.
Pharmaceutical Applications
An analog of amantadine, supplied as the hydrochloride for
oral administration.
Mechanism of action
Rimantadine hydrochloride (α-methyl-1-adamantanemethylamine hydrochloride) is a synthetic adamatane
derivative that is structurally and pharmacologically related to amantadine. It appears to be more
effective than amantadine hydrochloride against influenza A, with fewer CNS side effects. Rimantadine
hydrochloride is thought to interfere with virus uncoating by inhibiting the release of specific proteins. It
may act by inhibiting RT or the synthesis of virus-specific RNA, but it does not inhibit virus adsorption or
penetration. It appears to produce a virustatic effect early in the virus replication. It is used widely in
Russia and Europe.
Pharmacokinetics
Oral absorption: >90%
Cmax 100 mg oral (every 12 h): 0.4–0.5 mg/L after 2–6 h
Plasma half-life: c. 35 h
Volume of distribution: Very large
Plasma protein binding: c. 40%
Absorption and distribution
Single- and multiple-dose pharmacokinetic studies in elderly patients and young adults are remarkably similar. The steadystate concentration in nasal mucus develops by day 5 at a concentration approximately 1.5-fold higher than plasma.
Metabolism
In contrast to amantadine, rimantadine is extensively metabolized in the liver by hydroxylation and glucuronidation.
Excretion
Less than 20% is excreted unchanged in the urine and most of the breakdown products are excreted by this route. Thus, the plasma half-life is much less affected by renal dysfunction than that of amantadine.
Clinical Use
Different sources of media describe the Clinical Use of 13392-28-4 differently. You can refer to the following data:
1. rimantadine is used for the treatment
of diseases caused by influenza A strains.
2. Prophylaxis and treatment of influenza A H1N1 infections
Since prolonged administration is well tolerated by elderly
patients, the drug is preferable to amantadine.
Side effects
Rimantadine has significantly fewer side effects than amantadine
at equivalent doses, perhaps because of differences
in pharmacokinetics, since with equal doses the blood levels
are considerably lower. CNS side effects are not significantly
higher than placebo.
Check Digit Verification of cas no
The CAS Registry Mumber 13392-28-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,3,3,9 and 2 respectively; the second part has 2 digits, 2 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 13392-28:
(7*1)+(6*3)+(5*3)+(4*9)+(3*2)+(2*2)+(1*8)=94
94 % 10 = 4
So 13392-28-4 is a valid CAS Registry Number.
InChI:InChI=1/C12H21N/c13-2-1-12-6-9-3-10(7-12)5-11(4-9)8-12/h9-11H,1-8,13H2
13392-28-4Relevant articles and documents
A rimantadine Schiff base synthetic method (by machine translation)
-
, (2019/01/16)
The invention discloses a rimantadine Schiff base synthetic method, including adamantane chloride preparation, adamantane methyl preparation, 1 - adamantane methyl oxime preparation, rimantadine preparation, rimantadine Schiff base preparation, wherein the adamantane methyl preparation steps are as follows: in the flask to join the three trimethylaluminum, formic acid cerium, then dropwise adamantane formyl chloride [...], the adamantane chloride with three methyl aluminum reaction generating adamantane methyl ketone, after the reaction is completed in the reaction liquid into ice water, then filtering, drying, the resulting pale yellow precipitate adamantane methyl ketone. The beneficial effects: the reaction of this invention route changes before the adamantane methyl ketone synthesis route, the use of formic acid cerium auxiliary trimethyl aluminum reaction, mild reaction conditions, few by-products. The invention synthetic method mild condition, the process is simple and feasible, less catalyst levels, environmental protection, high product yield. (by machine translation)
Approaches to primary tert-alkyl amines as building blocks
Tzitzoglaki, Christina,Drakopoulos, Antonios,Konstantinidi, Athina,Stylianakis, Ioannis,Stampolaki, Marianna,Kolocouris, Antonios
, (2019/07/10)
Primary tert-alkyl amines include analogues of amantadine, a fragment commonly linked to pharmacophoric groups to enhance biological activity. The preparation of primary tert-alkyl amines is considered to be a difficult problem. Four synthetic procedures, some of which have been previously reported for the synthesis of amines with primary (RCH2NH2) or secondary (RR'CHNH2) alkyl and/or aryl groups, were tested for the synthesis of primary tert-alkyl amines (RR′R″CNH2) in aliphatic series including adamantane adducts. These procedures included the formation and reduction of tert-alkyl azides, the Ritter reaction in standard and modified conditions, the addition of organometallic reagents to N-tert-butyl sulfinyl ketimines and one-pot reactions between nitriles and organometallic reagents in the presence of a Lewis acid, Τi(iPrO)4 or CeCl3. These synthetic routes are unexplored for primary tert-alkyl amines. Studies on the synthetic routes for primary tert-alkyl amines are currently lacking. The reaction conditions and substrate limitations were studied for each procedure, with the first procedure being the most general and applicable also for compounds bearing bulky adducts.
Optical resolution of rimantadine
Han, Jianlin,Takeda, Ryosuke,Sato, Tatsunori,Moriwaki, Hiroki,Abe, Hidenori,Izawa, Kunisuke,Soloshonok, Vadim A.
, (2019/05/24)
This work discloses a new procedure for the resolution of commercially available racemic rimantadine hydrochloride to enantiomerically pure (S)-rimantadine using (R)-phenoxypropionic acid as a recyclable resolving reagent. Good chemical yields, operational ease, and low-cost structure underscore the preparative value of this method for the production of enantiomerically pure rimantadine for medicinal or synthetic studies.