13392-28-4

Basic information

• Product Name: Rimantadine
• Synonyms: 1-Adamantan-1-ylethylamine;1-Adamantanethylamine;Rimantadine & Rimantadine Hydrochloride;RiMantadine (FluMadine);RiMantidine;1-(adaMantan-1-yl)ethanaMine hydrochloride;1-(AdaMantan-1-yl)ethanaMine;α-Methyl-1-adamantanemethylamine
• CAS NO: 13392-28-4
• Molecular Formula: C₁₂H₂₁N
• Molecular Weight: 165.28
• EINECS: 1308068-626-2
• Product Categories: Inhibitors;Adamantane derivatives;API's
• Mol File: 13392-28-4.mol

Chemical Properties

• Boiling Point: 248°C
• Flash Point: 99°C
• Appearance: /
• Density: 1.033
• Vapor Pressure: 0.0249mmHg at 25°C
• Refractive Index: 1.539
• PKA: 11.17±0.29(Predicted)
• CAS DataBase Reference: Rimantadine(CAS DataBase Reference)
• NIST Chemistry Reference: Rimantadine(13392-28-4)
• EPA Substance Registry System: Rimantadine(13392-28-4)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 13392-28-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Rimantadine is used as an antiviral agent for the prophylaxis and treatment of influenza A. It was effective in shortening the duration and alleviating the symptoms of influenza. However, due to the development of resistance, its use has been discontinued since 2009.
Used in Research and Development:
Rimantadine is used in research to study the mechanisms of action and resistance in influenza A viruses. Understanding the role of the M2 protein and its ion channel in the susceptibility of the virus to Rimantadine can help in the development of new antiviral drugs and strategies to combat resistant strains.

References

https://www.drugbank.ca/drugs/DB00478 https://en.wikipedia.org/wiki/Rimantadine

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

rimantadine is used for the treatment of diseases caused by influenza A strains.

Clinical Use

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.

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

Upstream product

• 1707-40-0 1-((3r,5r,7r)-adamantan-1-yl)ethan-1-one oxime 
• 109-74-0 propyl cyanide 
• 1660-04-4 1-acetyladamantane 
• 100-47-0 benzonitrile 
• 75-05-8 acetonitrile 
• 107-12-0 propiononitrile 
• 78679-71-7 1-adamantyl methyl ketoxime 
• 1501-84-4 rimantadine hydrochloride 
• 2094-72-6 1-Adamantanecarbonyl chloride 
• 33932-92-2 1-(1-Chloro-ethyl)-adamantane 
• 281-23-2 adamantane 
• 768-90-1 1-Adamantyl bromide 
• 828-51-3 1-Adamantanecarboxylic acid 
• 23074-42-2 1-adamantanecarbonitrile 

Downstream Products

• 118202-62-3 N-<1-(1-Adamantyl)ethyl>-2-phenylisopropylamine 
• 90812-24-1 3-(1-aminoethyl)adamantan-1-ol hydrochloride 
• 1256382-59-8 N₃-(1-(1-adamantyl)ethyl)-1-ethyl-4-oxo-6-phenyl-1,4-dihydropyridine-3-carboxamide 
• 1256382-60-1 N₃-(1-(1-adamantyl)ethyl)-4-oxo-1-pentyl-6-phenyl-1,4-dihydropyridine-3-carboxamide 
• 1256382-61-2 N₃-(1-(1-adamantyl)ethyl)-1,6-diphenyl-4-oxo-1,4-dihydropyridine-3-carboxamide 
• 1363568-17-5 C₂₀H₂₇NO₂ 
• 1381771-50-1 C₂₀H₂₉NO₂ 
• 1313594-90-9 2-((1-(1-adamantan-1-yl)ethyl)-imino-methyl)-6-methoxyphenol 
• 391219-37-7 adamantyl-N-(ethyl)-(5-chlorosalicylidene)aniline 
• 201992-21-4 C₁₉H₂₄BrNO 
• 1638417-14-7 2-((1-(1-adamantan-1-yl)ethyl)iminomethyl)-4-chlorophenol 

Relevant articles and documents

Approaches to primary tert-alkyl amines as building blocks

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

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.

A rimantadine Schiff base synthetic method (by machine translation)

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)

Compounding agent of rimantadine hydrochloride and camphor tree essential oil and application thereof

The invention discloses a compounding agent of rimantadine hydrochloride and camphor tree essential oil and application thereof, wherein the weight ratio of the amantadine hydrochloride to the camphortree essential oil in the compounding agent is 1: 50-50: 1, Adamantanecarbonyl chloride as a raw material, trimethylaluminum as a reagent and cerium formate as an auxiliary agent are reacted to formadamantane methyl ketone, and the rimantadine hydrochloride is prepared by oximation and platinum-carbon hydrogenation reduction of the adamantane methyl ketone; and the camphor tree essential oil isprepared by crushing camphor tree seeds, leaves, bark and the like as raw materials, using sodium glycinate and citric acid to assist breaking of cell walls and using a distillation technique; and thebeneficial effects are that: high purity and high yield of the rimantadine hydrochloride and the camphor tree essential oil. The compound composition of the rimantadine hydrochloride and the camphortree essential oil has synergistic effect, can effectively reduce the application amount of single agents, expands the sterilization spectrum, reduces the phytotoxicity, significantly improves the control effect against pathogens and viruses, alleviates the resistance problem of pathogenic bacteria, and reduces the cost of prevention.

Preparation method of rimantadine hydrochloride

The invention belongs to the filed of preparation of chemical intermediates, and specifically relates to a preparation method of rimantadine hydrochloride. 1-adamantyl methy ketone is used as a starting material, then reacts with hydroxylamine hydrochloride, and catalyzed and hydrogenated to obtain rimantadine hydrochloride with a high yield. In the reaction of preparing the target object, oxime is prepared firstly, then is catalyzed and hydrogenated. Despite of additional oxime-preparing reaction, the reaction yield in each step is high. The preparation method has the characteristics of highyield, cheap raw materials, simple technical treatment and quality products, thus having certain application value.

A method for synthesizing diamond ethylamine

The invention discloses a synthetic method for rimantadine. The synthetic method is characterized by comprising the following steps: firstly, obtaining 1-bromoadamantane by reacting adamantine with liquid bromine; then, acidifying to obtain adamantanecarboxylic acid after reacting 1-bromoadamantane with magnesium and anhydrous ether; obtaining adamantine carbonyl chloride by performing reflux reaction on tehadamantanecarboxylic acid with thionyl chloride; obtaining adamantane methyl ketone by reacting the adamantine carbonyl chloride with (CH3)2CdCu; and finally, obtaining the rimantadine by hydriding and reacting adamantane methyl ketone with hydrochloric acid and ammonia water in the presence of sodium borohydride. The synthetic method disclosed by the invention is gentle in condition, simple in follow-up processing, high in yield, cheap in raw material and low in synthesis cost.

Synthesis, characterization, and crystal structure of three cobalt(II) complexes with Schiff bases derived from rimantadine

By condensation of rimantadine and substituted salicylaldehyde, three new Schiff bases, HL1, HL2 and HL3, were synthesized. Then, a mixture of one of the new ligands and cobalt(II) chloride hexahydrate in ethanol led to 1, 2, and 3, respectively. These complexes were characterized by melting point, elemental analysis, infrared spectra, molar conductance, thermal analysis, and single-crystal X-ray diffraction analysis. X-ray diffraction analysis reveals that 1 crystallizes in the orthorhombic system, Pbcn space group; each asymmetric unit consists of one cobalt(II) ion, two deprotonated ligands, and one lattice water. The central cobalt is four coordinate via two nitrogens and two oxygens from the corresponding Schiff base ligand, forming a distorted tetrahedral geometry. Complexes 2 and 3 crystallize in the monoclinic system, P21/c space group; each asymmetric unit consists of one cobalt(II), two corresponding deprotonated ligands, one lattice water, and one methanol. The central cobalt is also four-coordinate via two nitrogens and two oxygens from the corresponding Schiff base ligand, forming a distorted tetrahedral geometry. 2014

Synthesis, characterization, and antibacterial activity of two zinc(II) complexes with Schiff bases derived from rimantadine

The reactions of zinc(II) chloride and two Schiff base ligands derived from rimantadine and 5-chlorosalicylaldehyde/4-methoxysalicylaldehydes, generated two novel complexes [Zn(L1)2Cl2] (I) and [Zn(L2)2Cl2] (II), where L1 = 2-((1-(1-adamantan-1-yl)ethyl)-iminomethyl)-4-chlorophenol, L2 = 2-((1-(1-adamantan-1-yl)ethyl)iminomethyl)-5-methoxyphenol. The complexes were characterized by the means of IR, 1H NMR, elemental analysis, molar conductance and thermal analysis. A single-crystal X-ray diffraction analysis reveals that both complexes crystallize in orthorhombic system, space group Fdd2 for I and Pbcn for II. In two complexes crystals, each asymmetric unit consists of one zinc(II) ion, two corresponding Schiff base ligands and two chlorine atoms; the central zinc atom lies on a twofold rotation axis and is four-coordinate via two chlorine atoms and two oxygen atoms from the Schiff base ligands, forming a distorted tetrahedral geometry.

Synthesis of surfactants derived from adamantane

Quaternary [1-(1-adamantyl)ethyl]- and (1-adamantyl)trimethylammonium, and also 3-(1-adamantyl)-3-chloro-2-propenylammonium salts were prepared, and their surface activity was studied.

Synthesis of trichloronitrodienamino adamantane derivatives

Vilsmeier-Haack reaction with acetyladamantane gave 3-(1-adamantyl)-3-chloro-2-propenal which reacted with hydroxylamine to yield the corresponding oxime. The latter was reduced with metallic sodium in ethanol to 1-(1-adamantyl)-1-chloro-3-aminopropene wh