Rimantadine

Structural formula
General
Non-proprietary name	Rimantadine
other names	( RS ) -Adamantan-1-ylethylamine ( IUPAC ) ; Rimantadinum ( Latin ) ;
Molecular formula	C 12 H 21 N (rimantadine) ; C 12 H 21 N · HCl (rimantadine hydrochloride ) ;
External identifiers / databases
PubChem	5071
DrugBank	DB00478
Wikidata	Q42171
Drug information
ATC code	J05 AC02
Drug class	Antivirals
properties
Molar mass	179,30 g · mol -1 (rimantadine) ; 215.77 g · mol -1 (rimantadine hydrochloride) ;
Melting point	373–375 ° C (rimantadine hydrochloride, racemate ) ; 400–402 ° C (rimantadine hydrochloride, enantiomers ) ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
Toxicological data	640 mg kg −1 ( LD 50 , rat , oral , hydrochloride)
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Rimantadine (trade name in the USA: Flumadine ^® ) is an active ingredient for the treatment and, more rarely, prevention of type A influenza and was approved by the FDA in 1993.

The Centers for Disease Control and Prevention recommended discontinuing prescribing of rimantadine and oseltamivir for H3N2 influenza in January 2006 after an increase in resistance from 2% in 2004 to 11% in 2005 to 91%.

It is a derivative of adamantane .

synthesis

The synthesis of racemic rimantadine starts from 1-adamantoyl chloride, with 1-acetyladamantane being formed in the first step with diethyl malonate and magnesium . This can be converted to the target compound via the oxime with subsequent reduction using lithium aluminum hydride or directly via reductive amination in the presence of cobalt catalysts.

The racemate resolution can be carried out with enantiomerically pure tartranil .

Individual evidence

↑ ^a ^b ^c P.E. Aldrich, EC Hermann, WE Meier, M. Paulshock, WW Prichard, JA Synder, JC Watts: Antiviral agents. 2. Structure-activity relations of compounds related to 1-adamantanamine in J. Med. Chem. 14 (1971) 535-543, doi : 10.1021 / jm00288a019 .
↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ ^a ^b A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications , 4th edition (2001) Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 .
↑ FDA APPROVES NEW ORAL FLU DRUG , September 17, 1993.
↑ Influenza: This year's influenza virus resistant to drugs. In: Deutsches Ärzteblatt , January 16, 2006.
↑ ^a ^b German Patent 1 468 769 (DuPont, priority date: July 18, 1964).
↑ ^a ^b European Patent 178 668 (DuPont, priority date: October 17, 1985).

[Aldrich-1] P.E. Aldrich, EC Hermann, WE Meier, M. Paulshock, WW Prichard, JA Synder, JC Watts: Antiviral agents. 2. Structure-activity relations of compounds related to 1-adamantanamine in J. Med. Chem. 14 (1971) 535-543, doi : 10.1021 / jm00288a019 .

[NV-2] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[Kleemann-3] A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications , 4th edition (2001) Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 .

[4] FDA APPROVES NEW ORAL FLU DRUG , September 17, 1993.

[5] Influenza: This year's influenza virus resistant to drugs. In: Deutsches Ärzteblatt , January 16, 2006.

[DE-6] German Patent 1 468 769 (DuPont, priority date: July 18, 1964).

[EP-7] European Patent 178 668 (DuPont, priority date: October 17, 1985).