ChemInform Abstract: CHEMIE UND TOXIKOLOGIE EINER NEUEN ANTIVIRALEN SUBSTANZ, N-(1-ADAMANTYL)-2-(2-DIMETHYLAMINO-AETHOXY)-ACETAMID-HYDROCHLORID 1. MITT.

Peteri, D.; Sterner, W

doi:10.1002/chin.197330227

Cited by 4 publications

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“…Examination of other amantadine derivatives indicates the importance of an amide or thioamide group for antiherpetic activity, whereas for tromantadine, the side chain potentiates that activity (10,11,16,20). Weak bases other than tromantadine, such as VOL.…”

Section: Discussionmentioning

confidence: 99%

“…Virion synthesis and viral polypeptide synthesis were inhibited by addition of tromantadine at the time of infection or 4 h postinfection. The results are consistent with tromantadine inhibition of an early event in herpes simplex virus infection, before macromolecular synthesis, and a late event, such as assembly or release of virus.Tromantadine (N-1-adamantyl-N-[2-(dimethylamino)ethoxy]acetamide hydrochloride) (10,11,16,20) is one of relatively few amantadine (1-adamantanamine) derivatives which have antiherpetic activity. Amantadine has been shown to inhibit an early event before viral macromolecular synthesis in influenza A virus replication and is an alternative to vaccination against influenza A virus (15).…”

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confidence: 99%

“…Amantadine has been shown to inhibit an early event before viral macromolecular synthesis in influenza A virus replication and is an alternative to vaccination against influenza A virus (15). Tromantadine has been reported to inhibit herpes simplex virus type 1 (HSV-1) and HSV-2 replication and to be effective as a topical antiherpetic drug (1,4,7,9,12,16,20,25). In this paper, we report an improved synthetic scheme for the compound and describe its activity against HSV-1 infection.…”

mentioning

confidence: 99%

“…Tromantadine (N-1-adamantyl-N-[2-(dimethylamino)ethoxy]acetamide hydrochloride) (10,11,16,20) is one of relatively few amantadine (1-adamantanamine) derivatives which have antiherpetic activity. Amantadine has been shown to inhibit an early event before viral macromolecular synthesis in influenza A virus replication and is an alternative to vaccination against influenza A virus (15).…”

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confidence: 99%

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Tromantadine: inhibitor of early and late events in herpes simplex virus replication

Rosenthal¹,

Sokol²,

Ingram³

et al. 1982

Antimicrob Agents Chemother

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Unlike amantadine (1-adamantanamine), tromantadine (N-1-adamantyl-N-[2-(dimethyl amino)ethoxy]acetamide hydrochloride) inhibits herpes simplex virus type 1 (KOS strain)-induced cytopathic effect and virus replication with limited toxicity to the cells. Vero and HEp-2 cells tolerated up to 2 mg of tromantadine per 2 x 106 cells for 24-, 48-, or 96-h incubation periods with little change in cell morphology. Treatment of the cells with 10 to 50 p.g of tromantadine reduced herpes simplex virus-induced cytopathic effect. Treatment with 100 to 500 pg of tromantadine inhibited herpes simplex virus-induced cytopathic effect and reduced virus production. Complete inhibition of virus production was observed with treatments of 500 jig to 1 mg. The antiherpetic activity of tromantadine was dependent upon the viral inoculum size and the time of addition of the compound with respect to infection. Virion synthesis and viral polypeptide synthesis were inhibited by addition of tromantadine at the time of infection or 4 h postinfection. The results are consistent with tromantadine inhibition of an early event in herpes simplex virus infection, before macromolecular synthesis, and a late event, such as assembly or release of virus.Tromantadine (N-1-adamantyl-N-[2-(dimethylamino)ethoxy]acetamide hydrochloride) (10,11,16,20) is one of relatively few amantadine (1-adamantanamine) derivatives which have antiherpetic activity. Amantadine has been shown to inhibit an early event before viral macromolecular synthesis in influenza A virus replication and is an alternative to vaccination against influenza A virus (15). Tromantadine has been reported to inhibit herpes simplex virus type 1 (HSV-1) and HSV-2 replication and to be effective as a topical antiherpetic drug (1,4,7,9,12,16,20,25). In this paper, we report an improved synthetic scheme for the compound and describe its activity against HSV-1 infection. An indication of the HSV replication step(s) inhibited by tromantadine is discussed. Tromantadine was prepared by addition of N,N-dimethylethanolamine to N-(1-adamantyl)-2-chloroacetamide. First, the lithium alkoxide of N,N-dimethylethanolamine was prepared by the addition of 4.3 ml (0.009 mol) of 2.1 M n-butylithium in hexane to a cold solution of the amino alcohol (0.78 g, 0.0088 mol) in 10 ml of dry THF. A solution of N-(1-adamantyl)-2-chloroacetamide (2.0 g, 0.0088 mol) in 15 ml of dry THF was then added slowly, and the mixture was stirred overnight. The solution was next poured into 50 ml of 10% HCI, and the resulting solution was washed with ether. Addition of NaOH solution liberated the tromantadine, which was extracted into two 100-ml portions of ether. The combined ether extracts were dried over anhydrous Na2SO4, and the ether was evaporated to yield a viscous oil. The oil was dissolved in benzene, and tromantadine was precipitated by 1031 on April 1, 2019 by guest http://aac.asm.org/ Downloaded from

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Tromantadine: inhibitor of early and late events in herpes simplex virus replication

Rosenthal¹,

Sokol²,

Ingram³

et al. 1982

Antimicrob Agents Chemother

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“…Although numerous adamantane derivatives have been synthesized and shown to exhibit various kinds of antiviral activity [16], amantadine and rimantadine are still the only TADs recommended for wide use in medicine. There is only one more representative of this group -tromantadine [17], an acylated amantadine derivative N-(1-adamantyl)-2-(2-dimethylaminoethoxy)acetamide (IIc) -which is used in some cases for the treatment of HSV. Amantadine and (more recently) rimantadine are also used for the treatment of Parkinson's disease [18,19], while memantine (1-amino-3,5-dimethyladamantane, IId) is considered as a promising drug for the treatment of some kinds of dementia, in particular, Alzheimer's disease [20].…”

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confidence: 99%

Synthesis and antiherpetic activity of N-(3-amino-1-adamantyl)calix[4]arenes

Motornaya

Shokova

et al. 2006

Pharm Chem J

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p-(3-Amino-1-adamantyl)calix [4]arenes with free and alkylated lower rim, representing conjugates of the aminoadamantane pharmacophore fragment and the calixarene platform, were synthesized for the first time by the Curtius rearrangement route starting from p-(3-carboxy-1-adamantyl)calix [4]arenes. The synthesized compounds were evaluated for activity against herpes simplex virus 2 (HSV-2). The nonalkylated compound with free phenol hydroxy groups is the first aminoadamantylcalixarene reported to possess antiviral properties (chemotherapeutic safety index, SI » 12.5). Alkylation at the lower rim of the calixarene platform leads to an increase in cytotoxicity and to the disappearance of anti-HSV activity.Calix[4]arenes (I) represent cyclic metacyclophanes, which are composed of phenol fragments bridged by methylene groups. These compounds have recently received much attention for their ability to serve as receptors of metal ions and neutral molecules, which opens up ways to using them as carriers, sensors, chromatographic media, ligands in homogeneous catalysis, etc.[1].Although the antituberculous activity of p-tert-octylcalix[8]arene modified at the lower rim with poly(oxyethylene) substituents (I with R = tert-octyl, X = (CH 2 CH 2 O) n H, n = 8) was observed as long ago as in 1955 (then it was considered a tetramer) [2 -4], data available on the pharmacological properties of calixarene derivatives are still rather restricted. In 1996, Casnati et al. reported on the antimicrobial activity of vancomycin antibiotic mimetics based on calix[4]arenes modified with dipeptide bridges at the upper rim [5]. Various calixarene derivatives with sulfonate, carboxylate, phosphoryl, and sulfamide groups at the upper rim were patented as antithrombotic [6], antiviral [7 -9], antimicrobial [10], and antibacterial, antifungal, and antitumor [11] agents. Among calix[n]arenes (n = 4, 6, 8), derivatives with R = SO 3 Na, (CH 2 ) m CO 2 H (m = 0 -2), PO 3

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The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives

Wanka¹,

Iqbal²,

Schreiner³

2013

Chem. Rev.

566

475

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ChemInform Abstract: CHEMIE UND TOXIKOLOGIE EINER NEUEN ANTIVIRALEN SUBSTANZ, N-(1-ADAMANTYL)-2-(2-DIMETHYLAMINO-AETHOXY)-ACETAMID-HYDROCHLORID 1. MITT.

Abstract: Ausgehend von dem 1‐Chloracetamidoadamantan (I) und dem Alkoholat (II) wird durch Williamsonsche Äthersynthese N‐(1‐Adamantyl)‐2‐(2‐dimethylamin äthoxy)‐acetamid‐hydrochlorid (III) hergestellt, das sehr gute Wirkung gegen Herpes‐Viren zeigt.

Cited by 4 publications

References 0 publications

Tromantadine: inhibitor of early and late events in herpes simplex virus replication

Tromantadine: inhibitor of early and late events in herpes simplex virus replication

Synthesis and antiherpetic activity of N-(3-amino-1-adamantyl)calix[4]arenes

The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives

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