The unique structure of the ligand-binding sites of seven-fold membrane-crossing receptors makes it possible to bind ligands of various nature and molecular weight in a wide range from 32 for Ca2+ to more than 102 kDa for glycoproteins.

Most common low molecular weight hormones (such as adrenaline and acetylcholine) bind to sites within the hydrophobic core (a). Peptide and protein ligands attach to the outer surface of the receptor (b, c). Some low molecular weight ligands, Ca2+ and amino acids (glutamate, GABA) bind to the long regions at the N-terminus, inducing them to change to a new conformation in which the long region interacts with the receptor (d). In the case of receptors activated by the cutoff protease (e), the new N-terminus acts as an autoligand. The truncated peptide may also interact with another receptor.

1.3. Biological activity of adamantane derivatives

Adamantane derivatives as physiologically active substances have been widely used since the 70s of the XX century. Adamantane itself (tricyclodecane, C10H16) is one of the bridged tricyclic naphthenes (Fig. 6).

Rice. 6. Structure of adamantane molecule.

Its molecule consists of three fused cyclohexane rings in the chair conformation. The spatial model of the adamantane molecule is a highly symmetrical design with a small surface and insignificant forces of intermolecular interaction in the crystal lattice. Of all tricyclic hydrocarbons, adamantane is the most stable, which is explained by the tetrahedral orientation of the bonds of all carbon atoms and their fixed position.

The biological activity of adamantane derivatives is due to the symmetry and volume of the spatial structure, the significant lipophilicity of the rigid hydrocarbon skeleton of adamantane, which allows them to easily penetrate biological membranes. Therefore, the modification of organic compounds with the help of adamantyl radical significantly changes their biological activity, often enhancing it. Using the spin label method, it was shown that adamantane, getting into the lipid bilayer, is able to destroy the hexagonal packing of methylene groups, characteristic of the double layer of phospholipids, and disrupt the axial arrangement of the alkyl chains of phospholipids, thereby modifying the functional properties of cell membranes. Taking into account the importance of the order of arrangement of the methylene groups of lipids in biological membranes as a factor in the functioning of membrane-associated enzymes, an indirect effect of adamantane on their activity can be noted.

At the moment, more than 1000 new adamantane derivatives have been synthesized. A pharmacological study showed the presence among them of substances that have a pronounced psychotropic, immunotropic, antiviral, curariform, anticataleptic, antiallergic activity, as well as compounds that affect the enzymatic system of the liver. Amides of adamantanecarboxylic acids exhibit antibacterial activity.

There are data on the results of the modification of the enkephalin molecule by amino acids of the adamantane series. The (S)-adamantylalanine introduced into position 5 of the enkephalin molecule gives the opioid peptide resistance to enzymes that easily destroy unmodified enkephalin (chymotrypsin, pronase, neutral protease, thermolysin).

It has been shown that nitrogen-containing derivatives have physiological activity. The first to enter medical practice in 1966 was 1-aminoadamantane hydrochloride, which has antiviral activity against strains of A2 viruses, its brand names: midantan, symmetrel, amantadine. These drugs are used to prevent respiratory diseases, because they have the ability to block the penetration of the virus into the cell. It is assumed that these drugs are able to work at the initial stages of virus reproduction, blocking the synthesis of virus-specific RNA. The antiviral activity of some amino derivatives of adamantane is related to their ability to inhibit PCC. Remantadine (polyrem, flumadine), as a lipophilic weak base, is able to increase the pH of endosomal contents and prevent virus deproteinization.

In clinical practice, drugs such as acyclovir (virolex, herpesin, zovirax, lizavir, supraviran), didanosine, foscarnet (triapten), ganciclovir (cymeven), lamivudine, ribavirin (virazole, ribamidil), stavudine, trifluridine are also used in clinical practice for the treatment of viral diseases. , vidarabine, zalcitabine (HIVID), zidovudine (azidothymidine, retrovir). However, most of these drugs have a relatively narrow spectrum of antiviral activity, their disadvantage is the presence of a variety of adverse reactions, the emergence of resistant strains of viruses, etc.

Derivatives of alkyladamantanes also have antiviral activity against strains of A2 viruses: 1-hydroxy-3,5dimethyl-7-ethyladamantane, 1-methoxy-3,5dimethyladamantane, which, unlike midantane, showed high antiviral activity against strains of strains of rhino viruses and herpes simplex. A number of hydroxy-, halogen- and mercapto derivatives of adamantane amides also have antiviral activity.

It has been shown that amantadine is able to prevent the development of sarcoma foci on the embryonic culture, other adamantane derivatives can serve as hypnotics, antimalarial drugs, and insecticides. Experiments using HIV-infected human lymphoblastoid cells have shown that some adamantane derivatives have anti-HIV activity. Midantan is used in a neurological clinic for the treatment of Parkinson's disease and Parkinson's syndrome. Similar activity is shown by acid chlorides of 3,5,7-alkyl-substituted 1-aminoadamantanes, some of which have dopamine antagonistic properties. Some quaternary ammonium bases with a 2-adamantyl radical can act as peripheral muscle relaxants (curare-like activity). Derivatives of 1-aminoadamantane and 3,3-diamino-1,1-diadamantyl are anticataleptically active, adamantanecarboxylic acids and phosphates of adamantanethiols and their derivatives have a bacteriostatic effect. Dialkylamine esters of adamantanethiocarboxylic acid exhibit bactericidal, fungicidal, herbicidal activity. The sodium salt of β-(1-adamantane)-propionic acid has a choleretic effect. 1-adamantylammonium-β-chloroethyloxaminoate and some other adamantane derivatives of the 1-AdCH2OCH2CH(OH)CH2NRR΄ type have an anesthetic effect.

Antibacterial action comparable to the antibacterial drug 5-nitro-8-hydroxyquinoline is exerted by N-(nitrophenyl)-adamantyl-carboxamides and adamantyl-substituted N-(1-methylpyridinium) iodides.

Perfluorinated adamantane is used as a component of artificial blood. There are data on the anti-aggregation ability of adamantane derivatives in relation to various pathways of platelet aggregation.

The content of the article

ADAMANTAN– tricyclic bridging hydrocarbon of the composition С 10 H 16 , the molecule of which consists of three cyclohexane rings; the spatial arrangement of carbon atoms in the adamantane molecule is the same as in the crystal lattice of diamond. According to the systematic nomenclature, adamantane should be called tricyclodecane.

Usually adamantane is depicted in one of the following ways:

In organic chemistry, there are a small number of substances that have aroused great interest among chemists around the world. Among such compounds are the structures of benzene, ferrocene, carborane, fullerenes and adamantane, there are other molecular structures that have attracted and continue to attract the interest of organic chemists. This is probably largely due to the unusual structure of the molecules themselves, especially the high degree of their symmetry.

The structure of adamantane.

The carbon skeleton of the adamantane molecule is similar to the structural unit of diamond.

That is why the name "adamantan" comes from the Greek "adamas" - diamond. Experimentally obtained structural characteristics of adamantane:

A similar structure is retained in almost all adamantane derivatives, which is due to the high stability of the adamantane framework. Adamantane is the ancestor of the homologous series of the family of hydrocarbons of the diamond-like structure diamantane, triamantane, etc.:

Based on the chemistry of adamantane, one of the areas of modern organic chemistry, the chemistry of organic polyhedrans, arose and developed.

Adamantane, despite its low molecular weight, has an unusually high melting point for saturated hydrocarbons - 269 ° C. This abnormally high temperature is due to the high symmetry of the rigid diamond-like adamantane molecule. At the same time, a relatively weak intermolecular interaction in the crystal lattice leads to the fact that the hydrocarbon is easily sublimated, partially already at room temperature.

Unlike adamantane itself, its alkyl-substituted ones melt at much lower temperatures (1-methyladamantane at 103°C, and 1-ethyladamantane at –58°C) due to the violation of the symmetry of the molecule and an increase in the vibrational and rotational mobility of its units.

Despite the absence of an asymmetric carbon atom in adamantane (a carbon atom bonded to four different substituents located at the vertices of a tetrahedron), adamantane derivatives containing four different substituents in the nodal positions are optically active. The center of the molecule of such adamantane derivatives plays the role of a hypothetical asymmetric carbon atom.

In this case, the optical activity is due to the appearance special type asymmetries - asymmetries of the molecular tetrahedron. The value of optical rotation for such compounds is small and rarely exceeds 1°.

In addition to optical, structural isomerism is characteristic of substituted adamantanes, depending on whether a substituent is attached to the nodal or bridging carbon atom. For example, 1- and 2- propyladamantanes are possible, respectively:

For disubstituted adamantane derivatives with one bridging substituent, the spatial orientation of this substituent can be axial ( but) or equatorial ( e), depending on the location of the substituent relative to the plane of the cyclohexane ring common to both substituents (bold in the figure) or it can be denoted as cis- and trans-. For example, for 1,3-dibromoadamantane, two isomers are possible: 1,3 but -dibromoadamantane and 1,3 e -dibromoadamantane, respectively:

Obtaining adamantane and its alkyl derivatives

The only natural product containing adamantane and its homologues is petroleum. For the first time, adamantane was obtained in the study of oil from the Hodoninskoye field (former Czechoslovakia) in 1933 by S. Landa and V. Makhachek. However, due to the low content of adamantane in oil (it usually does not exceed 0.001% wt.), it is not advisable to obtain it from this raw material. The amount of adamantane in various types oil depends on its chemical nature oil. The highest content of adamantane in naphthenic type oil. On the contrary, paraffinic oil contains adamantane in significantly smaller quantities. Oil also contains alkyl derivatives of adamantane, in particular, 1-methyl, 2-methyladamantanes and 1-ethyladamantane.

Since the isolation of adamantane from oil is complicated by its low content, methods for the chemical synthesis of this substance have been developed.

For the first time, adamantane was synthetically obtained in 1941 by the Swiss Prelog according to the following scheme:

However, the total yield of adamantane was only 1.5%. Improved versions of the above synthesis have been proposed, but the complexity of the synthesis, as well as the practical impossibility of synthesizing substituted adamantanes, limits the preparative value of this method.

An industrially suitable method for the synthesis of adamantane from readily available raw materials was proposed and implemented by Schleyer in 1957. The method consists in the catalytic isomerization of a tricyclic hydrocarbon (according to the systematic nomenclature - tricyclodecane) to adamantane:

The method is practically interesting, since cyclopentadiene is a quite accessible substance (it is obtained by cracking petroleum fractions as a by-product) and easily dimerizes. Depending on the catalyst used, the yields of adamantane vary over a wide range. Various strong Lewis acids such as AlCl 3 , SbF 5 can be used as catalysts. Yields range from 15 to 40%.

This method is also suitable for the synthetic preparation of various alkyl-substituted adamantanes:

Characteristically, the presence of alkyl groups significantly increases the yield of final isomerization products.

A high yield of alkyladamantanes is obtained by isomerization (over aluminum halides or complexes based on them) of tricyclic perhydroaromatic hydrocarbons of composition C 12–C 14: perhydroacenaphthene, perhydrofluorene, perhydroanthracene, and other hydrocarbons.

The yield in the last reaction is 96%.

The availability of starting compounds (the corresponding aromatic hydrocarbons are easily isolated in significant amounts from liquid products of coal coking) and the high yield of final isomerization products make this method industrially attractive.

In the described methods of liquid-phase catalytic isomerization, catalysts (AlCl 3 , SbF 5 ) are used, which have a number of significant drawbacks: increased corrosivity, instability, impossibility of regeneration, formation of significant amounts of resin during the reaction. This was the reason for the study of isomeric transformations of polycycloalkanes using stable heterogeneous acid-type catalysts obtained on the basis of metal oxides. Alumina-based catalysts have been proposed that make it possible to obtain alkyladamantanes in yields up to 70%.

Catalytic methods for the isomerization of polycycloalkanes - effective methods production of hydrocarbons of the adamantane series, many of them are of preparative significance, and the process of obtaining adamantane by isomerization of the hydrogenated cyclopentadiene dimer is implemented on an industrial scale.

However, as the molecular weight increases and the number of cycles in the original hydrocarbon increases, the rate of rearrangement into adamantanoide hydrocarbons slows down. In some cases, isomerization methods do not give the desired result. So, with their help it is impossible to obtain 2-substituted alkyl- and aryladamantanes, in addition, the reaction products, as a rule, consist of a mixture of several isomers, and they need to be separated, therefore, synthetic methods for obtaining hydrocarbons of the adamantane series, based on the use of functional derivatives of adamantane as starting materials, as well as cyclization methods - building the structure of adamantane, based on aliphatic mono- and bicyclic compounds. Syntheses based on functional derivatives are widely used to obtain individual alkyl-, cycloalkyl-, and aryladamantanes. Cyclization methods are usually used in the synthesis of polyfunctional adamantane derivatives, adamantanoid hydrocarbons, and their derivatives.

One of the first successful synthesis of 1-methyladamantane was a multistage synthesis based on 1-bromoadamantane (usually the adamantyl radical is denoted as Ad in reaction schemes):

Later, other more efficient routes for the synthesis of 1-methyladamantane were found.

The method below can be considered as a general method for the synthesis of alkyladamantanes polysubstituted at the nodal positions. It allows one to obtain alkyladamantanes with different lengths of normal alkyl groups by gradually increasing the hydrocarbon chain.

The direct synthesis of adamantane derivatives substituted in bridging positions is difficult due to the low reactivity of the bridging carbon atoms of the adamantane ring. For the synthesis of 2-alkyl derivatives of adamantane, the interaction of Grignard reagents or alkyl lithium derivatives with readily available adamantanone is used. So, 2-methyladamantane can be obtained according to the scheme:

As for other methods for obtaining adamantane structures, the most common methods are the synthesis of bicyclononane derivatives by cyclization. Although such methods are multi-stage, they make it possible to obtain adamantane derivatives with substituents that are difficult to synthesize in any other way:

Functionalization of the nodal positions of the adamantane nucleus.

It is known that saturated hydrocarbons, including adamantane, are less reactive than unsaturated and aromatic hydrocarbons. This is due to the limiting nature of all C-C ties formed by sp 3 -hybridized carbon atoms. Saturated frame structure hydrocarbons also contain only s-bonds, however, such structural features as the presence of several tertiary carbon atoms alternating with methylene bridges and the bulky structure of the cell increase the reactivity of these compounds, especially in ionic reactions. The relatively high reactivity of adamantane in reactions of the ionic type is due to its ability to form a fairly stable carbocation. The formation of adamantyl carbocation was recorded, in particular, under the action of antimony pentafluoride on 1-fluoroadamantane:

The adamantyl cation is also generated from 1-chloro-, hydroxyadamantanes in superacids (SbF 5) or "magic acid" (SbF 5 in HSO 3 F) in SO 2 and SO 2 ClF.

The most common ionic reactions occurring in the nodal positions of the adamantane nucleus:

Adamantane and its derivatives are usually brominated with molecular bromine in the liquid phase, this is an ionic process catalyzed by Lewis acid and insensitive to radical type initiators. The use of Friedel-Crafts catalysts makes it possible to replace all four hydrogen atoms in the nodal positions of the adamantane nucleus with bromine:

Under the conditions of ionic halogenation, the process proceeds selectively with respect to the nodal carbon atoms of the adamantane nucleus.

In contrast to ionic halogenation, free radical halogenation of adamantane itself and its derivatives leads to a mixture of products consisting of 1- and 2-substituted derivatives.

To obtain fluorine derivatives of adamantane, 1-adamantanol is used:

Halogenated adamantanes are widely used for the synthesis of other functionally substituted adamantanes. The reactivity of adamantane halogen derivatives is greater than that of other saturated hydrocarbons. Oxidation of adamantane with sulfuric acid is an important preparative method, since it makes it possible to obtain adamantanone in high yield:

At the same time, the interaction of adamantane with concentrated sulfuric acid in a trifluoroacetic anhydride medium makes it possible to obtain a mixture of 1- and 2-adamantanols, with the predominant content of the first of them:

For the synthesis of carboxylic acids of the adamantane series, the carboxylation reaction is most often used. Koch and Haaf for the first time in 1960 carried out the direct synthesis of 1-adamantanecarboxylic acid in this way. The reaction is carried out in a medium of concentrated sulfuric acid or oleum, which ensures the formation of adamantyl cations.

Despite the unusual structure of adamantane, the reactions it enters into are quite traditional for organic chemistry. The peculiarity of adamantane manifests itself due to either steric effects associated with the large size of the adamantyl radical, or with the possibility of the formation of a relatively stable adamantyl cation.

Application.

The prospects for the use of adamantane derivatives are determined by a set of specific properties: the relatively large size of the adamantyl radical (its diameter is 5Å), high lipophilicity (solubility in nonpolar solvents), and conformational rigidity. The last two properties are especially important when creating new drugs. The introduction of the adamantyl radical increases, in general, the thermal stability of the substance and its resistance to oxidation and radiation exposure, which is important, in particular, in the preparation of polymers with specific properties.

All this stimulated a large-scale search for new drugs, polymeric materials, fuel and oil additives, explosives, liquid rocket propellants, stationary phases for gas-liquid chromatography based on adamantane derivatives.

Now adamantane itself is not used, but a number of its derivatives are widely used.

To the greatest extent, adamantane derivatives are used in pharmaceutical practice.

Thus, the drugs rimantadine (1-(1-adamantyl)ethylamine hydrochloride), and adapromine (a-propyl-1-adamantyl-ethylamine hydrochloride) are used as drugs for effective prevention viral infections, and amantadine (1-aminoadamantane hydrochloride) and gludantan (1-aminoadamantane glucuronide) are effective in parkinsonism caused by various causes, in particular, neuroleptic and post-traumatic syndrome.

Polymer analogs of adamantane are patented as antiviral compounds, including, in relation to HIV, polymer analogs of adamantane.

Substituted amides of adamantanecarboxylic acid can serve as hypnotics. The introduction of an adamantyl residue into 2-hydroxynaphthoquinone leads to the production of antimalarial drugs. Adamantylamino alcohols and their salts have a pronounced psychostimulating effect and are not toxic at the same time. Some N-(adamant-2-yl)anilines exhibit neurotropic activity, and the biological activity of N-(adamant-2-yl)hexamethyleneimine is manifested in relation to parkinsonism.

Alkyl derivatives of adamantane, in particular 1,3-dimethyladamantane, are used as working fluids in some hydraulic installations. The expediency of such their use is explained by the high thermal stability of dialkyl derivatives, their low toxicity and the large difference between the critical temperature and the boiling point.

In the chemistry of macromolecular compounds, the introduction of an adamantyl substituent made it possible in many cases to improve the performance characteristics of polymeric materials. Typically, polymers containing an adamantyl moiety are heat-resistant and their softening point is quite high. They are quite resistant to hydrolysis, oxidation, photolysis. In terms of these properties, adamantane-containing polymer materials surpass many well-known industrial polymers and can be used in various fields of technology as structural, electrical insulating, and other materials.

Vladimir Korolkov

Camphor belongs to bicycloteptane derivatives. Natural - camphor is obtained from the camphor tree (China, Japan) by steam distillation. Racemic camphor (3) is synthesized from a-pinene (1) via formate (2) It excites the central nervous system(CNS), stimulates respiration and metabolic processes in the myocardium (cardiotonic) It is prescribed for heart failure, drug poisoning and sleeping pills, and for rubbing with rheumatism Introduction of the atom

bromine in the -position to the ketone group dramatically changes the pharmacological picture of the camphor derivative. Bromocamphor (4), improving cardiac activity, acquires sedative properties and calms the central nervous system. It is used for neurasthenia and neuroses of the heart:

Derivatives of the polycyclic adamantane system have been proposed as antiviral agents. 1-Amino-adamantane (8) (midantane, amantadine) is obtained by bromination of adamantane (5) in the presence of copper to 1-bromoadamantane (6), which is converted into 1-formyl-amino derivative (7) by the action of formamide. Hydrolysis of the latter in the presence of HCI leads to midantan (the first synthetic anti-influenza agent). Alkylation of aminoadamantane with 1-chlorogluc-uronic acid in the presence of a base gives its glucuronide (9) (gludantan is a medicinal substance for the treatment of parkinsonism and viral eye diseases - conjunctivitis):

(Another anti-fippotic drug - rimantadine (13) - is synthesized by replacing bromine in compound (6) with a carboxyl group, acting with formic acid in oleum (this system generates CO, necessary for substitutional hydroxycarbonylation). Then acid (10) is converted using thionyl chloride into its acid chloride, which

treated with ethoxymagnesiummalonic diester and converted to the acyl derivative (11). It is hydrolyzed to diacid without isolation, and the latter is decarboxylated to give 4-acetyladamantane (12). Compound (12) is then subjected to reductive amination in the formamide/formic acid system, resulting in rimantadine (13):

As you already know, since March, one of us began to write a regular column in the favorite magazine of our childhood - "Chemistry and Life". The current text is about a substance that has become the chemical "signature" of the author - and the basis of some very common antiviral drugs. So this post is both about the history of adamantane and the history of rimantadine

It seems to me that in our time it is time to introduce, instead of the Soviet abbreviation full name, an extended version of FION: “surname-first name-patronymic-nickname”. I admit, I have a nickname too. Many on the Web know me under the nickname adamanta (well, or under the more familiar damantych). This word arose back in those distant years when I was a real chemist. In fact, I wanted to get myself the nickname adamantan in honor of
beautiful hydrocarbon, and the Greek word “irresistible” was enticing, but there were only eight boxes for letters in the paper questionnaire ... I still use this flawless molecule as a nickname, unique in that its structure, on the one hand, is rigid, and on the other hand, it is devoid of all possible spatial stresses that are characteristic of many cyclic molecules.

September 21-27, 1924 in Innsbruck
a major congress of natural scientists took place. Among others, a certain chemist by the name of Dekker spoke at it (in a report on the congress published in the authoritative journal Angewante
Chemie", he appears only as H. Decker from Jena) with a report "Ways for the synthesis of diamond". In this report, he considered the possibility of synthesizing hydrocarbons with a structure similar to
diamond atomic lattice, and predicted that molecules with 100-200 atoms
carbon will already strongly resemble a diamond. It was then that he mentioned the molecule
"decaterpene" C 10 H 16, somewhat surprised that it has not yet been synthesized.
So for the first time the hypothetical hydrocarbon adamantane came to the attention of chemists.

The most curious thing is that a substance with exactly the same structure has been known for a very long time. A similar substance was synthesized by the great Alexander Butlerov in 1859 by the interaction of ammonia and formaldehyde. It is called urotropine, or hexamethylenetetramine. True, in the structural nodes of this molecule there are not carbon atoms, but nitrogen atoms.

Alexander Butlerov

Urotropin

This substance is still well known and used in everyday life. Most people know it as a dry fuel, doctors use it as an antiseptic and call it "methenamine". By the way, this is one of the few cases when the currently used synthetic medical preparation has more than a century of history of use.

But back to our adamantans. In the same 1924, the famous German chemist Hans Meerwein (the author of the famous reagent of his own name, triethyloxonium tetrafluoroborate) nevertheless made an attempt to synthesize "decaterpene". He made formaldehyde react with malonic ester in the presence of piperidine. However, a substance was obtained that turned out to be not quite adamantane, and was called the "Meerwein ether."

Hans Meerwein

Aether of Meerwein

In 1933, interest in adamantane increased even more, since a pure substance was found in nature - in oil. Czech petrochemists Landa and Makhachek isolated it from the products of the Hodoninskoye deposit. Synthesis attempts continued, but nothing came of it for another eight years. As an example of an unsuccessful attempt, one can cite a synthesis from phloroglucinol and cyclohexanone.

In the year of the beginning of the Great Patriotic War, the future Nobel laureate, the Croatian-Swiss chemist (then he had not yet moved to Zurich) Vladimir Prelog, entered the business. He turned to the failure of Hans Meerwein and continued to "conjure" with the result of his synthesis. As a result, in four stages and with a yield of less than a percent, the world's first synthetic adamantane was obtained.

Vladimir Prelog

Synthesis of Prelog

The fact that it was Prelog who synthesized adamantane is very symbolic. After all, it was he who became the founder of modern stereochemistry, the man who brought order to the chemical nomenclature of optically active substances. Adamantane is remarkable not only for its structure - it turned out to be the first substance with a chiral center outside the molecule itself. After all, the entire adamantane molecule is like a single carbon atom. If you “hang” (without quotes?) on it four different substituents at tertiary carbon atoms, then they will be located at the vertices of an imaginary tetrahedron, and the molecule will be incompatible with its mirror image. In 1969, such compounds were obtained and separated into optical isomers. And they began to call them according to the Kahn-Ingold-Prelog system that arose between 1941 and 1969, in the creation of which the person who first synthesized adamantane took the most active part.

Adamantane derivatives may have optical isomers

But we still have not said anything about the practical benefits of such molecules. A little more than a quarter of a century has passed since the first synthesis of adamantane, and its simple derivative - aminoadamantane, or amantadine - began to be used as an antiviral agent.

amantadine

It turned out that this small molecule is very dangerous for the influenza virus. A little later it turned out that amantadine relieves the symptoms of parkinsonism well - faster than levodopa and with a minimum side effects. The pharmacochemistry of adamantanes is still developing in these directions. The two most famous adamantane preparations are just in these areas.

The first is rimantadine. This is also a monosubstituted adamantane, to which a CH3CHNH2 group is attached. It began to be tested as an antiviral agent even before amantadine (if the first was received in 1967, then rimantadine - back in 1963). It is still actively used against a wide variety of viruses - from influenza A and herpes to tick-borne encephalitis. It suppresses the reproduction of viruses at the initial stage - immediately after their penetration into the cell.

rimantadine

The second is memantine. As the name implies, this drug affects memory. It does improve it in Alzheimer's patients, but memantine is being tried to treat other types of dementia as well.

memantine

So adamantane, which almost accidentally became my chemical signature, is not only a perfectly shaped molecule, but an interesting and beneficial substance with a vibrant biography.