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A promising strategy in the synthesis of functional compounds with a cage structure is the use of 1,3-dehydroadamantane (tetracyclo[3.3.1.1.3,7.0.1,3]decane; 1,3-DHA; bridging [3.3.1]propellane) and its derivatives that are capable of restoring the adamantane structure in their reactions. The review provides information on the methods for the synthesis of 1,3-DHA, spectral characteristics, probable intermediates generated from propellanes, and the advantages of their using: low-stage syntheses of difficult-to synthesize adamantane derivatives, atomic precision, and "green chemistry." The reactions of 1,3-DHA with a wide range of organic compounds are considered, and its reactivity with respect to CH-, NH-, OH-, and SH-acids, as well as arenes, hydantoins, and heterocyclic compounds, is compared. New chemo- and regioselective methods for the one-step introduction of a 1-adamantyl group into the molecules of various substrates are classified. Particular attention is paid to the reactions of 1,3-DHA with various C–H acids, which enable the easy formation of C–CAd bonds to give hard-to-synthesize adamantane derivatives. The influence of pKa of the substrate on the selectivity of the reactions is demonstrated. Low-step methods for the synthesis of new adamantane derivatives, which have shown high activity as hsEH epoxide hydrolase inhibitors and antitumor agents, are described. [ABSTRACT FROM AUTHOR]

The reaction of 1,3-dehydroadamantane with alkylbenzenes was studied for the first time. It involved the C–H bond of the alkyl substituent in the α-position with respect to the aromatic ring. The proposed radical mechanism of the reaction was confirmed by the isolation of 1,1′-biadamantane and 1,2-diphenylethane derivatives. Difficultly accessible (adamantan-1-ylmethyl)arenes were synthesized in 53–78% yields. [ABSTRACT FROM AUTHOR]

The reaction of 1,3-dehydroadamantane with C2-C6 α,ω-alkanediols selectively afforded ω-(adamantan- 1-yloxy)alkan-1-ols in 87-94% yield. The reaction of 1,3-dehydroadamantane with ω-aminoalkan-1- ols (2-aminoethanol and 3-aminopropan-1-ol) gave mixtures of addition products through the oxygen and nitrogen atoms, which can be readily separated by fractional vacuum distillation or crystallization. [ABSTRACT FROM AUTHOR]

2-Fluorophenyl isocyanate reacted with adamantan-1(2)-amines and their homologs in DMF to give 31-92% of the corresponding N,N′-disubstituted ureas that are target-oriented human soluble epoxide hydrolase (sEH) inhibitors. Introduction of a fluorine atom increases the sEH inhibitory activity by a factor of 4.5. [ABSTRACT FROM AUTHOR]

Thioureas containing halogen- and dihalogen-substituted phenyl fragments were obtained based on adamantan-1-ylcarbonyl isothiocyanate in up to 76–94% yields. The effect of the carbonyl group on the melting point, lipophilicity, and water solubility of the thioureas was established. A computational screening of biological activity was carried out, which showed that 1-(adamantan-1-ylcarbonyl)-3-(aryl)thioureas can have antiviral activity and nootropic effect. Purinoceptors, along with epoxide hydrolase, were found to be the most likely targets. [ABSTRACT FROM AUTHOR]

1,3-Dehydroadamantane reacted with saturated carboxylic acid chlorides to give the corresponding 1-acyl-3-chloroadmantanes as the major products. In some cases, minor products of insertion into the Cα-H bond of acyl chloride were formed. The reactions of 1,3-dehydroadamantane with aromatic (heteroaromatic) carboxylic acid chlorides selectively afforded aryl (hetaryl) 3-chloroadamantan-1-yl ketones. The described reactions provide a synthetic route to difficultly accessible alkyl (aryl) ketones containing a 3-chloroadamantan- 1-yl group in one step under mild conditions with high yields. [ABSTRACT FROM AUTHOR]

A one-step synthesis of hard-to-reach adamantyl polyfluoroalkyl ethers in yields up to 95% comprises the reaction of strained 1,3-dehydroadamantane with polyfluorinated alcohols. In the competitive reactions of 1,3-dehydroadamantane with pentan-1-ol and its fluorinated analog, the latter compound is etherified predominantly (∼3:5). [ABSTRACT FROM AUTHOR]

A convenient one-step procedure has been developed for the synthesis of fluorine-containing 2-(adamant-l-yl)-1,3-diketones by reaction of fluorinated 1,3-diketones with 1,3-dehydroadamantane. The products can be used as starting compounds for the preparation of new fluorinated adamantyl-containing heterocyclic compounds. [ABSTRACT FROM AUTHOR]

A series of N,N′-disubstituted bis-ureas containing a lipophilic 4-(trifluoromethoxy)phenyl fragment were synthesized in 58–80% yields by reaction of 4-(trifluoromethoxy)phenyl isocyanate with aliphatic diamines. The synthesized compounds are promising as inhibitors of human soluble epoxide hydrolase. [ABSTRACT FROM AUTHOR]

The article focuses on the new oligomer softener Pyroplast for tyre rubbers. Topics discussed include the use of heavy pyrolysis resin (HPR) as a low-grade raw material in producing carbon black, the polymerisation temperature of gasoline HPR, and the comparison between the technology and quality of styrene-indene resin (SIR) and the oligomer softener.

4-(1-Adamantyl)-3-polyfluoromethylpyrazoles were synthesized for the first time in high yields by condensation of fluorinated 2-(1-adamantyl)-1,3-diketones with hydrazine hydrate. [ABSTRACT FROM AUTHOR]

N,N′-Disubstituted ureas and thioureas containing a 1,1,7-trimethylbicyclo[2.2.1]heptan-2-yl sub-stit-uent were synthesized in up to 99% yields by the reaction of exo-(R or S)-1,1,7-trimethylbicyclo[2.2.1]-heptan-2-amine with aromatic isocyanates and isothiocyanates with the goal of comprehensive estimation of enantiomeric stereospecificity of human soluble epoxide hydrolase (hsEH). The synthesized compounds are promising hsEH inhibitors. [ABSTRACT FROM AUTHOR]

This brief review highlights the history of the discovery of the phosphatase domain of human soluble epoxide hydrolase (sEH-P). The data on its structure and physiological role are summarized. State-of-the-art methods for the evaluation of the inhibitory activity of small molecules against sEH-P are described. The structures of endogenous substrates and known inhibitors of sEH-P are considered. The prospects of the development of this area of research in medicinal chemistry are analyzed. [ABSTRACT FROM AUTHOR]

Methods have been developed for the synthesis of N-[2-(adamantan-2-yl)ethyl]-N′-R-ureas and -thioureas in 36–87% yields by the reaction of 2-(adamantan-2-yl)ethanamine with aromatic isocyanates and isothiocyanates. The displacement of the ethylene bridge from position 1 to position 2 of the adamantane fragment has been found to exert no significant effect on the logP values and melting points of the corresponding ureas. [ABSTRACT FROM AUTHOR]

A series of N,N′-disubstituted ureas and bis-ureas were synthesized in 36–85% yields by the reaction 3-bromoadamantan-1-yl isocyanate with α,ω-alkanediamines, fluorinated anilines, and trans-4-[(4-aminocyclo-hexyl)oxy]benzoic acid. The hydrolysis of 3-bromoadamant-1-yl isocyanate in the presence of a catalytic amount of DBU gave 60% of symmetrical N,N′-bis(3-bromoadamantan-1-yl)urea. The synthesized compounds are promising as inhibitors of human soluble epoxide hydrolase (hsEH). [ABSTRACT FROM AUTHOR]

The reaction of bicyclo[2.2.1]hept-5-en-2-yl isocyanate with fluoro- and chloro-substituted anilines was used to synthesize in a yield of 25–68% a series of 1,3-disubstituted ureas containing a lipophilic group in their structure. The synthesized ureas are promising as inhibitors of RNA virus replication and human soluble epoxide hydrolase. [ABSTRACT FROM AUTHOR]

Methods have been developed for the synthesis of N,N′-disubstituted ureas containing an adamantane fragment separated from the urea nitrogen atom by an ethylene spacer in 29–88% yields on the basis of 2-(adamantan-1-yl)ethyl isocyanate and 2-(adamantan-1-yl)ethanamine. 1,1′-Carbonyldiimidazole was used for the first time to obtain 2-(adamantan-1-yl)ethyl isocyanate. The latter was formed through a stable intermediate product, N-[2-(adamantan-1-yl)ethyl]-1H-imidazole-1-carboxamide which could be isolated and used in the synthesis of symmetrically and unsymmetrically substituted ureas. [ABSTRACT FROM AUTHOR]

Ethyl [(adamantan-1-yl)alkylene(phenylene)amino]oxoacetates and N1,N2-bis[(adamantan-1-yl)-alkylene(phenylene)oxamides were prepared in yields of 72–87 and 18–60%, respectively, by the reaction of amines of the adamantane series with ethyl chlorooxoacetate and oxalyl chloride in methylene chloride in mild conditions. [ABSTRACT FROM AUTHOR]

The activity of the platinum (1%) catalysts supported on oxides of rare-earth elements of the cerium and yttrium groups was studied. Under the liquid-phase hydrogenation conditions, the studied catalytic systems are characterized by a high selectivity and the yield of 4-aminophenol is close to quantitative. In terms of the initial hydrogenation rate of 4-nitrophenol the system 1%Pt/Dy2O3 is 4.9 times superior to the standard 1%Pt/Al2O3 catalyst, whereas the system 1%Pt/Ce2O3 is 1.4 times more active than the standard catalyst. [ABSTRACT FROM AUTHOR]

A significant effect of the steric factor on the activity of 3,5-dimethyl-1H-pyrazolide as an acylating agent has been found using the example of acylation of camphane-type monoamines. The predominant contribution of the catalytic hydrogenation as a component of the Schwenk-Papa reaction has been confirmed by the synthesis of 4-chlorobenzoyl derivatives. [ABSTRACT FROM AUTHOR]

Amines of the adamantane series reacted with carbon disulfide and di-tert-butyl dicarbonate in the presence of triethylamine and a catalytic amount of 4-(dimethylamino)pyridine to give homologs of 1-isothiocyanatoadamantane in 80-86% yields. Adamantan-2-amine, 1-(adamantan-1-yl)ethanamine, and adamantan- 1-ylmethanamine turned out to be more reactive than adamantan-1-amine; in the latter case, the reaction time was twice as long. [ABSTRACT FROM AUTHOR]

Reactions of 3(4)-fluorophenyl isothiocyanates with amines of the adamantane series in DMF afforded 86-93% of the corresponding N,N′-disubstituted thioureas that are target-oriented inhibitors of human soluble epoxide hydrolase (hsEH). The effect of isosteric replacement of hydrogen in the aromatic fragment by fluorine and of oxygen in the urea fragment by sulfur on the IC50 value was estimated. The inhibitory activity increases twofold for the 3-fluorophenyl derivatives and ninefold for 4-fluorophenyl analogs. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the reactions of 1,3-dehydroadamantane with organic isocyanates through heating the reactants in boiling tetrahydrofuran over 2 hours in Russia. The study employs a Vavarian Mercury-300 spectrometer at 300 MHz using carbon tetrachloride as solvent and hexamethyldisiloxane or tetramethylsilane as internal reference in recording the H NMR spectra. A Hewlett-Packard HP 5972 mass-selective detector was used in obtaining mass spectra.

Possibility of synthesis of 1-adamantyl phenyl ethers by one stage without use of a catalyst was researched. [ABSTRACT FROM AUTHOR]

The article discusses the method for the synthesis of N-and C-adamantyl-containing pyrazoles based on acid-catalyzed adamantylation of pyrazoles with various functional derivatives of adamantine. This method ensures fairly poor yields of the target products and requires strongly acidic medium. Also, another method fro the preparation of N-adamantyl is mentioned and it involves the compounds propellane and dehydroadamantane which is characterized by a high proton affinity.

The article reports on the findings a study which examined the reaction of [3.3.1] propellanes 1,3-dehydroadamantane (Ia) and 5,7-dimethyl-1,3-dehydroadamantane (Ib) with diaryl diselenides. The study, which was performed under financial support by the Russian Foundation for Basic Research and by the Russian Academy of Sciences, revealed that propellanes Ia and Ib react with diphenyl diselenide (IIa) and bis (4-chlorophenyl) diselenide (IIb) on heating in boiling diethyl ether.

The article focuses on a study regarding the reaction of 1,3-dehydroadamantane with camphor and isocamphanone. The reaction of 1,3-dehydroadamantane (I) with bicyclic ketones including 1,7,7-trimethylbicyclo[2.2.1]- heptan-2-one (II, DL-camphor) and 5,5,6-trimethylbicyclo[ 2.2.1]heptan-2-one isocamphanone was examined. Its reaction with camphor gave approximately equal amounts of two stereoisomeric addition products.

The article discusses the direct noncatalyzed alkylation with 1,3-dehydroadamantane of a series of polycyclic hydrocarbons such as acenaphthylene, tetralin, and fluorene. It results to an isolated adamantylation products purely with the methylene group and not with the aromatic ring for hydrocarbons. It adds that the alkylation with polycyclic hydrocarbon ensures the better selectivity of the monoaddition of the 1,3-dehydroadamantane than at the equimolar reagents ratio.

The article discusses the acid catalysis of adamantyl-containing azoles such as imidazoles with the corresponding azoles of various functional derivatives of adamantane. It states that the catalysis using strong acids had provided relatively low yields of 45 to 75 percent of the target products. It adds that the adamantylation of imidazoles and molar reagents afforded the corresponding mild conditions with a good yield of synthesized N-adamantylimidazoles.

The article focuses on the synthesis of adamantyl-substituted keto esters. Reaction between 1,3-dehydroadamantane and a series of ketoesters, among which was cyclic methyl 2-oxocyclopentanonecarboxylate was performed. The adamantylation of ethyl acetoacetate in a boiling inert solvent, ethyl ether, under an atmosphere of dry nitrogen purified from oxygen at the molar ratio of reagents 1,3-dehydroadamantane and ethyl acetoacetate equal to 1: 1.5-2 within 1-2 hours afforded ethyl 2-(1-adamantyl)-3-oxobutanoate in a moderate yield.

A one-step synthesis of 1-(isocyanatomethyl)-3,5-dimethyladamantane with a yield of 87% is described. The reaction of 1-(isocyanatomethyl)-3,5-dimethyladamantane with aliphatic diamines gave a series of symmetrical 1,3-disubstituted ureas with 63–99% yields. The synthesized ureas hold promise as human soluble epoxide hydrolase inhibitors. [ABSTRACT FROM AUTHOR]

We have developed an improved two-stage approach to the synthesis of 2-fluorophenylisoselenocyanate from 2-fluoroaniline, which at the first stage uses a mixture of solvents, dichloromethane and tert-butanol, allowing us to significantly simplify the isolation and purification of the target product. The reaction of 2-fluorophenylisoselenocyanate with adamantyl-containing and bicyclic amines gave 1,3-disubstituted selenoureas in 27–83% yields. The obtained selenoureas were studied for their antioxidant properties and antiradical activity. A number of compounds demonstrated the antioxidant properties several times exceeding the values of the reference Trolox and Ionol. [ABSTRACT FROM AUTHOR]

A series of N,N′-(alkane-α,ω-diyl)bis[N′-(adamantan-1-yl)selenoureas] have been synthesized in 27–84% yields by the reaction of adamantan-1-yl isoselenocyanate with alkane-α,ω-diamines. The synthesized compounds melted in the range 105–164°C, which is lower by ~80°C than the melting point range of their isosteric analogs containing urea fragments. N,N′-(Alkane-α,ω-diyl)bis[N′-(adamantan-1-yl)selenoureas] are promising as inhibitors of human soluble epoxide hydrolase. [ABSTRACT FROM AUTHOR]

A three-stage method for the preparation of 3-fluoro-1-isocyanatoadamantane in 76% yield was developed using the reaction of 3-hydroxyadamantane-1-carboxylic acid with Ishikawa's reagent and subsequent reaction with diphenylphosphoryl azide. The reaction of 3-fluoro-1-isocyanatoadamantane with a number of aliphatic diamines, fluorine-containing anilines, and trans-4-amino(cyclohexyloxy)benzoic acid afforded a new series of targeted inhibitors of epoxide hydrolase sEH in 43–89% yields. The absence of a methylene bridge between the adamantane and urea moieties led to an increase in the melting points of the synthesized compounds, while the introduction of a fluorine atom reduces their melting points compared to nonfluorinated analogs. [ABSTRACT FROM AUTHOR]

A procedure has been developed for the synthesis of rac-1-[isocyanato(phenyl)methyl]adamantane from rac-2-(adamantan-1-yl)-2-phenylacetic acid in 95% yield. The reactions of rac-1-[isocyanato(phenyl)-methyl]adamantane with aliphatic diamines and trans-4-[(4-aminocyclohexyl)oxy]benzoic acid afforded a series of N,N′-disubstituted ureas in 60–91% yields, and its hydrolysis in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene gave 94% of symmetrical N,N′-bis[(adamantan-1-yl)(phenyl)methyl]urea. The structure of rac-2-(adamantan-1-yl)-2-phenylacetic acid was confirmed by X-ray analysis of its single crystal. [ABSTRACT FROM AUTHOR]

A two-step procedure to synthesize (3-fluoroadamantan-1-yl)methyl isocyanate from (3-hydroxyadamantane)acetic acid that involves fluorination with Ishikawa's reagent on the first step of the synthesis was developed. The reaction of (3-fluoroadamantan-1-yl)methyl isocyanate with aliphatic diamines gave 1,3-disubstituted bis-diureas in 60–97% yields. A strong decrease in the melting points of the obtained ureas (up to ∼70–144 °C) was observed upon introduction of the fluorine atoms at the bridgehead positions of the adamantane unit. [ABSTRACT FROM AUTHOR]

A one-step procedure has been developed for the synthesis of (3-bromoadamantan-1-yl)methyl isocyanate from 2-(3-bromoadamantan-1-yl)acetic acid and diphenylphosphoryl azide in 85% yield. The reac-tions of (3-bromoadamantan-1-yl)methyl isocyanate with aliphatic diamines and 4-(trans-4-aminocyclohexyl-oxy)benzoic acid gave a series of N,N′-disubstituted ureas and diureas in 52–85% yield. The hydrolysis of (3-bromoadamantan-1-yl)methyl isocyanate in the presence of a catalytic amount of DBU afforded symmetrical N,N′-bis[(3-bromoadamantan-1-yl)methyl]urea in 52% yield. [ABSTRACT FROM AUTHOR]

N,N′-Disubstituted ureas and thioureas containing a lipophilic optically active bicyclic fragment of natural origin were synthesized by reaction of (R)- and (S)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-amine (prepared from the natural terpenoid fenchone) with aromatic isocyanates and isothiocyanates in up to 88 and 87% yield, respectively, with the goal of assessing the enantiomeric specificity of human soluble epoxide hydrolase (hsEH). The synthesized compounds were found to be promising as inhibitors of RNA virus replication and hsEH. [ABSTRACT FROM AUTHOR]

A series of N,N′-disubstituted selenoureas containing an adamantane fragment have been synthesized in 23–75% yields. Procedures for the isolation and purification of aromatic isoselenocyanates have been improved. The chemical shift of the C=Se carbon nucleus in the 13C NMR spectra of selenoureas has been refined. The synthesized selenoureas have been found to be promising as inhibitors of not only epoxide hydrolase (sEH-H) but also phosphatase domains (sEH-P) of human soluble epoxide hydrolase. [ABSTRACT FROM AUTHOR]

The reactions of 1-isobutyl-4-(1-isocyanatoethyl)benzene with various amines and of 1-(4-isobutylphenyl)ethanamine with halogenated aromatic isocyanates gave a series of ureas containing an ibuprofen fragment in their structure. The yields of the target product yields were up to 95%. The synthesized ureas are potential multitarget inhibitors of soluble epoxide hydrolase (sEH) and cyclooxygenase (COX). [ABSTRACT FROM AUTHOR]

An addition of the Morita—Baylis—Hillman (MBH) carbonates to adamantane-containing isothiocyanates was studied. The MBH carbonates react with 1-(4-isothiocyanatophenyl)-adamantane in the presence of triphenylphosphine to give 5-aryl-substituted adamantane-containing 2-amino-4-methoxycarbonylthiophenes in 31–59% yields, while 1- and 2-isothio-cyanatoadamantanes were found unreactive in this reaction. [ABSTRACT FROM AUTHOR]

N,N′-Disubstituted ureas and thioureas containing a lipophilic optically active natural bicyclic moiety have been synthesized by reactions of (R)-, (S)-, and (RS)-1,1,7-trimethylbicyclo[2.2.1]heptan-2-amines with aromatic isocyanates and isothiocyanates in up to 85% and 88% yield, respectively, with the goal of estimating enantiomeric stereospecificity of human soluble epoxide hydrolase (hsEH). The synthesized com-pounds are promising as inhibitors of RNA viruses and hsEH. [ABSTRACT FROM AUTHOR]

A new procedure has been proposed for the synthesis of 3-chloroadamantan-1-ylmethyl isocyanate starting from 2-(3-chloroadamantan-1-yl)acetic acid. Reactions of 3-chloroadamantan-1-ylmethyl isocyanate with fluoro- and chloroanilines and alkane-α,ω-diamines afforded two series of N,N′-disubstituted ureas containing a 3-chloroadamantan-1-yl substituent in 53–94% yields. The synthesized ureas are promising as inhibitors of human soluble epoxide hydrolase. [ABSTRACT FROM AUTHOR]

A series of 1,3-disubstituted ureas containing a lipophilic adamantane moiety tethered to the ureido group by a methylene bridge were synthesized by the reaction of 1-(isocyanatomethyl)adamantane with monohalo- and dihaloanilines in yields of up to 92%. The synthesized ureas are target oriented inhibitors of human soluble epoxide hydrolase (sEH). [ABSTRACT FROM AUTHOR]

Anew method for assessing the structural similarity of pharmacologically active substances based on a hierarchical description of the chemical structure by QL-language descriptors with varying degrees of complexity was developed. The proposed QL-similarity coefficient was shown to enable recognition of structurally similar compounds. An in silico search for Maillard reaction inhibitors among new adamantane derivatives was carried out by the method of similarity to standards using the IT Microcosm software complex. Two compounds with greater activity than the reference compound (aminoguanidine) and seven compounds with comparable activity were found in in vitro experiments. [ABSTRACT FROM AUTHOR]

The reaction of (S)-(–)-1-isocyanato-4,7,7-trimethyl-2-oxabicyclo[2.2.1]heptan-3-one with fluoro- and chloro-substituted anilines afforded a series of N,N′-disubstituted ureas containing a natural lipophilic camphanic acid moiety in 42–75% yield. The synthesized compounds are promising as inhibitors of human soluble epoxide hydrolase. [ABSTRACT FROM AUTHOR]

A series of 1,3-disubstituted ureas containing a bicyclic lipophilic group of natural origin were synthesized by the reactions of bicyclo[2.2.1]heptane-2-yl isocyanate with amines in yields of up to 82% and by the reactions of bicyclo[2.2.1]heptan-2-amine and 1,7,7-trimethylbicyclo[2.2.1]heptan-2-amine with 1,1'-carbonyldiimidazole in yields of up to 94%. The synthesized ureas are potent inhibitors of RNA virus replication and soluble epoxide hydrolase. [ABSTRACT FROM AUTHOR]

A series of N-(4-oxoadamantan-1-yl)-N′-[fluoro(chloro)phenyl]ureas have been synthesized in 27–73% yields by reaction of 1-isocyanatoadamantan-4-one with fluoro- and chlorosubstituted anilines. The products are promising as human soluble epoxide hydrolase inhibitors. [ABSTRACT FROM AUTHOR]