A novel single-step method has been developed for the synthesis of 1-(1-isocyanoethyl)adamantane from 1-(1-adamantylethyl)amine, chloroform, and t-BuOK, in a dichloromethane/tert-butanol (1:1) medium, yielding 92%, which is 27% higher compared to the known method, without the use of highly toxic compounds. The product was characterized using 1H and 13C NMR spectroscopy, GC-MS, and elemental analysis.

A method comprising the use of a fluorinating agent, the Ishikawa’s reagent, at one of its steps was developed for the synthesis of 1,3,5-trifluoroadamantane-7-isocyanate from 3,5,7-trifluoroadamantane-1-carboxylic acid and diphenylphosphoryl azide. The reaction of 1,3,5-trifluoroadamantane-7-isocyanate with fluoroanilines gave 1,3-disubstituted ureas in the yields of 58–73

Selenoureas containing a halophenyl fragment were synthesized in 37–59

The title compound, 1-(3-isoselenocyanatopropyl)adamantane, was synthesized for the first time from 3-(adamantan-1-yl)propan-1-amine by the two-stage reaction with 1-(3-isocyanopropyl)adamantane as intermediate. The product was characterized by NMR, GC-MS, and elemental analysis.

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

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.

The soluble epoxide hydrolase (sEH) is a potential target to treat cardiovascular, renal and neuronal diseases. A series of sEH inhibitors containing naturally occurring lipophilic groups (originating from camphor and fenchone) were developed. Inhibitory potency ranging from 0.7 nM to 6.47 μM was obtained. It was discovered that ureas derived from L-camphor were more active against sEH (2.3-fold average) than the corresponding analogues derived from D-camphor indicating enantiomeric preference of sEH. Ureas derived from fenchone possess lower activity against sEH (ca. 80-fold on average) than their camphor-derived analogs due to the specific structure of the lipophilic fragment and show less enantiomeric preference (1.75-fold on average). Moreover, fenchone-derived ureas show no consistency in enantiomeric preference. Endo/exo-form of compound L-3a derived from L-camphor is 4-fold more potent than the corresponding analogue prepared from D-camphor (IC50 = 0.7 nM vs. 2.8 nM) making it the most promising sEH inhibitor among the tested series.

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

A series of N,N′-(alkane-α,ω-diyl)bis[N′-(adamantan-1-yl)selenoureas] have been synthesized in 27–84

The inhibitory potency of the series of inhibitors of the soluble epoxide hydrolase (sEH) based on the selenourea moiety and containing adamantane and aromatic lipophilic groups ranges from 34.3 nM to 1.2 μM. The most active compound 5d possesses aliphatic spacers between the selenourea group and lipophilic fragments. Synthesized compounds were tested against the LPS-induced activation of primary murine macrophages. The most prominent anti-inflammatory activity, defined as a suppression of nitric oxide synthesis by LPS-stimulated macrophages, was demonstrated for compounds 4a and 5b. The cytotoxicity of the obtained substances was studied using human neuroblastoma and fibroblast cell cultures. Using these cell assays, the cytotoxic concentration for 4a was 4.7–18.4 times higher than the effective anti-inflammatory concentration. The genotoxicity and the ability to induce oxidative stress was studied using bacterial lux-biosensors. Substance 4a does not exhibit genotoxic properties, but it can cause oxidative stress at concentrations above 50 µM. Put together, the data showed the efficacy and safety of compound 4a.

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.

Для расширения массива данных об энантиомерной специфичности растворимой эпоксидгидролазы человека (sEH), представляет интерес биоизостерическая замена (1,7,7-триметилбицикло[2.2.1]гептан-2-ильного) фрагмента на (1,3,3-триметилбицикло[2.2.1]-гептан-2-ильный), получаемый из фенхона.Фенхон является изомерным камфоре терпеноидом и в природе содержится в таких растениях как Foeniculum vulgare Mill.(фенхель), Pimpinella anisum L. (анис), Anethum graveolens L. (укроп) и других.Синтезированы 1,3-дизамещённые мочевины и тиомочевины, содержащие в своей структуре оптически активную бициклическую липофильную группу природного происхождения по реакции (R и S)-1,3,3-триметилбицикло[2.2.1]гептан-2-амина (полученного из терпеноида фенхона) с ароматическими изоцианатами и изотиоцианатами с выходами до 88% и 87 % соответственно.Образование мочевин протекает с приемлемым выходом при проведении реакции в диэтиловом эфире.Исходные изоцианаты и изотиоцианаты хорошо растворимы в эфире, как и 1,3,3-триметил бицикло[2.2.1]гептан-2-амин, поэтому применение ДМФА в качестве растворителя не требуется.S-изомер соединения 1 вводился в реакцию в виде гидрохлорида, а R-изомер

Mutant p53 rescue by small molecules is a promising therapeutic strategy. In this structure-activity relationship study, we examined a series of adamantyl isothiocyanates (Ad-ITCs) to discover novel agents as therapeutics by targeting mutant p53. We demonstrated that the alkyl chain connecting adamantane and ITC is a crucial determinant for Ad-ITC inhibitory potency. Ad-ITC 6 with the longest chain between ITC and adamantane displayed the maximum growth inhibition in p53R280K, p53R273H, or p53R306Stop mutant cells. Ad-ITC 6 acted in a mutant p53-dependent manner. It rescued p53R280K and p53R273H mutants, thereby resulting in upregulating canonical wild-type (WT) p53 targets and phosphorylating ATM. Ad-ISeC 14 with selenium showed a significantly enhanced inhibitory potency, without affecting its ability to rescue mutant p53. Ad-ITCs selectively depleted mutant p53, but not the WT, and this activity correlates with their inhibitory potencies. These data suggest that Ad-ITCs may serve as novel promising leads for the p53-targeted drug development.

Carboxamides and carbamoyl oximes containing both adamantyl and 3,6-diazahomoadamantyl fragments were synthesized. The reactions proceed in mild conditions and in high yields. The synthesized compounds are promising as soluble epoxide hydrolase inhibitors.

Синтезированы карбоксамиды и карбамоилоксимы содержащие одновременно адамантильный и 3,6-диазагомоадамантильный фрагменты. Реакции протекают с высокими выходами целевых продуктов в мягких условиях. Полученные соединения перспективны в качестве ингибиторов растворимой эпоксигидролазы.