Ekaterina A. Morozova

Highly potent activity of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol in animal models of Parkinson's disease.

(1R,2R,6S)-3-Methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 possesses potent antiparkinsonian activity in both MPTP and haloperidol animal models. The use of compound 1 resulted in nearly full recovery of the locomotor and exploratory activities and was as effective as the comparator agent (levodopa). All eight stereoisomers of compound 1 have been synthesized and the influence of the absolute configuration on the antiparkinsonian activity of compound 1 was shown.

Derivatives of pinane amino acids as new anticonvulsants

248 Epileptic seizures occurring in different life periods affect about 3% of the world population [1]. The aim of drug therapy for epilepsy is to effectively control convulsions and ultimately maintain a good quality of life. According to [1, 2], pharmaceuticals used to control seizures are ineffective in about 25% of patients. Therefore, the interest of researchers in the search for more effective anticonvulsants without side effects is unabated [2–5]. Among the compounds with anticonvulsant activity are amino acids structurally related to γ -aminobutyric acid I (GABA), including amino acids II – IV [6, 7].

[Curare-Like Camphor Derivatives and Their Biological Activity].

The synthesis of symmetric dimeric camphor derivatives containing two quaternary nitrogen atoms was performed and their myorelaxant activity in mice was evaluated. For the comparison, some salts derived from meta- and para-xylylene dibromides were synthesized and their activity was tested.

Synthesis and biological activity of heterocyclic borneol derivatives

A series of novel heterocyclic derivatives of (–)-borneol has been prepared by the interaction of (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]-heptan-2-yl 2-chloroacetate and (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl 3-chloropropanoate with different N- and S-nucleophiles. The obtained products were screened for antiviral, antiulcer, and analgesic activity.

Synthesis and analgesic activity of amines combining diazaadamantane and monoterpene fragments

BACKGROUND It was found earlier that compounds combining diazaadamantane and monoterpene moieties possessed promising analgesic activity along with low acute toxicity and the lack of ulcerogenic activity. OBJECTIVE In this paper, new structural analogues of the most active compounds were synthesized and evaluated for their analgesic activity. METHODS Their structures were confirmed by various analytical methods, such as 1H and 13C NMR, HRMS. All of them were evaluated for analgesic activity at a dose of 20 mg/kg or less using acetic acid-induced writhing test and hot plate test. RESULTS Some compounds showed analgesic activity in acetic acid-induced writhing test. One of the synthesized compounds demonstrated high analgesic activity in both tests with 46% effect in acetic acid-induced writhing test and 89% effect in hot plate test. Both structural fragments of this compound did not possess any analgesic effect at a dose of 20 mg/kg. CONCLUSION Structure-activity relationships indicated that the most active compound combines fragments of (-)-myrtenal and 6-amino-5,7-dimethyl-1,3-diazaadamantane. Both parts of the molecule are important for demonstrating analgesic activity.

Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position

HIGHLIGHTSFormation of C‐3&bgr;‐epoxy derivatives of DCA with high stereoselectivity.Synthesis of new DCA derivatives via an epoxide ring opening reaction with S‐nucleophiles.Sensitivity of tumor cell lines to synthesised compounds was HuTu‐80 > KB‐3–1 > HepG2 > MH‐22a.Epoxide moiety at the C‐3 position was key for high anti‐proliferative and anti‐NO activities.All tested compounds exhibited bioactivity in different edema models. ABSTRACT Novel deoxycholic acid (DCA) derivatives were stereoselectively synthesised with –OH and –CH2SR moieties at the C‐3 position, where R was a substituted aryl [2‐aminophenyl (8) or 4‐chlorophenyl (9)] or hetaryl [1‐methylimidazolyl (5), 1,2,4‐triazolyl (6), 5‐amino‐1,3,4‐thiadiazolyl (7), pyridinyl (10) or pyrimidinyl (11)]. These compounds were prepared in good yields from the C‐3&bgr;‐epoxy derivative 2 in the epoxide ring‐opening reaction by S‐nucleophiles. These derivatives were evaluated for their in vitro anti‐proliferation activity in a panel of tumor cell lines. Data showed that: (i) heterocycle‐containing derivatives displayed higher cytotoxicity profiles than the parent molecule; (ii) heterocyclic substituents were more preferable than aryl moieties for enhancing anti‐proliferation activity; (iii) the sensitivity of tumor cell lines to analysed compounds decreased in the following order: HuTu‐80 (duodenal carcinoma) > KB‐3–1 (cervical carcinoma) > HepG2 (hepatocellular carcinoma) > MH‐22a (hepatoma); (iv) compounds 5, 6 and 11 exhibited a high cytotoxic selectivity index (HuTu‐80: SI > 7.7, 38.5 and 12.0, respectively). Compounds 2 and 6–8 markedly inhibited NO synthesis by interferon &ggr;‐induced macrophages. Screening for anti‐inflammatory activity of these derivatives in vivo showed their high potency on histamine‐ (5, 10) and formalin‐ (2, 10, 11) induced paw edema models.

Synthesis and Analgesic Activity of 5,7- and 6-Substituted Diazaadamantanes Containing Monoterpene Moieties

A series of new compounds combining diazaadamantane and monoterpene moieties that were analogs of highly potent analgesic substituted 5,7-dimethyl-1,3-diazaadamantan-6-ones were prepared by reacting 1,5-diethyl- and 1,5-dipropyl-3,7-diazabicyclo[3.3.1]nonan-9-ones with monoterpenoid aldehydes. Another two structural analogs of these compounds were synthesized by reducing the carbonyl. The biological activity of the prepared compounds was studied in hot-plate and acetate-writhing tests.

Synthesis and Analgesic Activity of 4,7-Dimethyl-3,4,4a,5,8,8a-Hexahydro-2H-Chromen-4,8-Diols Containing Thiophene Substituents

Hexahydro-2H-chromenes with thiophene fragments were synthesized via reactions of a p-menthane monoterpenoid diol with several thiophenecarboxaldehydes. Most of the synthesized compounds with an additional thiophene fragment displayed analgesic activity in vivo tests at a dose of 10 mg/kg. It was found that the activity in either an acetate-writhing test or a hot-plate test depended on the type and location of substituent in the heteroaromatic ring.