Yu. B. Vikharev

Neuroprotective Activity of (+)-(S)-2-[(1S,5R)-(3,7-Dioxo-2,4,6,8-Tetraazabicyclo[3.3.0]oct-2-yl)]-4-methylthiobutanoic acid

A study of the neurotropic, neuroprotective, and antioxidant action of the enantiomers and racemate of 2-[(3,7-dioxo-2,4,6,8-tetraazabicyclo[3.3.0]oct-2-yl)]-4-methylthiobutanoic acid synthesized in a stereoselective reaction of (R)-, (S)-, or (R,S)-N-carbamoylmethionine with 4,5-dihydroxyimidazolidine-2-one showed that only (+)-(S)-2-[(1S,5R)-(3,7-dioxo-2,4,6,8-tetraazabicyclo[3.3.0]oct-2-yl)]-4-methylthiobutanoic acid had neuroprotective properties. X-ray structure analysis showed that the predominating racemate of glycolurils is crystallized from aqueous solutions as a conglomerate. Antioxidant activity was not detected.

Synthesis and Antiinflammatory and Analgesic Activity of Naproxen Amides with Amino Acid Derivatives

In recent years, there have been attempts to modify the well-known nonsteroidal antiinflammatory drugs by reactions with natural amino acids, aimed at eliminating undesired side effects of the drug action [1]. In particular, the synthesis of naproxen amide with glycine was reported in [2, 3]. The aim of this study was to obtain naproxen amides with some amino acid derivatives and characterize the products with respect to the antiinflammatory and analgesic activity and acute toxicity. The synthesis of naproxen amides (II – V) with methyl esters of (S )-methionine, (S )-phenylalanine, (S )-histidine, and (S )-leucine was based on the condensation of (S )-naproxen chloroanhydride (I) with the corresponding amino acid esters in DMF in the presence of triethanolamine (TEA) [4]:

Synthesis and biological activity of nitrogen-containing derivatives of methyl dehydroabietate

The biological activity of a series of new amino derivatives of dehydroabietic acid has been studied. 12-N,N-Diethylaminoacetyl-8,11,13-abietatrien-18-oate hydrochloride produces a calming effect, shows pronounced anxiolytic activity, and exhibits antipyretic action comparable with that of the reference drug (analgin).

ANTI-INFLAMMATORY ACTIVITY OF ISOBORNYLPHENOL DERIVATIVES

Nonsteroidal anti-inflammatory drugs and non-narcotic analgesics are widely used to treat various inflammatory diseases of infectious and noninfectious nature [1]. The development of new drugs based on terpenophenols, which have a unique set of pharmacological properties [2], is highly promising. The literature teaches that phenols with a bicyclic isobornyl moiety exhibit anti-infection activity [3]. The series of studies performed by us on the synthesis and investigation of terpenophenols showed that some alkylphenols exhibit hemorheological properties and improve brain blood flow [4, 5]. Thus, the synthesis of terpenophenols is critical for further studies of their physiological properties. Herein we present results from a study of the anti-inflammatory activity of the synthesized terpenophenols and their aminomethyl derivatives. A series of isobornylphenols (1a–e) with various substituents in the aromatic ring were prepared earlier via alkylation of phenols by the natural monoterpenoid camphene in the presence of the corresponding aluminum phenolates [6–8].

Synthesis and Antiinflammatory and Analgesic Activity of 2H-3,3-Dimethyl-3,4-dihydroisoquinolin-1-ones

The reactions of substituted arenes with isobutyric aldehyde and methylthiocyanate yield 1-methylthio-3,4-dihydroisoquinolines. The subsequent treatment with AcOH/AcONa yields 2H-3,3-dimethyl-3,4-dihydroisoquinolin-1-ones, some of which exhibit pronounced antiinflammatory and analgesic properties.

Synthesis and antiinflammatory and analgesic activity of amidines of 3,4-dihydroisoquinoline series

A series of substituted 1-arylamino-3,4-dihydroisoquinolines have been synthesized using reactions of 1-methylthio-3,3-dimethyl-3,4-dihydroisoquinolines with substituted anilines and 2-aminothiazoles. The products were tested for analgesic and antiinflammatory activity.

Synthesis and biological activity of mono- and diamides of 2,3-secotriterpene acids

Amides of four types were synthesized derived from 2,3-seco-18αH-oleanane and 2,3-secolupane mono- and dicarboxylic acids. The spectrum of diamide derivatives was expanded with C3-C3′ and C28-C28′ biscondensed amides with two A-secotriterpene backbones obtained by the interaction of monocarboxylic A-seco acids with lysine. Among the synthesized monoand diamide derivatives, potential inhibitors of herpes simplex virus type 1 replication were found, namely, some compounds with an ethyl β-alaninate fragment (EC50 8.7 and 4.1 μM). The ethyl β-alaninate diamide was shown to combine antiherpetic and anti-HIV activity (EC50 5.1 μM). For the active compounds, the ratios of maximum tolerable concentrations to EC50 ranged from 9.7 to 40.8. The synthesized amides did not show any marked cytotoxic effects against human rabdomiosarcoma RD TE32, A549 lung carcinoma, and melanoma MS cell lines.

The immunotropic activity of lupane and oleanane 2,3-seco-triterpenoids

The immunotropic effect of the 2,3-seco derivatives of allobetulon, betulonic acid, and the methyl ester of betulonic acid were studied. It was found that the highest activity is shown by compounds with an oleanane fragment. The presence of a free C28-carboxyl group enhances the activity of lupane 2,3-seco derivatives. A significant contribution to the development of the immune response is introduced by a functional group at the C3 atom in the A ring—the C3-carboxy derivatives intensify the processes of antibody production and alter the number and ratio of leukocyte forms. It is shown that 2,3-seco-1-cyano-19β,28-epoxy-18α-olean-3-oic acid stimulates humoral immunity with a positive influence on hematopoiesis.

Synthesis and biological activity of S-containing betulin derivatives

S-Containing derivatives of the natural triterpenoid betulin were synthesized. It has been found that the 30-thio- and 30-sulfinylbenzimidazole derivatives of betulin exhibit anti-inflammatory activity comparable to that of sodium diclofenac.

Synthesis and Antiinflammatory and Analgesic Activity of Amino Acids Acylated with Ibuprofen

As is known, the ulcerogenic properties of nonsteroidal antiinflammatory drugs is a factor limiting their use in clinics. It was established that the side effects can sometimes be reduced by attaching a pharmacophore fragment to a natural amino acid residue. In this context, we have synthesized ibuprofen amides (I – III) by the condensation of ibuprofen chloroanhydride with methyl esters of amino acids (methionine, phenylalanine, histidine) using the method described elsewhere [1] and characterized the products with respect to the antiinflammatory and analgesic activity. The proposed structures of compounds I – III were confirmed by the results of elemental analyses and by H NMR data. According to the H NMR data, the synthesized amides represent diastereomers mixed in a 1 : 1 ratio.