Synthesis of a new 1,4-dihydropyridine containing the imidazo[1,5-α]pyridine nucleus

The synthesis of the new dihydropyridine diethyl 1,4-dihydro-4-(imidazo[1,5-α]pyridin-8-yl)-2,6-dimethyl-pyridine-3,5-dicarboxylate ( 1 ) is described. After many attempts to prepare the key intermediate aldehyde 2a by different approaches, this compound has been obtained in good yields from methyl 2-cyano-3-pyridinecar-boxylate ( 10 ). A three-step procedure involving reduction to the amine, formylation with concomitant cyclization and reduction of the ester group was used.     

Silyl modification of biologically active compounds. 3. organosilicon derivatives of aminoalcohols in the series of tetrahydroquinoline,tetrahydroisoquinoline, and tetrahydrosilaisoquinoline

The N-(2-hydroxyethyl)-1, 2, 3, 4-tetrahydroquinoline, -isoquinoline, and -silaisoquinoline, and their trimethyland triethylsilyl derivatives and the corresponding methiodides were synthesized. The acute toxicity and psychotropic activity of the compounds synthesized were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 793–799, June, 1996. Original article submitted April 25, 1996.     

Silyl Modification of Biologically Active Compounds. 8. Trimethylsilyl Ethers of Hydroxyl-containing Thiazole Derivatives

Trimethylsilyl ethers of various hydroxyl-containing thiazole derivatives have been synthesized. The psychotropic activity (in vivo) and the cytotoxicity (in vitro on tumor cell lines HT-1080 and MG-22A) of these ethers and of their unsilylated precursors have been studied. It was discovered that the obtained compounds possess a sedative action. A moderate cytotoxic effect was detected for piperidine-containing thiazoles, displayed most strongly in relation to MG-22A cells.     

Synthesis in the fields of 5-nitrofuryl-2-polyalkenals and 5-nitrofuryl-2-polyalkenones. VII. Synthesis and investigation of the antibacterial properties of derivatives of α,β-unsaturated and polyene aldehydes and ketones of the 5-nitrofuran series

Antibacterial properties and toxicities were determined for 66 compounds of the 5-nitrofuran type to ascertain the connection between structure and biological activity.Unsaturated 5-nitrofuran aldehydes and some of their simplest derivatives (acetals, acylals) have high antibacterial activity and a broad spectrum. However, these compounds cannot be used in medicine because of their appreciable toxicities and low stabilities. One of the ,-unsaturated ketones in this series, 5-nitrofurfurylideneacetone, has a broad antibacterial spectrum combined with lower toxicity. Low-toxicity derivatives of 1-aminohydantoin and 3-amino-2-oxazolid-2-one are among the imino derivatives of high antibacterial activity investigated.For Part VI see [1].     

Silyl Modification of Biologically Active Compounds. 7. Synthesis, Structure, Physicochemical and Biological Properties of Some Silicon-containing “3+1” Oxorhenium(V) Complexes

With the aim of studying the structure-physicochemical properties-biological activity relation, we have synthesized a series of organosilicon neutral oxorhenium(V) complexes with mixed ligands and we have determined their lipophilicity. X-ray diffraction has been used to establish the molecular structure of (3-triphenylsiloxypropanethiolato)(3-thiapentane-1,5-dithiolato)oxorhenium(V), (2-trimethylsiloxy- and 2-hydroxyethanethiolato)[3-(N-methyl)azapentane-1,5-dithiolato]oxorhenium(V). We have studied the neurotropic properties and acute toxicity of the synthesized complexes in vivo and their dependence on the nature of the monodentate and tridentate ligands. We have established that all the studied compounds have pronounced sedative action (they prolong the life of mice under hypoxia conditions, they are phenamine antagonists, they exhibit anticonvulsive action and prevent retrograde amnesia).     

Nitrogen-containing organosilicon compounds. 151. Synthesis,NMR spectra,and biological activity of hetarylaminoalkylsiloxanes and their hydrochlorides and methiodides

Hetarylaminoalkylsiloxanes and their hydrochlorides and methiodides were synthesized. Their neurotropic, antitumorigenic, and antimicrobial properties were studied. It was established that the character of the heteroring, the number of siloxy groups, and the length of the methylene chain between the nitrogen and silicon atoms in the molecule affect the biological activity. It is shown that the changes in the chemical shifts in the ¹³C, ¹⁵N, ¹⁷O, and ²⁹Si NMR spectra of the synthesized compounds are determined chiefly by the presence of siloxy substituents, i.e., the effects in the Si-O-Si fragment prevail.See [1] for communication 150.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1653–1664, December, 1991.     

Synthesis and pharmacological activity of silyl isoxazolines 2

Silyl isoxazolines have been synthesized by [2+3] cycloaddition reaction of nitrile oxides to vinyl- and allylsilanes. The addition of 3-pyridylnitrile oxide to 1,3-divinyl-1,1,3,3-tetraphenyldisiloxane affords 1,3-bis{5-[3-(3-pyridyl)isoxazolin-2-yl]}-1,1,3,3-tetraphenyldisiloxane; the latter exists as a mixture of trans- and cis-isomers.The bond angle of the Si–O–Si fragment in thetrans-isomer equals 180(3)° and in the cis-isomer it is 162(3)°.The pharmacological properties of 4-[3-(5-trimethylsilylisoxazolin-2-yl)]pyridinium-chloride have been studied.     

Synthesis and psychotropic properties of bis(2-thenylidene)diamines and their silyl derivatives

Summary The condensation of diamines with the corresponding aldehydes gave bis(2-thenylidene)diamines and their silyl derivatives. The structure of the compounds has been confirmed by their PMR spectra. It has been shown that the introduction of the trimethylsilyl group increases the toxicity, prolongs the hexenal narcosis and the antihypoxy activity, has a positive effect on the memory processes, and has no influence on the coordination of movements, the muscle tone, and the body temperature. All compounds possess an antialcohol activity, whereby the silyl derivatives have the stronger one.Translated from Khimiya Geterotsikiicheskikh Soedinenii, No. 3, pp. 316–320, March, 1994.     

Synthesis and psychotropic properties of azomethine derivatives of thiophene

A series of azomethine derivatives was obtained by condensation of 2-thiophenaldehyde and 5-substituted (alkyl, bromine, tert-butyl, trimethylsilyl)-2-thiophenaldehydes withsemicarbazide, thiosemicarbazide, aminohydantoin, and 2-semicarbazide acetic acid. Their psychotropic activity was investigated. It was found that incorporation of a ten-butyl group in position 5 of the thiophene ring potentiates the toxicity of the compound. 5-Trimethylsilyl-and 5-ten-butyl-2-thiophenaldehyde thiosemicarbazones exhibit elevated neurotropic activity. These compounds cause the stimulating effect of phenamine to appear, increasing the motor activity of animals by two times and prolonging the effect of hexenal-induced sleep. Substitution of thiosemicarbazone by semicarbazone decreases the activity except for hexenal sleep, where the 5-tert-butyl-2-thiophenaldehyde semicarbazone was 1.5 times more active than the thiosemicarbazone.Latvian Institute of Organic Synthesis, Riga, LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 629-632, May, 1995. Original article submitted May 12, 1995.     

Synthesis of new ether glycerophospholipids structurally related to modulator

A series of new glycerophospholipids, bearing a short-chain carboxylic acid in position sn-1 and phosphocholine or phosphoserine in postion sn-3 of glycerol, have been prepared in good overall yields. Compound 11, 1-0-(6-carboxyhexyl)-sn-glycero-3-phosphoserine, a strict analog of the structure proposed for modulator, has been synthesized in a stereoselective way from (R)-1,2-isopropylideneglycerol 1.