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Biomedical subjects

D Danchev

Publications and source records attributed to D Danchev.

12 recordsLinked to original sources
PubMed1985

Antiviral effect of 1-morpholinomethyl-tetrahydro-2(1H)-pyrimidinone (DD-13) in experimental alphaviral infections in white mice.

1-Morpholinomethyl-tetrahydro-2(1H)-pyrimidinone (DD-13), a selective inhibitor of the alphaviral reproduction in vitro, manifests a pronounced antiviral activity in experimental infections with Semliki forest virus (SFV) and Sindbis virus in white mice (intraperitoneally inoculated with 10-10 000 LD50). Introduced subcutaneously in mice infected with SFV the compound was effective within the dose range of 4.7-300 mg/kg. The effective dose (ED)50 value of DD-13 is about 18.7 mg/kg and the maximum effect is reached with a 150-300 mg/kg dose. The protection index reached 80% and the mean survival time from approximately 7 days in the placebo group was lengthened to 26 days. This high antiviral effect is distinguished by its high selectivity, the selectivity ratio (LD50/ED50) being 385 (LD50 = 7200 mg/kg) and is manifested in infections with massive viral inocula (100-1000 LD50). The effective treatment schedule was determined: two divided daily doses of 37.5-150 mg/kg, beginning on the 3rd day after infection to the 8th day. After intravenous administration of DD-13 in mice infected with SFV a high protective effect was also observed, which was equal to that of the subcutaneous application, but with doses several times lower: in the 3-40 mg/kg. ED50 is about 3.5 mg/kg and the optimal effective dose is 10-20 mg/kg, i.e. 1/12-1/6 of LD50 (116 mg/kg). The selectivity ratio is about 33. The most effective treatment course is accomplished by a 10-20 mg/kg daily dose (in two applications) starting on the 2nd day after the virus inoculation up to the 8th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Antiviral activity of tetrahydro-2(1H)-pyrimidinones and related compounds.

24 derivatives of tetrahydro-2(1H)-pyrimidinone and related compounds were tested in vitro for antiviral activity against representatives of six viral taxonomic groups. The screening was carried out by a two-stage procedure including the agar-diffusion plaque-inhibition test and the one-step growth cycle setup. A distinct activity of three mono- and bis-morpholinomethyl derivatives of tetrahydro-2(1H)-pyrimidinone (THP), 1,3-bis(piperidinomethyl)-THP, the 1-morpholinomethyl derivative of tetrahydro-2(1H)-pyrimidinethione (THPT) and the related N,N'-bis(morpholinomethyl)-urea against the fowl plague virus was established. In the one-step growth cycle setup these compounds inhibited 87.5-99.6% of the infectious virus yield. Two of the compounds, namely 1-morpholinomethyl derivatives of THP and THPT manifested a strong inhibitory effect on the reproduction of Semliki Forest virus as well, exceeding 99.9% in the one-step growth cycle test. A borderline effect was observed in some derivatives against vaccinia virus and Newcastle disease virus. The structure-activity relationship of this group of compounds is discussed.

Alphavirus↗
PubMed1979

[Theoretical aspects of the quantitative study of the chemical structure-biological action relationship].

The study of the interrelationship between the chemical structure of the drug molecule and their biologic activity is one of the most modern aspects of current pharmacology and pharmacochemistry. The information, obtained by these studies, contributes for more precise and detailed understanding of the mechanisms of drug molecule interaction with some biologic structures, and this helps to clarify a series of biologic and physiological phenomena. The authors describe in this paper some methods, which are used, when the dependences between structure and action are search for as well as the basic physiocochemical and quantum -- chemical values, which determine the pharmacological effect of drugs.

Binding Sites↗
PubMed1979

Neuropharmacological activity of newly-synthethized derivatives of 3,3-diethyl-2,4-pyridinedione. III. N-Acyl derivatives of 3,3-diethyl-2,4-pyridinedione.

Neuropharmacological screening of five newly-synthesized derivatives of 3,3-diethyl-2,4-pyridinedione was carried out on albino mice. It was found that the N-acyl derivatives have a central depressive effect which is different in character compared with the effect of diethylpyridinedione. The compounds possess no hypnotic effect. All compounds potentiate hexobarbital sleep, while 1-(4-nitrobenzoyl)-3,3-diethyl-2,4-pyridinedione, 1-carbophenoxy-3,3-diethyl-2,4-pyridinedione inhibit the amphetamine-stimulated motor activity. 1-(4-nitrobenzoyl)-diethylpyridinedione manifests good analgetic effect (in the test with intraperitoneal administration of glacial acetic acid), while diethylpyridinedione increases the number of the abdominal spasms. The compounds studied manifest no anticonvulsive activity in corazol convulsions.

Analgesics↗
PubMed1979

Neuropharmacological activity of new derivatives of 3,3-diethyl-2,4-pyridinedione. IV. 1-alkyl derivatives of 3,3-diethyl-2,4-pyridinedione.

Neuropharmacological screening of five 1-alkyl derivatives of 3,3-diethyl-2,4-pyridinedione was performed on male albino mice. The substances studied manifest very good analgesic effect in the test involving intraperitoneal injection of glacial acetic acid. 1-Alkyl derivatives have no hypnotic effect. They potentiate hexobarbital anaesthesia (with the exception of 1-/4'-/2''-hydroxyethyl/-piperazinylpropano/-3,3-diethyl-2,4-pyridinedione). 1-/2-morpholinoethyl/-3,3-diethyl-5-hydroxymethyl-2,4-pyridinedione and 1-/2'-morpholinoethyl/-3,3-diethyl-5-/3',4',5'-trimethoxybenzoyloxymethyl/-2,4-pyridinedione inhibit the amphetamine-stimulated motor activity. The newly-synthesized substances have no anticonvulsant action in corazol convulsions. 1-Alkyl derivatives are found to manifest a central depressive action, differing from that of diethylpyridinedione.

Analgesics↗