Inducers of the phenobarbital type (a review)

Бакибаев, А. А.; Novozheeva, T. P.; Akhmedzhanov, R. R.; Saratikov, A. S.

doi:10.1007/bf02219056

Cited by 3 publications

(10 citation statements)

References 25 publications

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“…The relative errors of the coefficients a, for H = 5 do not exceed 23% at a confidence probability of 0.95. Most of the linear models provide adequate description at a significance level of 0.05 (the dispersion of reproducibility determined by data of [5,6] was 5.16 x I 0-3).…”

Section: Resultsmentioning

confidence: 99%

“…Experimental values of the enzyme-stimulating activity/j [5,6] and the numbers of prints Np are given in Table 1. The prints of ligands I and V'I, having the maximum values of/j in the series studied, were used as the multiplets.…”

Section: Resultsmentioning

confidence: 99%

“…Because the fragments of molecules I and VI possess elements of symmetry, some of their prints are identical from the standpoint of both geometry and the projection characteristics. Therefore, only 16 of the total of 33 independent prints (forming different pairs of structures) in both compounds were considered as The activity is evaluated as/i = log (100/~), where A. is the duration of hexobarbital-indueed sleep of ekperimental aftirnals (% o~control) [5,6].…”

Section: Resultsmentioning

confidence: 99%

“…Features of the structure description. The urea derivatives I --XXIV studied ha this work belong to cytochrome P-450 inductors of the phenobarbital type [5][6][7]. The rigid fragments were selected proceeding from the following considerations ( Fig.…”

Section: {3)mentioning

confidence: 99%

“…This group of inductors was only characterized by a few generalizations made on a qualitative level [6,7].…”

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confidence: 99%

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Quantitative structure—Activity relationships in a series of urea derivatives—Liver cytochrome P-450 inductors analyzed by the modified method of frontal polyhedra

et al. 1997

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In a series of recent publications [1][2][3][4] we have developed a method of frontal polyhedra (FP) for establishing the quantitative structure-activity relationships (QSAR). The method is based on modeling a proposed receptor by a set of structural fragments (multiplets) containing the activity centers. The fitting of some ligand molecule to the receptor is assessed by taking a kind of"prints" from approximately planar peripheral faces of the molecule and searching for the optimum superimpositions of the prints of this molecule onto the above multiplets. The ability of local description of molecules on the level of three-dimensional (3D) structure provides applicability of the PM method to a series of compounds with structurally different ligands [1][2][3]. Recently we have developed a modified version of the PM method, which solves to a considerable degree the task of describing conformationally labile molecules. This was demonstrated by establishing 3D-QSAR in a series of of Baker triazines-dihydrofolate reductase inhibitors [4], the molecules of which exhibit internal mobility.In this work the modified PM method is applied to a series of urea derivatives-liver cytochrome P-450 inductors [5 -7]. These ligands have markedly differing dimensions and shapes and possess internal rotational degrees of freedom. This last circumstance hinders the use of other approaches to solving the 3D-QSAR task for these compounds [8,9].Despite achievements in the biochemistry of cytochrome P-450 [10, I 1], no attempts at QSAR analysis for inductors of the phenobarbital type have been practically undertaken. This group of inductors was only characterized by a few generalizations made on a qualitative level [6,7].I Polzunov Altai State Technical University, Barnanl, Russia. 2 Tomsk Polytechnical University, Tomsk, Russia. 3 Siberian State Medical University, Tomsk, Russia. 320 DESCRIPTION OF METHOD General characteristic. The modified PM method [4]is based on representing ligands by combinations of fragments. Each terminal atom X connecting the given fragment to other parts of the molecule is ascribed a set of descriptors ax, characterizing this atom and the related radical R x. The quantities ax~ describe projections of the terminal atom on the prints and are taken into account in searching for the optimum superimpositions. Because the prints are taken only from rigid fragments, the structural information contained in these prints is independent of the internal rotation of molecules. It was suggested that the descriptors ax, can be represented by the effective charge on atom X, the refractivity, and the lipophilicity of radical R x [4]. If atomXis not terminal, it is described only by the effective charge.The results of searching for the optimum superimpositions with the aid ofa combinatory algorithm [2] based on the A optimum criterion F [1, 2] led to the N x K assignment matrix V where N is the number of compounds in the series studied and K is the total number of active centers in the multiplets [4]. In this work we have also ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: {3)mentioning

confidence: 99%

“…This group of inductors was only characterized by a few generalizations made on a qualitative level [6,7].…”

mentioning

confidence: 99%

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Quantitative structure—Activity relationships in a series of urea derivatives—Liver cytochrome P-450 inductors analyzed by the modified method of frontal polyhedra

et al. 1997

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Synthesis of glycolurils and hydantoins by reaction of urea and 1, 2‐dicarbonyl compounds using etidronic acid as a “green catalyst”

Бакибаев

Uhov

Malkov

et al. 2020

Journal of Heterocyclic Chem

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Most of the known methods for the synthesis of heterocyclic compounds have disadvantages, such as a long reaction time and aggressive conditions. We have developed a new, rather simple and efficient method for the synthesis of a number of glycoluryls and hydantoins in water using a etidronic acid (HEDP) as "Green catalyst." So, for the first time, the condensation reaction of ureas with 1, 2-dicarbonyl compounds was carried out in the presence of HEDP. Also based on NMR studies, a chemism of these reactions, which is stepwise, is proposed. It has been established that the optimal conditions for the synthesis of glycoluryls and hydantoins using HEDP are: temperature 80 C-90 C, 40-20 minutes, and the ratio of urea and HEDP is 1:1. In all cases, the remaining aqueous filtrate containing HEDP after the reaction can be reused for other cycles synthesis of glycoluril and other compounds, because HEDP is not converted during the reaction.

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New Cytochrome P-450 Ligands Based on Urea Derivatives

et al. 2005

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Cytochrome P-450 (CYPIIB1 isoform) ligands were constructed de novo on the basis of QSAR models derived using the frontal polygon (FP) method. The following compounds were designed and synthesized: 2-phenyl-6-benzyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione, N-acetyl-N¢-(1-phenylethyl)urea, and (1-phenyl-3-methylbutyl)urea. Their interaction with phenobarbital-induced microsomes isolated from rat liver was studied spectrophotometrically. The dissociation constants K s of the enzyme -substrate complexes measured are in good agreement with the values predicted using the QSAR models. The results show that the FP method has a high potential for designing biologically active compounds. 18 0091-150X/05/3901-0018

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Inducers of the phenobarbital type (a review)

Cited by 3 publications

References 25 publications

Quantitative structure—Activity relationships in a series of urea derivatives—Liver cytochrome P-450 inductors analyzed by the modified method of frontal polyhedra

Quantitative structure—Activity relationships in a series of urea derivatives—Liver cytochrome P-450 inductors analyzed by the modified method of frontal polyhedra

Synthesis of glycolurils and hydantoins by reaction of urea and 1, 2‐dicarbonyl compounds using etidronic acid as a “green catalyst”

New Cytochrome P-450 Ligands Based on Urea Derivatives

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