Influence of the structure of substituted benzodiazepines on their pharmacokinetic properties

Artemenko, Anatoly G.; Кузьмин, В. Е.; Muratov, Eugene; Polishchuk, Pavel; Borisyuk, I. Yu.; Golovenko, N. Ya.

doi:10.1007/s11094-009-0332-x

Cited by 8 publications

(7 citation statements)

References 15 publications

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“…Indeed, computational models are well established, and successfully/extensively used tools, and especially so for drug development [ 44 ]. They have already been applied to classical and designer benzodiazepines [ 45 , 46 ] and other NPS classes (e.g., synthetic cannabinoids [ 47 , 48 , 49 ], opioids [ 50 , 51 ], hallucinogenic phenylalkylamines [ 52 ], and tryptamines [ 53 ] and phenethylamines [ 54 , 55 ].…”

Section: Introductionmentioning

confidence: 99%

The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity

et al. 2021

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Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly reported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (i.e., quantitative structure-activity relationship/QSAR and Molecular Docking) were used to analyse DBZDs identified online by an automated web crawler (NPSfinder®) and to predict their possible activity/affinity on the gamma-aminobutyric acid A receptors (GABA-ARs). The computational software MOE was used to calculate 2D QSAR models, perform docking studies on crystallised GABA-A receptors (6HUO, 6HUP) and generate pharmacophore queries from the docking conformational results. 101 DBZDs were identified online by NPSfinder®. The validated QSAR model predicted high biological activity values for 41% of these DBDZs. These predictions were supported by the docking studies (good binding affinity) and the pharmacophore modelling confirmed the importance of the presence and location of hydrophobic and polar functions identified by QSAR. This study confirms once again the importance of web-based analysis in the assessment of drug scenarios (DBZDs), and how computational models could be used to acquire fast and reliable information on biological activity for index novel DBZDs, as preliminary data for further investigations.

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Section: Introductionmentioning

confidence: 99%

The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity

et al. 2021

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“…Systematic in vivo and in vitro work has also been carried out to investigate the structural characteristics that relate to pharmacological activity. From these studies estimations of activity of novel 1,4–benzodiazepines (Figure A) can be estimated for half‐life (t½), volume of distribution (V D ), bioavailability (F) as well as the potential toxicity of benzodiazepines, showing that hydrazone fragments, primary amines and saturated heterocyclic ring systems lead to increases in toxicity . The biological activity of benzodiazepines was initially studied by Hester who determined the effects of substituents on the biological activity.…”

Section: Prediction Of the Pharmacological Toxicological And Pharmamentioning

confidence: 99%

The emergence of new psychoactive substance (NPS) benzodiazepines: A review

Manchester

Lomas

Waters

et al. 2017

Drug Testing and Analysis

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The market for new psychoactive substances has increased markedly in recent years and there is now a steady stream of compounds appearing every year. Benzodiazepines consist of only a fraction of the total number of these compounds but their use and misuse has rapidly increased.Some of these benzodiazepines have only been patented, some of them have not been previously synthesised, and the majority have never undergone clinical trials or tests. Despite their structural and chemical similarity, large differences exist between the benzodiazepines in their pharmacokinetic parameters and metabolic pathways and so they are not easily comparable. As benzodiazepines have been clinically used since the 1960s, many analytical methods exist to quantify them in a variety of biological matrices and it is expected that these methods would also be suitable for the detection of benzodiazepines that are novel psychoactive substances. Illicitly obtained benzodiazepines have been found to contain a wide range of compounds such as opiates which presents a problem since the use of them in conjunction with each other can lead to respiratory depression and death. This review collates the available information on these benzodiazepines and provides a starting point for the further investigation of their pharmacokinetics which is clearly required.

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“…4.Why, during the configuration of isomerization, does the enantiomer not always pass through an achiral boundary? Antiviral activity, antimicrobial activity and antitumor activity Pharmacokinetic Parameter [25], [41][42][43][44][45] Affinity for different biological targets [46][47][48][49][50][51][52][53] Different types of toxicity [44], [54][55][56][57][58][59][60][61][62][63][64][65]…”

Section: The Methodology Of Sirmsmentioning

confidence: 99%

Section: Qsar Models Based On Simplex Descriptorsmentioning

confidence: 99%

“…A number of our works (see Table 1) are devoted to solving these problems on the basis of SiRMS. In particular, [42,43] discuss the influence of structure on the pharmacokinetic properties of 1,4 -benzodiazepine tranquilizers. Originally, QSAR models were intended to approximate bioavailability, elimination half-life, clearance, and distribution volume in the human organism for the development of benzodiazepine drugs.…”

Section: Qsar Models Of Pharmacokinetic Parameters Of Biologically Active Substancesmentioning

confidence: 99%

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Simplex representation of molecular structure as universal QSAR/QSPR tool

et al. 2021

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We review the development and application of the Simplex approach for the solution of various QSAR/QSPR problems. The general concept of the simplex method and its varieties are described. The advantages of utilizing this methodology, especially for the interpretation of QSAR/QSPR models, are presented in comparison to other fragmentary methods of molecular structure representation. The utility of SiRMS is demonstrated not only in the standard QSAR/QSPR applications, but also for mixtures, polymers, materials, and other complex systems. In addition to many different types of biological activity (antiviral, antimicrobial, antitumor, psychotropic, analgesic, etc.), toxicity and bioavailability, the review examines the simulation of important properties, such as water solubility, lipophilicity, as well as luminescence, and thermodynamic properties (melting and boiling temperatures, critical parameters, etc.). This review focuses on the stereochemical description of molecules within the simplex approach and details the possibilities of universal molecular stereo-analysis and stereochemical configuration description, along with stereo-isomerization mechanism and molecular fragment “topography” identification.

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Influence of the structure of substituted benzodiazepines on their pharmacokinetic properties

Cited by 8 publications

References 15 publications

The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity

The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity

The emergence of new psychoactive substance (NPS) benzodiazepines: A review

Simplex representation of molecular structure as universal QSAR/QSPR tool

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