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Sci. Pharm.
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Heterocyclic Chemistry in Drug Design
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Heterocyclic Chemistry in Drug Design

A special issue of Scientia Pharmaceutica (ISSN 2218-0532).

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 9845

Special Issue Editor

Prof. Dr. Roman B. Lesyk

E-Mail Website
Guest Editor
Head of Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Interests: medicinal chemistry; heterocyclic chemistry; organic synthesis; cancer biology; cancer cell line; pharmaceutical chemistry; anticancer compounds; apoptosis; QSAR
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, the available chemical space includes more than 100 million organic compounds, mainly related to a limited set of classes and types. At the same time, modern drug design trends require the development of synthetic approaches to equally and diversely fill the chemical space as a source of drug-like structures. These trends have affected heterocyclic chemistry as the main "supplier" of drug-like molecules (all top 10 brand name small molecule drugs contain heterocyclic moieties), which stipulate strict requirements, both for bioactive compounds, as well as the methods of their synthesis. Thus, synthetic methods should provide a diversity of molecular architectonics, high chemo-, regio- and stereoselectivity, as well as atomic efficiency, in order to be ecologically and economically justified. The simultaneous implementation of these requirements is a rather difficult task, and research aimed at achieving a certain balance between them is relevant. As heterocycles are common fragments in the vast majority of marketed drugs, they obviously have a central role in modern drug design. It also should be mentioned that oxygen, sulfur, and, especially, nitrogen-containing rings, prevail among drug molecules.

In this Special Issue, we will focus on recent advances in heterocyclic chemistry in drug design.

Prof. Dr. Roman B. Lesyk
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Scientia Pharmaceutica is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • heterocycles
  • diversity-oriented synthesis
  • regio-, stereo- and chemoselective synthesis
  • drug design
  • drug discovery
  • biological activity
  • SAR
  • lead generation

Published Papers (3 papers)

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Research

20 pages, 4668 KiB  
Article
The Crystal Structure of N-(1-Arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as the Factor Determining Biological Activity Thereof
by Igor V. Ukrainets, Ganna M. Hamza, Anna A. Burian, Natali I. Voloshchuk, Oxana V. Malchenko, Svitlana V. Shishkina, Irina A. Danylova and Galina Sim
Sci. Pharm. 2019, 87(2), 10; https://doi.org/10.3390/scipharm87020010 - 19 Apr 2019
Cited by 4 | Viewed by 3189
Abstract
In order to detect new structural and biological patterns in a series of hetaryl-3-carboxylic acid derivatives, the optically pure (S)- and (R)-enantiomers of N-(1-arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides, their true racemates, and mechanical racemic mixtures have been synthesized in independent [...] Read more.
In order to detect new structural and biological patterns in a series of hetaryl-3-carboxylic acid derivatives, the optically pure (S)- and (R)-enantiomers of N-(1-arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides, their true racemates, and mechanical racemic mixtures have been synthesized in independent ways. The particular features of the 1Н- and 13С-NMR spectra of all synthesized substances, liquid chromato-mass spectrometric behavior thereof under electrospray ionization conditions, and also the results of polarimetric and X-ray diffraction studies have been discussed. Pharmacological screening on a model of carrageenan inflammation has found a clear relationship between the spatial structure of the studied objects and biological activity thereof. Enantiomers with chiral centers having (S)-configuration showed weak inhibition of pain and inflammatory reactions, while their mirror (R)-isomers exhibited very powerful analgesic and antiphlogistic properties under the same conditions, with the level of specific activity exceeding that of Lornoxicam and Diclofenac. Taking obtained data into account, a noticeable decrease in the activity of mechanical racemic mixtures, consisting of one-half of the “wrong” (S)-enantiomers, is quite natural. The true racemate of N-(1-phenylethyl)-amide proved itself in a similar way, while 4-methoxy-substituted analog thereof stood out against this background with unexpectedly high analgesic and anti-inflammatory activities. A comparative analysis of X-ray diffraction data has found that crystalline and molecular structure of racemic N-[1-(4-methoxyphenyl)ethyl]-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide is completely different from that of the original enantiomers and, moreover, very unusual for racemates. Obviously, it is the factor determining the unique character of the biological effects of the said substance. Full article
(This article belongs to the Special Issue Heterocyclic Chemistry in Drug Design)
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8 pages, 614 KiB  
Article
Cardioprotective Activity of Some 2-Arylimino-1,3-Thiazole Derivatives
by Iryna Drapak, Lina Perekhoda, Natalya Demchenko, Marharyta Suleiman, Maryna Rakhimova, Inna Demchuk, Svitlana Taran, Nataliya Seredynska and Inna Gerashchenko
Sci. Pharm. 2019, 87(1), 7; https://doi.org/10.3390/scipharm87010007 - 18 Mar 2019
Cited by 8 | Viewed by 3127
Abstract
The article presents the synthesis of 2-arylimino-4-methyl-2,3-dihydro-1,3-thiazoles via Hantzsch reaction of thioureas and 3-chloropentane-2,4-dione or ethyl 2-chloro-3-oxobutanoate. The structure of synthesized compounds was confirmed by LCMS, 1H, and 13C NMR spectra. Cardioprotective activity of synthesized thiazole derivatives were studied in vitro [...] Read more.
The article presents the synthesis of 2-arylimino-4-methyl-2,3-dihydro-1,3-thiazoles via Hantzsch reaction of thioureas and 3-chloropentane-2,4-dione or ethyl 2-chloro-3-oxobutanoate. The structure of synthesized compounds was confirmed by LCMS, 1H, and 13C NMR spectra. Cardioprotective activity of synthesized thiazole derivatives were studied in vitro on the isolated rings of the thoracic aorta of laboratory rats. Based on pharmacological studies, the tested compounds possessed a moderate to high cardioprotective effect. A prospective 1-[2-(4-methoxyphenylimino)-4-methyl-3-(4-methylpiperazine-1-yl)-2,3-dihydro-1,3-thiazole-5-yl] ethan-1-one hydrochloride 4c was identified. The mentioned compound has delayed the development of constrictor responses of isolated rings of the thoracic rat aorta and exceeds the activity of L-carnitine by 18.2% and meldonium by 12.9%. The compound 4c may be proposed as a potential cardioprotective agent for in-depth pharmacological studies. Full article
(This article belongs to the Special Issue Heterocyclic Chemistry in Drug Design)
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27 pages, 11087 KiB  
Article
Molecular Conformations and Biological Activity of N-Hetaryl(aryl)alkyl-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides
by Igor V. Ukrainets, Ganna M. Hamza, Anna A. Burian, Natali I. Voloshchuk, Oxana V. Malchenko, Svitlana V. Shishkina, Lina A. Grinevich, Vasyl V. Grynenko and Galina Sim
Sci. Pharm. 2018, 86(4), 50; https://doi.org/10.3390/scipharm86040050 - 30 Nov 2018
Cited by 8 | Viewed by 3019
Abstract
The analysis of our previous studies on the search for synthetic analgesics among N-R-amides of bicyclic hetaryl-3-carboxylic acids has been performed; on its basis N-hetaryl(aryl)-alkyl-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides have been selected as new study objects. The “one pot synthesis” of [...] Read more.
The analysis of our previous studies on the search for synthetic analgesics among N-R-amides of bicyclic hetaryl-3-carboxylic acids has been performed; on its basis N-hetaryl(aryl)-alkyl-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides have been selected as new study objects. The “one pot synthesis” of these compounds, which is simple to perform and at the same time highly effective, has been offered. The method consists in the initial reaction of 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid and N,N′-carbonyldiimidazole in anhydrous N,N-dimethylformamide with the subsequent amidation of imidazolide formed with hetarylalkyl- or benzylamines in the same solvent. The peculiarities of 1H- and 13C-NMR spectra of the substances obtained, as well as their electrospray ionization liquid chromato-mass spectra are discussed. According to the results of the pharmacological tests carried out on the model of carrageenan inflammation it has been found that all without exception N-hetaryl(aryl)alkyl-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides demonstrate the statistically significant analgesic and anti-inflammatory properties. Among the substances presented in this article analgesics and antiphlogistics, which increase the pain threshold and suppress the inflammatory response more effectively than Lornoxicam and Diclofenac in the same doses, have been identified. The molecular and crystal structures of a large group of the substances synthesized have been studied by X-ray diffraction analysis. Comparison of these data with the results of biological tests has revealed the fact of excellent correlation between the molecular conformations of N-hetaryl(aryl)alkyl-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides recorded in the crystal and the potency of their analgesic effect. N-Thiophen-2-ylmethyl- and N-4-methoxybenzyl-amides of 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid has shown a high analgesic and anti-inflammatory effect, therefore, they deserve more careful research. Full article
(This article belongs to the Special Issue Heterocyclic Chemistry in Drug Design)
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