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Background: Cancer has been considered to be a global health concern due to the impact of disease on the quality of life. The continual increase of cancer cases as well as the resistance of cancer cells to the existing drugs have driven the search for novel anticancer drugs with better potency and selectivity, improved pharmacokinetic profiles, and minimum toxicities. Pyridine and pyrimidine are presented in natural products and genetic materials. These pyridine/pyrimidine core structures have been noted for their roles in many biological processes as well as in cancer pathogenesis, which make such compounds become attractive scaffolds for discovery of novel drugs. Results & Conclusion: In the recent years, pyridine- and pyrimidine-based anticancer drugs have been developed based on structural modification of these core structures (i.e., substitution with moieties and rings, conjugation with other compounds, and coordination with metal ions). Detailed discussion is provided in this review to highlight the potential of these small molecules as privileged scaffolds with attractive properties and biological activities for the search of novel anticancer agents.

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A variety of novel thiazolidine derivatives (2-Thioxothiazolidin-4-one and thiazolidine-2, 4-dione derivatives) have been prepared by using 2,4-diphenyl-2Hchromene- 3-carbaldehyde and its derivatives as starting materials. This is the first example of the preparation of thiazolidine derivatives through this novel method. Structure evolution of the resulting thiazolidine derivatives leads to anticancer agents. Our preliminary data for some model compounds on three cancer cell lines (MCF7, A549 and B-16) suggested reasonable anticancer activity against the A549 and B-16 cell lines, with IC50 values of 20.7 and 20.4 muM, respectively. This method is operationally simple and works with a diverse range of substrates.

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HIV integrase inhibitors based on a novel bicyclic pyrimidinone core is presented. Nine variations of the core scaffold are evaluated leading to optimization of the 6:6 core giving compound 48 with an EC50 of 3 nM against wild type HIV infected T-cells.

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Chemical space describes all possible molecules as well as multi-dimensional conceptual spaces representing the structural diversity of these molecules. Part of this chemical space is available in public databases ranging from thousands to billions of compounds. Exploiting these databases for drug discovery represents a typical big data problem limited by computational power, data storage and data access capacity. Here we review recent developments of our laboratory, including progress in the chemical universe databases (GDB) and the fragment subset FDB-17, tools for ligand-based virtual screening by nearest neighbor searches, such as our multi-fingerprint browser for the ZINC database to select purchasable screening compounds, and their application to discover potent and selective inhibitors for calcium channel TRPV6 and Aurora A kinase, the polypharmacology browser (PPB) for predicting off-target effects, and finally interactive 3D-chemical space visualization using our online tools WebDrugCS and WebMolCS. All resources described in this paper are available for public use at www.gdb.unibe.ch.

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New Advances in Chemical Research, May 2021. Synthetic Route of 7025-19-6, Having gained chemical understanding at molecular level, chemistry graduates may choose to apply this knowledge in almost unlimited ways, as it can be used to analyze all matter and therefore our entire environment. In a document type is Patent, and a compound is mentioned, 7025-19-6, 3-(4-Oxo-2-thioxothiazolidin-3-yl)propanoic acid, introducing its new discovery.

Provided is an evaluation probe capable of optically evaluating permeability of a substance through a central nervous system tissue. Also provided is an evaluation method for permeability of a substance through a central nervous system tissue using an evaluation probe for central nervous system permeability. Also provided is a screening method using an evaluation probe for central nervous system permeability. The evaluation probe for central nervous system permeability includes, as an active ingredient, at least one kind of compound represented by the following general formula (1).

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Structural modification of the calcium antagonist fostedil (KB-944) and their coronary vasodilator activity are described.Amidophosphonate 4a-m, lactam amidophosphonate 7a-l, and diamide dilactam 10 were prepared, and their coronary vasodilator activity was assessed in dogs.Many compounds exhibited coronary vasodilator activity superior to that of fostedil.Among them, the 2-oxopyrrolidine derivative 7a was the most effective compound.Its action as a coronary vasodilator was 3 and 2 times more potent than that of fostedil and diltiazem hydrochloride, respectively.

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New Advances in Chemical Research, May 2021. Application In Synthesis of 4-(4-((2,4-Dioxothiazolidin-5-ylidene)methyl)-2-methoxyphenoxy)-3-(trifluoromethyl)benzonitrile, Having gained chemical understanding at molecular level, chemistry graduates may choose to apply this knowledge in almost unlimited ways, as it can be used to analyze all matter and therefore our entire environment. In a document type is Article, and a compound is mentioned, 1055361-35-7, 4-(4-((2,4-Dioxothiazolidin-5-ylidene)methyl)-2-methoxyphenoxy)-3-(trifluoromethyl)benzonitrile, introducing its new discovery.

A series of piperidine-based derivatives were identified as novel and potent inhibitors of the influenza virus through structural modification of a compound that was selected from a high-throughput screen. Various analogues were synthesized and confirmed as inhibitors. The structure-activity relationship (SAR) studies suggested that the ether linkage between the quinoline and piperidine is critical for the inhibitory activity. The optimized compound tert-butyl 4-(quinolin-4-yloxy)piperidine-1-carboxylate 11e had an excellent inhibitory activity against influenza virus infection from a variety of influenza virus strains, with EC50values as low as 0.05 muM. The selectivity index value (SI = MLD50/EC50) of 11e is over 160 000 based on cytotoxicity, measured by MTT assays of three cell lines. We carried out a time-of-addition experiment to delineate the mechanism of inhibition. The result indicates that 11e interferes with the early to middle stage of influenza virus replication.

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Some derivatives of ibuprofen bearing 4H-thiazolidin-4-one moiety were synthesized from ibuprofen and studied for their pharmacological activities. Methyl ester of ibuprofen I was synthesized from ibuprofen and then converted to hydrazide II with the reaction of hydrazine hydrate. Hydrazide of ibuprofen then reacted with aromatic aldehydes in the presence of glacial acetic acid to yield the hydrazones III which on reaction with thioglycolic acid and dimethyl formamide in presence of catalytic amount of anhydrous zinc chloride furnished the title compounds IV. The structures of synthesized compounds were elucidated mainly by spectral evidence. All the synthesized title compounds were screened for their anti-inflammatory activity. Title compounds were also studied for their ulcerogenic potential. The compounds exhibited moderate to significant activities.

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Background: The increasing predominance of microbial resistance towards available antimicrobial drugs urges the need to develop novel antimicrobial agents that will be effective against resistant bacteria and fungi. Objective: A series of 3-(benzothiazol-2-yl)-2-(4-substituted phenyl) thiazolidin-4-one derivatives were synthesized as pharmacophore hybrid of benzothiazole and thiazolidin-4-one moieties as exclusive antimicrobial agents. Methods: Proposed compounds were synthesized by four step reactions. First three steps involved synthesis of phenylthiourea, benzothiazol-2-ylamine and Schiff?s base srespectively. Finally, Schiff`s baseswere cyclized in the presence of thioglycolic acid to yield 4-thiazolidinone derivatives (2a-g), characterized by spectroscopic and elemental analysis. Resulted compounds were evaluated for their in vitro antimicrobial activities against four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) and two fungal (A. niger and P. crysogenum) strains using agar diffusion method. The minimum inhibitory concentrations (MIC) of the synthesized compounds were also determined by tube dilution method. Results: All the compounds displayed good to moderate antimicrobial activity. Compound 2d was found most potent against Bacillus subtilis (MIC25mug/ml), whereas compound 2e was most active (MIC 25mug/ml) against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Conclusion: The compounds having electron-withdrawing groups in the phenyl ring exhibited promising activity. A correlation between the antimicrobial activity and Log P was also established. Most active compounds can be considered as the potential antibacterial agents and deserve further investigation for their pharmacological and toxicological profiling.

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Fungi place a huge burden on global healthcare systems attributed to the fact that fungal infections are responsible for the high morbidity and mortality rates in patients who received stem cell transplantation, antineoplastic chemotherapy, organ transplants or suffered Human Immunodeficiency Virus (HIV) infection. Unfortunately, almost none of the representative anti-fungal agents currently used in clinical therapy are ideal in terms of efficacy, anti-fungal spectrum or safety. Moreover, the rapid development of resistance to existing anti-fungal drugs has further aggravated the mortality and spread of fungi, creating an urgent need for novel anti-fungal agents. The broad spectrum of biological activities and successful usage in clinic made coumarins a promising anti-fungal candidate. Furthermore, hybridization of other pharmacophores with coumarin motif may enhance the anti-fungal efficacy, broaden the anti-fungal spectrum and improve the safety profiles. Thus, numerous coumarin hybrids have been assessed for their anti-fungal activities, and some of them showed promising potency and may have a novel mechanism of action. This review aims to outline the recent development of coumarin hybrids as potential anti-fungal agents and summarize their Structure-Activity Relationship (SAR) to provide an insight for rational designs of more active agents.

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