Studies on Chemotherapeutics for Mycobacterium tuberculosis. XXII. : Synthesis and Antibacterial Activity on Mycobacterium tuberculosis of N&lt;SUP&gt;2&lt;/SUP&gt;-(2-Pyridyl)-3-p-ethoxyphenylpseudothiohydantoin and N&lt;SUP&gt;2&lt;/SUP&gt;-(2-Benzothiazolyl)-3-allylpseudothio-hydantoin Derivatives

Fujikawa, Fukujiro; Hirai, Kunio; Hirayama, Teruhisa; Yoshikawa, T. T.; Nakagawa, T; Naito, Masukazu; Tsukuma, Shunji; KAMADA, MICHIKO; Ohta, Yoshiko

doi:10.1248/yakushi1947.89.8_1099

Cited by 7 publications

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“…These include one report that some 2-imino-4-thiazolidinones showed antitubercular activity comparable to streptomycin or phthivazid 30. A few derivatives were reported to inhibit the growth of H37Rv at a concentration of 12.5 μg/mL,31 and related analogs were reported by others 32…”

Section: Resultsmentioning

confidence: 85%

Antituberculosis activity of the molecular libraries screening center network library

et al. 2009

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SUMMARYThere is an urgent need for the discovery and development of new antitubercular agents that target novel biochemical pathways and treat drug-resistant forms of the disease. One approach to addressing this need is through high-throughput screening of drug-like small molecule libraries against the whole bacterium in order to identify a variety of new, active scaffolds that will stimulate additional biological research and drug discovery. Through the Molecular Libraries Screening Center Network, the NIAID Tuberculosis Antimicrobial Acquisition and Coordinating Facility tested a 215,110-compound library against M. tuberculosis strain H37Rv. A medicinal chemistry survey of the results from the screening campaign is reported herein. CONFLICT OF INTEREST STATEMENTCompeting interests: Dr. Goldman is a NIAID staff member who either in the past or currently provides oversight for the project that generated the data used as the basis for this work.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public AccessAuthor Manuscript Tuberculosis (Edinb) The MLSCN was established in 2005 as a pilot program to assemble a large library of biologically relevant small molecules and make them available through a network of HTS laboratories to researchers worldwide through a competitive assay submission process. Acceptance of the TAACF assay into the MLSCN program made available the unique resources of the NIH Small Molecule Repository (SMR), significantly expanding the spectrum of molecules tested for activity against TB. For this screen, a 215,110-compound library from the SMR was examined for anti-TB activity using the assay described previously, 7 with the only change to the screening protocol being the elimination of the polyethylene incubator bags, resulting in the identification of a number of novel chemical scaffolds. Moreover, even for classes of compounds identified earlier during testing of the NIAID ChemBridge library, 7 additional examples emerged that further clarified the structure-activity picture. Since the compounds in the SMR have been examined in scores of diverse assays undertaken by the MLSCN, and the results published on the NIH PubChem website, 8 another motivation for conducting the MLSCN campaign is the ability to correlate antituberculosis activity of the hits with other biological activities that these compounds may possess, potentially providing information about possible mechanisms of action or toxicity. The raw screening results upon which the structural analysis below is based are now publicly available on PubChem (assay AIDs 1332 and 1626). MATERIALS ...

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Section: Resultsmentioning

confidence: 85%

Antituberculosis activity of the molecular libraries screening center network library

et al. 2009

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“…A general procedure for the synthesis of 2-iminothiazolidin-4-ones is based on cyclocondensation of monoand disubstituted thioureas with α-halo acids and their esters [2,12]. However, the application of this procedure is limited due to the fact that the cyclization is selective only when the nitrogen atoms in thioureas are characterized by considerably different nucleophilicities [13] or when other structural factors are favorable (e.g., hydrogen bond formation) [14].5-Benzyl-2-iminothiazolidin-4-ones can be prepared by reaction of 3-aryl-2-bromopropionic acid esters with thiourea [15,16]. In the present work we made an attempt to synthesize 5-benzylthiazolidin-4-ones containing a 2-pyridylimino group in position 2.…”

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“…Compounds IVa-IVp and Va-Ve were isolated in high yields as colorless crystalline substances which were sparingly soluble in alcohol, dioxane, and DMF. It should be noted that some 2-(2-pyridylimino)thiazolidin-4-ones were found to exhibit antibacterial activity [13].Esters IIa-IIr were prepared by reaction of arenediazonium bromides Ia-Ir with methyl or ethyl acrylate according to Meerwein [17]. The reactions were exothermic, and they were carried out at room temperature or on slight heating.…”

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Synthesis of Heterocycles from Arylation Products of Unsaturated Compounds: XIII. 5-R1-Benzyl-2-(R2-2-pyridylimino)thiazolidin-4-ones

2005

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Meerwein reactions of arenediazonium bromides with methyl and ethyl acrylates gave 3-aryl-2-bromopropionic acid esters which were subjected to cyclocondensation with N- (2-pyridyl)-and N-(6-methyl-2-pyridyl)thioureas to obtain 5-R 1 -benzyl-2-(R 2 -2-pyridylimino)thiazolidin-4-ones. The latter were shown to exist in solution as E isomers of the imino form. * For communication XII, see [1].The thiazolidine ring is a promising and effective structural fragment for the design of biologically active compounds [2][3][4]. Methods of synthesis of combinatorial libraries of 4-thiazolidinone derivatives have been developed [5][6][7]. In the recent time, 5-R-benzylthiazolidine-2,4-diones attract increased interest, and some compounds of this series have already been introduced into medical practice as antidiabetic agents [8][9][10][11]. By contrast, 2-imino derivatives of 4-thiazolidinone have been studied to a lesser extent, despite the possibility for introducing an additional pharmacophoric fragment into the 2-position. A probable reason is the limited set of convenient methods for the synthesis of such compounds with various substituents in both the thiazolidine ring and the imino fragment. A general procedure for the synthesis of 2-iminothiazolidin-4-ones is based on cyclocondensation of monoand disubstituted thioureas with α-halo acids and their esters [2,12]. However, the application of this procedure is limited due to the fact that the cyclization is selective only when the nitrogen atoms in thioureas are characterized by considerably different nucleophilicities [13] or when other structural factors are favorable (e.g., hydrogen bond formation) [14].5-Benzyl-2-iminothiazolidin-4-ones can be prepared by reaction of 3-aryl-2-bromopropionic acid esters with thiourea [15,16]. In the present work we made an attempt to synthesize 5-benzylthiazolidin-4-ones containing a 2-pyridylimino group in position 2. We found that methyl and ethyl 3-aryl-2-bromopropionates IIa-IIr react with N-(2-pyridyl)thioureas IIIa and IIIb to give the corresponding 5-R 1 -benzyl-2-(R 2 -2-pyridylimino)thiazolidin-4-ones IVa-IVp and Va-Ve (Scheme 1). The reactions were carried out by heating the reactants for a short time in alcohol in the presence of a base. No elimination of hydrogen bromide from esters IIa-IIr (with formation of cinnamic acid derivatives) occurred under these conditions. Compounds IVa-IVp and Va-Ve were isolated in high yields as colorless crystalline substances which were sparingly soluble in alcohol, dioxane, and DMF. It should be noted that some 2-(2-pyridylimino)thiazolidin-4-ones were found to exhibit antibacterial activity [13].Esters IIa-IIr were prepared by reaction of arenediazonium bromides Ia-Ir with methyl or ethyl acrylate according to Meerwein [17]. The reactions were exothermic, and they were carried out at room temperature or on slight heating. Compounds IIa-IIr can be distilled under reduced pressure; they were isolated as light yellow liquids or crystalline substances. N-(2-Pyridyl)thioureas IIIa and IIIb wer...

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ChemInform Abstract: CHEMOTHERAPEUTICA FUER MYCOBACTERIUMTUBERCULOSIS 22. MITT. SYNTH. UND ANTIBAKTERIELLE WIRKUNG VON N(2)‐(2‐PYRIDYL)‐3‐P‐AETHOXYPHENYLPSEUDOTHIOHYDANTOIN‐ UND N(2)‐(2‐BENZOTHIAZOLYL)‐3‐ALLYLPSEUDOTHIOHYDANTOIN‐DERIVATEN AUF MYCOBACTERIUM TUBERCULOSIS

Fujikawa¹,

Hirai²,

Hirayama³

et al. 1970

Chemischer Informationsdienst. Organische Chemie

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Studies on Chemotherapeutics for Mycobacterium tuberculosis. XXII. : Synthesis and Antibacterial Activity on Mycobacterium tuberculosis of N<SUP>2</SUP>-(2-Pyridyl)-3-p-ethoxyphenylpseudothiohydantoin and N<SUP>2</SUP>-(2-Benzothiazolyl)-3-allylpseudothio-hydantoin Derivatives

Cited by 7 publications

References 0 publications

Antituberculosis activity of the molecular libraries screening center network library

Antituberculosis activity of the molecular libraries screening center network library

Synthesis of Heterocycles from Arylation Products of Unsaturated Compounds: XIII. 5-R1-Benzyl-2-(R2-2-pyridylimino)thiazolidin-4-ones

ChemInform Abstract: CHEMOTHERAPEUTICA FUER MYCOBACTERIUMTUBERCULOSIS 22. MITT. SYNTH. UND ANTIBAKTERIELLE WIRKUNG VON N(2)‐(2‐PYRIDYL)‐3‐P‐AETHOXYPHENYLPSEUDOTHIOHYDANTOIN‐ UND N(2)‐(2‐BENZOTHIAZOLYL)‐3‐ALLYLPSEUDOTHIOHYDANTOIN‐DERIVATEN AUF MYCOBACTERIUM TUBERCULOSIS

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