- A simple synthesis of 2-thiohydantoins
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2-Thiohydantoin derivatives are produced by heating a mixture of thiourea and an a-amino acid. The method described offers the advantages of simplicity, low cost, easy work-up and scalability.
- Wang, Zerong Daniel,Sheikh, Samia O.,Zhang, Yulu
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Read Online
- Synthesis and antimicrobial activity of thiohydantoins obtained from L-amino acids
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Background: Thiohydantoins are an important class of heterocyclic compounds in drug discovery since they are related to a wide range of biological properties including antimicrobial activity. Objective: The objective of this study was to synthesize a series of thiohydantoins derived from L-aminoacids and to evaluated their inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. Methods: All title compounds were synthetized by reaction of L-amino acids with thiourea or ammonium thiocyanate. Their antimicrobial activities were evaluated against bacterial strains by broth microdilution assays. The time-kill kinetics, the antibiofilm activity and the cytotoxicity to mammalian cells were determined for the compound that exhibited the best antimicrobial profile (1b). Results: Eleven thiohydantoins were readily obtained in good yields (52-95%). In general, thiohydantoins were more effective against Gram-positive bacteria. Compound 1b (derived from L-alanine) showed the best antibacterial activity against Staphylococcus epidermis ATCC 12228 and S. aureus BEC 9393 with MIC values of 940 and 1921 μM, respectively. The time-kill kinetics demonstrated time-dependent bactericidal effect in both strains for this derivative. Besides, 1b also exhibited antibacterial activity against biofilms of S. epidermidis ATCC 12228, leading to a 40% reduction in their metabolic activity compared to the untreated control. No cytotoxicity of 1b to mammalian cells was observed at MIC values. Conclusion: The data reported herein indicate relevant antimicrobial activity of thiohydantoins derived from L-aminoacid, mainly 1b, as potential pharmacophore to guide further chemical modification aiming at the search for new and improved antimicrobial agents.
- Bispo, Marcelle de Lima Ferreira,Garbin, Renata Perugini Biasi,Macedo, Fernando,Nakazato, Gerson,Ogatta, Sueli Fumie Yamada,Ribeiro, Jhonatan Macedo,de Carvalho, Priscila Goes Camargo,de Fátima, ?ngelo
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- Utility of 3-(thiophen-2-yl)prop-2-enoyl isothiocyanate in heterocyclic synthesis
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Convenient syntheses of quinazoline, benzothiazole, thiadiazole, imidazole, and thiourea derivatives starting from 3-(thiophen-2-yl)prop-2-enoyl isothiocyanate are described. The structures of the synthesized compounds are confirmed from their microanalytical and spectral data. Some of the products are examined for their antibacterial activity against Gram-positive and Gram-negative bacteria and fungi.
- El-Sayed, Amira A,Atta-Allah, Saad R,Hemdan, Magdy M
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p. 307 - 312
(2019/07/19)
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- A heterocyclic compound and use thereof
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The invention relates to a heterocyclic compound as shown in a general formula I which is described in the specification and application of the heterocyclic compound as a plant disease resistance activator. In the general formula I, R1 is selected from the group consisting of hydrogen, a C1-C6 alkyl group and a C3-C6 cycloalkyl group, R2 is selected from the group consisting of hydrogen, a C1-C6 alkyl group, a substituted or non-substituted C1-C14 aryl group and a five-membered or six-membered heterocycle containing nitrogen, oxygen and sulfur, and n is a positive integer in a range of 2 to 4. The compound provided by the invention inhibits pathogens through inducing a plant to generate disease resistance against pathogens instead of directly killing or inhibiting pathogens. The compound provided by the invention has the advantages of systematicness, persistence, broad spectrum activity, security, etc., enables the usage amount of highly toxic pesticides to be reduced and is friendly to the environment; so the compound has great industrial and commercial prospects and a great market value.
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Paragraph 0117; 0121-0123
(2017/11/16)
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- Compound capable of inhibiting activity of NEDD8 kinase as well as preparation method and pharmaceutical application of compound
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The invention belongs to the field of medicines and in particular relates to a compound with the structure of a formula I, a stereomer of the compound or pharmaceutically acceptable salts of the compound as well as a preparation method of the compound and application of the compound to preparation of anti-tumor medicines. A pharmacological experiment result shows that the compound can be used for inhibiting the activity of NEDD8 kinase and has the inhibition effect on proliferation of a plurality of types of tumor cells, so that the compound can be used as an NEDD8 kinase activity inhibitor for preparing the anti-tumor medicines. The formula I is shown in the description.
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Paragraph 0082; 0083; 0084
(2016/10/10)
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- Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds
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Somatic mutations of isocitrate dehydrogenase 1 (IDH1) at R132 are frequently found in certain cancers such as glioma. With losing the activity of wild-type IDH1, the R132H and R132C mutant proteins can reduce α-ketoglutaric acid (α-KG) to d-2-hydroxyglutaric acid (D2HG). The resulting high concentration of D2HG inhibits many α-KG-dependent dioxygenases, including histone demethylases, to cause broad histone hypermethylation. These aberrant epigenetic changes are responsible for the initiation of these cancers. We report the synthesis, structure-activity relationships, enzyme kinetics, and binding thermodynamics of a novel series of 2-thiohydantoin and related compounds, among which several compounds are potent inhibitors of mutant IDH1 with Ki as low as 420 nM. X-ray crystal structures of IDH1(R132H) in complex with two inhibitors are reported, showing their inhibitor-protein interactions. These compounds can decrease the cellular concentration of D2HG, reduce the levels of histone methylation, and suppress the proliferation of stem-like cancer cells in BT142 glioma with IDH1 R132H mutation.
- Wu, Fangrui,Jiang, Hong,Zheng, Baisong,Kogiso, Mari,Yao, Yuan,Zhou, Chao,Li, Xiao-Nan,Song, Yongcheng
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supporting information
p. 6899 - 6908
(2015/09/22)
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- PEPTIDYLARGININE DEIMINASES (PAD) INHIBITORS
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The present invention relates to compounds of the formula (I): as inhibitors of peptidylarginine deiminases (PADs). It also concerns their use in therapy, particularly in the prophylaxis or treatment of neural injury, and other conditions including cancer, multiple sclerosis, glaucoma, arthritis, rheumatoid arthritis lupus, Alzheimer's disease, and ulcerative colitis.
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Page/Page column 60
(2014/12/12)
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- Facile synthesis of hydantoins and thiohydantoins in aqueous solution
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A series of hydantoins and thiohydantoins have been synthesized in water at room temperature from urea (or N-methylurea, or thiourea) and simple aldehydes (as glyoxal, and its simple derivatives) in the presence of phosphoric anhydride. The reaction time is 10 min using an equimolar amount of P 4O10 with respect to the other reagents, but the reaction occurs also, even if with longer reaction times, with very small amounts of P4O10. In addition, this method provides a clean and 'green' approach to hydantoins, compounds of great interest in biological and pharmacological fields.
- Baccolini, Graziano,Boga, Carla,Delpivo, Camilla,Micheletti, Gabriele
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experimental part
p. 1713 - 1717
(2011/05/05)
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- Thiohydantoins: Selective N- and S-functionalization for Liebeskind-Srogl reaction study
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Thiohydantoins formed by the Schlack-Kumpf protocol were selectively functionalized at the nitrogen, sulfur, or carbon atom to test the Liebeskind-Srogl reaction possibilities. Georg Thieme Verlag Stuttgart. New York.
- Gosling, Sandrine,Rollin, Patrick,Tatibouet, Arnaud
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experimental part
p. 3649 - 3660
(2011/12/21)
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- α-Thioureidoalkylation of urea heteroanalogs
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α-Thioureidoalkylation of urea heteroanalogs such as thiosemicarbazide, amino-guanidine, sulfamide, and sulfonamides with 4,5-dihydroxyimidazolidine-2-thiones has been studied. Previously unknown 4,5-bis[thiosemicarbazido(guanidinoamino)]imidazolidine-2-thiones, 5,7-dialkylperhydroimidazo[4,5- e][1,2,4]triazine-3,6-dithiones, 4,6-diethyl-5(3H)-thioxotetrahydro-1 H-imidazo[4,5- c][1,2,5]thiadiazole 2,2-dioxide, and 1,3-dialkyl-4-[guanidinoimino(arylsulfonylimino)]imidazolidine- 2-thiones have been synthesized.
- Gazieva,Nelyubina,Kravchenko,Sigachev,Glukhov,Struchkova,Lyssenko,Makhova
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scheme or table
p. 1945 - 1954
(2011/01/07)
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- Process for the preparation of memantine and its hydrochloric acid salt form
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The present invention relates to the synthesis of 1-amino-3,5-dimethyladamantane ("memantine") and its hydrochloric acid salt form. In particular a new intermediate (N-chloro-acetylamino-3,5-dimethyladamantane) for the synthesis of memantine as well as a new process for the preparation of memantine and its hydrochloric acid salt form using said intermediate is disclosed.
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Page/Page column 8
(2008/06/13)
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- On formation of thiohydantoins from amino acids under acylation conditions
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Reactions of glycine, alanine, and phenylalanine with acetic anhydride and ammonium thiocyanate give the 1-acetyl-2-thiohydantoins 2a-c. These results appear to contradict prior literature reports pertaining to this reaction.
- Reyes, Samuel,Burgess, Kevin
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p. 2507 - 2509
(2007/10/03)
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- Ultrashort acting hypnotic barbiturates
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The subject invention concerns novel compounds that are useful as ultrashort acting hypnotic barbiturates. Specifically exemplified are derivatives of barbituric and thiobarbituric acids. They are rapidly metabolized by blood and tissue enzymes to form polar metabolites with no hypnotic activity and which are rapidly eliminated.
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- Reaction of 2-thiohydantoins with some diazoalkanes and some amines
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Reaction of 2-thiohydantoin derivatives with diazoalkanes as diazomethane, diphenyldiazomethane and/or 9-diazofluorene was investigated. Several 2-thio- and 2-methylthiohydantoins (IIa,b), (IIIa,b) (XI) and (XII) were prepared via the reaction of 2-thiohydantoins (Ia,b) and (X) with diazomethane. 2-Morpholino- and/or 2-piperidino- glycocyamidines (VIIa,b) and (XVa,b) were prepared by reacting 2-alkylthiohydantoins (IIIa) and (XII), respectively, with morpholine and/or piperidine. Moreover, treating of two equivalents of XIVa-d with one equivalent of piperazine afforded 1,4[di-(5-phenylmethylene-hydantoinyl)]-piperazines (XVIa,b). The hehaviour of 2-alkylthiohydantoins towards alanine and arthranilic acid was also investigated. The structure of the products was established by correct analytical and spectral data as well as by chemical evidencies.
- El-Barbary, Ahmed A.,Aly, Youssef L.,Hashem, Abdel-Fatah M.,El-Shehawy, Ashraf A.
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- Process for the preparation of alfa-L-aspartyl-L-phenyl-alanine alkyl esters
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A new process for preparing alfa-L-aspartyl-L-phenylalanine alkyl esters of formula I STR1 wherein R represents an alkyl group having from 1 to 5 carbon atoms, starting from the corresponding alfa-haloacyl-alfa-L-aspartyl-L-phenylalanine alkyl esters.
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- Soil disease-controlling imides
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A soil disease controlling agent for preventing and controlling diseases caused by pathogenic fungi living in soil, which comprises an effective amount of at least one of a 2-cycloalkenylamine derivative and its salts as an active ingredient, and at least one inert carrier or diluent.
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