- DUAL-INHIBITORS OF CELLULAR NECROPTOSIS AND FERROPTOSIS FOR USE IN THE TREATMENT OF ORGAN TRANSPLANT PATIENTS
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The invention relates to chemical compounds for use as a medicament in the prevention of organ transplant rejection and/or transplant organ damage. In embodiments of the invention, the compound inhibits and/or reduces ferroptosis and necroptosis of cells of the transplanted organ. In further embodiments, the patient is at risk of transplant rejection and/or is at risk of or shows signs of ischemia-reperfusion injury and/or necroinflammation.
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Paragraph 0170
(2021/09/09)
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- USE OF HETEROCYCLIC DERIVATIVES WITH CARDIOMYOCYTE PROLIFERATION ACTIVITY FOR TREATMENT OF HEART DISEASES
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Provided herein is the use of heterocyclic derivatives with cardiomyocyte proliferation activity for treatment of heart diseases. Specifically, disclosed is the use of compounds of formula (I) or a pharmaceutically acceptable salt, a solvate, a stereoisomer or a prodrug thereof; and application thereof. Definition of each group in the formula can be found in the specification for details.
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Page/Page column 17
(2021/06/22)
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- NOVEL HETEROCYCLIC DERIVATIVES WITH CARDIOMYOCYTE PROLIFERATION ACTIVITY FOR TREATMENT OF HEART DISEASES
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Provided are novel heterocyclic derivatives with cardiomyocyte proliferation activity for treatment of heart diseases. Specifically, provided are the compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, prepa
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Page/Page column 20; 22; 23
(2021/06/22)
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- N-ACYL AMINO ACID COMPOUNDS AND METHODS OF USE
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The invention relates to compounds of formula (I), or a salt thereof wherein R1, A, L, and R2 and n are as described herein. Compounds of formula (I) and pharmaceutical compositions thereof are ανβ1 integrin inhibitors that are useful for treating tissue specific fibrosis.
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Paragraph 0511
(2018/03/28)
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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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- Synthesis of N,N′-bis(5-arylidene-4-oxo-3,5-dihydro-4H-imidazol-2-yl) diamines bearing various linkers and biological evaluation as potential inhibitors of kinases
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The synthesis in 4 steps of new N,N′-bis(5-arylidene-4-oxo-3,5- dihydro-4H-imidazol-2-yl)diamines issued from various symmetric primary diamines as linkers was reported. The key step of our strategy has been the sulphur/nitrogen displacement of (5Z)-5-arylidene-2-ethylsulfanyl-3,5-dihydro- 4H-imidazol-4-ones 6 with respectively ethylenediamine 7a, piperazine 7b and N,N′-bis(3-aminopropyl)piperazine 7c using solvent-free reaction conditions under microwave irradiation with retention of configuration. These compounds were tested for their kinase inhibitory potencies toward four kinases (GSK-3α/β, DYRK1A, CLK1 and CLK3).
- Coulibaly, Wacothon Karime,Paquin, Ludovic,Bénie, Anoubilé,Bekro, Yves-Alain,Durieu, Emilie,Meijer, Laurent,Bazureau, Jean Pierre
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p. 581 - 590
(2013/02/23)
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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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- IMIDAZAOLONE DERIVATIVES,PREPARATION THEREOF AND BIOLOGICAL USE OF SAME
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Imidazolone derivatives, as medicaments, of formula wherein: R1═H, C1 to C5 alkyl, aryl or a 5- or 6-membered heterocyclic group;Ar1=optionally substituted aryl or an aromatic heterocycle;R═R2—S—, Rs
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Page/Page column 8
(2010/09/05)
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- 5-(Pyridylmethylidene)-substituted 2-thiohydantoins and their complexes with CuII, NiII, and CoII: Synthesis, electrochemical study, and adsorption on the cystamine-modified gold surface
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A series of CuII, NiII, and CoII complexes with 5-(pyridylmethylidene)-substituted 2-thiohydantoins (L) were synthesized by the reactions of the corresponding organic ligands with MCl 2?nH2O. The resu
- Beloglazkina,Majouga,Yudin,Frolova,Zyk,Dolzhikova,Moiseeva,Rakhimov,Butin
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p. 1015 - 1027
(2008/02/01)
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- Microwave-mediated solventless synthesis of new derivatives of marine alkaloid Leucettamine B
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New access to N-alkyl derivatives of the marine alkaloid Leucettamine B are described using two three-step convergent routes. For the formation of the 2-amino imidazolone ring, the key steps involve solvent-free condensations under microwaves and guanylation reactions with non-sterically hindered primary amines.
- Chérouvrier, Jean-René,Carreaux, Fran?ois,Bazureau, Jean Pierre
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p. 3581 - 3584
(2007/10/03)
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- A practical and eco-friendly synthesis of stereocontrolled alkylaminomethylidene derivatives of 2-thiohydantoins by dimethylamine substitution
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3-Alkyl-5-dimethyaminomethylidene-2-thioxo-imidazolidin-4-ones 3(a-c) available in two steps from methyl glycinate hydrochloride, represent a useful synthetic tool for efficient and mild solventless preparations of new alkylaminomethylidene derivatives of 2-thiohydantoins 8(a-e), 10(a-c) and 12(a-d) by stereocontrolled transamination reactions under microwave irradiations. The 1H, 13C NMR spectrum and the (5Z)-conformation of some representatives products are also discussed.
- Chérouvrier, Jean-René,Carreaux, Fran?ois,Bazureau, Jean Pierre
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p. 8745 - 8749
(2007/10/03)
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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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- A New and Convenient Synthesis of Some Substituted Thiohydantoins
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3-Substituted thiohydantoins (2a-g) were synthesized in satisfactory yields by the reaction of N-substituted thioureas (la-g) with chloroacetylchloride in the presence of triethylamine under reflux in dioxane. S-Alkylated products (7, 8) were obtained from the reaction of 3-p-tolyl-thiohydantoin (2d) with p-nitrobenzylchloride and 3-phenyl-5-chloromethyl-1,2,4-oxadiazole.
- Dueruest, Yasar,Nohut, Fatma
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p. 1997 - 2006
(2007/10/03)
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- A New Method of Synthesis of 3-Monosubstituted-2-thiohydantoins and -Hydantoins
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A new method of synthesis of 3-monosubstituted derivatives of 2-thiohydantoin and hydantoin in reaction of isothiocyanate or isocyanate glycin ethyl ester with primary aliphatic and aromatic amines has been described. Crude products were obtained with high yield and purity. The structure of these compounds was confirmed by spectral methods. Key words: 2-thiohydantoin, hydantoin, isothiocyanate glycin ethyl ester, isocyanate glycin ethyl ester
- Ryczek, J.
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p. 2599 - 2604
(2007/10/02)
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- BASE CATALYZED CYCLIZATION OF SUBSTITUTED ESTERS OF HYDANTOIC AND THIOHYDANTOIC ACID
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Base catalyzed cyclization rates have been measured of 22 derivatives of hydantoic and thiohydantoic acid esters in water and methanol.The cyclization of methyl and ethyl esters of hydantoic and 5-methylhydantoic acids is accompanied by hydrolysis of the ester group, whereas with the other derivatives the hydrolysis does not take place.Hydrolysis of the cyclization products (hydantoin and thiohydantoin derivatives) is not significant under the kinetic conditions.The cyclization of methyl ester of 5-phenylhydantoic acid in methanol is reversible; the equilibrium mixture contains 30percent of the starting ester.In all the cases the cyclization is subject to specific base catalysis; exceptions are esters of 5-phenylthiohydantoic and 5-phenyl-2-methylthiohydantoic acids whose cyclizations are subject to general base catalysis.Substituents always accelerate the cyclization.The 3-substituents have the greatest effects, the cyclization rate being considerably increased with bulk of the substituents; similarly large effect of 5-phenyl group consists mainly in its polar effects on the pre-equilibrium.The cyclizations are slower in methanol at the same concentration of the lyate ion: the greatest difference (up to 3 orders of magnitude) is observed with the 5-phenyl derivatives.
- Kavalek, Jaromir,Machacek, Vladimir,Svobodova, Gabriela,Sterba, Vojeslav
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p. 375 - 390
(2007/10/02)
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