2215-20-5Relevant articles and documents
An investigation on 4-thiazolidinone derivatives as dual inhibitors of aldose reductase and protein tyrosine phosphatase 1B, in the search for potential agents for the treatment of type 2 diabetes mellitus and its complications
Maccari, Rosanna,Del Corso, Antonella,Paoli, Paolo,Adornato, Ilenia,Lori, Giulia,Balestri, Francesco,Cappiello, Mario,Na?, Alexandra,Wolber, Gerhard,Ottanà, Rosaria
, p. 3712 - 3720 (2018/10/20)
Designed multiple ligands (DMLs), developed to modulate simultaneously a number of selected targets involved in etiopathogenetic mechanisms of a multifactorial disease, such as diabetes mellitus (DM), are considered a promising alternative to combinations of drugs, when monotherapy results to be unsatisfactory. In this work, compounds 1–17 were synthesized and in vitro evaluated as DMLs directed to aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two key enzymes involved in different events which are critical for the onset and progression of type 2 DM and related pathologies. Out of the tested 4-thiazolidinone derivatives, compounds 12 and 16, which exhibited potent AR inhibitory effects along with interesting inhibition of PTP1B, can be assumed as lead compounds to further optimize and balance the dual inhibitory profile. Moreover, several structural portions were identified as features that could be useful to achieve simultaneous inhibition of both human AR and PTP1B through binding to non-catalytic regions of both target enzymes.
Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds
Wu, Fangrui,Jiang, Hong,Zheng, Baisong,Kogiso, Mari,Yao, Yuan,Zhou, Chao,Li, Xiao-Nan,Song, Yongcheng
supporting information, p. 6899 - 6908 (2015/09/22)
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.
Identification of 5-arylidene-4-thiazolidinone derivatives endowed with dual activity as aldose reductase inhibitors and antioxidant agents for the treatment of diabetic complications
Ottanà, Rosaria,MacCari, Rosanna,Giglio, Marco,Del Corso, Antonella,Cappiello, Mario,Mura, Umberto,Cosconati, Sandro,Marinelli, Luciana,Novellino, Ettore,Sartini, Stefania,La Motta, Concettina,Da Settimo, Federico
experimental part, p. 2797 - 2806 (2011/07/08)
In continuing the search for more effective 5-arylidene-4-thiazolidinones as aldose reductase inhibitors, a new set of suitably substituted compounds (4, 5 and 8) was explored. Acetic acids 5, particularly 5a and 5h, proved to be interesting inhibitors of the enzyme as well as excellent antioxidant agents that are potentially able to counteract the oxidative stress associated with both diabetic complications as well as other pathologies. Molecular docking experiments supported SAR studies.
Polymorphism of 5-(pyridin-2-ylmethylene)-3-phenyl-2-methylthio-3,5- dihydro-4H-imidazole-4-one
Guzei, Ilia A.,Gunn, Erica M.,Spencer, Lara C.,Schomaker, Jennifer M.,Rigoli, Jared W.
experimental part, p. 3444 - 3450 (2012/02/16)
The title compound, C16H13N3OS (1), exists in three polymorphic forms. Crystalline 1 undergoes an enantiotropic, first-order, k2 phase transition at 262.9(5) K with ΔH = 0.3(1) kJ mol-1. Upon cooling below the transition temperature, the high temperature orthorhombic polymorph (Form I, space group Pbcm) transforms into a low temperature orthorhombic polymorph (Form II, space group Pbca) with a unit cell twice the size of that of the Form I. A molten 1 can be cooled in a controlled fashion to generate a monoclinic Form III of 1 with the unit cell size similar to that of Form I. Metastable Form III, once isolated, is indefinitely stable between 100 K and its melting point of 466 K. If crystals of Form III are in contact with seed crystals of Form I, a monotropic t2 first-order Form III → Form I phase transition occurs upon heating with the onset between 420 and 448 K and ΔH = -1.7(4) kJ mol-1. The most substantial differences among the molecular geometries of 1 in Forms I-III are observed in the position and tilt of the phenyl ring relative to the rest of the molecule. The packing in Form III is very different from those in the other polymorphs. DFT molecular geometry optimizations produce the following order of stable molecule configurations: Form II (most stable), Form I (0.50 kJ mol -1), Form III (2.81 kJ mol-1).
The highly enantioselective Michael addition of ketones to nitrodienes catalyzed by the efficient organocatalyst system of pyrrolidinyl-thioimidazole and chiral thioureido acid
Li, Zhao-Bo,Luo, Shu-Ping,Guo, Yi,Xia, Ai-Bao,Xu, Dan-Qian
supporting information; experimental part, p. 2505 - 2508 (2010/08/07)
The highly enantioselective Michael addition reaction of ketones to nitrodienes was promoted efficiently by the accessible and fine-tunable organocatalytic system of pyrrolidinyl-thioimidazole and chiral thioureido acid. The corresponding adducts were afforded in good yields with high diastereoselectivities (up to 99:1) and excellent enantioselectivities (up to 99% ee). The Royal Society of Chemistry 2010.
A chiral thioureido acid as an effective additive for enantioselective organocatalytic Michael additions of nitroolefins
Xu, Dan-Qian,Yue, Hua-Dong,Luo, Shu-Ping,Xia, Ai-Bao,Zhang, Shuai,Xu, Zhen-Yuan
supporting information; experimental part, p. 2054 - 2057 (2009/02/01)
A novel and effective organocatalytic system consisting of pyrrolidinyl-thioimidazole and a chiral thioureido acid efficiently catalyzed the asymmetric Michael addition reactions of ketones to nitroolefins to afford the adducts with high diastereoselectivities (up to 99: 1) and excellent enantioselectivities (up to 99% ee). The Royal Society of Chemistry 2008.
Facile conversion of amino acids into 1-alkyl imidazole-2-thiones, and their oxidative desulfurization to imidazoles with benzoyl peroxide
Wolfe, Derek M.,Schreiner, Peter R.
, p. 2002 - 2008 (2008/02/11)
Glycine was acylated with isothiocyanates and condensed to 3-alkyl 2-thiohydantoins, which were reduced with a mixture of sodium borohydride and lithium chloride and dehydrated to 1-alkyl imidazole-2-thiones. These were oxidatively desulfurized to imidazoles with benzoyl peroxide. No chromatography was required for model compounds. The methods developed were used to elaborate tyrosine to 1,4-di(p-methoxybenzyl)imidazole, a common intermediate in the syntheses of three imidazoles from the sponge Leucetta. Georg Thieme Verlag Stuttgart.
2-Polystyrylsulfonyl ethanol supports for the solid-phase syntheses of hydantoins and ureas
Huang, Wenqiang,Cheng, Shaoling,Sun, Weimin
, p. 1973 - 1974 (2007/10/03)
Reaction of sodium polystyrylsulfinate 1 with 2-chloroethanol gave the 2-arylsulfonyl ethanol resin 2, which was converted to the polymer-supported amine 5. Amine 5 was coupled with an isocyanate or an isothiocyanate to give the polymer-supported urea der
KINETICS OF REACTION OF ISOTHIOCYANATE DERIVATIVES OF STILBENE WITH GLYCINE AND OF PHENYLISOTHIOCYANATE WITH ALANINE ETHYL ESTER
Kuczek, Marian,Nowak, Kornel
, p. 1691 - 1696 (2007/10/02)
The kinetics of reaction of isothiocyanate derivatives of trans-stilbene with glycine, the kinetics of cyclization reaction of derivatives of stilbenethiocarbamylglycine to thiohydantoins and the kinetics of reaction of phenylisothiocyanate with alanine ethyl ester were studied.
