Brief introduction of Thiazolidin-2-one

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Crystal structure of methyl (Z)-2-[(Z)-3-methyl-2-({(E)-1-[(R ?)-4-methylcyclohex-3-en-1-yl]ethylidene}hydrazinylidene)-4-oxothiazolidin-5-ylidene]acetate

The new title 4-thiazolidinone derivative, C 16 H 21 N 3 O 3 S, was obtained from the cyclization reaction of 4-methyl-3-thiosemicarbazone and dimethyl acetylenedicarboxylate (DMAD). The cyclohexylidene ring has an envelope conformation with the stereogenic centre C atom as the flap. Its mean plane makes a dihedral angle of 56.23(9) with the thiazolidine ring mean plane. In the crystal, molecules are linked by C – H?O hydrogen bonds forming chains propagating in the [001] direction. Within the chains there are offset pi-pi interactions between the thiazolidine rings of inversion-related molecules [centroid-centroid distance = 3.703(1)A]. The chains are linked by further C – H?O hydrogen bonds, forming slabs parallel to the ac plane.

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A new sulfenylation reagent, 3-phenylsulfenyl-2-(N- cyanoimino)thiazolidine, and its optically active version

We have developed a new sulfenylation reagent, 3-phenylsulfenyl-2-(N- cyanoimino)thiazolidine 3, that is readily available and stable upon storage. Compound 3 easily reacts with amines or thiols to give the corresponding sulfenamides or asymmetrical disulfides in excellent yields. It was also found that the alpha-sulfenylation reaction of carbonyl compounds with 3 proceeds smoothly. Furthermore, optically active 4-diphenylmethyl derivative 4 was synthesized as an asymmetric sulfenylation reagent, which realized 96% e.e. upon alpha-sulfenylation of a cyclic beta-keto ester.

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BCL6 INHIBITORS

The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity Formula (I) wherein X1, X2, R1, R2, R30, R31 and Ring A are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

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A new application about Thiazolidin-2-one

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PRODRUGS ACTIVATED BY REACTIVE OXYGEN SPECIES FOR USE IN THE TREATMENT OF INFLAMMATORY DISEASES AND CANCER

Prodrugs activated predominantly or exclusively in inflammatory tissue, more particularly prodrugs of methotrexate and derivatives thereof, which are selectively activated by Reactive Oxygen Species (ROS) in inflammatory tissues associated with cancer and inflammatory diseases, as well as method for preparing said prodrugs.

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Synthesis, characterization and preliminary anti-inflammatory evaluation of 5-benzylidine thiazolidine-4-one derivatives

A series of four compounds which contain thiazolidine-4-one ring were synthesized and preliminarily assessed as anti-inflammatory agents with anticipated selectivity against COX-2 enzyme. The synthesized compounds structures have been recognised according to their spectral FT-IR and 1H NMR data. GOLD software was used to perform molecular docking study. The crystallographic structure of the molecular target cyclo-oxygenase enzyme-2 (COX-2) was taken from PDB database however, the celecoxib and naproxen were selected as a positive controls. The docking results of the newly synthesized compounds shown that they can enter the substrate-binding area of the active site .The compound (Ia) showed the highest PLP fitness,while compound (Ic) appeared to have the lowest binding ability compared to celecoxib which may be due to the presence of para nitro group that deactivates the ring system. Whereas In vivo acute anti-inflammatory effects of the synthesized compounds were evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant decrease in the paw edema with respect to the effect of propylene glycol 50%v/v (control group). Compounds Ia,b,d showed potent anti-inflammatory effect than naproxen (50mg/kg, i.p.) at 180 min., while compound Ic exhibited lower anti-inflammatory effect.

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SUBSTITUTED 2, 4-DIAMINO-QUINOLINE DERIVATIVES FOR USE IN THE TREATMENT OF PROLIFERATIVE DISEASES

This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein which exhibit strong inhibition effects on various cancer cell lines. The compounds disclosed herein are useful for the treatment of proliferative diseases, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient and optionally one or more additional therapeutically active agents, including anticancer agents. This application also discloses methods for treating a proliferative disease, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis.

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Awesome Chemistry Experiments For (R)-2-Oxothiazolidine-4-carboxylic acid

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Collateral sensitivity of multidrug-resistant cells to the orphan drug tiopronin

A major challenge in the treatment of cancer is multidrug resistance (MDR) that develops during chemotherapy. Here we demonstrate that tiopronin (1), a thiol-substituted N-propanoylglycine derivative, was selectively toxic to a series of cell lines expressing the drug efflux pump P-glycoprotein (P-gp, ABCB1) and MRP1 (ABCC1). Treatment of MDR cells with 1 led to instability of the ABCB1 mRNA and consequently a reduction in P-gp protein, despite functional assays demonstrating that tiopronin does not interact with P-gp. Long-term exposure of P-gp-expressing cells to 1 sensitized them to doxorubicin and paclitaxel, both P-gp substrates. Treatment of MRP1-overexpressing cells with tiopronin led to a significant reduction in MRP1 protein. Synthesis and screening of analogues of tiopronin demonstrated that the thiol functional group was essential for collateral sensitivity while substitution of the amino acid backbone altered but did not destroy specificity, pointing to future development of targeted analogues. This article not subject to U.S. Copyright. Published 2011 by the American Chemical Society.

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A new application about 5908-62-3

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BROMODOMAIN INHIBITORS

The present invention provides for compounds of formula (I) wherein A1, A2, A3, A4, X1, X2, Y1, L1, G1, Rx, and Ry have any of the values defined thereof in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

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1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position

The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure-activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index.

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Structure-Based Discovery and Development of a Series of Potent and Selective Bromodomain and Extra-Terminal Protein Inhibitors

BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited good antitumor effects in an MM.1S xenograft model by oral administration. Encouraged by its high potency and interesting scaffold, we performed further lead optimization to generate a novel potent series of bromodomain and extra-terminal (BET) inhibitors with a (1,2,4-triazol-5-yl)-3,4-dihydroquinoxalin-2(1H)-one structure. Among them, compound 19 was found to have the best balance of activity, stability, and antitumor efficacy. After confirming its low brain penetration, we conducted comprehensive preclinical studies, including a multiple-species pharmacokinetics profile, extensive cellular mechanism studies, hERG assay, and in vivo antitumor growth effect testing, and we found that compound 19 is a potential BET protein drug candidate for the treatment of cancer.

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