2010-15-3

Usage

Uses

Used in Pharmaceutical Industry:
PTH-GLYCINE is used as a therapeutic agent for the treatment of hypoparathyroidism, a condition characterized by insufficient levels of parathyroid hormone leading to low blood calcium levels. It is utilized for its ability to mimic the effects of natural PTH, thereby stimulating calcium release from bones, increasing calcium reabsorption in the kidneys, and promoting the production of active vitamin D, all of which help to raise blood calcium levels.
Used in Endocrinology:
PTH-GLYCINE is used as a hormone replacement therapy in endocrinology for patients suffering from hypoparathyroidism. It addresses the underlying deficiency of PTH by providing a synthetic version that can effectively manage the symptoms and complications associated with low calcium levels in the blood.
Used in Patient Care:
PTH-GLYCINE is used as a convenience medication for patients with hypoparathyroidism, offering a longer-lasting effect due to its extended half-life compared to natural PTH. This allows for less frequent dosing, which can improve patient compliance and overall quality of life.

InChI:InChI=1/C9H8N2O2S/c12-8-6-11(9(13)10-8)14-7-4-2-1-3-5-7/h1-5H,6H2,(H,10,12,13)

Upstream product

• 103-72-0 phenyl isothiocyanate 
• 56-40-6 glycine 
• 121928-40-3 N-phenyl-N'-methoxycarbonylmethyl thiourea 
• 1516-85-4 tetraphenyloxalic amidine 
• 24066-82-8 ethyl 2-isothiocyanatoacetate 
• 62-53-3 aniline 
• 29022-11-5 N-(fluoren-9-ylmethoxycarbonyl)glycine 
• 123-91-1 1,4-dioxane 
• 4464-35-1 glycyl=>L-leucyl=>-L-leucine 
• 4337-37-5 Leucyl-glycyl-glycin 
• 81511-63-9 2-(N-phenyl carboxamidomethyl thio)-5-phenyl-1,3,4-oxadiazole 
• 4530-20-5 BOC-glycine 
• 107-07-3 2-chloro-ethanol 
• 5680-79-5 glycine ethyl ester hydrochloride 

Downstream Products

• 87736-68-3 4-furfurylidene-1-phenyl-2-thioxoimidazolidin-5-one 
• 87736-69-4 4-thenylidene-1-phenyl-2-thioxoimidazolidin-5-one 
• 122351-43-3 5-[2-Oxo-2-phenyl-eth-(E)-ylidene]-3-phenyl-2-thioxo-imidazolidin-4-one 
• 32832-07-8 (E)-5-benzylidene-3-phenyl-2-thioxoimidazolidin-4-one 
• 82754-77-6 5-Amino-1-oxo-2,7-diphenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile 
• 53514-58-2 5-(4-nitro-benzylidene)-3-phenyl-2-thioxo-imidazolidin-4-one 
• 82754-78-7 5-Amino-7-(4-nitro-phenyl)-1-oxo-2-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile 
• 82754-75-4 5-Fluoren-9-ylidene-3-phenyl-2-thioxo-imidazolidin-4-one 
• 82754-80-1 C₂₅H₁₆N₄OS 
• 143827-48-9 1-acetyl-3-phenyl-2-thio hydantoine 
• 82754-81-2 6-cyano-1-oxo-3-thioxo-2,5,7-triphenyl-2,3,7,7a-tetrahydro-1H-pyrrolo<1,2-a>imidazole 
• 32832-07-8 phenylmethylene-3-phenyl-2-thioxoimidazolidin-4-one 
• 145693-88-5 5-[1-Naphthalen-2-yl-meth-(E)-ylidene]-3-phenyl-2-thioxo-imidazolidin-4-one 
• 87736-71-8 2,3,5,6-tetrahydro-5-imino-2,7-diphenyl-6-thenylidene-3-thioxo-1H-pyrrolo<1,2-c>pyrimidin-1-one 

Relevant academic research and scientific papers

2-Polystyrylsulfonyl ethanol supports for the solid-phase syntheses of hydantoins and ureas

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

Synthesis of new thiohydantoin derivatives under phase transfer catalysis

A novel synthesis of thiohydantoin derivatives is achieved using phase transfer catalysis conditions via nucleophilic displacement of organohalogen compounds by 3-phenyl-2-thiohydantoin (1) and its arylidene derivative (5), yielding new thiohydantoin derivatives (2-9), which have pronounced biological activities and wide applications. Copyright Taylor & Francis Group, LLC.

Identification of 2-thioxoimidazolidin-4-one derivatives as novel noncovalent proteasome and immunoproteasome inhibitors

This paper describes the design, synthesis, and biological evaluation of 2-thioxoimidazolidin-4-one derivatives as inhibitors of proteasome and immunoproteasome, potential targets for the treatment of hematological malignancies. In particular, we focused our efforts on the design of noncovalent inhibitors, which might be a promising therapeutic option potentially devoid of drawbacks and side-effects related to irreversible inhibition. Among all the synthesized compounds, we identified a panel of active inhibitors with Ki values towards one or two chymotrypsin-like activities of proteasome (β5c) and immunoproteasome (β5i and β1i subunits) in the low micromolar range. Docking studies suggested a unique binding mode of the molecules in the catalytic site of immunoproteasome proteolytic subunits.

Design, synthesis, characterization, molecular docking and computational studies of 3-phenyl-2-thioxoimidazolidin-4-one derivatives

Breast cancer is the most widely recognized intrusive disease in women and the second leading cause of cancer death worldwide. Thiohydantoins possess wide and interesting pharmacological properties such as antitumor agents, anticonvulsants, antidepressants, antiviral, antithrombotic activities, etc. 3-phenyl-2-thioxoimidazolidin-4-one derivatives were synthesized and thoroughly characterized by FT-IR, 1H NMR, 13C NMR spectroscopic techniques. The structures of the compounds (5a-c) were further confirmed by single-crystal XRD analysis. Molecular docking studies were utilized to foresee the binding interactions of 3-phenyl-2-thioxoimidazolidin-4-one derivatives with the Estrogen Receptor (3ERT) and evaluated their ADME properties for finding the lead compound. Receptor-ligand docking studies were executed using Schr?dinger software. Computational studies such as Density Functional Theory and Hirshfeld surface analysis were used to identify the electronic states and molecular parameters of the compounds (5a-c). Further, in vitro and in vivo anticancer activities of these compounds will be evaluated in future.

Design and evaluation of non-carboxylate 5-arylidene-2-thioxo-4-imidazolidinones as novel non-competitive inhibitors of protein tyrosine phosphatase 1B

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin and leptin signalling and is crucially involved in the development of type 2 diabetes mellitus, obesity, cancer and neurodegenerative diseases. Pursuing our efforts to identify PTP1B inhibitors endowed with drug-like properties, we designed and evaluated 3-aryl-5-arylidene-2-thioxo-4-imidazolidinones (7) as a novel class of non-carboxylate PTP1B inhibitors. In agreement with our design, kinetic studies demonstrated that selected compounds 7 act as reversible, non-competitive inhibitors of the target enzyme at low micromolar concentrations. Accordingly, molecular docking experiments suggested that these inhibitors can fit an allosteric site of PTP1B that we previously individuated. Moreover, cellular assays demonstrated that compound 7e acts as a potent insulin-sensitizing agent in human liver HepG2 cells. Taken together, our results showed that these non-competitive PTP1B inhibitors can be considered promising lead compounds aimed to enhance druggability of the target enzyme and identify novel antidiabetic drugs.

NOVEL AZULENYL COMPOUND

PROBLEM TO BE SOLVED: To provide: a method for determining amino acid sequences such as trace peptides and proteins; as well as a compound that can be used as an Edman reagent suitable for said method, specifically a compound that has a high UV absorbance and efficiently reacts with peptides. SOLUTION: Provided is an azulenyl isothiocyanate compound represented by the formula (1). (Each R independently is a halogen atom, an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, a cycloalkyl group having 3 to 10 carbon atoms, an aryl group or heteroaryl group having 6 to 10 carbon atoms; n is an integer from 0 to 7; in particular, R preferably is an alkyl group having 1 to 10 carbon atoms, and further preferably has substituent group at 1 or more of the carbon 3-, 5-, 8-position.). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

Simple and Efficient Synthesis of 5-Substituted-3-phenyl-2-thioxoimidazolidin-4-one Derivatives from S -Amino Acids and Phenylisothiocyanate in et 3N/DMF-H 2O

A concise approach for the transformation of various S-amino acids into the 5-alkyl-3-phenyl-2-thioxoimidazolidin-4-one heterocycles using phenylisothiocyanate is described. Phenylthiohydantoins of amino acid were synthesized at room temperature in Et3N/DMF-H2O with easy workup and excellent yields.

Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds

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.

Thiazolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral activity in cell culture

The protease of dengue virus is a promising target for antiviral drug discovery. We here report a new generation of peptide-hybrid inhibitors of dengue protease that incorporate N-substituted 5-arylidenethiazolidinone heterocycles (rhodanines and thiazolidinediones) as N-terminal capping groups of the peptide moiety. The compounds were extensively characterized with respect to inhibition of various proteases, inhibition mechanisms, membrane permeability, antiviral activity, and cytotoxicity in cell culture. A sulfur/oxygen exchange in position 2 of the capping heterocycle (thiazolidinedione-capped vs rhodanine-capped peptide hybrids) has a significant effect on these properties and activities. The most promising in vitro affinities were observed for thiazolidinedione-based peptide hybrids containing hydrophobic groups with Ki values between 1.5 and 1.8 μM and competitive inhibition mechanisms. Rhodanine-capped peptide hybrids with hydrophobic substituents have, in correlation with their membrane permeability, a more pronounced antiviral activity in cell culture than the thiazolidinediones.

5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl-DNA Phosphodiesterase i

Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC50 = 0.87 μM). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.