5349-42-8

Usage

InChI:InChI=1/C11H10N2O3/c1-16-8-4-2-7(3-5-8)6-9-10(14)13-11(15)12-9/h2-6H,1H3,(H2,12,13,14,15)/b9-6+

Upstream product

• 120697-20-3 5-(4-methoxy-benzylidene)-imidazolidine-2,4-dione 
• 461-72-3 2,4-imidazolidinedione 
• 123-11-5 4-methoxy-benzaldehyde 
• 95474-45-6 5-p-methoxybenzylidene-2-thiohydantoin 
• 107-95-9 3-amino propanoic acid 
• 95378-36-2 diethyl 2,4-dioxoimidazolidin-5-yl-phosphonate 
• 141-43-5 ethanolamine 
• 154198-90-0 (E)-3-p-anisyl-2-cyano-2-propenoyl azide 
• 154198-92-2 (E)-2-Isocyanato-3-(4-methoxy-phenyl)-acrylonitrile 
• 27888-23-9 (E)-3-p-anisyl-2-cyano-2-propenoyl chloride 
• 14378-08-6 (E)-2-cyano-3-(4-methoxyphenyl)acrylic acid 
• 154199-20-9 [(E)-1-Cyano-2-(4-methoxy-phenyl)-vinyl]-urea 
• 7253-52-3 5-[1-(4-Methoxy-phenyl)-meth-(Z)-ylidene]-2-thioxo-imidazolidin-4-one 

Downstream Products

• 120697-20-3 5-(4-methoxy-benzylidene)-imidazolidine-2,4-dione 
• 1416719-84-0 (Z)-5-(4-methoxybenzylidene)-3-(oxiran-2-ylmethyl)imidazolidine-2,4-dione 
• 6318-42-9 5-(4-methoxy-benzyl)-hydantoin 
• 161194-17-8 5-(4-METHOXYBENZYLIDENE)-3-ISOSTEARYL HYDANTOIN 
• 871496-84-3 2-[5-(4-methoxy-benzylidene)-2,4-dioxo-imidazolidin-3-yl]-N-thiazol-2-yl-acetamide 
• 880796-49-6 2-[5-(4-methoxy-benzylidene)-2,4-dioxo-imidazolidin-3-yl]-N-(3-trifluoromethyl-phenyl)-acetamide 
• 867311-91-9 N-(2-chloro-5-trifluoromethyl-phenyl)-2-[5-(4-methoxy-benzylidene)-2,4-dioxo-imidazolidin-3-yl]-acetamide 
• 881042-57-5 2-[5-(4-methoxy-benzylidene)-2,4-dioxo-imidazolidin-3-yl]-N-(4-methoxy-phenyl)-acetamide 
• 28030-16-2 3-(4-methoxyphenyl)-2-oxopropanoic acid 
• 68383-86-8 2-hydroxy-3-(4-methoxyphenyl)acrylic acid 
• 3682-16-4 2-(hydroxyimino)-3-(4-methoxyphenyl)propanoic acid 

Relevant academic research and scientific papers

Enantioselective Synthesis of Chiral Substituted 2,4-Diketoimidazolidines and 2,5-Diketopiperazines via Asymmetric Hydrogenation

An enantioselective hydrogenation of 5-alkylidene-2,4-diketoimidazolidines (hydantoins) and 3-alkylidene-2,5-ketopiperazines catalyzed by the Rh/f-spiroPhos complex under mild conditions has been developed, which provides an efficient approach to the highly enantioselective synthesis of chiral hydantoins and 2,5-ketopiperazine derivatives with high enantioselectivities up to 99.9% ee.

Synthesis and structure-activity relationship studies of 2,4-thiazolidinediones and analogous heterocycles as inhibitors of dihydrodipicolinate synthase

Dihydrodipicolinate synthase (DHDPS), responsible for the first committed step of the diaminopimelate pathway for lysine biosynthesis, has become an attractive target for the development of new antibacterial and herbicidal agents. Herein, we report the di

The structural determinants for α1-adrenergic/ serotonin receptors activity among phenylpiperazinehydantoin derivatives

Several studies confirmed the reciprocal interactions between adrenergic and serotoninergic systems and the influence of these phenomena on the pathogenesis of anxiety. Hence, searching for chemical agents with a multifunctional pharmacodynamic profile may bring highly effective therapy for CNS disorders. This study presents a deep structural insight into the hydantoin-arylpiperazine group and their serotonin/α-adrenergic activity. The newly synthesized compounds were tested in the radioligand binding assay and the intrinsic activity was evaluated for the selected derivatives. The computer-aided SAR analysis enabled us to answer questions about the influence of particular structural fragments on selective vs. multifunctional activity. As a result of the performed investigations, there were two leading structures: (a) compound 12 with multifunctional adrenergic-serotonin activity, which is a promising candidate to be an effective anxiolytic agent; (b) compound 14 with high α1A/α1D affinity and selectivity towards α1B, which is recommended due to the elimination of probable cardiotoxic effect. The structural conclusions of this work provide significant support for future lead optimization in order to achieve the desired pharmacodynamic profile in searching for new CNS-modulating agents.

Chemoenzymatic synthesis of L-3,4-dimethoxyphenyl-alanine and its analogues using aspartate aminotransferase as a key catalyst

In this study, a chemoenzymatic synthesis method for the production of L-3,4-dimethoxyphenyl-alanine and its analogues from phenylpyruvate derivatives was developed. The aspartate aminotransferase from Escherichia coli was engineered by error prone PCR and the improved variants were identified. When 3, 4-dimethoxy phenylpyruvate was added by fed-batch on a preparative scale, L-3,4-dimethoxyphenyl-alanine was formed in 95.4% conversion and > 99% ee with the best aspartate aminotransferase variant as the catalyst. This study provided an efficient method for the production of methoxy substituted phenylalanines using the engineered aspartate aminotransferase.

Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors

Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3′-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC50 values of 3.0 ± 1.0 μM and 4.3 ± 1.5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (Ki = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.

Discovery of novel UV-filters with favorable safety profiles in the 5-arylideneimidazolidine-2,4-dione derivatives group

Effective protection from the harmful effects of UV radiation may be achieved by using sunscreens containing organic or inorganic UV filters. The number of currently available UV filters is limited and some of the allowed molecules possess limitations such as systemic absorption, endocrine disruption properties, contact and photocontact allergy induction, and low photostability. In the search for new organic UV filters we designed and synthesized a series consisting of 5-benzylidene and 5-(3-phenylprop-2-en-1-ylidene)imidazolidine-2,4-dione (hydantoin) derivatives. The photoprotective activity of the tested compounds was confirmed in methanol solutions and macrogol formulations. The most promising compounds possessed similar UV protection parameter values as selected commercially available UV filters. The compound diethyl 2,20-((Z)-4-((E)-3-(4-methoxyphenyl)allylidene)-2,5-dioxoimidazolidine-1,3-diyl)diacetate (4g) was characterized as an especially efficient UVA photoprotective agent with a UVA PF of 6.83 ± 0.05 and favorable photostability. Diethyl 2,20-((Z)-4-(4-methoxybenzylidene)-2,5-dioxo-imidazolidine-1,3-diyl)diacetate (3b) was the most promising UVB-filter, with a SPFin vitro of 3.07 ± 0.04 and very good solubility and photostability. The main photodegradation products were geometric isomers of the parent compounds. These compounds were also shown to be non-cytotoxic at concentrations up to 50 μM when tested on three types of human skin cells and possess no estrogenic activity, according to the results of a MCF-7 breast cancer model.

Synthesis of chiral hydantoin derivatives by homogeneous Pd-catalyzed asymmetric hydrogenation

5-Aryl substituted chiral hydantoin derivatives were synthesized via asymmetric hydrogenation of prochiral exocyclic alkenes using a Pd/BINAP catalyst. Moderate to good enantioselectivity were obtained (21–90% ee). A chiral Br?nsted acid additive was foun

Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP)

C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD+ as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50 = 0.24 μM). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50 = 0.18 μM) and 3-chloro- (IC50 = 0.17 μM) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer.

Synthesis, biological evaluation and molecular modeling studies of psammaplin A and its analogs as potent histone deacetylases inhibitors and cytotoxic agents

In this study, a concise synthetic method of psammaplin A was achieved from 3-bromo-4-hydroxybenzaldahyde and hydantoin through a four-step synthesis via Knoevenagel condensation, hydrolysis, oximation and amidation in 37% overall yield. A collection of novel psammaplin A analogs focused on the variations of substituents at the benzene ring and modifications at the oxime moiety were synthesized. Among all the synthesized compounds, 5d and 5e showed better HDAC inhibition than psammaplin A and comparable cytotoxicity against four cancer cell lines (PC-3, MCF-7, A549 and HL-60). Molecular docking and dynamics simulation revealed that (i) hydrogen atom of the oxime group interacts with Asp99 of HDAC1 through a water bridged hydrogen bond and (ii) a hydroxyl group is optimal attached on the para-position of benzene, interacting with Glu203 at the entrance to the active site tunnel.

Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2

The dual-specificity tyrosine-regulated kinase 1A (Dyrk1A) has gathered much interest as a pharmacological target in Alzheimer's disease (AD), but it plays a role in malignant brain tumors as well. As both diseases are multi-factorial, further protein kin