29587-80-2

Upstream product

• 108-31-6 maleic anhydride 
• 75-15-0 carbon disulfide 
• 7446-70-0 aluminium trichloride 
• 100-41-4 ethylbenzene 
• 937-30-4 4-ethylacetophenone 
• 298-12-4 Glyoxilic acid 
• 39644-63-8 1-(4-Ethyl-phenyl)-2-(triphenyl-λ⁵-phosphanylidene)-ethanone 
• 39644-71-8 (Z)-4-(4-Ethyl-phenyl)-4-oxo-but-2-enoic acid ethyl ester 

Downstream Products

• 1362038-20-7 6-(4-ethylphenyl)-2-(4-(aminosulfonyl)phenyl)pyridazin-3(2H)-one 
• 39644-71-8 (Z)-4-(4-Ethyl-phenyl)-4-oxo-but-2-enoic acid ethyl ester 

Relevant academic research and scientific papers

Microwave-assisted synthesis of 4-oxo-2-butenoic acids by aldol-condensation of glyoxylic acid

4-Oxobutenoic acids are useful as biologically active species and as versatile intermediates for further derivatisation. Currently, routes to their synthesis can be problematic and lack generality. Reaction conditions for the synthesis of 4-oxo-2-butenoic

Design, synthesis and biological evaluation of benzoylacrylic acid shikonin ester derivatives as irreversible dual inhibitors of tubulin and EGFR

In this study, a series of shikonin derivatives combined with benzoylacrylic had been designed and synthesized, which showed an inhibitory effect on both tubulin and the epidermal growth factor receptor (EGFR). In vitro EGFR and cell growth inhibition assay demonstrated that compound PMMB-317 exhibited the most potent anti-EGFR (IC50 = 22.7 nM) and anti-proliferation activity (IC50 = 4.37 μM) against A549 cell line, which was comparable to that of Afatinib (EGFR, IC50 = 15.4 nM; A549, IC50 = 6.32 μM). Our results on mechanism research suggested that, PMMB-317 could induce the apoptosis of A549 cells in a dose- and time-dependent manner, along with decrease in mitochondrial membrane potential (MMP), production of ROS and alterations in apoptosis-related protein levels. Also, PMMB-317 could arrest cell cycle at G2/M phase to induce cell apoptosis, and inhibit the EGFR activity through blocking the signal transduction downstream of the mitogen-activated protein MAPK pathway and the anti-apoptotic kinase AKT pathway; typically, such results were comparable to those of afatinib. In addition, PMMB-317 could suppress A549 cell migration through the Wnt/β-catenin signaling pathway in a dose-dependent manner. Additionally, molecular docking simulation revealed that, PMMB-317 could simultaneously combine with EGFR protein (5HG8) and tubulin (1SA0) through various forces. Moreover, 3D-QSAR study was also carried out, which could optimize our compound through the structure-activity relationship analysis. Furthermore, the in vitro and in vivo results had collectively confirmed that PMMB-317 might serve as a promising lead compound to further develop the potential therapeutic anticancer agents.

Synthesis of 1,5-benzodiazepine derivatives using p-toluenesulfonic acid as catalyst

A series of substituted ethyl 4-oxo-4-phenylbut-2-enoates were prepared and reacted with substituted o-phenylenediamine, undergone Michael addition reactions and cyclodehydration to provide novel 4-phenyl-2,3-dihydro-1,5-benzodiazepine-2-carboxylate derivatives with excellent yields. The synthetic protocol fulfilled many green-chemical requirements by using simple catalyst p-toluenesulfonic acid as activator and ethanol as solvent at room temperature.

Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones

A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety (2a-h) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives (2a, 2b, 2d, 2g and 2h) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI50 value of less than 0.1 μM. It also displayed good activity against leukemia (CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226), non-small cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA-MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI 50 less than 1.0 μM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents.

Antiproliferative activity of aroylacrylic acids. Structure-activity study based on molecular interaction fields

Antiproliferative activity of 27 phenyl-substituted 4-aryl-4-oxo-2-butenoic acids (aroylacrylic acids) toward Human cervix carcinoma (HeLa), Human chronic myelogenous leukemia (K562) and Human colon tumor (LS174) cell lines in vitro are reported. Compounds are active toward all examined cell lines. The most active compounds bear two or three branched alkyl or cycloalkyl substituents on phenyl moiety having potencies in low micromolar ranges. One of most potent derivatives arrests the cell cycle at S phase in HeLa cells. The 3D QSAR study, using molecular interaction fields (MIF) and derived alignment independent descriptors (GRIND-2), rationalize the structural characteristics correlated with potency of compounds. Covalent chemistry, most possibly involved in the mode of action of reported compounds, was quantitatively accounted using frontier molecular orbitals. Pharmacophoric pattern of most potent compounds are used as a template for virtual screening, to find similar ones in database of compounds screened against DTP-NCI 60 tumor cell lines. Potency of obtained hits is well predicted.

2-[(Carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids selectively suppressed proliferation of neoplastic human HeLa cells. A SAR/QSAR study

A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 μM/L. Two compounds exhibit antiproliferative activity in sub-micromolar concentrations (16, 19). Five compounds act in low micromolar concentrations ( 10). A strong structure-activity relationship, using estimated log P values and BCUT descriptors, was observed.