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Twenty polyphenols were synthesized and evaluated for their effect on Helicobacter pylori urease. Among these compounds, 4-(p-hydroxyphenethyl)pyrogallol (15) (IC(50)=0.03 mM) and 7,8,4'-trihydroxyisoflavone (19) (IC(50)=0.14 mM) showed potent inhibitory activities, and inhibited Helicobacter pylori urease in a time-dependent manner. The structure-activity relationship of these polyphenols revealed: the two ortho hydroxyl groups were essential for inhibitory activity of polyphenol. When the C-ring of isoflavone was broken, the inhibitory activity markedly decreased. As for deoxybenzoin, the carboxyl group was clearly detrimental.

Twenty-four enamines were synthesized and reported for the first time. Their chemical structures were confirmed by means of 1 H NMR, ESI mass spectra, and elemental analyses, and four of them were determined by single crystal X-ray diffraction analysis. All of the compounds were assayed for antibacterial ( Bacillus subtilis ATCC 6633, Escherichia coli ATCC 35218, Pseudomonas fluorescens ATCC 13525, and Staphylococcus aureus ATCC 6538) and antifungal ( Aspergillus niger ATCC 16404, Candida albicans ATCC 10231, and Trichophyton rubrum ATCC 10218) activities by MTT method. Compounds ( E )-ethyl 3-(4-hydroxyphenylamino)-2-(4-methoxyphenyl)acrylate ( 9b ), ( E )-ethyl 3-(3,5-difluorophenylamino)-2-(4-chlorophenyl)acrylate ( 11b ), ( E )-ethyl 3-(3,5-dichlorophenylamino)-2-(4-chlorophenyl)acrylate ( 12b ), and ( E )-ethyl 3-(4-methylphenylamino)-2-(4-chlorophenyl)acrylate ( 15b ) showed considerable antibacterial activities against S. aureus ATCC 6538 with MICs of 3.8, 1.9, 1.1, and 0.9 μg/mL, respectively. Structure–activity relationship (SAR) analysis disclosed, generally, an E -isomer exhibited higher antibacterial activity than the corresponding Z -isomer. An electron-withdrawing group on A-ring led to some decrease in activity, while on B-ring, a similar substitution provided higher activity. Figure options Download full-size image Download as PowerPoint slide

Background The activation of NOD-like receptor (NLR) family, pyrin-domain containing 3 (NLRP3) inflammasome has now been proven to have a close connection with myocardial ischemia (MI) during acute phase, but the mechanisms are not completely clear. This study investigated the role of NLRP3 inflammasome in pathogenesis of MI injury including inflammation and lipid accumulation, as well as the effects of sodium tanshinone IIA sulfonate (STS) and diltiazem hydrochloride (DI). Methods Occlusion of left anterior descending (LAD) in canines was employed to induce MI. STS and DI were given intravenously 15min after LAD occlusion. Cardiac function, inflammation and lipid levels, as well as related signaling pathways were determined. Results MI induced in Beagle dog was characterized by elevated ST-segment and increased CK-MB level in serum. Cardiac NLRP3 inflammasome was activated with elevated myocardial IL-1β and IL-18 concentrations mediated by ROS over-production and TXNIP over-expression in MI dogs. Additionally, pro-inflammatory cytokines induced impairment of cardiac JAK2-STAT3 inflammatory pathway and insulin signaling pathway in this model, resulting in down-regulation of cardiac PPAR-α expression, subsequently causing lipid metabolism disorders characterized by elevation of myocardial lipid concentrations. These abnormalities were attenuated by the treatment of STS and DI. Conclusions These data firstly demonstrated that cardiac NLRP3 inflammasome activation driven by cardiac ROS over-production and TXNIP up-expression resulted in impairment of the JAK2–STAT3 and insulin signaling pathways, leading to disorder of lipid metabolism in myocardial ischemic dogs through PPAR-α over-expression. STS and DI might target cardiac NLRP3 inflammasome in preventing MI injury.

The synthesis and structure-activity studies of a series of quinoline-3-carbonitriles as inhibitors of Tpl2 kinase are described. Potent inhibitors of Tpl2 kinase with selectivity against a panel of selected kinases in enzymatic assays and specificity in cell-based phosphorylation assays in LPS-treated human monocytes were identified. Selected inhibitors with moderate activity in human whole blood assay effectively inhibited LPS/D-Gal induced TNFalpha release when administered intraperitoneally in mice.

The synthesis and structure-activity studies of a series of 6-substituted-4-anilino-[1,7]-naphthyridine-3-carbonitriles as inhibitors of Tpl2 kinase are described. The early exploratory work described here may lead to the discovery of compounds with significant therapeutic potential for treating rheumatoid arthritis and other inflammatory diseases.

Reaction of RSO2N(H)CH2CH2N(H)SO2R [R = Bu (1), 4-nitrobenzene (7), 1-naphthalene (9a), 2-naphthalene (9b)] with PhPCl2 or EtPCl2 gives monodentate phosphorus compounds 2 and 3 (R = Bu, PhP and EtP), and 8 (R = 4-nitrobenzene, PhP), and with Ph2PCl gives the corresponding bidentate phosphine ligands Ph2PN(SO2R)CH2CH2N(SO2R)PPh2 [R = Bu (10), 4-nitrobenzene (11), 1- and 2-naphthalene (12a,b)]; similar reactions of N,N′-(1-butanesulfonyl)-2,2′-diaminobiphenyl (4) give monodentate 5 (PhP) and 6 (EtP) and N,N′-bis(diphenylphosphino)-N,N′-(1-butanesulfonyl)-2,2′-diaminobiphenyl (16). A monodentate analogue of 10 was also prepared, Ph2PN(Et)SO2Bu (14). Diphosphorus compounds with two butanesulfonylamino groups on phosphorus were also prepared from 1 and Cl2P(CH2)nPCl2 (n = 2, 4) to give 19 and 20. Details of the 13C NMR false AA′X systems are reported for 19 and 20. Rhodium-catalyzed hydroformylation reactions were run at 60 and 80 °C, at CO/H2 pressures from 4–11 atm, and in THF, toluene, CH2Cl2, and dioxane. Results show that the highest ratios of linear (n) to branched (iso) aldehydes were obtained with arenesulfonamides (n∶iso > 10) while the bidentate alkanesulfonamide 10 gave a lower n∶iso ratio of 7.2 but the highest rate [k1 = 1.98 h−1, turnover frequency = 1130 mol aldehyde (mol Rh)−1 h−1] in THF at 80 °C. Both the rate and n∶iso ratio for 10 were found to increase with decreasing CO/H2 pressure in THF and in toluene, although the rate change was small for toluene. Both the rate and n∶iso ratio for 10 also increased in CH2Cl2, but this was found not to be due to lower CO/H2 concentrations in solution, on the basis of solubility measurements in THF and CH2Cl2.

The direct trifluoromethylation of nitriles using TMSCF 3 is reported. This reaction is promoted by TBABF and provides α,α-bistrifluoromethylated amines in moderate to good yields. The reaction conditions are mild and tolerate a range of functional groups. The X-ray crystal structure of a bistrifluoromethylamine was obtained.

Introduction The signaling pathways downstream of epidermal growth factor receptor (EGFR) are central to the biology of colorectal cancer. EGFR kinase represents an attractive target for the development of novel therapies for the treatment of cancers. A considerable achievement during the past 2 years was the development of targeted therapies against EGFR using small-molecule inhibitors such as quinazoline derivatives, pyrimidine derivatives, thiazole derivatives, acrylamide derivatives and urea derivatives. Some new methods and technologies were also used to discover novel reversible and irreversible EGFR inhibitors. In this review, recent advances in the research of EGFR inhibitors are reviewed. Areas covered This review summarized new patents and articles published on EGFR inhibitors within 2010 to present. Expert opinion From 2010 to present, some novel scaffolds have been discovered as first-generation EGFR inhibitors, which are more potent against both EGFR-activating (EGFR WT) and resistance mutations (EGFRDM, T790M/L858R). 'Fast-Forwarding Hit to Lead' and 'Combi-Molecule' postulate to represent a novel approach to cancer therapy. The focus on irreversible inhibitors is also of significance for the design of kinase inhibitors. Searching nature for novel scaffolds is a promising way to find new chemical tools with which we can better understand the development of drug resistance to current targeted therapy and study ways to bypass and overcome such drug resistance.

Two new series of new compounds containing a 6-amino-substituted group or 6-acrylamide-substituted group linked to a 4-anilinoquinazoline nucleus have been discovered as potential EGFR inhibitors. These compounds proved efficient effects on antiproliferative activity and EGFR-TK inhibitory activity. Especially, N(6)-((5-bromothiophen-2-yl)methyl)-N(4)-(3-chlorophenyl)quinazoline-4,6-diamine (5e), showed the most potent inhibitory activity (IC50=3.11μM for Hep G2, IC50=0.82μM for A549). The EGFR molecular docking model suggested that the new compound is nicely bound to the region of EGFR, and cell morphology by Hoechst stain experiment suggested that these compounds efficiently induced apoptosis of A549 cells.

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive glucocorticoid cortisone to its active form, cortisol. The glucocorticoid receptor (GR) signaling pathway has been linked to the pathophysiology of diabetes and metabolic syndrome. Herein, the structure-activity relationship of a series of piperazine sulfonamide-based 11β-HSD1 inhibitors is described. (R)-3,3,3-Trifluoro-2-(5-(((R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-yl)sulfonyl)thiophen-2-yl)-2-hydroxypropanamide 18a (HSD-621) was identified as a potent and selective 11β-HSD1 inhibitor and was ultimately selected as a clinical development candidate. HSD-621 has an attractive overall pharmaceutical profile and demonstrates good oral bioavailability in mouse, rat, and dog. When orally dosed in C57/BL6 diet-induced obesity (DIO) mice, HSD-621 was efficacious and showed a significant reduction in both fed and fasting glucose and insulin levels. Furthermore, HSD-621 was well tolerated in drug safety assessment studies.

A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed the most potent EGFR inhibitory activity (IC(50) = 0.43 μM and 1.54 μM, respectively). Molecular docking of I(12) into EGFR TK active site was also performed. This inhibitor nicely fitting the active site might well explain its excellent inhibitory activity.

Two series of urea and thiourea derivatives (1a-11a, 1b-11b) have been synthesized; all the 22 compounds were reported for the first time. Their anti-proliferative activities against the melanoma cell line B16-F10 were evaluated. Among the compounds tested, compound 6b exhibited the most potent activity in melanoma cells growth inhibition (IC(50) = 0.33 μM). The bioassay tests showed that anti-proliferative activities of these novel compounds were possibly caused by inhibition of ERK1/2 phosphorylation level. Therefore, compound 6b can be a potential anti-melanoma agent and an inhibitor of ERK1/2 phosphorylation deserving further research.

Cortisol and the glucocorticoid receptor (GR) signaling pathway has been linked to the development of diabetes and metabolic syndrome. In vivo, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to its active form, cortisol. Existing clinical data have supported 11β-HSD1 as a valid therapeutic target for type 2 diabetes. In our research program, (R)-1,1,1-trifluoro-2-(3-((R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)phenyl)propan-2-ol (HSD-016) was discovered to be a potent, selective, and efficacious 11β-HSD1 inhibitor and advanced as a clinical candidate. Herein, a reliable and scalable synthesis of HSD-016 is described. Key transformations include an asymmetric synthesis of a chiral tertiary alcohol via Sharpless dihydroxylation, epoxide formation, and subsequent mild reduction. This route ensured multikilogram quantities of HSD-016 necessary for clinical studies.

A series of salicylanilide derivatives (compounds 1-32) were synthesised by reacting substituted salicylic acids and anilines. The chemical structures of these compounds were determined by (1)H-NMR, electrospray ionisation mass spectrometry (ESI-MS) and elemental analysis. The compounds were assayed for their antiproliferative activities against the Hep-G2 cell line by the 3-(4,5-dimethylthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Among the compounds tested, 22 and 28 showed the most favouable antiproliferative activities with 50% inhibitory concentration (IC(50)) values of 1.7 and 1.3 μM, respectively, which were comparable to the positive control of 5-fluorouracil (IC(50)=1.8 μM). A solid-phase ELISA assay was also performed to evaluate the ability of compounds 1-32 to inhibit the autophosphorylation of the epidermal growth factor receptor tyrosine kinase (EGFR TK). Docking simulations of 22 and 28 were carried out to illustrate the binding mode of the molecule into the EGFR active site, and the result suggested that both compounds 22 and 28 could bind the EGFR kinase well.

A series of new metronidazole-deoxybenzoin derivatives were synthesized and evaluated for their antimicrobial activity against Helicobacter pylori. Highly selective anti-H. pylori activity was also observed in synthesized compounds. Compound 34 exhibited the most potent activity, similar to the positive control amoxicillin. Furthermore, compounds 17 and 34 were able to significantly decrease H. pylori water extract (HPE)-induced production of interieukin-8 (IL-8) in gastric mucosal cells, which did not show any effect on the cell viability.

Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity. Compound 3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) displayed the most potent EGFR inhibitory activity with IC₅₀ of 0.07 μM, which was comparable to the positive control erlotinib. Docking simulation was performed to position compound C5 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the pyrazole derivatives own high antiproliferative activity against MCF-7. Compound C5 showed significant antiproliferative activity against MCF-7 with IC₅₀ of 0.08 μM. Therefore, compound C5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.

Nine 2-arylthiazolidine-4-carboxylic acid derivatives and nine 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives were synthesized to screen for their antibacterial activities. Compounds 5, 14–18 were first reported. Their chemical structures were clearly determined by 1H NMR, 13C NMR, ESI mass spectra and elemental analyses, coupled with one selected single-crystal structure. All the compounds were assayed for antibacterial activities against two Gram-positive bacterial strains (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and two Gram-negative bacterial strains (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) by MTT method. Most of the 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives exhibited better antibacterial activities against the four bacterial strains than relative 2-arylthiazolidine-4-carboxylic acid derivatives. Compound (2RS,4R)-3-(tert-butoxycarbonyl)-2-(5-fluoro-2-hydroxyphenyl)thiazolidine-4-carboxylic acid (14) showed powerful antibacterial activities against P. aeruginosa with IC50 value of 0.195 μg/mL, which was superior to the positive controls Penicillin G and Kanamycin B, respectively. On the basis of the biological results, structure–activity relationships were discussed.

In the title compound, C15H12ClN3O2S2, the dihedral angle between the aromatic rings is 89.71 (10)°. In the crystal, inversion dimers linked by pairs of N—H...S hydrogen bonds occur.

Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. The synthesis and biological evaluation halide-deoxybenzoins derivatives are described in this Letter. Potent FabH inhibitory and selective anti-Gram-negative bacteria activities were observed in deoxybenzoin derivatives. Furthermore, compound 19 was able to reduce the ECE-induced IL-8 production in gastric mucosal cells significantly. Based on the biological data and molecular docking, compound 19 is a potential FabH inhibitor and anti-inflammatory agent deserving further research.

Two series of thiazolidinone derivatives designing for potential EGFR and HER-2 kinase inhibitors have been discovered. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Compound 2-(2-(5-bromo-2-hydroxybenzylidene)hydrazinyl)thiazol-4(5H)-one (12) displayed the most potent inhibitory activity (IC50 = 0.09 μM for EGFR and IC50 = 0.42 μM for HER-2), comparable to the positive control erlotinib. Docking simulation was performed to position compound 12 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the thiazolidinone derivatives own high antiproliferative activity against MCF-7. Compound 12 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.

Fourteen metronidazole derivatives (compounds 3a – f and 4b – h ) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by 1 H NMR, MS, and elemental analysis. The inhibitory activities against Helicobacter pylori urease have been investigated in vitro and many compounds have showed promising potential inhibitory activities of H. pylori urease. The effect of compounds 4b (IC 50 = 26 μM) and 4g (IC 50 = 12 μM) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC 50 showed that inhibitor was potent urease inhibitor. A docking analysis using the autodock 4.0 program could explain the inhibitory activities of compound 4g against H. pylori urease.

A series of deoxybenzoin derivatives from genistein were synthesized and their structures were elucidated by 1H NMR, mass spectral data and micro analyses. The structures of 2, 7 and 10 were determined by single-crystal X-ray analysis. These obtained compounds were evaluated for their assayed antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescence and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. Most compounds have displayed comparable antibacterial activity against bacterial. On the basis of the biological results, structure–activity relationships are discussed.

The antiproliferative activities of 36 3-aryl-1H-quinolin-4-ones were determined against two cancer cell lines (Hep G2 and KB) in vitro. The results indicate that most of these compounds show good cytotoxic activity against human cancer cell lines, but no cytotoxicity against a human normal cell line (L02). The positive control compounds genistein and 5-fluorouracil show no selectivity at inhibiting the growth of the above three cell lines. Generally, compounds that bear a halogen atom at the 8 position and a methoxy group at the 3' position exhibited remarkable cytotoxicity toward human cancer cell lines. Electron-withdrawing substituents at the 6 position decrease the antiproliferative activity significantly. We also put forward a pharmacophore model for 3-aryl-4-quinolinones binding with epidermal growth factor receptor protein tyrosine kinases (EGFR PTK). Out of the 36 synthetic compounds, 34 are reported for the first time.

Thirteen resveratrol (=5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol) analogues with a CHO group have been prepared by partial synthesis from resveratrol. The synthesized compounds have been evaluated for their cytotoxic activity against a human nasopharyngeal epidermoid tumor cell line KB, as well as for their xanthine oxidase inhibitory activity. Compounds 2, 3, and 6a showed the most significant cytotoxic activities against the cell line KB, and compound 2 also exhibited strong xanthine oxidase inhibitory activity.

Twenty-six depsides were synthesized to screen for their antibacterial activity. All of them were reported for the first time. Their chemical structures were clearly determined by 1 H NMR, 13 C NMR, ESI mass spectra and elemental analyses, coupled with one selected single-crystal structure. All the compounds were assayed for antibacterial activities against three Gram-positive bacterial strains ( Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538 and Streptococcus faecalis ATCC 9790) and three Gram-negative bacterial strains ( Escherichia coli ATCC 35218, Pseudomonas aeruginosa ATCC 13525 and Enterobacter cloacae ATCC 13047) by MTT method. Compound 2-(2-methoxy-2-oxoethyl)phenyl 3-nitrobenzoate ( C10 ) and 2-(2-ethoxy-2-oxoethyl)phenyl 3-nitrobenzoate ( C23 ) showed powerful antibacterial activities against B. subtilis with MIC of 0.78 μg/mL while compound 2-(2-methoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate ( C8 ) and 2-(2-ethoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate ( C21 ) exhibited significant antibacterial activities against E. coli with MIC of 1.562 μg/mL, which were superior to the positive controls penicillin G and kanamycin B, respectively. On the basis of the biological results, structure–activity relationships were discussed.

Twenty-four new 1,3-disubstituted urea derivatives (compounds 1–24) were synthesized and reported for the first time. The antiproliferative activities of these compounds were evaluated against a panel of one human liver cell line (L02) and two human tumor cell lines (KB and K562) by applying the MTT colorimetric assay. The series of 1,3-disubstituted urea derivatives show good antiproliferative activity against human cancer cell lines (KB and K562) and no antiproliferative activity against liver cell line (L02). The potent in vitro antiproliferative activity of these derivatives and their selectivity for L02 are quite important points for an anticancer drug candidate with fewer side effects. Structure–activity relationships were also discussed based on the obtained experimental data. The hydroxyl groups on the phenyl ring reduced the antiproliferative activities of 1,3-disubstituted urea derivatives. The OH groups could be responsible for a reduction in the permeability of the cell membrane. Generally, an aromatic ring on N-3 seems to be in favor of enhancing the inhibitory activity, compounds introduced a nitro group substituent at C-3 position on the aromatic ring approved to generally decrease activity.

A series of substituted urea derivatives, compounds 1-14, were synthesized and evaluated for their cytotoxic activities against the human-leukemia K562 cell line. Two structurally simple compounds, 7 and 12, both incorporating a morpholine ring, were found to be highly active, with IC50 values of ca. 0.25 microM.

Thirty genistein (= 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; GEN) derivatives were synthesized from genistein through a facile approach in high yields. Compounds 9, 11, 12, 23-30 were reported for the first time, while 13-22 have already been reported in our recent paper. The cytotoxic activities of these compounds were evaluated against a human nasopharyngeal epidermoid tumor cell line KB. Compounds 7-9, 12, 14, 16-19, 21, 24, 27, 29 showed remarkable antitumor activities in vitro, which was comparable with 5-fluorouracil, an anticancer drug. On the basis of the obtained experimental data, structure-effect relationships were discussed.

The title compound, (E)-4-(2-hydroxy­phenyl)­but-3-en-2-one, C10H10O2, was synthesized from salicyl­aldehyde and acetone. The mol­ecule is essentially planar, suggesting a high degree of conjugation throughout the system. Intermolecular hydrogen bonds link adjacent mol­ecules to form one-dimensional chains.

In the title compound, C15H13N3O2S2, the dihedral angle between the aromatic rings is 87.8 (2)°. In the crystal, inversion dimers occur linked by pairs of N—H...S hydrogen bonds.

Several α-aminoalkyl phosphonate derivatives of resveratrol were first prepared by partial synthesis from resveratrol. Antitumour activities of the synthesized compounds were determined against a human nasopharyngeal epidermoid tumour cell line KB and a human normal cell line L02 in vitro. The results indicated that these compounds showed good cytotoxic activity against KB but weak cytotoxic activity against L02. Compounds 5c and 5d showed significant cytotoxic activity against KB, with median inhibition concentration (IC50) values of 0.4 μM and 0.9 μM, respectively. On the basis of the biological results, the structure–activity relationship is discussed concisely. The potent antitumour activities shown by 5c and 5d make these resveratrol phosphonate derivatives of great interest for further investigations.

The title compound, C24H18O9S3, crystallizes with two mol­ecules per asymmetric unit, with distinctly different conformations, as quanti­fied by the C—O—S—C torsion angles.

In the title mol­ecule, C19H15NO9S2, the dihedral angle between the nitro group and the benzene ring to which it is attached is 11.68 (8)°. The N—C bond length of 1.466 (3) A indicates that no conjugation exists between the nitro group and the benzene ring.

In the title compound, C13H13N3O3, the nitro group is twisted away from the attached benzene ring by 19.5 (3)°. The dihedral angle between the benzene and pyridine rings is 78.2 (1)°. In the crystal structure, mol­ecules are connected into chains along the [001] direction by N—H⋯N hydrogen bonds.

In the genistein-related title compound, C19H16O6, the dihedral angle between the two benzene-ring planes is 52.81 (9)°.

In the genistein-related title mol­ecule, C18H16O5, the dihedral angle between the two benzene rings is 59.25 (6)°.

Twenty-four new enamines [(Z)-4–15 and (E)-4–15] were synthesized for the first time. Their chemical structures were determined by means of 1H NMR spectroscopy, electrospray ionization-mass spectrometry, and elemental analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis ATCC 6633, Escherichia coli ATCC 35218, Pseudomonas fluorescens ATCC 13525, and Staphylococcus aureus ATCC 6538) and antifungal (Aspergillus niger ATCC 16404, Candida albicans ATCC 10231, and Trichophyton rubrum ATCC 10218) activities by the 3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Four compounds, (E)-ethyl 3-(4-fluorophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-6), (E)-ethyl 3-(4-chlorophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-9), (E)-ethyl 3-(4-bromophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-12), and (E)-ethyl 3-(2,4-dibromophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-13) showed considerable antibacterial activity against Pseudomonas fluorescens with minimum inhibitory concentrations of 12.5, 12.5, 3.12, and 6.25 μg mL–1, respectively. Structure–activity relationship analyses revealed that, in general, an (E)-isomer exhibited higher antibacterial activity than the corresponding (Z)-isomer.