Synthesis and Antiproliferative Potential of Thiazole and 4-Thiazolidinone Containing Motifs as Dual Inhibitors of EGFR and BRAFV600E.

Thiazole and thiazolidinone recur in a wide range of biologically active compounds that reach different targets within the context of tumors and represent a promising starting point to access potential candidates for treating metastatic cancer. Therefore, searching for new lead compounds that show the highest anticancer potency with the fewest adverse effects is a major drug-discovery challenge. Because the thiazole ring is present in dasatinib, which is currently used in anticancer therapy, it is important to highlight the ring. In this study, cycloalkylidenehydrazinecarbothioamides (cyclopentyl, cyclohexyl, cyclooctyl, dihydronapthalenylidene, flurine-9-ylidene, and indolinonyl) reacted with 2-bromoacetophenone and diethylacetylenedicarboxylate to yield thiazole and 4-thiazolidinone derivatives. The structure of the products was confirmed by using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and single-crystal X-ray analyses. The antiproliferative activity of the newly synthesized compounds was evaluated. The most effective inhibitory compounds were further tested in vitro against both epidermal growth factor receptor (EGFR) and B-Raf proto-oncogene, serine/threonine kinase (BRAFV600E) targets. Additionally, molecular docking analysis examined how these molecules bind to the active sites of EGFR and BRAFV600E.

Impact of the SARS-CoV-2 pandemic on the overall respiratory viruses' transmission in a cancer care setting.

INTRODUCTION AND OBJECTIVE: The emergence of the COVID-19 pandemic raised questions about the interaction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. The objective of this study is to validate the impact of the SARS-CoV-2 pandemic and its interventional measures on the respiratory viruses' transmission/infection rates. METHODS: A retrospective chart review was conducted for cancer patients who underwent laboratory-confirmed respiratory virus polymerase chain reaction (PCR) testing from January 2018 to June 2022. COVID-19 PCR tests from March 2020 to June 2022 were also included. Joinpoint regression analysis was applied to evaluate trends in respiratory virus rates. Statistical analysis was performed using Statistical Package for Social Science software. RESULTS: A total of 6298 respiratory virus PCRs and 40,000 COVID-19 PCRs were performed. Data showed a significant decrease in respiratory viruses' positive cases, total respiratory tests, and respiratory viruses' activity during the pandemic period compared with the pre-pandemic period (p = .0209, .026, and .028, respectively). The joinpoint regression analysis showed a significant decrease of 13.85% in the tested positive cases of respiratory viruses between the years 2018 and 2022. Monthly, the analysis indicated a significant decrease in the positive cases by 13.46% from December 2019 to May 2021. Weekly analysis following lockdown initiation showed a reduction in respiratory virus cases. CONCLUSION: This study provides valuable insights into the interplay between COVID-19 and other respiratory viruses, suggesting that the measures taken for COVID-19 were effective in reducing the spread of viral respiratory infections, aiding future infection control strategies to protect vulnerable populations, including cancer patients, from seasonal respiratory infections.

Synthesis and Structure Determination of Substituted Thiazole Derivatives as EGFR/BRAFV600E Dual Inhibitors Endowed with Antiproliferative Activity.

2,3,4-trisubstituted thiazoles 3a-i, having a methyl group in position four, were synthesized by the reaction of 1,4-disubstituted thiosemicarbazides with chloroacetone in ethyl acetate/Et3N at room temperature or in ethanol under reflux. The structures of new compounds were determined using NMR spectroscopy, mass spectrometry, and elemental analyses. Moreover, the structure of compound 3a was unambiguously confirmed with X-ray analysis. The cell viability assay of 3a-i at 50 µM was greater than 87%, and none of the tested substances were cytotoxic. Compounds 3a-i demonstrated good antiproliferative activity, with GI50 values ranging from 37 to 86 nM against the four tested human cancer cell lines, compared to the reference erlotinib, which had a GI50 value of 33 nM. The most potent derivatives were found to be compounds 3a, 3c, 3d, and 3f, with GI50 values ranging from 37 nM to 54 nM. The EGFR-TK and BRAFV600E inhibitory assays' results matched the antiproliferative assay's results, with the most potent derivatives, as antiproliferative agents, also being the most potent EGFR and BRAFV600E inhibitors. The docking computations were employed to investigate the docking modes and scores of compounds 3a, 3c, 3d, and 3f toward BRAFV600E and EGFR. Docking computations demonstrated the good affinity of compound 3f against BRAFV600E and EGFR, with values of -8.7 and -8.5 kcal/mol, respectively.

Synthesis of bis-thiohydantoin derivatives as an antiproliferative agents targeting EGFR inhibitory pathway.

(R)/(S)-the two enantiomers of 3-substituted-1-[2-(5)-3-substituted-4-benzyl-5-oxo-4-phenyl-2-thioxoimid-azolidin-1-yl]ethyl/propyl-5-benzyl-5-phenyl-2-thioxoimidazolidin-4-ones were formed during the diastereoselective reaction between N,N″-1,ω-alkanediylbis[N'-organylthiourea] derivatives and 2,3-diphenylcyclopropenone in refluxing ethanol. The structures of the isolated compounds were confirmed by NMR, IR, mass spectra and elemental analyses. Moreover, single-crystal X-ray structure analysis was also used to elucidate the structure of the isolated compounds. The mechanism describes the reaction was also discussed. The tested compounds showed EGFR inhibitory activity with IC50 values ranging from 90 to 178 nM in comparison to the erlotinib as a reference with IC50 value of 70 nM. Compound 4c (R = allyl, n = 3) was found as the most potent antiproliferative, had the highest inhibitory effect on EGFR with an IC50 value of 90 nM, compared to erlotinib's IC50 value of 70 nM. The second and third-most active compounds were 4e (R = phenyl, n = 3) and 4d (R = ethyl, n = 3) and with IC50 values of 107 nM and 128 nM. These findings imply that the compounds tested had a significant antiproliferative effect as well as the ability to act as an EGFR inhibitor. Docking studies showed that compound 4c showed high affinity to EGFR based on its docking score (S; kcal/mol) within five test compounds.

Novel quinoline/thiazinan-4-one hybrids; design, synthesis, and molecular docking studies as potential anti-bacterial candidates against MRSA.

In an attempt to develop effective and safe antibacterial agents, we synthesized novel thiazinanones by combining the quinolone scaffold and the 1,3-thiazinan-4-one group by reaction between ((4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)methylene)hydrazinecarbothioamides and 2,3-diphenylcycloprop-2-enone in refluxing ethanol in the presence of triethyl amine as a catalyst. The structure of the synthesized compounds was characterized by spectral data and elemental analysis, IR, MS, 1H and 13C NMR spectroscopy which showed two doublet signals for CH-5 and CH-6 and four sharp singlets for the protons of thiazinane NH, CH[double bond, length as m-dash]N, quinolone NH and OH, respectively. Also, the 13C NMR spectrum clearly showed the presence of two quaternary carbon atoms which were assigned to thiazinanone-C-5 and C-6. All the 1,3-thiazinan-4-one/quinolone hybrids were screened for antibacterial activity. Compounds 7a, 7e and 7g showed broad spectrum antibacterial activity against most of the tested strains either G +ve or G -ve. Compound 7e is the most potent antibacterial agent against MRSA with the minimum inhibitory concentration against MRSA found to be 48 µg mL-1 compared to the drug ciprofloxacin (96 µg mL-1). Additionally, a molecular docking study was performed to understand the molecular interaction and binding mode of the compounds on the active site of S. aureus Murb protein. In silico docking assisted data strongly correlated with the experimental approach of antibacterial activity against MRSA.

Synthesis of novel amidines via one-pot three component reactions: Selective topoisomerase I inhibitors with antiproliferative properties.

Novel series of amidines were synthesized via the interaction between alicyclic amines, cyclic ketones, and a highly electrophilic 4-azidoquinolin-2(1H)-ones without any catalyst or additive. All the obtained products were elucidated based on NMR spectroscopy, mass spectrometry, and elemental analysis. The reaction conditions were optimized using cyclohexanone (2), piperidine (3a), and 4-azido-quinolin-2(1H)-one (1a) under an air atmosphere. The new compounds 4a-l and 5a-c were tested for antiproliferative activity against four cancer cell lines using doxorubicin as a reference drug. The most potent derivatives were compounds 4b, 4d, 4e, 4i, and 5c, with GI50 ranging from 1.00 µM to 1.50 µM. Compound 5c was the most effective derivative against the four cancer cell lines, outperforming doxorubicin. The compounds 4b, 4d, 4e, 4i, and 5c were studied further as topoisomerase I and IIα inhibitors. The compounds tested showed selective inhibition of topo I over topo IIα. Finally, docking studies explain why these compounds prefer topo I over topo IIα.

Heterocycles from cyclopropenones.

Great attention has been paid to cyclopropenones as they are present in many natural sources. Various synthesized cyclopropenone derivatives also show a wide range of biological activities. The cyclopropenone derivatives undergo a variety of reactions such as ring-opening reactions, isomerization reactions, C-C coupling reactions, C-H activation, cycloaddition reactions, thermal and photo-irradiation reactions, and acid-base-catalyzed reactions under the influence of various chemical reagents (electrophiles, nucleophiles, radicals, and organometallics) and external forces (heat and light). Many previous reviews have dealt with the chemistry and reactions of cyclopropenones. However and to the best of our knowledge, the utility of cyclopropenones in the synthesis of heterocycles has not been reported before. Therefore, it would be interesting to shed light on this new topic. The present review article provides, for the first time, a comprehensive compilation of synthetic methods for the synthesis of various heterocyclic ring systems, as a significant family in the field of organic chemistry.

Autoxidation of 4-Hydrazinylquinolin-2(1H)-one; Synthesis of Pyridazino[4,3-c:5,6-c']diquinoline-6,7(5H,8H)-diones.

An efficient synthesis of a series of pyridazino[4,3-c:5,6-c']diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1H)-ones. IR, NMR (1H and 13C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure. The possible mechanism for the reaction is also discussed.

Salivary markers and coronavirus disease 2019: insights from cross-talk between the oral microbiome and pulmonary and systemic low-grade inflammation and implications for vascular complications.

To date, coronavirus disease 2019 (COVID-19) has affected over 6.2 million individuals worldwide, including 1.46 million deaths. COVID-19 complications are mainly induced by low-grade inflammation-causing vascular degeneration. There is an increasing body of evidence that suggests that oral dysbiotic taxa are associated with worse prognosis in COVID-19 patients, especially the Prevotella genus, which was retrieved from nasopharyngeal and bronchoalveolar lavage samples in affected patients. Oral dysbiosis may act by increasing the likelihood of vascular complications through low-grade inflammation, as well as impairing respiratory mucosal barrier mechanisms against SARS-CoV-2. Salivary markers can be used to reflect this oral dysbiosis and its subsequent damaging effects on and the lungs and vasculature. Salivary sampling can be self-collected, and is less costly and less invasive, and thus may be a superior option to serum markers in risk stratification of COVID-19 patients. Prospective studies are needed to confirm such hypothesis. Video Abstract: http://links.lww.com/CAEN/A28.

Crystal structure of (E)-1-(3-benzyl-5-phenyl-1,3-thia-zol-2-yl-idene)-2-[(E)-1,2,3,4-tetra-hydro-naphthalen-1-yl-idene]hydrazin-1-ium bromide.

In the title mol-ecular salt, C26H24N3S+·Br-, the dihedral angles between the thia-zole ring and its attached phenyl and benzoyl rings are 54.81 (7) and 85.51 (7)°, respectively. In the crystal, ion pairs are linked by C-H⋯Br and N-H⋯Br hydrogen bonds and are connected into helical chains extending along the c-axis direction by weak, electrostatic S⋯Br- inter-actions. A Hirshfeld surface analysis was performed, which showed the dominant role of H⋯H contacts (51.3%).

Hypoxia-inducible factor (HIF): The link between obesity and COVID-19.

The COVID-19 death toll has involved to date more than 1 million confirmed deaths. The death rate is even higher in the obese COVID-19 patients, as a result of hypoxia, due to the interplay between adipose tissue hypoxia and obstructive sleep apnea. The discrepancy of manifestations seen in COVID-19 seems to be mediated by a differential immune response rather than a differential viral load. One of the key players of the immune response is HIF. HIF-1ß is a stable constitutively expressed protein in the nucleus; and under hypoxic changes, its activity is unaffected, whereas the HIF-α subunit has a short half-life and because of its degradation by an enzyme known as propyl hydroxylase; under hypoxic conditions, propyl hydroxylase gets deactivated thus leading to the stabilization of HIF-1α. As mentioned before, HIF-1α expression is triggered by hypoxic states, this crippling condition will aggravate the pro-inflammatory characteristics of HIF-1α. The vast majority of decompensated COVID19 cases manifest with drastic lung injury and severe viral pneumonia, the infection-induced hypoxia will the existing hypoxia in obesity. This will additionally augment HIF-1α levels that will provoke the already existing cytokines' storm to fulminant. Consequently, this will directly correlate the effect of a hypoxic environment with the increase of HIF-1α level. HIFɑ exists in two main isoforms HIF-1α and HIF-2α. HIF-1α and HIF-2α act in distinct ways in how they work on different target genes. For example, HIF-2α may act on hemopoietin genes (heme-regulating genes); while HIF-1α acts on EPO. HIF-1α release seems to be markedly augmented in obesity due to adipose tissue hypoxia and obstructive sleep apnea resulting in cyclic hypoxia. HIF-1α can also be secreted by direct viral proteolytic effects. Whereas, HIF-2α is stimulated by chronic hypoxia. HIF-1α exerts detrimental effects on the immune system, characterized by unopposed pro-inflammation at the macrophages, dendritic cells, T cells, and complement levels resulting in cytokines' storm, which is linked to the poor outcomes of COVID-19. On the other hand, HIF-2α role is regulatory and largely opposes the actions mediated by HIF-1α. In view of this, inhibiting HIF-1α release or switching its production to HIF-2α by natural products such as resveratrol or by synthetic drugs, offer a good therapeutic strategy that can prevent COVID-19 worst outcome in infected patients. The approach of breaking the vicious circle between lung damage-induced hypoxia and HIF-1α pro-inflammatory stimulant through drugs is considered to be extremely promising as a therapeutic manner to combat further deterioration of COVID19 cases.

Design and synthesis of hydrazinecarbothioamide sulfones as potential antihyperglycemic agents.

New hydrazinecarbothioamides with a phenylsulfonyl group were synthesized and their structures were identified by different spectroscopic data (1 H NMR, 13 C NMR, two-dimensional NMR, mass spectrometry, elemental analysis, and single-crystal X-ray analysis). The mechanism describing the formation of the products was also discussed. The antidiabetic activity of the isolated products was investigated histochemically. The synthesized sulfonylalkylthiosemicarbazide exhibited antihyperglycemic activity in streptozotocin-induced diabetic mice. Compounds 5a and 5c significantly lowered the blood glucose level to 103.3 ± 1.8 and 102 ± 3.9 mg/dl, respectively. Also, they caused a significant decrease in malondialdehyde levels and normalized the glutathione levels in streptozotocin-induced diabetic mice, compared with the diabetic group. The results suggest that the synthesized hydrazinocarbothioamides may effectively inhibit the development of oxidative stress in diabetes.

Synthesis of 3,3'-methylenebis(4-hydroxyquinolin-2(1H)-ones) of prospective anti-COVID-19 drugs.

During formylation of 2-quinolones by DMF/Et3N mixture, the unexpected 3,3'-methylenebis(4-hydroxyquinolin-2(1H)-ones) were formed. The discussed mechanism was proved as due to the formation of 4-formyl-2-quinolone as intermediate. Reaction of the latter compound with the parent quinolone under the same reaction condition gave also the same product. The structure of the obtained products was elucidated via NMR, IR and mass spectra. X-ray structure analysis proved the anti-form of the obtained compounds, which were stabilized by the formation hydrogen bond. Molecular docking calculations showed that most of the synthesized compounds possessed good binding affinity to the SARS-CoV-2 main protease (Mpro) in comparable to Darunavir.

Regioselective and stereoselective synthesis of epithiomethanoiminoindeno[1,2-b]furan-3-carbonitrile: heterocyclic [3.3.3]propellanes.

Synthesis of heteropropellanes in one step: the reaction between dicyanomethylene-1,3-indanedione (CNIND) and N-substituted-2-(2,4-dinitrophenyl)hydrazinecarbothioamides, furnished (3aR,8bS,Z)-2-amino-9-substituted-10-(2-(2,4-dinitrophenyl)hydrazono)-4-oxo-4H-3a,8b-(epithiomethanoimino)indeno[1,2-b]furan-3-carbonitrile as a type of (2,4-dinitrophenyl)hydrazono[3.3.3]propellanes in good yields as single diastereomers. Structure determination and confirmation of the synthesized products have been achieved using various and modern spectroscopic techniques such as IR, NMR (1H NMR and 13C NMR), mass spectrometry, as well as X-ray crystal analysis. The X-ray structure data cleared that the molecule of 7a was crystalized as monoclinic, space group C2/c (no.15).

Case Report: Stem cell therapy in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to loss of upper and lower motor neurons at both spinal and bulbar levels.   For patients with ALS rehabilitation is important to maintain functional independence, ensure safety and optimize quality of life but is not curative. Stem cell therapy (SCT) provides a new approach to treat previously incurable diseases although peer reviewed published evidence has shown no benefit in ALS for slowing disease progression or functional loss.   This case report presents a patient with ALS who underwent SCT but deteriorated rapidly after the procedure. Whether the deterioration was due to the natural progress of the disease or expedited by SCT remains unknown. The ethical considerations of how marketing influences healthcare and individuals' decisions in desperate situations along with reasons for taking desperate measures are discussed.  Patient education and open communication with ALS patients are imperative in gaining patient satisfaction and overcoming ill effects that marketing could have on unconventional methods of intervention. Raising awareness about the availability and access to multidisciplinary care, the timing of decisions with regards to symptom management and end of life care have proven to enhance the quality of life for such patients.

Design, Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents.

Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a-e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c-e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4'-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4'-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4'-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC50 of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1.

Chemistry of Substituted Thiazinanes and Their Derivatives.

Thiazinanes and its isomeric forms represent one of the most important heterocyclic compounds, and their derivatives represented a highly potent drug in disease treatment such as, 1,1-dioxido-1,2-thiazinan-1,6-naphthyridine, which has been shown to have anti-HIV activity by a mechanism that should work as anti-AIDS treatment, while (Z)-methyl 3-(naphthalen-1-ylimino)- 2-thia-4-azaspiro[5 5]undecane-4-carbodithioate showed analgesic activity, cephradine was used as antibiotic and chlormezanone was utilized as anticoagulants. All publications were interested in the chemistry of thiazine (partially or fully unsaturated heterocyclic six-membered ring containing nitrogen and sulfur), but no one was dealing with thiazinane itself which encouraged us to shed new light on these interesting heterocycles. This review was focused on the synthetic approaches of thiazinane derivatives and their chemical reactivity.

New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies.

A new series of methyl 2-(2-(4'-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates 3a-f were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides 2a-f with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds 3a-f were screened against 60 cancer cell lines. They displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The activity of compound 3a was found as the most cytotoxic potency against 60 cancer cell lines. Consequently, it was selected for further five doses analysis according to National Cancer Institute (NCI) protocol. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI50 and total growth inhibition (TGI) levels, respectively. Accordingly, compound 3a underwent further mechanistic study against the most sensitive leukemia RPMI-8226 and SR cell lines. It showed antiproliferation with IC50 = 1.61 ± 0.04 and 1.11 ± 0.03 µM against RPMI-8226 and SR cell lines, respectively. It also revealed a remarkable tubulin inhibitory activity, compared to colchicine with IC50 = 4.97 µM/mL. Caspase-3, BAX, and Bcl-2 assays for 3a using annexin V-FITC staining revealed significant pro-apoptotic activity. Furthermore, multidrug-resistant leukemia SR cells were used to show better resistance indices (1.285 ng/mL, 1.15-fold) than the reference. Docking studies with ß-tubulin indicate that most of the tested compounds illustrated good binding at the colchicine binding site of the enzyme, especially for compound 3a, which made several interactions better than that of the reference colchicine.

Synthesis of New Planar-Chiral Linked [2.2]Paracyclophanes-N-([2.2]-Paracyclophanylcarbamoyl)-4-([2.2]Paracyclophanylcarboxamide, [2.2]Paracyclophanyl-Substituted Triazolthiones and -Substituted Oxadiazoles.

The manuscript describes the synthesis of new racemic and chiral linked paracyclophane assigned as N-5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carbamoyl)-5'-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carboxamide. The procedure depends upon the reaction of 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)hydrazide with 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)isocyanate. To prepare the homochiral linked paracyclophane of a compound, the enantioselectivity of 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carbaldehyde (enantiomeric purity 60% ee), was oxidized to the corresponding acid, which on chlorination, gave the corresponding acid chloride of [2.2]paracyclophane. Following up on the same procedure applied for the preparation of racemic-carbamoyl and purified by HPLC purification, we succeeded to obtain the target Sp-Sp-N-5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carbamoyl)-5'-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)carboxamide. Subjecting N-5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)hydrazide to various isothiocyanates, the corresponding paracyclophanyl-acylthiosemicarbazides were obtained. The latter compounds were then cyclized to a new series of 5-(1,4(1,4)-dibenzenacyclohexaphane-12-yl)-2,4-dihydro-3H-1,2,4-triazol-3-thiones. 5-(1,4(1,4)-Dibenzenacyclohexaphane-12-yl)-1,3,4-oxadiazol-2-amines were also synthesized in good yields via internal cyclization of the same paracyclophanyl-acylthiosemicarbazides. NMR, IR, and mass spectra (HRMS) were used to elucidate the structure of the obtained products. The X-ray structure analysis was also used as an unambiguous tool to elucidate the structure of the products.

Synthesis of New Fused Heterocyclic 2-Quinolones and 3-Alkanonyl-4-Hydroxy-2-Quinolones.

Herein, we report the synthesis of 5,12-dihydropyrazino[2,3-c:5,6-c']difuro[2,3-c:4,5-c']-diquinoline-6,14(5H,12H)diones, 2-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-1,4-diphenyl- butane-1,4-diones and 4-(benzo-[d]oxazol-2-yl)-3-hydroxy-1H-[4,5]oxazolo[3,2-a]pyridine-1-one. The new candidates were synthesized and identified by different spectroscopic techniques, and X-ray crystallography.