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The CuI promoted one‐pot multi‐component synthesis of new fused [1,2,3]triazolo[5,1‐a]isoquinoline derivatives (4 a–4 h, 8 a–8 f & 9 a–9 f) without isolating unsafe azides and their in vitro cytotoxic activity against MCF‐7 & MDA‐MB‐231 (breast cancer cells) and A‐549 (alveolar carcinoma) was reported herein. Out of all, compounds 9‐chloro‐1‐(morpholinomethyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (8 d), 9‐fluoro‐1‐(morpholinomethyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (8 e), 9‐chloro‐1‐((1,1‐dioxidothiomorpholino)methyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (9 d), and 1‐((1,1‐dioxidothiomorpholino)methyl)‐9‐fluoro‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (9 e) showed superior potency against all the cell lines than the standard drug erlotinib with IC50 values ranging from 2.45 to 7.19 μM. The most active compounds 8 d, 8 e, 9 d, and 9 e were also screened for their efficacy in inhibiting tyrosine kinase EGFR and results revealed that compound 9 d showed comparable activity with standard drug erlotinib, whereas, compounds 8 d, 8 e, and 9 e showed superior activity than the erlotinib. Molecular modeling studies for active compounds on EGFR (PDB‐ID‐4HJO) were also conducted and the obtained free energies were observed to be in agreement with the in vitro activity data. Finally, compounds 8 d, 8 e, 9 d, and 9 e didn't show AMES toxicity and followed the rules of Egan, Ghose, Veber, Lipinski, and Muegge rules without any deviation. [ABSTRACT FROM AUTHOR]

For the first time, amides and ureas based on both 5-nitroisoquinoline and 5-nitrosoisoquinoline were obtained by direct nucleophilic substitution of hydrogen in the 5-nitroisoquinoline molecule. In the case of urea and monosubstituted ureas, only 5-nitrosoisoquinoline-6-amine is formed under anhydrous conditions. [ABSTRACT FROM AUTHOR]

Cationic polycyclic aromatic compounds containing one or more nitrogen atom(s), also known as azonia polycyclic aromatic compounds, form a valuable class of molecules because of their fluorescent and/or medicinal properties. N -Arylated hydroisoquinoline derivatives were synthesized through an aryne aza-Diels–Alder cycloaddition/ N -arylation sequence. A subsequent two-electron oxidation allowed the synthesis of some axially chiral cationic benzo[ c ]phenanthridinium derivatives. The structural and optical properties of some of these molecules were determined. Their chirality was evidenced experimentally by single-crystal X-ray diffraction and1 H NMR spectroscopy, and their conformational behavior was examined by computational DFT methods. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs. [ABSTRACT FROM AUTHOR]

An operationally simple Ag(I)-catalyzed approach for the synthesis of isoquinoline and quinazoline fused 1,2,3-triazoles was developed by a condensation and amination cyclization cascade of amino-NH-1,2,3-triazoles with 2-alkynylbenzaldehydes involving three new C-N bond formations in one manipulation, in which the group of -NH of the triazole ring serves as a nucleophile to form the quinazoline skeleton. The efficient protocol can be applied to a variety of substrates containing a range of functional groups, delivering novel pentacyclic fused 1,2,3-triazoles in good-to-excellent yields. [ABSTRACT FROM AUTHOR]

Background/purpose: The effect of roxadustat on iron homeostasis in patients with chronic kidney disease (CKD) is unclear. This study aimed to evaluate the efficacy of roxadustat for the treatment of iron metabolism disorders in dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD patients.Methods: We searched the PubMed, Embase, China National Knowledge Internet and Web of Science databases for randomized controlled trials (RCTs). The primary outcomes were changes in serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT), ferritin, transferrin, and hepcidin. The secondary outcomes included the changes in hemoglobin (Hb) and the incidences of adverse events (AEs) and severe adverse events (SAEs).Results: Twelve RCTs comprising 4976 participants were included. Compared to the control group, increases in the serum iron (SMD = 0.21, 95% CI: 0.15 to 0.27, P < 0.00001), TIBC (SMD = 1.02, 95% CI: 0.82 to 1.22, P < 0.00001) and transferrin levels (WMD = 0.55, 95% CI: 0.41 to 0.69, P < 0.00001) were found in the roxadustat group. Compared to the control group, decreases in the ferritin levels (WMD = -37.82, 95% CI: -59.89 to -15.74, P = 0.0008) and hepcidin levels (WMD = -24.04, 95% CI: -36.28 to -11.79, P = 0.0001) were observed in the roxadustat group. The meta-analysis showed that roxadustat significantly increases Hb levels (WMD = 0.77, 95% CI: 0.42 to 1.12, P < 0.0001). The incidences of AEs and SAEs in the roxadustat group was significantly higher than that in the control group (RR = 1.03, 95% CI: 1.00 to 1.07, P = 0.04; RR = 1.08, 95% CI: 1.00 to 1.15, P = 0.04).Conclusion: Our findings suggest that roxadustat could effectively improve iron metabolism in patients with CKD. [ABSTRACT FROM AUTHOR]

A variety of pyran-fused isoquinoline derivatives were prepared in moderate to good yields through the rhodium-catalyzed dual C–H functionalization/annulation of methyl benzimidates and diazo compounds. A one-pot procedure, broad substrate scope, diversified products, and mild reaction conditions make this transformation a powerful tool for the synthesis of fused heteroarenes. In addition, the synthetic application was extended by large-scale synthesis and late-stage functionalization via Pd-catalyzed Suzuki–Miyaura, Heck, and Sonogashira cross-coupling reactions. Furthermore, a photophysical survey reveals that the pyran-fused isoquinoline products exhibit fluorescence properties and show potential for exploring fluorescent material applications. [ABSTRACT FROM AUTHOR]

Two new alkaloids, leptocarpinine B (1) and corydamine acid (2), with thirteen known alkaloid compounds (3–15), were isolated from Hypecoum leptocarpum. The structures of the isolated compounds were determined based on spectroscopic data analyses, including IR, ESI-MS, 1 D, and 2 D NMR. In addition, all the isolates were evaluated for cytotoxic activities. Compound 6 showed moderate cytotoxicity against human ovarian cancer cell lines (A2780), human cervical cancer cell lines (HeLa), and human hepatocellular carcinomas cell lines (HepG2). [ABSTRACT FROM AUTHOR]

Reaction of isoquinoline 1 with hydrazonoyl chlorides 2A–E gave the corresponding triazoloisoquinolines 4A–E. The latter products 4A–E were reacted with 4-(piperidin-1-yl)benzaldehyde 5a and 4-morpholinobenzaldehyde 5b to afford the corresponding chalcones 6a,b. Some of chalcones 6 were reacted with hydrazine hydrate in refluxing ethanol to give the corresponding 8,9-dimethoxy-1-aryl-4,5-dihydro-1H-pyrazol-3-yl-1,5,6,10b-tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline derivatives 7A–C. Antimicrobial studies were performed using gram-negative bacteria (Escherichia coli) and (Klebsiella pneumonia), a gram-positive bacteria (Streptococcus mutans) and (Staphylococcus aureus), filamentous fungus (Asperagillus Nigar) and yeast (Candida albicans). Data revealed that chalcone 6Aa achieved the lowest MIC values (high efficient derivative) against the sensitive bacterial strain E. coli with MIC value 130 µg/ml. The most effective compound 6Aa, which demonstrated the highest binding affinity toward tested protein [thymidine phosphorylase enzyme, (PDB ID:4EAD)], was docked using MOE 2014.09 software. [ABSTRACT FROM AUTHOR]

Nowadays, infectious diseases caused by microorganisms are a major threat to human health, mostly because of drug resistance, multi-drug resistance and extensive-drug-resistance phenomena to microbial pathogens. During the last few years, obtaining hybrid azaheterocyclic drugs represents a powerful and attractive approach in modern antimicrobial therapy with very promising results including overcoming microbial drug resistance. The emphasis of this review is to notify the scientific community about the latest recent advances from the last five years in the field of hybrid azine derivatives with antimicrobial activity. The review is divided according to the main series of six-member ring azaheterocycles with one nitrogen atom and their fused analogs. In each case, the main essential data concerning synthesis and antimicrobial activity are presented. [ABSTRACT FROM AUTHOR]

Many heterocyclic compounds can be synthetized using diaza-1,3-butadienes (DADs) as key structural precursors. Isolated and in situ diaza-1,3-butadienes, produced from their respective precursors (typically imines and hydrazones) under a variety of conditions, can both react with a wide range of substrates in many kinds of reactions. Most of these reactions discussed here include nucleophilic additions, Michael-type reactions, cycloadditions, Diels–Alder, inverse electron demand Diels–Alder, and aza-Diels–Alder reactions. This review focuses on the reports during the last 10 years employing 1,2-diaza-, 1,3-diaza-, 2,3-diaza-, and 1,4-diaza-1,3-butadienes as intermediates to synthesize heterocycles such as indole, pyrazole, 1,2,3-triazole, imidazoline, pyrimidinone, pyrazoline, -lactam, and imidazolidine, among others. Fused heterocycles, such as quinazoline, isoquinoline, and dihydroquinoxaline derivatives, are also included in the review. [ABSTRACT FROM AUTHOR]

Data on alkaloid interactions with the physiologically important transition metals, iron and copper, are mostly lacking in the literature. However, these interactions can have important consequences in the treatment of both Alzheimer's disease and cancer. As isoquinoline alkaloids include galanthamine, an approved drug for Alzheimer's disease, as well as some potentially useful compounds with cytostatic potential, 28 members from this category of alkaloids were selected for a complex screening of interactions with iron and copper at four pathophysiologically relevant pH and in non-buffered conditions (dimethyl sulfoxide) by spectrophotometric methods in vitro. With the exception of the salts, all the alkaloids were able to chelate ferrous and ferric ions in non-buffered conditions, but only five of them (galanthine, glaucine, corydine, corydaline and tetrahydropalmatine) evoked some significant chelation at pH 7.5 and only the first two were also active at pH 6.8. By contrast, none of the tested alkaloids chelated cuprous or cupric ions. All the alkaloids, with the exception of the protopines, significantly reduced the ferric and cupric ions, with stronger effects on the latter. These effects were mostly dependent on the number of free aromatic hydroxyls, but not other hydroxyl groups. The most potent reductant was boldine. As most of the alkaloids chelated and reduced the ferric ions, additional experimental studies are needed to elucidate the biological relevance of these results, as chelation is expected to block reactive oxygen species formation, while reduction could have the opposite effect. [ABSTRACT FROM AUTHOR]

Transformations of 1-methoxymethylethynyl substituted isoquinolines triggered by terminal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6–C8 allene fragment and the -ylidene derivatives 6-methoxymethylene-3-benzazecines. The reaction mechanisms were investigated and a preliminary in vitro screening of their potential inhibitory activities against human acetyl- and butyrylcholinesterases (AChE and BChE) and monoamine oxidases A and B (MAO-A and MAO-B) showed that the allene compounds were more potent than the corresponding -ylidene ones as selective AChE inhibitors. Among the allenes, 3e (R3 = CH2OMe) was found to be a competitive AChE inhibitor with a low micromolar inhibition constant value (Ki = 4.9 μM), equipotent with the corresponding 6-phenyl derivative 3n (R3 = Ph, Ki = 4.5 μM), but 90-fold more water-soluble. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel palladium-catalyzed domino carbonylative cyclization. • Carbonylative cyclization of alkene-tethered indole derivatives with alkyne-tethered nucleophiles. • Several pharmaceutical and bioactive molecule related compounds were also suitable substrates here. A novel palladium-catalyzed domino carbonylative cyclization of alkene-tethered indole derivatives with alkyne-tethered nucleophiles has been developed, which provides a straightforward and efficient platform for the rapid construction of functionalized heterocycles. By using benzene-1,3,5-triyl triformate (TFBen) as the CO source, this domino reaction proceeded smoothly with the consecutive formation of three C C bonds and one C-X bond to furnish a variety of biologically relevant indolo[2,1- a ]isoquinoline-indole and indolo[2,1- a ]isoquinoline-dihydrobenzofuran derivatives in good yields. [ABSTRACT FROM AUTHOR]

Herein, we report an efficient strategy towards the synthesis of amino acid substituted isoquinoline derivatives via reaction of unprotected amino acid/amino acid ester/amino acid based drugs with 2-(2-oxo-2-aryl/alkylethyl)benzonitrile under metal-free conditions. The developed protocol is highly simple and shows functional group tolerance to provide corresponding novel amino acid substituted isoquinolines in aqueous medium. The applicability of the reaction is an easier modification of well-known drugs and successfully extended to gram-scale synthesis., (© 2024 Wiley-VCH GmbH.)

Alkaloids are a complex class of biologically active compounds with a broad spectrum of health-related applications. Particularly the alkaloids of indole, steroidal, terpenoids, isoquinoline, and bisbenzylisoquinoline have been extensively investigated. Ultimately, substantial advancement has been highlighted in the investigation of chemical constituents and the therapeutic benefits of plant alkaloids, particularly during the last ten years. A total of 386 alkaloids have been isolated from over 40 families, including Apocynaceae, Annonaceae, Rubiaceae, Menispermaceae, Ranunculaceae, Buxaceae, Papaveraceae, Magnoliaceae, Rutaceae and Phyllanthaceae. This paper will investigate several alkaloids that have been isolated from botanical medicines as well as offer an in-depth analysis of their cytotoxic properties., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To observe the effect of different antiemetic drugs for the prevention of postoperative nausea and vomiting (PONV) after gynaecological day surgery under remimazolam general anesthesia. Methods: One hundred ninety-two patients were selected for gynaecological day surgery and randomly divided into three groups: droperidol group (DD group), tropisetron group (DT group) and control group (DC group). Flurbiprofen axetil 50 mg and dexamethasone 5 mg were given intravenously before induction of anesthesia, and 2 min later droperidol 1 mg was given intravenously to the DD group, tropisetron 5 mg to the DT group and saline (5 ml) to the DC group. Induction of anesthesia: remimazolam 6 mg/kg/h was continuously infused until sleep, mivacurium 0.2 mg/kg and alfentanil 20ug/kg were slowly pushed, 3 min later intubation was performed to control breathing. Maintenance of anesthesia: 40ug/kg/h of alfentanil, 1 mg/kg/h of remimazolam continuous infusion. After awakening and extubation, the patient was transferred to the PACU. PONV were recorded in the PACU and an electronic questionnaire was pushed 24 h after surgery. Results: The incidence of PONV within the PACU was significantly lower in the DD (14.5%)and DT(26.7%) groups than in the DC(50%) group (p < 0.01), there was no significantly difference between the DT and DD groups. There were no significant difference in the incidence of PONV in 24 h after surgery between the three groups(DD:DT:DC = 44.5%:45.1%:63.8%,p > 0.05). Conclusions: Droperidol or tropisetron combined with dexamethasone is superior to dexamethasone alone for the prevention of PONV in the PACU after remimazolam combined with alfentanil anesthesia, with no significant difference in the incidence of PONV in 24 h after surgery. [ABSTRACT FROM AUTHOR]

This manuscript reports the synthesis, X-ray characterization and DFT study of a series of all-cis 3a,6 : 4,5 : 7,9a-triepoxy and 3a,6 : 7,9a-diepoxybenzo[de]isoquinolines obtained by the tandem intramolecular [4 + 2]/[4 + 2] cycloaddition in bis-furans (the IMDAF reaction) between difurfurylamine derivatives and dimethyl acetylenedicarboxylate (DMAD) as a dienophile. In one compound instead of DMAD, 1-phenyl-1H-pyrrole-2,5-dione (N-phenylmaleimide) was used as a dienophile. The existence of a "through-space" alpha-effect is analyzed in these compounds, since in three of them N–H⋯O2 H-bonds are observed in the solid state promoting the formation of self-assembled dimers. That is, the close O⋯O distance between the O-bridge atoms due to the rigidity of these molecules causes a lone pair⋯lone pair (LP⋯LP) interaction that enhances the H-bond acceptor ability of the bridging atoms (through-space α-effect). This fact has been studied using DFT calculations, molecular electrostatic potential (MEP) surfaces, electron localization function (ELF), quantum theory of atoms-in-molecules (QTAIM) and noncovalent interaction plot (NCIplot) index computational tools. This is the third study of the literature where "α-effect" hydrogen bonds (AEHBs) are described. The novelty of the present work resides in the utilization of an amine linker between the furan rings that allows the incorporation of a good H-bond donor in the model system. As a result, NH⋯O2 instead of CH⋯O2 AEHBs described in previous works are established. The X-ray analyses of the synthesized di- and tri-epoxides reveal that the AEHBs are predominant in the X-ray architecture of these compounds. [ABSTRACT FROM AUTHOR]

A metal‐free radical relay addition/cyclization of activated alkenes with ethers, cycloalkanes, toluenes, and alcohols has been achieved, leading to a range of functionalization of 5,6‐dihydrobenzo[4,5]imidazo[2,1‐a]isoquinolines with the yield of 43% ‐ 84%. This protocol exhibits advantages of metal‐free, base‐free, and shorter reaction time. [ABSTRACT FROM AUTHOR]

We report here a mechanochemical Cu‐catalyzed [3+2] cycloaddition of azinium‐N‐imines with nitriles under solventless grinding conditions. Various 1,2,4‐triazolos derivatives were obtained in 51–80% yields. The developed protocol offers advantages in functional‐group compatibility, scalability, no use of solvents, shorter reaction time, and without external heating. In addition, heterocyclic N‐imines such as quinolinium and isoquinolinium salts are also suitable substrates, resulting in the production of 1,2,4‐triazolo[1,5‐a]quinoline and 1,2,4‐triazolo[5,1‐a]isoquinoline derivatives under mechanochemical conditions. [ABSTRACT FROM AUTHOR]

Herein, we report our investigations on the reaction of a variety of substituted oxazoles with o‐(trimethylsilyl)aryl triflates promoted by potassium fluoride and 18‐crown‐6‐ether. Several functionalized isoquinoline compounds were obtained in moderate to good yields when the transformation was carried out at room temperature, followed by acidic workup, presumably via a [4+2] cycloaddition‐ring‐opening reaction pathway. Alternatively, bicyclic ethers were produced in reasonable yields when performing the transformation at 60 °C via a sequence of [4+2] cycloaddition, retro‐Diels‐Alder, and [4+2] cycloaddition reactions. [ABSTRACT FROM AUTHOR]

A new series of pyrazolo[3,4-g]isoquinoline derivatives, diversely substituted at the 4- or 8-position, were synthesized. The results of the kinase inhibitory potency study demonstrated that the introduction of a bromine atom at the 8-position was detrimental to Haspin inhibition, while the introduction of an alkyl group at the 4-position led to a modification of the kinase inhibition profiles. Altogether, the results obtained demonstrated that new pyrazolo[3,4-g]isoquinolines represent a novel family of kinase inhibitors with various selectivity profiles. [ABSTRACT FROM AUTHOR]

The genus Pyrenophora includes two important cereal crop foliar pathogens and a large number of less well-known species, many of which are also grass pathogens. Only a few of these have been examined in terms of secondary metabolite production, yet even these few species have yielded a remarkable array of bioactive metabolites that include compounds produced through each of the major biosynthetic pathways. There is little overlap among species in the compounds identified. Pyrenophora tritici-repentis produces protein toxin effectors that mediate host-specific responses as well as spirocyclic lactams and at least one anthraquinone. Pyrenophora teres produces marasmine amino acid and isoquinoline derivatives involved in pathogenesis on barley as well as nonenolides with antifungal activity, while P. semeniperda produces cytochalasans and sesquiterpenoids implicated in pathogenesis on seeds as well as spirocyclic lactams with phytotoxic and antibacterial activity. Less well-known species have produced some unusual macrocyclic compounds in addition to a diverse array of anthraquinones. For the three best-studied species, in silico genome mining has predicted the existence of biosynthetic pathways for a much larger array of potentially toxic secondary metabolites than has yet been produced in culture. Most compounds identified to date have potentially useful biological activity. [ABSTRACT FROM AUTHOR]

The isoquinoline alkaloids 4-O-methylsinomenine and C-annelated tetrahydrothebaine were modified by addition of 1,2,3-triazolyl substituents in the C-1 position of the morphinane skeleton via a Cu-catalyzed reaction of 1-ethynyl-substituted alkaloid derivatives with various azides. Analgesic activity in a chemical irritation model was found for 1-triazolyl-substituted derivatives of 6,7,8,14-tetrahydrothebaine. [ABSTRACT FROM AUTHOR]

Novel examples for dipolar cycloaddition of isoquinolinium ylides to nitriles leading to new imidazo[2,1‐a]isoquinolines were described and the potential of this reaction in synthetic chemistry was explored. As a by‐product of this research, a number of N‐substituted, 3,4‐dihydro‐1H‐isoquinoline‐1‐carbonitriles were synthesized by a simple, efficient reaction of a series of isoquinolinium bromides and ethyl cyanoformate in the presence of triethylamine. [ABSTRACT FROM AUTHOR]

An efficient and enantioselective phosphonation protocol for construction of chiral α-aminophosphates and α-aminodiarylphosphine oxides has been developed based on chiral phosphoric acid-catalyzed dearomatization of isoquinolines. A series of chiral 1,2-dihydroisoquinolines with dimethoxy phosphoryl or diphenylphosphono substituents at the C1-position were constructed with good to excellent yields and enantioselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Modification of pyrrolo[2,1‐a]isoquinolines through Fe(OTf)3 catalyzed aminomethylenation with amines and dimethyl sulfoxide has been realized. A series of highly functionalized pyrroloisoquinolines have been prepared in acceptable to good yields (17–72 % yields). Dimethyl sulfoxide serves as the source of methylene group under a catalytic system. Lactam‐fused pyrrolo[2,1‐a]isoquinoline can be obtained through simple chemical transformation. [ABSTRACT FROM AUTHOR]

A new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus) strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant S. aureus (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear intracellular MRSA. Additionally, both HSN584 and HSN739 exhibited a low propensity to develop resistance. We utilized comparative global proteomics and macromolecule biosynthesis assays to gain insight into the alkynyl isoquinoline mechanism of action. Our preliminary data show that HSN584 perturb S. aureus cell wall and nucleic acid biosynthesis. The alkynyl isoquinoline moiety is a new scaffold for the development of potent antibacterial agents against fatal multidrug-resistant Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

An unprecedented TMEDA‐catalyzed, regioselective, decarboethoxy direct C−N coupling protocol towards the synthesis of dibenzopyrrocolines 17 a–i and 5,6‐dihydroindolo[2,1‐a]isoquinoline 15 a–f/18 a–c alkaloids via the identification of N,N,N′,N′‐tetramethylethylenediamine (TMEDA) as a homogeneous catalyst is reported. The transition‐metal‐free, TMEDA‐catalytic novel protocol is operationally simple and showed a wide range of functional group tolerance and substrate compatibility. The gram‐scale application and synthesis of naturally occurring Cryptaustoline (dibenzopyrrocoline) alkaloid, further highlights the importance and versatile nature of the developed protocol. This finding also offers a TMEDA‐catalyzed direct synthesis of dibenzopyrrocolines and substituted 5,6‐dihydroindolo[2,1‐a]isoquinoline compounds in a one‐pot. The probable reaction pathway involves the free‐radical sequential approach via a single electron transfer (SET) mechanism. [ABSTRACT FROM AUTHOR]

Cu(OAc)2.H2O has shown good catalytic efficiency in the presence of AgSbF6 as additive for the synthesis of isoquinoline from diphenylmethylene)hydrazine and 1,2-diphenylethyne under optimized reaction condition. Particular synthesized derivatives exhibited decent anti-fungal activity. The structure of all synthesized compounds was confirmed using spectroscopic techniques. Simple reaction process, easy work procedure, low cost and readily availability of catalyst are the some benefits of reported protocol. [ABSTRACT FROM AUTHOR]

In this work, synthesis of pyrido[2,1-a]isoquinolines and pyrido[1,2-a]quinolines in excellent yield using multicomponent reactions of isoquinoline, methyl malonyl chloride, alkyl bromides, and triphenylphosphine in the presence of catalytic amount of Fe3O4-MNPs in water at 80 °C were investigated. The reduction of ferric chloride solution with Clover Leaf water extract caused to synthesis of magnetic iron oxide nanoparticles (Fe3O4-NPs) as a green method. As well, antioxidant activity was studied for some newly synthesized compounds such as 6a, 6b, 8b, and 8c using the DPPH radical trapping and reducing of ferric ion experiments and comparing results with synthetic antioxidants (TBHQ and BHT). As a result, compounds 6a, 6b, 8b, and 8c show trace DPPH radical trapping and excellent reducing strength of ferric ion. These compounds have biological potential because of isoquinoline or quinoline core. For this reason, the antimicrobial activity of some synthesized compounds was studied employing the disk diffusion test on Gram-positive bacteria and Gram-negative bacteria. The results of disk diffusion test showed that compound 6a, 6c, 6d, 8a, and 8b prevented the bacterial growth. Organic solvents that are needed for performing some organic reactions are often toxic and expensive. For this reason, elimination of these solvents is a suitable work for nature. The present procedure avoids the use of toxic solvent. Isoquinoline or quinoline derivatives are one of the important heterocyclic compounds that have outstanding moiety in medicinal chemistry and display a broad variety of biological and pharmacological properties. This recoverable catalyst is very easy and performed by external magnet. [ABSTRACT FROM AUTHOR]

Bromination of various dihydropyrrolo[2,1‐a]isoquinolines have been reached in moderate to good yields by the use of alkylacyl bromides and dimethyl sulfoxide as brominating reagent. Other N‐containing heterocycles of interest such as pyrrolo[2,1‐a]isoquinoline and multisubstituted pyrroles can also be brominated successfully under the current reaction system. Distinct reactivities between alkylacyl and arylacyl bromides resulting in bromination and dicarbonylation respectively have been investigated. [ABSTRACT FROM AUTHOR]

In this work, we synthesized new Schiff base of benzoxazine derivatives in excellent yields using multicomponent reactions of phthalaldehyde or its derivatives, primary amines, isothiocyanate, 2,4-dihydroxyacetophenone, isopropenylacetylene and methyl or ethyl amine in the presence of catalytic amount of Cu/KF/CP@MWCNTs NCs in water at room temperature. Also, the catalytic activity of the green synthesized Cu/KF/CP@MWCNTs NCs was evaluated in the reduction in organic pollutants such as 4-nitrophenol (4-NP) in water at mild conditions. The results indicated that the biosynthesized NCs have very high and effective catalytic activity for organic pollutants within few seconds. As well the antioxidant activity of some synthesized benzoxazine was studied using trapping of radical by DPPH and ferric reduction activity potential (FRAP) experiment. The short time of reaction, high yields of product, easy separation of catalyst and products are some benefits of this procedure. [ABSTRACT FROM AUTHOR]

A novel and efficient catalyst-free and oxidant-free tandem aza-Mannich/cyclization/aromatization reaction of C,N-cyclic azomethine imines with enamides has been developed. This practical one-step protocol enables a simple and environmentally friendly route toward the straightforward synthesis of highly substituted 5,6-dihydropyrazolo[5,1-a]isoquinolines. Different types of enamides and enamines, especially enamides derived from marketed drugs as well as bioactive molecules, are suitable substrates. CB1 cannabinoid receptor antagonist could be synthesized efficiently based on this methodology, illustrating that this would be a practical strategy to synthesize valuable structural motifs. [ABSTRACT FROM AUTHOR]

Heterocyclic N‐oxides are prevalent in numerous natural products with broad applications in pharmaceuticals, agrochemicals, material sciences, and asymmetric synthesis. Owing to their profound biological and physiological activity and unique chemical reactivity, the importance of these compounds has stimulated substantial interest among organic synthetic chemists. More importantly, C‐2 functionalization of heterocyclic N‐oxides, including pyridine‐, isoquinoline‐, pyrazine‐, quinoxaline‐, and quinoline N‐oxides, is among the most important strategies for heterocyclic functionalization. Besides, deoxygenation of heterocyclic N‐oxides has also emerged as a reaction of significance in organic chemistry. In the past decade, visible light photoredox catalyzed C‐2 functionalization and deoxygenation of these heterocyclic N‐oxides have drawn substantial attention owing to their mild reaction conditions. This review has been categorized based on visible‐light‐mediated nondeoxygenative C‐2 functionalization (alkylation, fluoroalkylation, arylation, acylation, and amination), deoxygenative C‐2 functionalization (sulfonylation, alkynylation, alkylation, and acylation), and deoxygenation (without C−H functionalization) of heterocyclic N‐oxides. For most part of the work, the substrate scope, limitation, and mechanism of the reactions have been discussed. [ABSTRACT FROM AUTHOR]

In this study, a series of pyrazoloisoquinoline compounds with novel structures were synthesized by 1,3-dipolar cycloaddition method. The products demonstrate good fluorescence emission and the fluorescent probe molecules potential. [ABSTRACT FROM AUTHOR]

Colitis is an important risk factor for the development of colorectal cancer (CRC). The inhibitory effect and the underlying mechanism of neferine on colitis-associated colorectal cancer (CA-CRC) were investigated using an azoxymethane (AOM)/dextran sulfate sodium (DSS) triggered mice model. Compared with the CA-CRC model, oral treatment of neferine (2.5 and 5.0 mg/kg) significantly inhibited the DAI scores, decreased the tumor number, and reduced the tumor size. Neferine decreased inflammatory cell infiltration and epithelial hyperplasia in colon tissues. The levels of tumor necrosis factor- α (TNF- α) , interleukin-1beta (IL-1 β) , and interleukin 6 (IL-6) in colon tissues were decreased by neferine. Furthermore, neferine significantly decreased protein expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), p-p65, and p-STAT3 in both tumor and non-tumor tissues. In addition, neferine inhibited LPS and IL-6-induced phosphorylation of both NF- κ B p65 and STAT3. Molecular docking demonstrated the interactions of neferine with both NF- κ B p65 and STAT3. In conclusion, these results suggested that neferine inhibited CA-CRC carcinogenesis possibly by regulating NF- κ B and STAT3. Neferine might be a lead compound for the chemoprevention of CA-CRC. [ABSTRACT FROM AUTHOR]

This review describes the procedures for the synthesis of thieno[3,2-c]quinoline derivatives by use of the following reagents and aryl-amine derivatives as starting material, and the chemical reactions of the resulting thieno[3,2-c]quinolines: 1-naphthyl amine, 2,4-dichloroquinoline-3-carbonitrile, methyl 2-bromothiophene-3-carboxylate, methyl 2-amino-3-bromobenzoate, 4-chloro-3-(2-chloroallyl)-2-methylquinoline, methyl 2-[(1-phenylethylidene)amino]benzoate, 2-methylquinolin-4-ol, 4-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde, 1,2-dichloro-3,3,4,4,5,5-hexafluorocyclopent-1-ene, benzo[b]thiophen-2(3H)-one, 2-(thiophen-2-yl)aniline, 2-chlorothiophene-3-carboxylic acid, 2-chlorothiophene-3-carboxylic acids, N-[2-(thiophen-2-yl)phenyl]formamide, 2-(2-isocyano-5-methylphenyl)thiophene, boric acid, [1,1'-biphenyl]-2-amine, benzo[b]thiophene, methyl 4-amino-3-(benzo[b]thiophen-2-yl)benzoate, 1-(2-substituted-phenyl)-4-substituted-4,5-dihydro-1H-1,2,3-triazol-5-yl)morpholine, 6,8-dibromo-4-chloro-quinoline-3-carbaldehyde. [ABSTRACT FROM AUTHOR]

Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC50 values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects. [ABSTRACT FROM AUTHOR]

Ketonic hydrolysis of 7‐acetyl‐4‐cyano‐1,6‐dimethyl‐6‐hydroxy‐8‐phenyl‐5,6,7,8‐tetrahydro‐isoquinoline‐3(2H)‐thione (1) via heating with aqueous solution of potassium hydroxide resulted in both deacetylation and dehydration affording new 7,8‐dihydroisoquinoline scaffold (7,8‐DHISQ) 2. Two simple mechanistic approaches are postulated for this synthesis. One of them was supported by converting 7‐acetyl‐4‐cyano‐1,6‐dimethyl‐8‐phenyl‐7,8‐dihydroisoquinoline‐3(2H)‐thione (3) into 7,8‐DHISQ 2 via heating with aqueous solution of potassium hydroxide. Compound 2 was used as a key intetermediate for synthesizing other 7,8‐DHISQ's 4 and 6, as well as 7,8‐dihydrothienoisoquinoline 7. Reaction of compound 3 with 2‐chloroacetamide (8) by refluxing in ethanol containing sodium acetate gave 7‐acetyl‐1‐amino‐5,8‐dimethyl‐6‐phenyl‐6,7‐dihydrothieno[2,3‐c] isoquinoline‐2‐carboxamide (10) which was converted into full aromatized pyrimidothienoisoquinoline 12 on treatment with triethyl orthoformate. Reaction of 3 with both hydrazine hydrate and hydroxylamine hydrochloride afforded tetrahydropyrazolo‐isoquinoline 13 and tetrahydroisoxazoloisoquinoline 14, respectively. Reaction of 14 with N‐(4‐chlorophenyl)‐2‐chloroacetamide (15) produced (N‐phenylcarbamoylmethylthio)tetra‐hydroisoxazoloisoquinoline 16 which was coverted into tetrahydroisoxazolothieno‐isoquinoline 17 upon heating with sodium ethoxide. Also, crystal structures of compounds 4 and 13 were determined via X‐rays diffraction analysis. [ABSTRACT FROM AUTHOR]

The Fe3O4/ZnO/MWCNTs magnetic nanocomposites as a high performance organomettalic catalyst was employed for the preparation of naphthyridine derivatives in high yields via five component reaction of isoquinoline, dialkyl acetylenedicarboxylates or propiolates, α-haloketones, triphenyphophine and ammonium acetate in aqueous media at ambient temperature. The Fe3O4/ZnO/MWCNTs MNCs were synthesized using ionic liquid [OMIM]Br as a stabilizer and soft template. As well Fe3O4/ZnO/MWCNTs MNCs show a good improvement in the yield of the product and showed significant reusable ability. Due to having isoquinoline core, we investigate antioxidant property of some synthesized compounds by diphenyl-picrylhydrazine (DPPH) radical trapping and power of ferric reduction experiment. Furthermore, the disk diffusion test on Gram positive and negative bacteria are utilized for investigation of antimicrobial activity of some naphthyridines. The achieved outcomes of this experiment demonstrate that these synthesized compounds could prevent from growth of bacteria. Short time of reaction, high yields of product, easy separation of catalyst and products are some benefits of this process. Green chemistry is the use of a set of principles to reduce or eliminate the use or generation of unsafe materials in the design, fabrication and applications of chemical products. Among solvents, water is a green solvents and very suitable for performing organic reaction. The present procedure avoids the use of toxic solvent. Compounds containing a naphthyridine scaffold are a small class of bispyridine structures identified in various living organisms (plants, sponges, tunicates, bryozoans). These natural products usually possess variant biological activities, which make them attractive lead compounds for further drug discovery. [ABSTRACT FROM AUTHOR]

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Over metal catalysts, N‐heteroarenes, as one of the most versatile building blocks in pharmaceuticals, bioactive molecules and natural products, can be easily accessed by the oxidation of N‐heterocycles. Herein, we describe N‐doped hierarchical pore carbons (N‐HPCs) derived from readily available biomass (flour) efficiently catalyzed aerobic dehydrogenation of N‐heterocycles without any additives under mild conditions, owing to N dopant and high surface area indicated by characterization analysis. A wide range of N‐heteroarenes including quinolines, quinolinol, dihydroisoquinolines, isoquinolines, indoles, quinoxaline and acridine were obtained in good to excellent yields (36 examples, up to 99% yield). Mechanistic studies revealed a strikingly different non‐free radical process from metal catalysts, for which an apparent activation energy of 66.4 kJ mol−1 was found. Moreover, the N‐doped carbon exhibited robust stability and yielded 74.5% quinoline at the sixth reaction. The use of metal‐free catalysts in organic synthesis is attractive but practically challenging. This work provides a promising example for metal‐free catalysis. [ABSTRACT FROM AUTHOR]