9-Aminoacridine structures hold much potential for accessing small molecule therapeutics. This core is present in a range of pharmaceuticals for the treatment of ailments such as malaria, inflammation, viral and bacterial infections, and cancer. For the latter, there remains a need to develop and/or improve chemotherapeutics to counteract issues of uptake, drug resistance, and selectivity for cancer cells over healthy cells. In the design of molecules to address these issues, identifying structural units that present as promising leads for drug developments is key. In this study, four 9-aminoacridine derivatives under consideration as precursors for a drug design project are assessed for their cytotoxicity with representative cell lines PC3 and A549, and for their leadlikeness with SwissADME. Together, the cytotoxicity and investigations coalesce around the same derivative as the most promising lead.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the ongoing pandemic named COVID-19 which causes a serious emergency on public health hazards of international concern. In the face of a critical medical emergency, repositioning of drugs is one of the most authentic options to design an adequate treatment for infected patients immediately. In this strategy, Remdesivir (Veklury), Hydroxychloroquine appears to be the drug of choice and garnered unprecedented attention as potential therapeutic agents against the pandemic realized worldwide due to SARS-CoV-2 infection. These are the breathtaking instances of possible repositioning of drugs, whose pharmacokinetics and optimal dosage are familiar. In this review, we provide an overview of these medications, their synthesis, and the possible mechanism of action against SARS-CoV-2.

Diverse new azoloazines were synthesized from the reaction of fluorinated hydrazonoyl chlorides with heterocyclic thiones, 1,8-diaminonaphthalene, ketene aminal derivatives, and 4-amino-5-triflouromethyl-1,2,4-triazole-2-thiol. The mechanistic pathways and the structures of all synthesized derivatives were discussed and assured based on the available spectral data. The synthesized azoloazine derivatives were evaluated for their antifungal and antibacterial activities through zone of inhibition measurement. The results revealed promising antifungal activities for compounds , , ,, , and against the pathogenic fungal strains used; and compared to ketoconazole. In addition, compounds , , , and showed moderate antibacterial activities against most tested bacterial strains. Molecular docking studies of the promising compounds were carried out on leucyl-tRNA synthetase active site of , suggesting good binding in the active site forming stable complexes. Moreover, docking of the synthesized compounds was performed on the active site of SARS-CoV-2 3CLpro to predict their potential as a hopeful anti-COVID and to investigate their binding pattern.

Substituted aminopyrimidines are an important class of compounds, in part because they frequently show biological activity. Facile synthesis of polysubstituted aminopyrimidines is highly desirable for the synthesis of screening libraries. We describe a route to 4,6-diamino-5-alkoxypyrimidines via a SAr-alkylation-SAr sequence from readily available 4,6-dichloro-5-methoxypyrimidine, which allows the synthesis of such compounds with regiochemical control. The extension of this approach to alkylating agents bearing amino substituents led to unexpected and, in some cases, unprecedented products resulting from intramolecular SAr cyclization and subsequent fragmentation.

A one-pot quick and efficient multicomponent reaction has been developed for the synthesis of a new series of functionalized 8-hydroxy-4-phenyl-1,2-dihydroquinoline derivatives using 30 mol% ammonium acetate in ethanol as solvent. This economical protocol run smoothly to give variety of quinoline derivatives in 55% to 98% yield from inexpensive reagents and catalyst in mild reaction conditions. Various spectroscopic techniques like FTIR, H NMR and C NMR, MALDI-TOF-MS, and EI-MS were used to study and confirm their structure.

Heterocycles that bear the novel 5,6,14,14a-tetrahydro-8H-benzo[6,7][1,4] thiazepino[3,4-a]isoquinoline and the 5,6,14,14a-tetrahydro-8H-13l2-benzo [6,7][1,4]diazepino[3,4-a]isoquinoline frameworks were synthesized in a facile manner. These tetrahydroprotoberberine (THPB)-inspired scaffolds demonstrate selective affinity for the σR in contrast to the naturally occurring THPB congeners that show DR and σR selectivity.

Several studies have suggested functional association between μ-opioid and δ-opioid receptors and showed that μ-activity could be modulated by δ-ligands. The general conclusion is that agonists for the δ-receptor can enhance the analgesic potency and efficacy of μ-agonists. Our preliminary investigations demonstrate that new bivalent ligands constructed from the μ-agonist fentanyl and the δ-agonist enkephalin-like peptides are promising entities for creation of new analgesics with reduced side effects for treatment of neuropathic pain. A new superposition of the mentioned pharmacophores led to novel μ-bivalent/δ-bivalent compounds that demonstrate both μ-opioid and δ-opioid receptor agonist activity and high efficacy in anti-inflammatory and neuropathic pain models with the potential of reduced unwanted side effects.

Many 1,2,4-benzotriazine 1,4-dioxides display the ability to selectively kill the oxygen-poor cells found in solid tumors. As a result, there is a desire for synthetic routes that afford access to substituted 1,2,4-benzotriazine 1-oxides that can be used as direct precursors in the synthesis of 1,2,4-benzotriazine 1,4-dioxides. Here we describe the use of Suzuki-Miyaura and Buchwald-Hartwig cross-coupling reactions for the construction of various 1,2,4-benzotriazine 1-oxide analogs bearing substituents at the 3-, 6-, and 7-positions.

Azomethine linked pyrrole bishetarylazoles containing benzimidazole/pyrazolone/1,3,4-oxadiazole were synthesized in satisfactory yields. Their structures were confirmed by IR, H-NMR, C-NMR and elemental analysis. Evaluation for the cytotoxic activities against a panel of breast cancer cell lines (MDA-AB-231, BT-474 and Ishikawa cells) revealed that the pyrrole-benzimidazole hybrids are more potent than the pyrazolone and 1,3,4-oxadiazole hybrids in all cell lines. Compound () displayed promising cytotoxicity against BT-474 cell line with IC values, 7.7 µM.

A hydroxypyridinone building block, bifunctionalized with thiazoline, has been prepared from orthogonally protected 2-(3-(benzyloxy)-4-(ethoxycarbonyl)-6-methyl-2-oxopyridin-1(2H)-yl) acetic acid. The reactivity of the dithiazolide has been explored with two primary amines, leading to the synthesis and characterization of four new hexadentate ligands. Their complexes with selected hard trivalent ions pertinent to potential molecular imaging applications have been surveyed.

We report herein the preparation of two families of secondary amines by the reactions of two equivalents of monoamines with either 2,4 or 2,6-difluoronitrobenzenes in -dimethylacetamide in the presence of anhydrous potassium carbonate, as precursors of biologically important nitric oxide donating -nitrosamines. In both instances, these compounds could be prepared in quantitative yield when the reaction temperature was held below 130°C. Above this reaction temperature, an unexpected cyclization reaction between the nitro and newly formed adjacent secondary amine group leads to the formation of benzimidazole or quinoxaline rings in low yields. Reasonable reaction mechanisms for the cyclization reaction are proposed.

The bicyclic pyran thiolone tetrahydro-3αH-[1,3]dithiolo[4,5-β]pyran-2-thione () engages in a highly unusual fragmentation in the presence of DDQ. The pyran thiolone, , was synthesized by chlorination of 3,4-dihydro-2H-pyran (), followed by condensing with CS and NaSH. Reaction of with DDQ generates the isomerized pyran thiolone tetrahydro-3αH-[1,3]dithiolo[4,5-β]pyran-2-thione () and 4-benzyl-5-(3-hydroxypropyl)-1,3-dithiole-2-thione () via a deep-seated rearrangement. The identity of was confirmed by single crystal X-ray analysis: P2/c, a=5.807(9) Å, b = 12.99(2) Å, c = 11.445(15), β=113.23(6)°. Mechanistic experiments and computational insight is used to explain the likely sequence of events in the highly unusual formation of . Collectively, these results establish fundamental reactivity patterns for further research in this area.

Novel arylamino alcohols were synthesized and these alcohols were used to prepare 12 novel N-(2-hydroxy-ethyl)-2,3-didehydroazapodophyllotoxins, in one step, by simple reflux in ethanol. Isolated yields in the range of 50-70% were obtained.

Synthesis of a series of 2-substituted benzimidazoles was carried out for screening anti-inflammatory activities. 2-(N-benzylpyrrolyl)-benzimidazoles 9a-k were synthesized from N-benzyl-2-pyrrole carboxylic acids 8a-d and 4-substituted-1,2-phenylenediamines by cyclocondensation utilizing polyphosphoric acid (PPA) as condensing agent. The N-benzyl-2-pyrrole carboxylic acids were prepared by standard method of N-benzylation of 2-pyrrole carboxylate using NaH/DMF and appropriately substituted benzyl halides followed by alkaline hydrolysis.

Syntheses of new formyl ester- and cyano ester-substituted bithiophenes, bifurans, and furanothiophenes in good yield are described. The key synthetic step uses Stille coupling of appropriately substituted bromo 5-ring heterocycles with stannyl-substituted 5-ring heterocycles.

A straightforward and practical approach was established for the synthesis of nicotine and anabasine analogues by the cyclization of mesylated 1-(3-pyridinyl)-1,4, and 1,5-diol derivatives to form the pyrrolidino or piperidino fragments. Nicotine analogue (S)-15 was prepared with good enantioselectivity using the developed azacyclization procedure of nonracemic (R)-1-pyridin-3-yl-butane-1,4-diol, which was obtained by the borane-mediated reduction of ketone 12 in the presence of the spiroborate ester derived from diphenyl prolinol and ethylene glycol.

Fourteen novel substituted N-[4(5-methyl/phenyl-1,3,4-oxadiazol-2-yl)-3,6-dihydropyridin-1(2H)-y1] benzamide/benzene sulfonamides (11a-n) were synthesized in fair to good yields via sodium borohydride reduction of the corresponding substituted N-(benzoylimino)-4-(5-methyl/5-phenyl-1,3,4-oxadiazol-2yl) pyridinium ylide (10a-n) in absolute ethanol.

Fifteen novel 1-(substituted phenylcarbonyl/sulfonylamino)-1,2,3,6-tetrahydro- pyridine-5-carboxylic acid diethylamide (7, 15) were synthesized in fair to good yields via sodium borohydride reduction of the corresponding 1-(substituted phenylcarbonyl/ sulfonylimino)-3-diethylcarbamoyl pyridinium ylides (6, 14) in absolute ethanol.

This communication reports on the investigation of a new recyclization conversion of a pyrimidine ring, which can be referred to as C-C recyclization. In this reaction the nucleophile cleaves the pyrimidine ring at the N(3)-C(4) bond, and following rotation around the single C(5)-C(6) bond the new cyclization takes place. This type of recyclization has general applicability, and takes place upon alkali treatment of substituted 4-methyl-5-ethoxycarbonyl- and 4-amino-5-ethoxycarbonyl-pyrimidines (1) which are transformed respectively to 4-hydroxy-5-acetyl- and 4-hydroxy-5-carbamoylpyrimidines (2). The obtained pyrimidyl-ketones can be readily converted to their hydrazones 7-12.

chemical structure image Environmentally benign oxidation methods satisfy the postulates of green chemistry. Heterocyclic Noxides have applications in synthetic organic chemistry, chemotherapy and agrochemicals. Synthesis of Noxides using green oxidants will be attractive over the conventional methods. The presence of the N-oxide group in the azine ring makes it more subject to electrophilic and nucleophilic attack and substantially expands the synthetic approaches for the modification of nitrogen-containing heterocyclics. That is the reason for the increasing interest in the chemistry of heterocyclic N-oxides. Some reactions adopted for oxidation of N-heterocyclics have been discussed. Stereochemical and spectroscopic aspects have been mentioned. It will be advantageous if anchored catalysts are employed for industrial exploitation. Several physiochemical aspects of various methods have been discussed.