Aluru Rammohan

Cyclic fused imidazoles such as pyrrolo[1,2-c]imidazoles are biologically significant and novel aza-heterocycles, and very few examples are available in the literature. Accordingly, the present study describes a sustainable and one-step solvent-free protocol for the thermal annulation of aryl-2-carbonitriles 1a-d with cyclic amines 2a-e. This thermal-promoted reaction is simplified for facile access to imidazole-fused polycyclic frameworks 3aa-dc via a three-component dimerization-coupling sequence in low to moderate yields (up to 29%). Concurrently, competitive hydrolysis pathways result in the formation of the corresponding tertiary carboxamides 4aa-dc (17–45% yields) and primary carboxamides 5a-d (5–34% yields). The structures of all the synthesized bis-aryl cyclic[1,2-c]imidazoles and carboxamides have been established through complete NMR and mass spectral data. The X-ray crystal structures of compounds 3aa and 3da were confirmed through XRD crystallographic studies. In addition, a conceivable mechanistic approach has been established for the annulation of cyclic fused imidazoles and their carboxamides. The reaction proceeds through a complex, competing pathway to simultaneously afford three distinct classes of products without any external catalyst or solvent. The substrate scope was explored using various cyclic amines 2a-e including pyrrolidine, piperidine, morpholine, thiomorpholine, and piperazine, as well as the electronically distinctive derivatives quinoline (1a,b,d) and naphthalene carbonitrile (1c). The present study demonstrates the distinct reactivity profile of heterocyclic nitriles under thermal conditions and provides valuable insights into atom-economical tandem operations and amide-driven functional group transformations.

Hyperlipidemia, a major global health concern and a primary cause of high mortality, is exacerbated by elevated cholesterol and triglyceride profiles. Thus, it is possible to optimally control lipid levels and prevention of the progression of hyperlipidemia and associated diseases through drug treatments, emerging therapies, and lifestyle modifications. Among antihyperlipidemia therapeutic drugs, the cholesterol absorption inhibitor (CAI) ezetimibe is an important lipid‐lowering agent that actively reduces dietary and biliary cholesterol absorption. Accordingly, the present review summarizes the prominent synthetic approaches of ezetimibe and their synthetic analogues, as well as their process impurities. In addition, the inclusive study highlights the expansions of API impurities and their optimization for scale‐up techniques for ezetimibe drug. Further, this study also collectively abridges the research and developments of ezetimibe analogues such as glucuronide fluorescent derivatives, sulfonyl‐glucuronides, amide‐, and sulfonamide derivatives for enriched antihyperlipidemia drug developments. Therefore, this review précises the important synthetic developments of ezetimibe and its derivatives that could be assisted as a template for the further expansion of antihyperlipidemia and azetidinone based drug leads.

The reactions of 5-R-6-aryl-3-(2-pyridyl)-1,2,4-triazines with a 4,5-dimethylaryne intermediate generated in situ, which had not previously been used for this purpose, was studied. The reaction outcome depends on the nature of the substituent at the C⁵ position of 1,2,4-triazine: the introduction of electron-donating substituents leads to the preferential domino transformation of the 3-(2-pyridyl)-1,2,4-triazine system with the formation of 2,3-dimethyl-10-(1,2,3-triazol-3-yl)pyrido[1,2-a]indoles, and electron-withdrawing ones leads to the formation of the corresponding 6,7-dimethylisoquinolines. The main difference between dimethylaryne and its unsubstituted analogue is a significant increase in the proportion of isoquinolines in the reaction products when 5,6-diaryl-3-(2-pyridyl)-1,2,4-triazines are used as substrates.

The reactions of isoxazol-3-amine, thiazol-2-amine, benzo[d]thiazol-2-amine with 4-nitrobenzaldehyde and indole in the absence of a solvent under ball-milling conditions were studied. The reactions proceed through the in situ formation of a Schiff base and subsequent nucleophilic addition of indole at the C=N fragment to form the addition products, α,α-disubstituted azolyl-amines, in yields up to 80%. The structure of the products was proved by physicochemical methods.

Polyureas (PUs) have already found wide practical applications, and various methods of their synthesis have been reported. In this manuscript, we wished to report the very first mechanochemical approach towards aromatic PUs via reactions between isomeric 2,2′-, 3,3′-, and 4,4′-diaminobiphenyls and triphosgene under solvent-free conditions following ball-milling. By using this synthetic approach, both PUs and azomethine-capped Pus were obtained. The fluorescence response of the above-mentioned PUs towards various anions in solutions were studied and selective fluorescence responses towards the hydroxyl and fluoride anions were observed.

Natural products are a boundless source for the development of pharmaceutical agents against a wide range of human diseases. Accordingly, naturally occurring aurones possess various biological benefits, such as anticancer, antioxidant, antimicrobial, antidiabetic, anti-inflammatory, antiviral and neuroprotective effects. In addition, various studies have revealed that aurones are potential templates for the regulation of diabetes mellitus and its associated complications. Likewise, certain aurones and their analogues have been found to be remarkable kinase inhibitors of DARK2, PPAR-γ, PTPM1, AGE, α-amylase and α-glucosidase, which represents a promising approach for the treatment of chronic metabolic disorders such as diabetes. Therefore, in our present study, we provide a detailed account of the advances in aurones as antidiabetic agents over the past decade.

We previously reported the solvent-free reaction of 5-aryl-3-(pyridin-2-yl)-1,2,4-triazine-5-carbo­nitriles with 2-amino-4-aryl-1,3-oxazoles, which afforded 4,5-diaryl-3-hydroxy-2,2′-bipyridine-6-carbonitriles. Similar reaction in anhydrous medium led to the formation of two products, previously described 4,5-diaryl-3-hydroxy-2,2′-bipyridine-6-carbonitriles (up to 44%) and 4,5-diaryl-2,2′-bipyridine-6-carbonitriles (up to 32%).

Two new azaheterocycle-based bolas, such as (1-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)-1H-1,2,3-triazol-4-yl)-methylenyls α,ω-bisfunctionalized PEGs, were prepared via Cu-catalyzed click reaction between 2-(4-azidophenyl)-5-(aryl)-oxadiazole-1,3,4 and terminal ethynyls derived from PEG-3 and PEG-4. Due to the presence of two heteroaromatic cores and a PEG linker, these bola molecules are considered as promising fluorescent chemosensors for electron-deficient species. As a result of a well-pronounced “turn-off” fluorescence response towards common nitro-explosive components, such as 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT), hard-to-detect pentaerythritol tetranitrate (PETN), as well as Hg²⁺ cation was observed.