Thromboembolic disorders affect millions of people worldwide. Anticoagulant drugs, such as Dabigatran etexilate, Rivaroxaban, Argatroban, Enoxaparin, and Fondaparinux, are commonly used in treating most of these diseases. Dabigatran etexilate (PRADAXA), the first oral direct thrombin inhibitor of its kind, has become a leading anticoagulant therapy for various thromboembolic disorders. Numerous efforts have been made to synthesize API and its intermediates. This review comprehensively examines the diverse methodologies employed for the synthesis of the Key Starting Materials (KSMs), Key Intermediates, and the final API of Dabigatran etexilate. The review also details the various impurities generated during the process. For the reader's convenience, the review is organized into sections that separately describe each of the Key Starting Materials and Intermediates' synthetic processes. This review of recent advancements serves as a valuable resource for researchers, chemists, and pharmaceutical scientists engaged in the development and optimization of synthetic routes to produce Dabigatran etexilate.

The emergence of antibiotic resistance to S. aureus and M. tuberculosis, particularly MRSA, VRSA, and drug-resistant tuberculosis, poses a serious threat to human health. Towards discovering new antibacterial agents, we designed and synthesized a series of new naphthalimide-thiourea derivatives and evaluated them against a panel of bacterial strains consisting of E. coli, S. aureus, K. pneumoniae, P. aeruginosa, A. baumannii and various mycobacterial pathogens. Compounds 4a, 4l, 4m, 4n, 4q, 9f, 9l, 13a, 13d, 13e, 17a, 17b, 17c, 17d, and 17e demonstrated potent antibacterial activity against S. aureus with MIC 0.03-8 mu g mL-1. In addition, these compounds have also exhibited potent inhibition against MDR strains of S. aureus, including VRSA with MICs 0.06-4 mu g mL(-1). Compounds 4h, 4j, 4l, 4m, 4q, 4r, 9a, 9b, 9c, 9d, 9e, 9g, 9h, 9j, 13f and 17e also exhibited good antimycobacterial activity against M. tuberculosis with MIC 2-64 mu g mL(-1). The cytotoxicity assay using Vero cells revealed that all the compounds were non-toxic and exhibited a favorable selectivity index (SI >40). Time kill kinetics data indicated that compounds exhibited concentration-dependent killing. Furthermore, in silico studies were performed to decipher the possible mechanism of action. Comprehensively, these results highlight the potential of naphthalimide-thiourea derivatives as promising antibacterial agents.

In this work, a novel series of naphthalimide hydrazide derivatives were designed, synthesized and evaluated against a bacterial pathogen panel. Most of the compounds were found to exhibit potent antibacterial activity against carbapenem-resistant A. baumannii BAA 1605, with MIC ranging from 0.5 to 16 μg mL-1. Compounds 5b, 5c, 5d and 5e showed the most potent antibacterial activity, with an MIC range of 0.5-1 μg mL-1. These compounds were also found to be non-toxic to Vero cells with a high selectivity index. Further, they were active against 24 clinical isolates of MDR-AB with potent antibacterial activity. In addition, synergistic studies revealed that compound 5d exhibited synergism with FDA-approved drugs, as further validated through time-kill kinetic studies. These results highlight the potential of the synthesized compounds as promising leads for the development of novel and selective agents against carbapenem-resistant A. baumannii.

The human carbonic anhydrase (hCA) IX and XII isoforms are overexpressed in hypoxic conditions, contributing to cancer. Lack of isoform selectivity has been one of the main challenges associated with the existing drugs targeting hCAs. Hence, the development of alternative approaches, such as tail approach to develop more selective hCA IX and XII inhibitors is need of the hour. In the present work, we designed and synthesized 24 new 1,3.5-trisubstituted-pyrazoline derivatives with diverse substitutions. The synthesized analogs were evaluated for their hCA inhibitory activities against hCA I, II, IX, and XII isoforms. Among the tested compounds, derivative 8 displayed good inhibitory activity against hCA IX (K-i = 331 nM) and XII (K-i = 96.7 nM). In addition, 9a-g also exhibited some inhibitory activities against hCA IX and XII, with K(i)s ranging from 574-799 nM and 137-369 nM, respectively. Molecular modelling studies of compound 8 displayed metal coordination with zinc ion and hydrophobic, hydrophilic interactions with adjacent amino acid residues, and maintained stable interactions throughout 100 ns. In addition, ADMET studies demonstrated that compound 8 obeyed the Lipinski's rule of five and was found to be druggable and non-toxic. Hence, compound 8 was identified as potential lead for further development.

The dominance of N-Heterocycles' in chemical sciences, especially in drugs and pharmacological agents, makes them fascinating to advance their sustainable chemistry. Besides, the microwave technique enables functioning at higher temperatures beyond the boiling point of the reaction medium to offer adequate chemical transformations, which tend to be hassled with the classical approach. Herein, we have discussed microwave- assisted chemical transformations of paramount N-heterocycles (five- and six-membered) from the past decade. The role of microwave technique and its benefits has been emphasized in terms of reaction time, product yields, neat and clean reaction products, chemo/regio/enantioselectivity, and mild reaction conditions to achieve efficient transformations.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Traumatic brain injury (TBI) is a debilitating mental condition which causes physical disability and morbidity worldwide. TBI may damage the brain by direct injury that subsequently triggers a series of neuroinflammatory events. The activation of NLRP3 inflammasome and dysregulated host immune system has been documented in various neurological disorders such as TBI, ischemic stroke and multiple sclerosis. The activation of NLRP3 post-TBI increases the production of pro-inflammatory cytokines and caspase-1, which are major drivers of neuroinflammation and apoptosis. Similarly, GSK-3β regulates apoptosis through tyrosine kinase and canonical Wnt signalling pathways. Thus, therapeutic targeting of NLRP3 inflammasome and GSK-3β has emerged as promising strategies for regulating the post-TBI neuroinflammation and neurobehavioral disturbances. In this review, we discuss the identification & development of several structurally diverse and pharmacologically interesting small molecule inhibitors for targeting the NLRP3 inflammasome and GSK-3β in the management of TBI.

Cancer is associated with uncontrolled cell proliferation invading adjoining tissues and organs. Despite the availability of several chemotherapeutic agents, the constant search for newer approaches and drugs is necessitated owing to the ever-growing challenge of resistance. Over the years, DNA has emerged as an important druggable therapeutic drug due to its role in critical cellular processes such as cell division and maintenance. Further, evading apoptosis stands out as a hallmark of cancer. Hence, designing new compounds that would target DNA and induce apoptosis plays an important role in cancer therapy. In the current work, we carried out the synthesis and anticancer evaluation of 1-aryl-4,6-dihydrobenzo[b]pyrazolo[3,4-d]azepin-5(1H)-ones/thiones (26 compounds) against selected human cancer cell lines. Among these, compounds 8ae, 8ad, 8cf, 10ad and Kenpaullone have shown good inhibitory properties against HeLa cells (IC50 < 2 mu M) with good selectivity over the non-cancerous human embryonic kidney (Hek293T) cells. In cell cycle analysis, the compounds 8ad and 8cf have exhibited G2/M cell cycle arrest in HeLa cells. In addition, the compounds 8ad and 8cf induced apoptosis in a dose-dependent manner in the Annexin-V FITC staining assay. The DAPI staining clearly demonstrated the condensed and fragmented nuclei in 8ad, 8cf, 8ae and Kenpaullone-treated HeLa cells. In addition, these compounds strongly suppressed the healing after 48 h in in vitro cell migration assay. The DNA binding experiments indicated that compounds 8ae, 8cf, and 8ad as well as Kenpaullone interact with double-stranded DNA by binding in grooves which may interrupt the DNA replication and kill fast-growing cells. Molecular docking studies revealed the binding pose of 8ad and Kenpaullone at HT1 binding pocket of double-stranded DNA. Compounds 8ad and 8cf demonstrated moderate topo II inhibition which could be a possible reason for their anticancer properties. Compounds 8ad and 8cf may cause the topo II and DNA covalent complex, which leads to the inhibition of DNA replication and transcription. This eventually increases the DNA damage in cells and promotes cell apoptosis. With the above interesting biological profile, the new 1-aryl-2,6-dihydrobenzo[b] pyrazolo[3,4-d]azepin-5(4H)-one/thione derivatives have emerged as promising leads for the discovery of new anticancer agents.

One-pot tandem synthesis of diverse pyrido[2′,1′:2,3]imidazo[4,5-c]quinolines as new antimycobacterial agents through a Cu(i)-catalyzed microwave-assisted protocol.

A novel, base- and ligand-free one pot protocol for the synthesis of fused-quinazolinone under microwave irradiation using environmentally friendly PEG-400 as a solvent has been developed. Besides benzaldehyde, various benzyl alcohols and methyl arenes were used in this protocol, which extend its synthetic applicability. Photophysical study of this highly fluorescent framework was studied by fluorescent study. DFT and ESI/MS studies were carried out to justify the proposed mechanism.

Acinetobacter baumannii, a Gram-negative, glucose non-fermentative coccobacilli are responsible for causing a wide range of opportunistic nosocomial infections, thus listed as a WHO "critical priority pathogen", for which identification and development of new antibacterial agents are an urgent unmet medical need. The current review attempts to present an overview of various mechanisms (enzymatic and non-enzymatic), virulence factors responsible for A. baumannii resistance. Furthermore, inhibitors of A. baumannii are categorized into different classes highlighting their MDR inhibition properties. In addition, novel adjuvants that potentiate existing antibiotics, as well as natural and synthetic compounds that limit biofilm formation in A. baumannii infections are discussed.

Fused-azepinones are interesting heterocyclic scaffolds present in various natural products and synthetic derivatives with potent kinase inhibition, anti-cancer, anti-inflammatory, anti-HIV, neuroprotective, anti-fouling and other biological activities. These fused-azepinones are also known for their antimicrobial activity against the Plasmodium falciparum, Leishmania, Escherichia coli, and Streptococcus pneumonia. In the present work, we synthesized a library of 3,4-dihydro-1H-benzo[b]azepine-2,5-dione derivatives and evaluated them for their antibacterial potential against a panel of bacterial pathogens. The Structure-activity relationship studies revealed the essential structural features for the promising antibacterial properties against Staphylococcus aureus and Mycobacterium tuberculosis with MIC 4-64 mu g/mL. In addition, these compounds exhibited favourable selectivity index (SI >= 10) in cytotoxicity studies. With the interesting antibacterial properties exhibited and good selectivity index, these compounds have emerged as promising candidates for further development.

The application of microwave technique in chemical laboratory rooted back in 1986 and found advantageous over conventional approaches. On the other side, poly‐aza‐heterocycles are influencing organic frameworks with a fascinating chemistry and well explored by employing microwave‐assisted organic reactions. In the present review, we have thoroughly updated rousing literatures of microwave‐assisted synthesis and reactions of various poly‐aza‐heterocycles viz., triazole, tetrazole, triazine, and tetrazine from the past decade (2010–2020). The expedient chemistry and enabling role of microwave heating for adequate chemical transformations of such heterocycles, which were more challenging using classical approaches, are appropriately elucidated. This review also highlights the potential applications of these heterocyclic scaffolds and their derivatives in different scientific domains. Remarkably, such chemical architects possess wide applications as crucial building blocks in synthesis of biologically relevant compounds, agrochemicals, and compounds of interest in material science.

Microwave technology has emerged as a great tool for the efficient synthesis of organic compounds and it provides opportunities for chemists to achieve chemical transformations that tend to be challenging using classical approaches. Additionally, N-heterocycles are well-known for their medicinal/biological significance, along with their applications as excellent building blocks in chemical synthesis. The dominance of N-heterocycles in drug molecules and other pharmacological agents makes them attractive scaffolds, which encourages chemists to develop a wide range of strategies towards the greener synthesis and functionalization of these heterocycles. In this regard, we have collated and discussed literature relating to the microwave-assisted synthesis and the modification of non-(benzo)fused single-nitrogen-containing N-heterocycles from the past decade. The role of the microwave technique and its benefits over the conventional approach have also been emphasized in terms of overall reaction efficiency, reaction time, yield, reduced side-product generation, neat and clean reactions, chemo-/regio-/enantio-selectivity, and the use of mild reagents/reaction conditions to achieve the objectives of green and sustainable chemistry.