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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.

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. baumanniiBAA 1605, with MIC ranging from 0.5 to 16 μg mL−1. Compounds 5b, 5c, 5dand 5eshowed 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 5dexhibited 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 emergence of antibiotic resistance to S. aureusand 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. baumanniiand various mycobacterial pathogens. Compounds 4a, 4l, 4m, 4n, 4q, 9f, 9l, 13a, 13d, 13e, 17a, 17b, 17c, 17d, and 17edemonstrated potent antibacterial activity against S. aureuswith MIC 0.03–8 μg mL−1. In addition, these compounds have also exhibited potent inhibition against MDR strains of S. aureus, including VRSA with MICs 0.06–4 μg mL−1. Compounds 4h, 4j, 4l, 4m, 4q, 4r, 9a, 9b, 9c, 9d, 9e, 9g, 9h, 9j, 13fand 17ealso exhibited good antimycobacterial activity against M. tuberculosiswith MIC 2–64 μg 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 silicostudies were performed to decipher the possible mechanism of action. Comprehensively, these results highlight the potential of naphthalimide–thiourea derivatives as promising antibacterial agents.