Benzodiazepines are widely used drugs for several indications. This study provides, on the other hand, a global vision of the family starting for their fortuitous discovery, the synthesis of their derivatives, their mechanism of action widely known nowadays, the actual classification according to the chemical structure and pharmacokinetic properties, and their uses and indications, the traditional and the new ones. On the other hand,the study is focused in the mainly problems of benzodiazepines, depedence, and tolerance, many times led by a misuse of the patient, wrong prescriptions, or extended treatments. A withdrawal program is proposed that includes the important factors or criteria to success, with a slow and gradual reduction of these drugs, avoiding relapse or severe adverse effects. New lines of research related to benzodiazepines are taken into account, which not only include the new therapeutic uses but also the adverse effects in short and long term. They are also analyzed the new discoveries concerning the nonbenzodiazepine drugs due to the close relation they have with benzodiazepines.
2-Aminopyrazine was halogenated with NIS, NCS, and NBS under different reaction conditions. Chlorination and bromination were achieved with good yields by using acetonitrile as the solvent. However, iodination was only obtained in poor yields. Undoubtedly, the best conditions for both mono- and dihalogenation were the use of NBS, acetonitrile, and microwave assistance for short periods. 3,5-Dibromo-2-aminopyrazine is an excellent functionalized starting material for the synthesis of nitrogen heterocycles.
Structural features from the anticancer prodrug nemorubicin (MMDX) and the DNA-binding molecule DRAQ5™ were used to prepare anthraquinone-based compounds, which were assessed for their potential to interrogate cytochrome P450 (CYP) functional activity and localisation. 1,4-disubstituted anthraquinone 8 was shown to be 5-fold more potent in EJ138 bladder cancer cells after CYP1A2 bioactivation. In contrast, 1,5-bis((2-morpholinoethyl)amino) substituted anthraquinone 10 was not CYP-bioactivated but was shown to be fluorescent and subsequently photo-activated by a light pulse (at a bandwidth 532-587 nm), resulting in punctuated foci accumulation in the cytoplasm. It also showed low toxicity in human osteosarcoma cells. These combined properties provide an interesting prospective approach for opto-tagging single or a sub-population of cells and seeking their location without the need for continuous monitoring.
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