Medicinal Chemistry

Obesity and its comorbidities have become pandemic, posing a challenge to the global healthcare system. To address such a public health burden, lifestyle changes, nutritional interventions, and pharmaceuticals should be combined in a personalised strategy. Obesity and glucose metabolism dysfunctions are exacerbated by altered brown adipose tissue function. Through uncoupled respiration, BAT thermogenic activity burns glucose and fatty acids to produce heat, which can dissipate excess calorie intake, reduce glycemia, and circulate fatty acids released from white adipose tissue. Thus, BAT activity is expected to contribute to overall energy homeostasis and protect against obesity, diabetes, and lipid profile changes. To date, clinical trials for pharmacological therapies aimed at activating brown fat have failed due to cardiovascular side effects or insufficient efficacy.

Nitro compounds are a type of organic molecule that has a wide range of applications in organic synthesis, medicinal chemistry, and materials science. The direct oxidation of primary amines is an appealing alternative route among the various methodologies available for their synthesis. Efforts to develop oxidative procedures for the synthesis of nitro derivatives have spanned decades, yielding a wide range of protocols for the selective oxidative conversion of amines to nitro derivatives. This review summarises methods for the synthesis of nitroarenes via aryl amine oxidation, with a focus on recent advances in the field. The harsh reaction conditions, as well as the poor functional group tolerance and regioselectivity, are the main drawbacks of this route. Many aromatic nitro derivatives are still difficult to synthesise via this method. Alternative nitration reagents and methodologies, including transition-metal-catalyzed ipso-nitration methodologies, have emerged as powerful tools for nitroarenes synthesis.