Serendipity of fluorine in discovery and development of antidiabetic agents: A bottleneck Systemic Review
Type 2 diabetes is metabolic disorder characterized by insulin resistance at peripheral target tissues and pancreatic β-cell dysfunction. Fluorine is an element of a wide range of modern drugs with anti-cancer and anti-viral agents, anti-inflammatory drugs, antibiotics, central nervous system agents, diuretics and antihypertensive agents and antiarrhythmic heart drugs. There will be focus on topics that include fluorinated drugs for treatment of diabetes. The resultant hyperglycemia if left untreated can eventually lead to the debilitating vascular complications of type 2 diabetes, including retinopathy, end stage renal disease, neuropathy and cardiovascular disease. Current therapies may also be associated with an increased risk of hypoglycemia, weight gain and gastrointestinal intolerance, which represents major barriers to optimal glycemic control. These huge successes of fluorine-containing drugs continue to stimulate research on fluorine in medicinal chemistry for drug discovery. It would not be an exaggeration to say that currently every new drug discovery and development program without exception explores fluorine-containing drug candidates. Accordingly a wide variety of fluorine-containing compounds based either on known natural products or on new skeletons have been synthesized or subjected to biological evaluation. Lipophilicity of Fluorine and Fluorine containing groups play important role in drug receptor interaction and selectivity of drugs. The absorption and distribution of a drug molecule in-vivo are controlled by its balance of lipophilicity and hydrophilicity as well as ionization. Enhanced lipophilicity together with change in amine often leads to increase in blood-brain barrier (BBB) permeability or binding free energy through favorable partition between the polar aqueous solution and the less-polar binding site. Inhibition of dipeptidyl peptidase 4 is a promising new approach for the treatment of type 2 diabetes. Fluorine play important role in development of DPP-4 inhibitors like Denagliptin, Gemigliptin and Sitagliptine. Hence, DPP-4 inhibition has the potential to be a novel, efficient and tolerable approach to treat type 2 diabetes to its solution form.
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