Fluorine important element in new drugs synthesis : Review Study

Objective:To evaluate the role of fluorine atom in modern drug synthesis. Methods: Different types of fluorinated were prepared, antimicrobials, antivirals, FNSAIDs, peptides and protein synthesis. Results: Recent developments and future prospects of fluorine in medicinal chemistry and chemical biology. The extraordinary potential of fluorine containing biologically relevant molecules in antimicrobial or antivirial agents, or peptide or protein chemistry, medicinal chemistry, chemical biology, pharmacology, and drug discovery as well as diagnostic and therapeutic applications, was recognized by researchers who are not in the traditional fluorine chemistry field, and thus the new wave of fluorine chemistry has been rapidly expanding its biomedical frontiers. Conclusion: This review how to list of fluorinated drugs( Antimicrobial agents , anticancer agents, Antiviral agents, and study their physicochemical properties of fluorine drugs.


F
Fluorine rarely occurs naturally in biological molecules, and many compounds containing fluorine are toxic. Fluorine is a common element added to pharmaceuticals because it can increase the drug's selectivity, enable it to dissolve in fats, and decrease the speed at which the drug is metabolized, thus allowing it more time to work 1,2 .
The effect has been associated with the conversion of the enamel hydroxyapatite Ca5(PO4)3(OH) to fluorapatite with a reduction in acid solubility 3 and increase selectivity. It has important effects on the oral bacteria of dental plaque, which are responsible for the acidification of plaque that results in demineralization. Other uses in the isotopic form 19 F in chemistry and 18 F is a commercially important source of positrons. Its major value is in the production of the radiopharmaceutical fludeoxygluco se, used in positron emission tomography in medicine 4 . General properties of Fluorine Some properties are affecting the drugs: 1-pKa 2-Steric effects 3-Lipophilicity 4-Inductive effect 5-Hydrogen bonding 6-Isoster.

Fluorine antimicrobial drugs
The history of work on the prevention of bacterial infection can be traced back to the 20th century. New fluoroquinolones classification is a useful tool for physicians to use when empirically prescribing these drugs or evaluating new agents introduced to the market 5 . Drugs in each group are similar in antimicrobial activity. With each successive generation, a significant new group of pathogens is added to the coverage.
These newer fluoroquinolones have a wider clinical use and a broader spectrum of antibacterial activity including G (-) ve & G (+) ve aerobic and anaerobic organisms. Some of the newer fluoroquinolones have an important role in the treatment of community-acquired pneumonia and intra-abdominal infection They are primarily used against urinary tract infections and are also clinically useful against prostatitis, infections of skin and bones and penicillin resistant sexually transmitted diseases 5&6 .

Beta-Lactamase inhibitors
Novel compounds have activity against β-lactamase producing strains, it is possible that their molecular target is different than the known targets of the β-lactams 7 . Voriconazole is a second generation synthetic derivatives of fluconazole by addition of methyl group to the propyl backbone and substitution of triazole moiety with a fluropyrmidine group. Active against yeast and moulds. Fungicidal in vitro against Aspergillus spp and fungistatic in vitro against Candida spp. It is active against a limited range of systemic fungal infections, being effective mainly in those caused by yeast. It has activity against Candida spp., C. neoformans and some fungi causing chromoblastomycosis.
Monotherapy now limited, can be used in combination therapy due to restricted spectrum activity 7 .

Anti-viral fluorinated drugs
The Ledipasvir and sofosbuvir are antiviral medications that prevent hepatitis C virus (HCV) from multiplying in your body.
It is a combination medicine used to treat chronic hepatitis C in adults and children who are at least 12 years old or who weigh at least 77 pounds (35 kilograms) 8 .

Other medical uses of Fluorinate drugs
Fluoroine play an important role in the steroid skeletondrugs, It is prevents the conversion of testosterone to dihydrotestosterone (DHT) in the body. DHT is involved in the development of benign prostatic hyperplasia (BPH) 9 .
Respiratory system drugs, Roflumilast ; phosphodiesterase-4 Enzyme inhibitors Indicated to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

Anti-Diabetes
Drugs are another types of fluorinated drugssuch as Sitagliptin; brand name,Januvia® It is used to lower blood sugar in patients with high blood sugar (diabetes) type II.
Also, fluorinated non steroidal anti-inflammatory F-NSAIDs as new family such as Celecoxib 10 .
Analytical methods used for determination of F-agents Currently, various instrumental analytical methods based on chromatography, spectroscopy, and electrochemistry are used to determine some of these fluorine-containing compounds 11 . Chromatographic techniques such as thin layer chromatography, HPLC, gas chromatography or capillary electrophoresis, and spectrophotometric Ultraviolet (UV), Nuclear Magmatic Resonance (NMR). Fluorinated gas agent can be used as contrast media in Ultrasound for diagnostic cardiac diseases such as Perflutren 11 .

Modulating the properties of bioactive peptides
Fluorination has also been used as a tool to modify the properties of biologically active peptides and investigate their mechanism of action. In particular, some classes of peptides, notably antimicrobial peptides (AMPs) and venom peptides, exert their biological effect through direct disruption of cell membranes, rather than specific peptide-protein or peptide-nucleic acid interactions. This disruptive effect depends on the overall balance of positively charged and hydrophobic residues, rather than sequence-specific interactions, making fluorination an ideal method to alter the hydrophobicity of these peptides in a nondisruptive manner 12 .

Conclusion
Our conclusion fluorine -containing substituents and functional groups from a medicinal chemistry point of view and then the applications of those characteristics to organic, bioorganic, as well as chemical and biomedical researches.