New Chemical Entity

There are many REASONS for using fluorine in the drug molecule or New Chemical Entity research and development process including:

• Higher bioavailability;
  
• Replacement of H by F causes less steric hindrance than other halogens or substituents as it is a small atom;
  
• Forms relatively stronger C-F bond;
  
• Good Hydrogen bond acceptor with three loan pairs – important for binding in biological systems, Fluorine make a good hydrogen mimic and a good alternative to Oxygen as well while designing novel chemical entities (non-naturally occurring);
  
• Substantially electronegative to produce inductive effects on parts of the molecule even when distantly placed in the molecule, and can substantially affect the dipole and basicity/acidity of the molecule;
  
• Less abundant in nature - Free Fluoride ion is very much less abundant in nature than chloride ions and as a result bacteria less likely to incorporate fluorine than other halogens – which is most helpful in designing better molecules;
  
• Strong electronic influence in the molecule at the point of contact and also at a site slightly away from the point of attachment – a good molecule for designing of active molecules;
  
• Fluorine increases fat solubility of the molecule and thereby increases bioavailability of the molecule, the trifluoromethyl group is perhaps the most lipophilic group known.
  
  

All the above and many more...

Fluorine in Pharmaceutical Chemistry

Fluorine has become an essential tool in drug discovery today and is present in many top selling drugs such as: Lipitor (atorvastatin), a block buster which as an aromatic fluorine substituent: Prevacid (lansoprazole), which includes difluoromethylene unit; and Seretide, which has three Fluorine substituents in the molecule. Other statins like Lipitor, Lescol (Fluvastatin), Crestor (Rosuvastatin) all containing aromatic fluoro derivatives are commonly known. Statins alone probably account for revenues of more than 10 Billion USD annually.

One of the most popular groups for NCE (New Chemical Entities) as drug is the trifluoromethyl group as it contains three F groups and exerts significant changes in the neighboring groups. Two best selling molecules PROSAC (fluoxetine) and Luvox (Fluoxamine) contain trifluoromethyl groups.

Fluorine in Agroinputs

Nature makes very few molecules with Fluorine. Fluorine is used in all three classes of products in Agri Inputs - herbicides, insecticide and fungicides. Amongst the herbicides, Diflufenican is a nicotinanilide containing aromatic trifluoromethyl group. Fluroxypyr is a fluorinated pyridine herbicide of Dupont, and trifluralin is a dinitroaniline herbicide with a herbicide with aromatic trifluoromethyl group.