Varenicline: Pharmaceutical of the Future
The project that I chose was a study of Chantix™, also known as Varenicline, and different analogs of it. After altering the original structure of Varenicline, I ran the new molecules through a program to determine their ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) properties. Based on the computer-generated properties, I would potentially be able to determine whether or not the new molecules would be suitable candidates.
Tobacco is a naturally occurring plant that was first used by the Native Americans as a vehicle to communicate with the spiritual world. The introduction of the plant to the newly arrived Europeans consequently led to the invention of the cigarette, tobacco rolled in paper. After a little less than 500 years, the smoking of cigarettes continues today even though scientists and doctors alike can prove its damaging effects. Smoking continues today because of addiction, something so powerful and difficult to overcome that a person usually needs help.
This so-called help can come from many things including, but not limited to, the more common patches and lozenges, and the less conventional use of hypnosis. Although the fore mentioned methods do work on occasion, their success rates are far from stellar and their side effects are numerous. Fortunately, there is a new pharmaceutical out on the market by the name of Chantix™, scientifically known as Varenicline, which seems to have an edge when it comes to smoking cessation.
Chantix™ or Varenicline was approved by the Federal Drug Administration for the treatment of nicotine addiction in 2006. Since then there have been many case studies done, like the one comparing the drug with Bupropion SR and placebo. According to the chart to the left, Varenicline was much more effective than Bupropion SR and placebo. While the results appear promising, the side effects are yet another obstacle that smokers must overcome. During a randomized, controlled trial of Varenicline, the Varenicline Phase 3 Study Group revealed that “nearly 30% of the participants reported nausea,” along with “abnormal dreams.”1 This is the main reason that I have chosen this particular project. By creating analogs of Varenicline and studying their ADMET properties, I could potentially find a better form of the drug, and by better I mean more effective with less side effects.
Prior to creating analogs of Varenicline, I first had to build the actual molecule. Although the ChemDraw3D program could not find a molecule by the name of Varenicline, it could find 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino(2,3-h)(3)benzazepine, the molecular formula of Varenicline. After I transferred the molecule generated by ChemDraw3D to GaussView, I changed parts of the molecules. Once I was satisfied with the changes made, I ran the molecule through Gaussian 03W to optimize its structure. To determine...