Chapter 14Pharmaceuticals.ppt

Chapter 14Pharmaceuticals CHM 585 / 490 Pharmaceuticals Industry Synthetic Considerations Nabumetone Methotrexate Natural Products Antidepressants Antihistamines Chirality cGMP 10,300 FDA approved drugs in U.S. 50% of all new drugs currently available worldwide have been launched in the U.S. The discovery/preclinical stage takes from 3–7 years and only about 1 of every 10,000 compounds evaluated enters human trials Top 10 Pharma Companies by 2002 Revenues ($B) GlaxoSmithKline Paxil (SSRI -selective serotonin reuptake inhibitor – depression) Advaire (for asthma) Augmentin (for asthma) Augmentin (antibiotic) Avandia (diabetes) Combivir (HIV) Flonase (allergies) Imitrex ( migraines) Pfizer Lipitor (#1 prescribed drug) (cholesterol) $8.6B in revenue Norvasc (hypertension) Zoloft (SSRI) Merck Zocor (cholesterol) Vioxx (osteoarthritis – joint disease) Fosamax (osteoporosis – bone loss) Cozaar (hypertension) Singulair (asthma) About 12 Years to bring a drug to market $ Cost for a single new drug averages $1.7 B 2003 $33 B invested in Pharma Research 86 new medicines 21 new molecular entities (NMEs) 14 biologics 51 additional drugs Over the past 20 years, for every dollar invested in health care, between $2.40 - $3.00 in gains have been realized Top Reasons for Drug Recalls in 2001 Deviations from cGMP Subpotency Stability data failed to support expiration data Failure of drug to dissolve properly Wrong packaging Incorrect labeling Microbial contamination Pharmaceuticals Industry Synthetic Considerations Nabumetone Methotrexate Natural Products Antidepressants Antihistamines Chirality cGMP Nabumetone See handout for various syntheses and discussion on this NSAID Multistep Syntheses Even when each step is a high yield step, the overall yield can be low. For example a 5 step synthesis where each step is a 90% yield reaction has an overall yield of 59% 0.90 x 0.90 x 0.90 x 0.90 x 09.0 = 0.59 $ For an effective cost position, important to have: As few steps as possible H