DR ANTHONY CRASTO, PROCESS RESEARCH OVERVIEW, Glenmark scientist helping millions, Million hits on Google amcrasto@gmail.com

1. DR ANTHONY M CRASTO (Ph.D) PRINCIPAL SCIENTIST PROCESS RESEARCH DEC 2011 “ A SHORT PRESENTATION”

3. Net Cost: $802 Million Invested Over 15 Years 5,000–10,000 Screened 250 Enter Preclinical Testing 5 Enter Clinical Testing 1 Compound Success Rates by Stage 16 14 12 10 8 6 4 2 0 Phase II 100–300 Patient Volunteers Used to Look for Efficacy and Side Effects Phase III 1,000–5,000 Patient Volunteers Used to Monitor Adverse Reactions to Long-Term Use FDA Review Approval Additional Post-Marketing Testing Phase I 20–80 Healthy Volunteers Used to Determine Safety and Dosage Preclinical Testing Laboratory and Animal Testing Discovery (2–10 Years) Years New Product Development – A Risky and Expensive Proposition Approved by the FDA

14. Med Chem Clinical Chem E R&D Pharm R&D Safety Analytical Process

15. responsible for developing In-process assay and critical evaluation of drug substance and intermediates Med Chem Clinical Chem E R&D Pharm R&D Safety Analytical Process

16. responsible for toxicity studies: (carcinogen, teratogen, gene toxicity ) Med Chem Clinical Chem E R&D Pharm R&D Safety Analytical Process

17. responsible for formulating drug substance (API) into drug product Med Chem Clinical Chem E R&D Pharm R&D Safety Analytical Process

18. Oversee process transfer into Pilot plants Med Chem Clinical Chem E R&D Pharm R&D Safety Analytical Process

19. Conducts clinical trials (Ph I-III) and evaluates data Med Chem Clinical Chem E R&D Pharm R&D Safety Analytical Process

20. Discovers new chemical entities (NCE’s) and prepares intitial quantities Med Chem Clinical Chem E R&D Pharm R&D Safety Analytical Process

29. Selective Dopamine-2 Antagonist Indication: Anti-psychotic (Depression/Schizophrenia) Clinical Trials: halted in 1993 due to anemia side-effects

32. Auerbach, Weissman Tet Letters 1993, 931

34. Drawbacks: 1. Use of costly Oxalyl Chloride 2. CO and CO 2 by-products 3. Lengthy time cycle due to exothermic amination reaction 4. Need for 3 equiv of volatile t -butylamine 5. Filtration/Disposal of voluminous amine hydrochloride salt

36. A: 179/[124+127+73+73] = 45 % B: 179/[105 + 98 +74 +18] = 61%