This section needs expansion with: sourced DOB, middle name, and other sourced information on early life. You can help by adding to it. (February 2016)
Roth has held a number of positions in his career, from "Scientist" (medicinal chemist) through to vice president-level positions in drug discovery, and his accomplishments in his career include the discovery of the molecule atorvastatin, which would become the drug Lipitor.[citation needed]
In 1982, 28-year-old Roth began work as a medicinal chemist for the Parke Davis research area of Warner-Lambert,[2][3] becoming the chemistry co-chair of the statins effort, with biologist Roger Newton, in 1984.[2] By 1985, he was at Warner-Lambert's Parke-Davis Pharmaceutical Research facility in Ann Arbor, Michigan.[4] He was promoted to Research Associate in 1986, Senior Research Associate in 1988, Section Director in 1990, Director of Atherosclerosis and Exploratory Chemistry in 1992, and Senior Director of Atherosclerosis, Inflammation and Exploratory Chemistry in 1993.[citation needed]
By the early 1990s he held managerial positions and was no longer doing laboratory work.[5]: 98 In 2000 Warner-Lambert acquired Parke-Davis. He was appointed Vice President of Chemistry just prior to the merger between Warner-Lambert and Pfizer in 2000 and remained in that role as a part of Pfizer Global Research and Development in Ann Arbor, Michigan until 2007.[5] He then joined GenentechinSan Francisco, California as Vice President of Discovery Chemistry.[6]
Before atorvastatin, Roth worked to develop a different drug, but Sandoz AG beat his team to a patent.[clarification needed][4] In 1985, while working at Warner-Lambert's Parke-Davis research facility, Roth "identified a molecule" that inhibited HMG CoA reductase, a "key enzyme in the metabolic pathway the body uses to produce cholesterol."[7]
Roth was listed as the inventor of trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one, patented in 1986, and developed into the on-market drug, atorvastatin, which ultimately would be sold as Lipitor,[2][8][9][10] and which would become the largest-selling drug in pharmaceutical history by 2003.[3]Pfizer acquired Warner-Lambert and Lipitor in 2000.[3][11][12]
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According to the Chemical Heritage Foundation, in "addition to his discovery of atorvastatin, Roth is the inventor or co-inventor of 42 patents and the author or co-author of 48 manuscripts, 35 published abstracts and eight book chapters."[16]
His publications include:
Baumann, K.L.; Butler, D.E.; Deering, C.F.; et al. (1992). "The convergent synthesis of CI-981, an optically active, highly potent, tissue selective inhibitor of HMG-CoA reductase". Tetrahedron Lett.33 (17): 2283–2284. doi:10.1016/S0040-4039(00)74190-6.
Brower PL, Butler DE, Deering CF, Le TV, Millar A, Nanninga TN, Roth BD (1992). "The synthesis of (4R-Cis)-1, 1-dimethylethyl, 6-cyanomethyl-2,2-dimethyl-1,3- dioxane-4-acetate, a key intermediate for the preparation of CI-981, a highly potent, tissue selective inhibitor of HMG-CoA reductase". Tetrahedron Lett. 33 (17): 2279–82. doi:10.1016/s0040-4039(00)74189-x.
Roth BD; Blankley CJ; Chucholowski AW; Ferguson E; Hoefle ML; Ortwine DF; Newton RS; Sekerke CS; Sliskovic DR; Stratton CD; et al. (Jan 1991). "Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran-2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus". J Med Chem. 34 (1): 357–66. doi:10.1021/jm00105a056. PMID1992137.
Roth BD; Bocan TM; Blankley CJ; Chucholowski AW; Creger PL; Creswell MW; Ferguson E; Newton RS; O'Brien P; Picard JA; et al. (Jan 1991). "Relationship between tissue selectivity and lipophilicity for inhibitors of HMG-CoA reductase". J Med Chem. 34 (1): 463–6. doi:10.1021/jm00105a071. PMID1992149.
Shaw MK, Newton RS, Sliskovic DR, Roth BD, Ferguson E, Krause BR (Jul 1990). "Hep-G2 cells and primary rat hepatocytes differ in their response to inhibitors of HMG-CoA reductase". Biochem Biophys Res Commun. 170 (2): 726–34. doi:10.1016/0006-291x(90)92151-o. PMID2166504.
Roth BD, Ortwine DF, Hoefle ML, Stratton CD, Sliskovic DR, Wilson MW, Newton RS (Jan 1990). "Inhibitors of cholesterol biosynthesis. 1. trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones, a novel series of HMG-CoA reductase inhibitors. 1. Effects of structural modifications at the 2- and 5-positions of the pyrrole nucleus". J Med Chem. 33 (1): 21–31. doi:10.1021/jm00163a005. PMID2296019.
Sliskovic DR, Roth BD, Wilson MW, Hoefle ML, Newton RS (Jan 1990). "Inhibitors of cholesterol biosynthesis. 2. 1,3,5-trisubstituted [2-(tetrahydro-4-hydroxy-2-oxopyran-6-yl)ethyl]pyrazoles". J Med Chem. 33 (1): 31–8. doi:10.1021/jm00163a006. PMID2296027.
Roth BD, Bocan TMA, Blankley CJ, Chucholowski AW, Creger PL, Creswell MW, Ferguson E, Newton RS, O'Brien P, Picard JA, Roark WH, Sekerke CS, Sliskovic DR, Wilson MW. The Relationship Between Tissue Selectivity and Lipophilicity for Inhibitors of HMG-CoA Reductase. J. Med. Chem. 1991, 34, 463-6.
Kende AS, Roth B, Sanfilippo PJ (1982). "Facile, palladium (II)- mediated synthesis of bridged and spirocyclic bicycloalkenones". J Am Chem Soc. 104 (6): 1784–5. doi:10.1021/ja00370a076.
Kende AS, Roth B, Sanfilippo PJ, Blacklock TJ (1982). "Mechanism and regioisomeric control in palladium (II) - mediated cycloalkenylations. A novel total synthesis of (+/-)-quadrone". J Am Chem Soc. 104 (21): 5808–10. doi:10.1021/ja00385a053.
Roth BD, Roark WH (1988). "Synthesis of a chiral synthon for the lactone portion of compactin and mevinolin". Tetrahedron Lett. 29 (11): 1255–8. doi:10.1016/s0040-4039(00)80269-5.
The following are good sources from which further information on the article's subject may be found, that may be of interest to readers and article editors. It includes sources not yet cited, and sources whose content may yet provide further insights into the subject.
Roth, Bruce D. (2003) "Discovery and development of Lipitor (atorvastatin calcium),"ACS Award for Creative Invention Symposium: New Therapies for Atherosclerosis, MEDI 158 (March 24), The 225th ACS National Meeting, New Orleans, LA, March 23–27, 2003.
^ abcSimons, John (2003). "The $10 Billion Pill: Hold the Fries, Please"(online). Fortune (January 20). Retrieved 2 February 2016. "Subtitle: Lipitor, the cholesterol-lowering drug, has become the bestselling pharmaceutical in history. Here's how Pfizer did it.
^Rowe, Aaron (2008). "Meet the Guy Who Invented Lipitor"(online). Wired. No. August 20. Retrieved 2 February 2016. Bruce Roth, the inventor of Lipitor, calls the people who make those tough decisions 'drug hunters' and says that it takes between 10 and 15 years to train them. / 'Unfortunately, there are some things that are hard to predict,' said Roth, during a panel discussion this Monday at the American Chemical Society meeting in Philadelphia. 'We still are not very good at understanding which compounds are going to be successful, and which ones will be toxic.'
^US patent 4681893, Roth BD, "Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis", issued 21 July 1987
^Roth, Bruce D. (2003) "Discovery and development of Lipitor (atorvastatin calcium),"ACS Award for Creative Invention Symposium: New Therapies for Atherosclerosis, MEDI 158 (March 24), The 225th ACS National Meeting, New Orleans, LA, March 23–27, 2003.
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