Monsanto/Searle

Before the formation of Pharmacia through the merger of Pharmacia Upjohn with Monsanto-Searle in 2000, each company had its own approaches to augment and diversify their compound collections, and these approaches set the stage for the procedure implemented at Pharmacia. Thus, it was felt that a brief description of the historical background to the present work would be informative and would afford additional insights that bear directly on the development of the compound acquisition strategy described here. 

The literature has many examples of ligands that have been developed to effect asymmetric hydrogenations of a variety of functional groups [4—8]. The reductions of enamides to provide a-amino acids derivatives has been of importance since the pioneering work of Knowles and his colleagues at Monsanto [9, 10]. This approach has been used by Monsanto, Searle and now Egis for the production of L-dopa (Fig. 1) [4]. The chemistry related to L-dopa is discussed in more detail in Chapter I 1, by W.S. Knowles. 

Celecoxib was the first modern COX-2 inhibitor, which was introduced to the market in 1998. Developed by Monsanto/Searle, this drug is 375 times more selective for COX-2 over COX-1, based on assays with recombinant human enzymes (Fig. 5.88). [187]... 

The Batch Reaction Subcommittee was chaired by Walter L. Lrank of EQE International. Current members of the subcommittee, listed alphabetically are David J. Christensen, Union Carbide Corporation Warren Greenfield, International Specialty Products Philip P. Malkewicz, Nalco Chemical Company Peter L. McGrath, Olin Corporation Louisa A. Nara, Bayer Corporation Leslie A. Seller, CCPS Staff Consultant Robert Schisla, Eastman Chemical Company Anthony Torres, Eastman Kodak Company Dr. Jan C. Windhorst, Nova Chemicals and Paul Wood, Eli Lilly Company. Eormer subcommittee members who contributed much in getting this project started were Eelix Ereiheiter, CCPS Staff Consultant (deceased) A1 Noren, Monsanto Company-Searle (deceased) John Noronha, Eastman Kodak Company (retired) and Robert Stankovich, Eli Lilly Company. 

Cytotec (Monsanto 1987) GB Arthrotec (Searle)-comb. Cytotec (Searle)... 

Searle, Parallel Medicinal Chemistry, Monsanto Company,... 

Aspartame is a high intensity dipeptide sweetener, ca. 200 times as sweet as sncrose. It was originally developed by G.D.Searle Co. prior to their acqnisition by Monsanto. Chemically synthesised aspartame has rapidly acqnired a major share of the world high intensity sweetener market, particnlarly in soft drinks. Until recently it has all been snpplied by a monopoly snpplier, the Nntrasweet Corp (a Monsanto-AJinomoto joint ventnre) protected by prodnct patents. Recently biocatalytic methods... 

The profit potential of aspartame was a major factor in the takeover of Searle by Monsanto. (Current aspartame sales are ca. 10 ton/a, equivalent to ca. 850 x lO /a). The success of the Nutrasweet Co. in establishing aspartame in the market. This has... 

Aspartame. Aspartame [22839-47-0] [53906-69-1] (APM, L-aspartyl-L-phenylalanine methyl ester) (1), also known under the trade names of NutraSweet and EQUAL, is the most widely used nonnutritive sweetener worldwide. This dipeptide ester was synthesized as an intermediate for an antiulcer peptide at G. D. Searle in 1965. Although this compound was known in the literature, its sweet taste was serendipitously discovered when a chemist licked his finger which was contaminated with it. Many analogues, especially the more stable esters, were made (6) and their taste qualities and potencies determined. It was the first compound to be chosen for commercial development. Following the purchase of G. D. Searle by Monsanto, the aspartame business was split off to become a separate Monsanto subsidiary called the NutraSweet Company. 

RAJESH V. DEVRAJ and JOHN J. PARLOW Searle/Monsanto Life Sciences Company... 

Rajesh V. Devraj, Parallel Medicinal Combinatorial Chemistry Unit, Searle/Monsanto Life Sciences Company, 800 N. Lindbergh Blvd., St. Louis, MO 63167, USA... 

Both Celebrex and Bextra were developed by Searle, which was subsequently purchased by Monsanto. Monsanto later merged with Pharmacia and Upjohn, and the resultant company later merged with Pfizer. 23 University of Rochester v. G.D. Searle Co., 249 F.2d 216 (W.D. N.Y. 2003). The District Court also held the claims to be invalid due to lack of enablement, an issue we will discuss further later in this chapter. 

D Corigasl (Searle) wfm F Pro-Banthine (Monsanto) J Pro-Banthine (Dainippon)... 

Aspartame, the artificial sweetener marketed as NutraSweet , is a dipeptide, which was discovered in 1965 by accident to be 100-200 times sweeter than sucrose. The discovery was originally made at G.D. Searle, which was later acquired by Monsanto. 

According to the authors, an economic evaluation showed that the electrochemical step was reasonably cheap. Unfortunately, this is not the whole truth. In a recent publication [84], authors from Searle and (formerly) Monsanto describe the workup procedure. The removal of colloidal metal, the handling of the oxide and salt mixture, the... 

By 1994 agricultural biological and chemical products accounted for 27 percent of Monsanto s revenues and 48 percent of its operating income. Its fabrics and plastics and other industrial chemicals represented 25 percent of revenues and 27 percent of income NutraSweet, 8 percent and 14 percent and Searle, 20 percent and 7 percent, respectively. At the same time, Monsanto, which, unlike Dow and Du Pont, had not gone extensively overseas, concentrated on increasing its foreign sales, which grew from less than 10 percent of total sales in 1989 to 49 percent in 1994. 

In 1997 Monsanto divested the 3 billion a year chemicals segment of its business (now called Solutia). Management shifted its focus to life sciences such that the company now consists of life sciences and agricultural products, Searle pharmaceuticals, and food ingredients. Monsanto investors now are likely to be interested in higher risk and higher returns but this may take time. This is a company in transition. 

Discovery Medicinal Chemistry, G.D. Searle, a Division of Monsanto,... 

Also, the composition of firms in the pharmaceutical industry changes as mergers and acquisitions alter SIC codes. For example, the acquisition in 1985 of G.D. Searle Company by Monsanto Corporation, a chemical firm, probably caused Searle s spending on R D to be counted in SIC 281 (chemicals) in subsequent years. Because the SIC classifications change with merger and acquisition activity, NSF is probably a less reliable source of industrywide R D growth rates than is PM A. 

To appreciate the painstaking research that is process chemistry, consider an example furnished by chemists at G. D. Searle, now part of Monsanto. In making LiCHgCl, they ascertained that the molar ratio of the reagents BrCHgCl to -BuLi ideally lay between 1.25 and 1.33 (Liu et ai,... 

Gateway Chemical Technology Monsanto Life Sciences Co. Reliable Biopharmaceutical Corporation Searle... 

Monsanto employs organic chemists as researchers both in its St. Louis headquarters and its Chesterfield site, which houses G. D. Searle, its subsidiary. 

We wish to thank everyone who has contributed positively to this project, including our colleagues at Monsanto Corporate Research and G. D. Searle Co., our consultants, and our external collaborators. We want to acknowlegde with special thanks the expert molecular pharmacology leadership of Drs. Mark Currie and Daniela Salvemini of the G. D. Searle Co. 

Searle (Monsanto) SmithKline Beecham Wellcome Trust... 

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