GlaxoSmithKline forming

Two Americans, Silas Mainville Burroughs and Henry Solomon Wellcome, found Burroughs Wellcome in London. After more than a century of success, the company will merge with several others to form GlaxoSmithKline. 

GlaxoSmithKline is formed with the merger of Glaxo Wellcome and SmithKline Beecham... 

Sanofi-Aventis is formed from the takeover of Aventis by Sanofi-Synthelabo. June 2 New York attorney general Eliot Spitzer sues the maker of Paxil, GlaxoSmithKline, for fraud in concealing the dangers of the drug for children under age 17 (the suit is settled when the company agrees to publish all its results). 

Zolmitriptan (2, BW-311C90) was discovered by Wellcome in the United Kingdom and then transferred to AstraZeneca upon the acquisition of Wellcome by Glaxo (now GlaxoSmithKline). The synthesis began with 4-nitro-L-phenylalanine (29), which was converted to the methyl ester and then reduced with NaBHj to give the amino alcohol (Scheme 8). ° Oxazolidinone 30 was formed by treating the amino alcohol... 

When the drug was invented, the company was called Smith, Kline, and French [SKF) but after a merger with Beechams the company became SmithKline Beecham or SB. SB and Glaxo-Welcome have now also merged to form GlaxoSmithKline [GSK). Things may have changed further by the time you read this book. 

Another example is the recent effort by GlaxoSmithKline (GSK) to find some distinguishing genotype— now found in the form of 89 SNPs ( Snips )— that would predict adverse effects of their HIV-antiviral dmg (Abacovir) and enable patient screening, thereby permitting GSK to keep the drug on the market, at least until someone displaces it with a dmg that does not require such screening efforts. 

Paroxetine is an antidepressant marketed by GlaxoSmithKline as Paxil. Example 2 of U.S. 4,007,196 (to A/S Eerrosan) describes preparation on the free base from of paroxetine, while U.S. 4,721,723 (to Beecham Group Pic.) describes the synthesis of the crystalline hydrochloride hemihydrate, which is the preferred form to administer the drug. What is the cost of production of the API in the crystalline hydrochloride hemihydrate form ... 

The obvious answer is as early as possible. The first chiral intermediate is 146 and that already has two chiral centres. The first intermediate with a useful functional group is 149 with its two alcohols. The chemists at what was then Glaxo (now GlaxoSmithKline) chose an ingenious resolution of the stable ketone 147. Because this is a strained ketone it forms a stable adduct with bisulfite and that could be resolved as a salt with our old friend 1-phenylethylamine 2. The bisulfite compound reverts to the ketone 147 on treatment with base and the resolution was complete. 

Figure 2 Calorimetry can be useful for examining relative polymorphic stability by comparing the solubility of the forms. Solubility can be derived from the heats of solution for a polymorphic form dispersed into a solvent divided by the enthalpy change offusion (A H). A correction can be made for the enthalpy of solvation using the amorphous form of the material. The graph shows the relative solubility of two polymorphs of a drug substance in development with GlaxoSmithKline...

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