Evaluation of Novel Synthetic Methods for the Preparation of the Sodium Channel Inhibitor, GW273225X

Author:

Walker Matthew D.1,Albinson F. David1,Clark Hugh F.1,Clark Stacy1,Henley Nicholas P.1,Horan Richard A. J.1,Jones Chris W.1,Wade Charles E.1,Ward Richard A.1

Affiliation:

1. Product Development, GlaxoSmithKline Pharmaceuticals, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, U.K.

Publisher

American Chemical Society (ACS)

Subject

Organic Chemistry,Physical and Theoretical Chemistry

Reference12 articles.

1. aNobbs, M. S.; Rodgers, S. J.Preparation of (R)-2,4-diamino-5-(2,3-dichlorophenyl)-6-fluoromethylpyrimidine as a drug. World Patent WO 9709317 A2, 1997.

2. bMiller, A. A.; Nobbs, M. S.; Hyde, R. M.; Leach, M. J.Preparation and formulation of phenylpyrimidines for treating central nervous system disorders. European Patent EP 372934, 1996.

3. cAlvaro, G.; Large, C.Pharmaceutical compositions comprising 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine or R-(−)-2,4-diamino-5-(2,3-dichlorophenyl)-6-(fluoromethyl)pyrimidine and an NK1 antagonist. World Patent WO 2008090117 A1, 2008.

4. The UK HSE has assigned a SLOD DTL (Specified Likelihood of Death Dangerous Toxic Load) for ethyl fluoroacetate as 1840 ppm·min. For example, it is estimated that, for exposure of a population to 80 ppm of ethyl fluoroacetate for 23 min (1840 ppm·min), 50% of this population would be killed [Assessment of the Dangerous Toxic Load (DTL) for Specified Level of Toxicity (SLOT) and Significant Likelihood of Death (SLOD)].http://www.hse.gov.uk/chemicals/haztox.html(accessed April 19, 2013) .

5. The first synthesis and cytostatic activity of novel 6-(fluoromethyl)purine bases and nucleosides

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