An improved synthesis of 2-amino-5-[(4-chlorophenyl)thio]4- morpholinopyrimidine (BW 394U) - A potential antisenility agent

Journal of Heterocyclic Chemistry

Volumn 37, Issue 1, 2000, Pages 183-185

  Samano, Vicente ^a   Styles, Virgil L ^a   Chan, Joseph H ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 5 (4 CHLOROPHENYL)THIO 4 MORPHOLINOPYRIMIDINE; NOOTROPIC AGENT; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CHLORINATION; DRUG ACTIVITY; DRUG SYNTHESIS; REACTION ANALYSIS; SENILITY; TRANSAMINATION;

EID: 0034065356     PISSN: 0022152X     EISSN: None     Source Type: Journal    
DOI: 10.1002/jhet.5570370131     Document Type: Article

References (17)

1. F. Hefti and L. S. Schneider, Clin. Neuropharm., 14, 63 (1991).
2. D. R. Rosenberg, B. A. Wright, and S. Gershon, Drugs Today, 26, 449 (1990).
3. E. K. Perry, Br. Med. Bull., 42, 63 (1986).
4. D. M. Fink, G. M. Bores, R. C. Effland, F. P. Huger, B. E. Kurys, D. K. Rush, and D. E. Selk, J. Med. Chem., 38, 3645 (1995).
5. H. M. Bryson and P. Benfield, Drugs and Aging, 10, 234 (1997).
6. British Patent 9514531 (1964); Chem. Abstr., 60, 14520b (1964).
7. H. L. White (deceased, formely of Burroughs Wellcome Co.) and P. W. Scates (Division of Pharmacology, Glaxo Wellcome Inc.), unpublished results.
8. A. Pradines, M. Magazin, P. Schiltz, G. L. Fur, D. Caput, and P. J. Ferrara, Neurochem., 64, 1954 (1995) and references cited therein.
9. B. Roth and G. H. Hitchings, J. Org. Chem., 26, 2770 (1961).
10. For representative examples on the synthesis and therapeutic use of other arylthiopyrimidines, see: [a] W. Klose and K. Schwarz, J. Heterocyclic Chem., 19, 1165 (1982);
11. [b] J. Chen and G. T. Crisp, Synth.Commun., 22, 683 (1992);
12. [c] United States Patent 3,154,551 (1964); Chem. Abstr., 55, 4546e (1964).
13. C. Just, in Adv. Org. Chem: Methods and Results; H. Bohme, H, Viehe, eds., Wiley-Interscience: New York, 9, 225 (1976).
14. H. L. Wheeler and T. B. Johnson, J. Amer. Chem. Soc., 29, 492 (1903).
15. R. Knorr, P. Low, P. Hassel, and H. Bronberger, J. Org. Chem. 49, 1288 (1984).
16. In a separate experiment we isolated and characterized pure 3b; however, significant degradation of the amidine moiety was observed during purification.
17. W. C. Still, M. Kahn, and A. Mitra, J. Org. Chem. 43, 2923 (1978).