Structure-activity relationships of 3-hydroxy-2(1H)-quinolinones as N-methyl-D-aspartate (glycine site) receptor antagonists

Medicinal Chemistry Research

Volumn 6, Issue 9, 1996, Pages 581-592

  Fray, M Jonathan ^a   Bull, David J ^a   Carr, Christopher L ^a   Stobie, Alan ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000815447     PISSN: 10542523     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (32)

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9. 50 = 210 ± 100 nM
10. Leeson, P.D.; Carling, R.W.; Moore, K.W.; Moseley, A.M.; Smith, J.D.; Stevenson, G.; Chan, T.; Baker, R.; Foster, A.C.; Grimwood, S.; Kemp, J.A.; Marshall, G.R.; Hoogsteen, K.; J. Med. Chem., 1992, 35, 1954.
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19. Prepared by the method of ref. 9a in 63% yield from commercially available 3,5-difluoroaniline.
20. CAUTION: The ethyl diazoacetate is added gradually to moderate the rate of nitrogen evolution, and to avoid accumulation of reagent. Since ethyl diazoacetate is explosive, protective shielding around the reaction flask is advised. At the end of the reaction, the crude reaction mixture is poured slowly into excess dilute hydrochloric acid to decompose the excess diazoacetate and precipitate the product.
21. 18 reverse phase, MeOH/0.1% aq. trifluoroacetic acid) was used to show that there was ≤ 5% of 8 present in 3.
22. United States Patent US 3,920,839 (1975).
23. Makosza, M., Synthesis, 1991, 103.
24. Zelle, R.E.; McClellan, W.J.; Tetrahedron Lett., 1991, 32, 2461.
25. Ninomiya, K.; Shioiri, T.; Yamada, S.; Chem. Pharm. Bull., 1974, 22, 1398.
26. Prepared by the method of ref. 9a, using methyl diazoacetate, 4,6-dichloroisatin and zinc chloride. CAUTION: Methyl diazoacetate presents a greater explosion hazard than ethyl diazoacetate, and suitable precautions must be taken during its preparation and use.
27. Kristensen, J.; Lawesson, S.-O. Tetrahedron, 1979, 35, 2075.
28. The free acid was liberated by treatment with HCl and used in the next reaction immediately.
29. Morris, J.J.; Taylor, P.J.; et al. J. Chem. Soc. Perkin Trans II, 1989, 1355.
30. Sybyl Version 6.2, TRIPOS Inc., St. Louis, MO; Spartan SGI Version 4, Wavefunction Inc., Irvine, CA. The molecules were built in Sybyl, and the gridsearch method used to locate the minimum energy conformations. These were AM1 geometry optimised in Spartan. The addition of the dummy atom and the fitting was accomplished in Sybyl.
31. Sybyl Version 6.2, TRIPOS Inc., St. Louis, MO; Spartan SGI Version 4, Wavefunction Inc., Irvine, CA. The molecules were built in Sybyl, and the gridsearch method used to locate the minimum energy conformations. These were AM1 geometry optimised in Spartan. The addition of the dummy atom and the fitting was accomplished in Sybyl.
32. Kemp, J.A.; Marshall, G.R.; Priestley, T.; Mol. Neuropharm. 1991, 1, 65.