The design of 8,8-dimethyl[1,6]naphthyridines as potential anticonvulsant agents

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 10, 2003, Pages 1627-1629

  Austin, Nigel E ^a   Hadley, Michael S ^a   Harling, John D ^a   Harrington, Frank P ^a   Macdonald, Gregor J ^a   Mitchell, Darren J ^a   Riley, Graham J ^a   Stean, Tania O ^a   Stemp, Geoffrey ^a   Stratton, Sharon C ^a   Thompson, Mervyn ^a   Upton, Neil ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICONVULSIVE AGENT; N (8,8 DIMETHYL 5,6,7,8 TETRAHYDRO[1,6]NAPHTHYRIDIN 3 YL) 4 METHOXY 3 TRIFLUOROMETHYLBENZAMIDE; NAPHTHYRIDINE DERIVATIVE; SB 270664; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTICONVULSANT ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG IDENTIFICATION; DRUG SYNTHESIS; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

EID: 0037687928     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00288-9     Document Type: Article

References (18)

1. (a) Nicolson A., Leach J.P. CNS Drugs. 15:2001;955
2. (b) Chadwick D. Arch Neurol. 55:1998;1140.
3. Upton N. Trends Pharmacol. Sci. 15:1994;456.
4. Hovinga C.A. Exp. Opin. Invest. Drugs. 11:2002;1387.
5. Upton N., Thompson M. Progress in Medicinal Chemistry, Vol. 37. King F.D., Oxford A.W. 2000;177 Elsevier Science, Oxford.
6. Chan W.N., Hadley M.S., Harling J.D., Herdon H.J., Orlek B.S., Riley G.J., Stead R.E.A., Stean T.O., Thompson M., Upton N., Ward R.W. Bioorg. Med. Chem. 8:2000;2085.
7. Austin, N. E., Jeffrey, P. Unpublished observations.
8. Preliminary results are in: (a) Herdon H., Jerman J., Stean T.O., Chan W., Middlemiss D.N., Upton N. Eur. J. Pharmacol. 314:1996;R7
9. (b) Herdon H.J., Jerman J.C., Stean T.O., Middlemiss D.N., Chan W.N., Vong A.K., Evans J.M., Thompson M., Upton N. Brit. J. Pharmacol. 121:1997;1687.
10. Upton N., Blackburn T.P., Campbell C.A., Cooper D., Evans M.L., Herdon H.J., King P.D., Ray A.M., Stean T.O., Chan W.N., Evans J.M., Thompson M. Brit. J. Pharmacol. 121:1997;1679.
11. Litchfield J.T., Wilcoxon F. J. Pharmacol. Exp. Ther. 96:1949;99.
12. 50>35 μM at 1A2, 2C9, 2C19, 2D6 and 3A4). Intrinsic clearance rates in microsomes were mouse <0.5, rat 1.1, dog <0.5 and human <0.5 mL/min/g liver.
13. De Lean A., Munson P.J., Rodbard D. Am. J. Physiol. 235, E97. 1978.
14. 1H NMR.
15. Harling J.D., Harrington F.P., Thompson M. Synth. Commun. 31:2001;787.
16. Olofson R.A., Martz J.T., Senet J.P., Piteau M., Malfroot M. J. Org. Chem. 49:1984;2081.
17. Takada S., Sasatani T., Chomei N., Adachi M., Fujishita T., Eigyo M., Murata S., Kawasaki K.; Matsushita. J. Med. Chem. 39:1996;2844.
18. +: 378.1 (MH+; 100%); aqueous solubility >1 mg/mL.