Discovery of novel and orally active NR2B-selective N-methyl-d-aspartate (NMDA) antagonists, pyridinol derivatives with reduced HERG binding affinity

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 20, 2007, Pages 5533-5536

  Kawai, Makoto ^a   Nakamura, Hiroshi ^a   Sakurada, Isao ^a   Shimokawa, Hirohisa ^a   Tanaka, Hirotaka ^a   Matsumizu, Miyako ^a   Ando, Kazuo ^a   Hattori, Kazunari ^a   Ohta, Atsuko ^a   Nukui, Seiji ^a   Omura, Atsushi ^a   Kawamura, Mitsuhiro ^a  

^a PFIZER INC   (United States)

Author keywords

HERG; NMDA; NR2B; Pain; Solubility

Indexed keywords

DOFETILIDE; N [4 HYDROXY 4 (5 HYDROXYPYRIDIN 2 YL)CYCLOHEXYL] 3 HENYLPROPANAMIDE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; POTASSIUM CHANNEL HERG; PYRIDINOL; UNCLASSIFIED DRUG;

ALLODYNIA; ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; MOUSE; NERVE LIGATION; NONHUMAN; SCIATIC NERVE; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; DRUG DESIGN; ETHER-A-GO-GO POTASSIUM CHANNELS; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; N-METHYLASPARTATE; PYRIDINES; RECEPTORS, N-METHYL-D-ASPARTATE; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34548565588     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.08.039     Document Type: Article

References (17)

1. Parsons C.G., Danysz W., and Quack G. Drug News Perspect. 11 (1998) 523
2. Hughes A.M., Rhodes J., Fisher G., Sellers M., and Growcott J.W. Br. J. Clin. Pharmacol. 53 (2002) 604
3. Knox D.J., McLeod B.J., and Goucke C.R. Anaesthesia Intensive Care 23 (1995) 620
4. Max M.B., Byas-Smith M.G., Gracely R.H., and Bennett G.J. Clin. Neuropharmacol. 18 (1995) 360
5. Ilkjaer S., Dirks J., Brennum J., Wernberg M., and Dahl J.B. Br. J. Anaesthesia 79 (1997) 600
6. McCartney C.J.L., Sinha A., and Katz J. Anesthesia Analgesia (Hagerstown, MD, United States) 98 (2004) 1385
7. Nelson K.A., Park K.M., Robinovitz E., Tsigos C., and Max M.B. Neurology 48 (1997) 1212
8. Chenard B.L., Bordner J., Butler T.W., Chambers L.K., Collins M.A., De Costa D.L., Ducat M.F., Dumont M.L., Fox C.B., et al. J. Med. Chem. 38 (1995) 3138
9. Sang C.N., Jinga L., Wouden J., and Saltarelli M.D. Soc. Neurosci. Abstr. (2003) 814
10. Kawai, M., Bioorg. Med. Chem. Lett., in press.
11. Eiskjaer H., Schmiegelow M., Jespersen B., Tietze I.N., Jensen J.D., Soerensen S.S., Thomsen K., and Pedersen E.B. Eur. J. Clin. Pharmacol. 41 (1991) 547
12. Usuki E., Van Der Schyf C.J., and Castagnoli Jr. N. Drug Metab. Rev. 30 (1998) 809
13. Kornberg B.E., Nikam S.S., Wright J.L., Kesten S.R., Meltzer L.T., Coughenour L., Barr B., Serpa K.A., and McCormick J. Bioorg. Med. Chem. Lett. 14 (2004) 1213
14. Cavalli A., Poluzzi E., De Ponti F., and Recanatini M. J. Med. Chem. 45 (2002) 3844
15. Du L.-P., Tsai K.-C., Li M.-Y., You Q.-D., and Xia L. Bioorg. Med. Chem. Lett. 14 (2004) 4771
16. 3: C, 70.56; H, 7.11; N, 8.23. Found: C, 70.19; H, 7.11; N; 7.99.
17. The method of PSL in mice is described in WO2005035523.