A-ring modifications on the triazafluorenone core structure and their mGluR1 antagonist properties

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 8, 2010, Pages 2474-2477

  Sasikumar, T K ^a   Qiang, Li ^a   Burnett, Duane A ^a   Greenlee, William J ^a   Li, Cheng ^a   Grilli, Mariagrazia ^b   Bertorelli, Rosalia ^b   Lozza, Gianluca ^b   Reggiani, Angelo ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Schering Plough Research Institute   (Italy)

Author keywords

mGluR1 antagonist; Neuropathic pain

Indexed keywords

FLUORENONE DERIVATIVE; HETEROCYCLIC COMPOUND; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR ANTAGONIST;

AREA UNDER THE CURVE; ARTICLE; BIOTRANSFORMATION; CHEMICAL MODIFICATION; DRUG PENETRATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

AZA COMPOUNDS; HUMANS; MOLECULAR STRUCTURE; RECEPTORS, METABOTROPIC GLUTAMATE;

EID: 77950051353     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.03.004     Document Type: Article

References (16)

1. Higgins G.A., and Miczek K.A. Psychopharmacology 179 (2005) 1
2. Kew J.N.C., and Kemp J.A. Psychopharmacology 179 (2005) 4
3. Steckler T., Lavreysen H., Oliveira A.M., Aerts N., Van Craenendonck H., Prickaerts J., Megens A., and Lesage A.S.J. Psychopharmacology 179 (2005) 198
4. Niswender C.M., Jones C.K., and Conn P.J. Curr. Top. Med. Chem. 5 (2005) 847
5. Kunishima N., Shimada Y., Tsuji Y., Sato T., Yamamoto M., Kumasaka T., Nakanishi S., Jingami H., and Morikawa K. Nature 407 (2000) 971
6. Constantino G., Macchiarulo A., and Pellicciari R. Bioorg. Med. Chem. 9 (2001) 847
7. Zheng G.Z., Bhatia P., Daanen J., Kolasa T., Patel M., Latshaw S., Kouhen O.F.E., Chang R., Uchic M.E., Miller L., Nakane M., Lehto S.G., Honore M.P., Moreland R.B., Brioni J.D., and Stewart A.O. J. Med. Chem. 48 (2005) 7374
8. Our efforts in the modification of tricyclic structure is being published in the following patents, WO 2006/002051 and US 2006/167029. Also see: Wu, W.-L.; Burnett, D. A.; Domalski, D.; Greenlee, W. J.; Li, C.; Bertorelli, R.; Fredduzzi, S.; Lozza, G.; Veltri, A.; Reggiani, A. J. Med. Chem. 2007, 50, 5550 (Biology materials and methods were described in this Letter).
9. Owen D.R., Dodd P.G., Gayton S., Greener B.S., Harbottle G.W., Mantell S.J., Maw G.N., Osborne S.A., Rees H., Ringer T.J., Rodriguez-Lens M., and Smith G.F. Bioorg. Med. Chem. Lett. 17 (2007) 486
10. Mantell S.J., Gibson K.R., Osborne S.A., Maw G.N., Rees H., Dodd P.G., Greener B., Harbottle G.W., Million W.A., Poinsard C., England S., Carnell P., Betts A.M., Monhemius R., and Prime R.L. Bioorg. Med. Chem. Lett. 19 (2009) 2190
11. Wang X., Kolasa T., El Kouhen O.F., Chovan L.E., Black-Shaefer C.L., Wagenaar F.L., Garton J.A., Moreland R.B., Honore P., Lau Y.Y., Dandliker P.J., Brioni J.D., and Stewart A.O. Bioorg. Med. Chem. Lett. 17 (2007) 4303
12. Varty G.B., Grilli M., Forlani A., Fredduzzi S., Grzelak M.E., Guthrie D.H., Hodgson R.A., Sherry X.L., Nicolussi E., Pond A.J., Parker E.M., Hunter J.C., Higgins G.A., Reggiani A., and Bertorelli R. Psychopharmacology 179 (2005) 207
13. Khalil Z.H., Yanni A.S., Gaber A.M., and Abdel-Mohsen S.A. Phosphorus, Sulfur Silicon Relat. Elem. 162 (2000) 65
14. Wang Y., and Guziec F.S. J. Org. Chem. 66 (2001) 8293
15. Sasikumar T.K., Qiang L., Burnett D.A., Greenlee W.J., Li C., Heimark L., Pramanik B., Grilli M., Bertorelli R., Lozza G., and Reggiani A. Bioorg. Med. Chem. Lett. 19 (2009) 3199
16. Korfmacher W.A., Cox K.A., Ng K.J., Veals J., Hsien Y., Wainhaus S., Broske L., Prelusky D., Nomeir A., and White R.E. Rapid Commun. Mass Spectrom. 15 (2001) 335