N-Acyl-N′-arylpiperazines as negative allosteric modulators of mGlu1: Identification of VU0469650, a potent and selective tool compound with CNS exposure in rats

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 13, 2013, Pages 3713-3718

  Lovell, Kimberly M ^a   Felts, Andrew S ^a   Rodriguez, Alice L ^a   Venable, Daryl F ^a   Cho, Hyekyung P ^a   Morrison, Ryan D ^a   Byers, Frank W ^a   Daniels, J Scott ^a   Niswender, Colleen M ^a   Conn, P Jeffrey ^a   Lindsley, Craig W ^a,b   Emmitte, Kyle A ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY   (United States)

Author keywords

Allosteric modulator; CNS; Glutamate; GPCR mGlu1; Piperazine

Indexed keywords

METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR AGONIST; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG; VU 0469650; YM 298198;

ALLOSTERISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING KINETICS; CALCIUM MOBILIZATION; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; ENANTIOMER; LIPOPHILICITY; NONHUMAN; NUCLEOPHILICITY; PROTEIN TARGETING; RAT; STRUCTURE ACTIVITY RELATION;

ALLOSTERIC REGULATION; ANIMALS; CENTRAL NERVOUS SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; MOLECULAR STRUCTURE; PIPERAZINES; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS;

EID: 84878859327     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2013.05.020     Document Type: Article

References (42)

1. D.D. Schoepp, D.E. Jane, and J.A. Monn Neuropharmacology 38 1999 1431
2. P.J. Conn, and J.-P. Pin Annu. Rev. Pharmacol. Toxicol. 37 1997 205
3. B.J. Melancon, C.R. Hopkins, M.R. Wood, K.A. Emmitte, C.M. Niswender, A. Christopoulos, P.J. Conn, and C.W. Lindsley J. Med. Chem. 55 2012 1445
4. P.J. Conn, A. Christopolous, and C.W. Lindsley Nat. Rev. Drug Disc. 8 2009 41
5. T.M. Bridges, and C.W. Lindsley ACS Chem. Biol. 3 2008 530
6. A. Ritzén, J.M. Mathiesen, and C. Thomsen Basic Clin. Pharmacol. Toxicol. 97 2005 202
7. J.N.C. Kew Pharmacol. Ther. 104 2004 233
8. D.R. Owen ACS Chem. Neurosci. 2 2011 394
9. A. Lesage, and T. Steckler Eur. J. Pharmacol. 639 2010 2
10. J.H. Kotlinska, M. Bochenski, and W. Danysz Eur. J. Pharmacol. 670 2011 154
11. O.A. Dravolina, E.S. Zakharova, E.V. Shekunova, E.E. Zvartau, W. Danysz, and A.Y. Bespalov Neuropharmacology 52 2007 263
12. A. Satow, S. Maehara, S. Ise, H. Hikichi, M. Fukushima, G. Suzuki, T. Kimura, T. Tanaka, S. Ito, H. Kawamoto, and H. Ohta J. Pharmacol. Exp. Ther. 326 2008 577
13. L.M. Rorick-Kehn, J.C. Hart, and D.L. McKinzie Psychopharmacology 183 2005 226
14. H.A. Shannon, S.C. Peters, and A.E. Kingston Neuropharmacology 49 2005 188
15. M.E. Barton, S.C. Peters, and H.E. Shannon Epilepsy Res. 56 2003 17
16. C.E. Bennett, D.A. Burnett, W.J. Greenlee, C.E. Knutson, P. Korakas, C. Li, D. Tulshian, W.-L. Wu, R. Bertorelli, S. Fredduzzi, M. Grilli, G. Lozza, A. Reggiani, and A. Veltri Bioorg. Med. Chem. Lett. 22 2012 1575
17. T.K. Sasikumar, L. Qiang, D.A. Burnett, W.J. Greenlee, C. Li, L. Heimark, B. Pramanik, M. Grilli, R. Bertorelli, G. Lozza, and A. Reggiani Bioorg. Med. Chem. Lett. 19 2009 3199
18. W.-L. Wu, D.A. Burnett, M. Domalski, W.J. Greenlee, C. Li, R. Bertorelli, S. Fredduzzi, G. Lozza, A. Veltri, and A. Reggiani J. Med. Chem. 50 2007 5550
19. G.B. Varty, M. Grilli, A. Forlani, S. Fredduzzi, M.E. Grzelak, D.H. Guthrie, R.A. Hodgson, S.X. Lu, E. Nicolussi, A.J. Pond, E.M. Parker, J.C. Hunter, G.A. Higgins, A. Reggiani, and R. Bertorelli Psychopharmacology 179 2005 207
20. H. Hikichi, M. Nishino, M. Fukushima, A. Satow, S. Maehara, H. Kawamoto, and H. Ohta Eur. J. Pharmacol. 639 2010 99
21. T. Steckler, H. Lavreysen, A.M. Oliveira, N. Aerts, H. Van Craenendonck, J. Prickaerts, A. Megens, and A.S.J. Lesage Psychopharmacology 179 2005 198
22. X. Xie, D.R. Ramirez, H.C. Lasseter, and R.A. Fuchs Psychopharmacology 208 2010 1
23. C. Achat-Mendes, D.M. Platt, and R.D. Spealman J. Pharmacol. Exp. Ther. 343 2013 214
24. G.Z. Zheng, P. Bhatia, T. Kolasa, M. Patel, O.F. El Kouhen, R. Chang, M.E. Uchic, L. Miller, S. Baker, S.G. Lehto, P. Honore, J.M. Wetter, K.C. Marsh, R.B. Moreland, J.D. Brioni, and A.O. Stewart Bioorg. Med. Chem. Lett. 16 2006 4936
25. C.Z. Zhu, S. Baker, O. El-Kouhen, S. Lehto, P.R. Hollingsworth, D.M. Gauvin, G. Hernandez, G.Z. Zheng, R. Chang, R.B. Moreland, A.O. Stewart, J.D. Brioni, and P. Honore Eur. J. Pharmacol. 580 2008 314
26. S.J. Mantell, K.R. Gibson, S.A. Osborne, G.N. Maw, H. Rees, P.G. Dodd, B. Greener, G.W. Harbottle, W.A. Million, C. Poinsard, S. England, P. Carnell, A.M. Betts, R. Monhemius, and R.L. Prime Bioorg. Med. Chem. Lett. 19 2009 2190
27. A. Kohara, T. Toya, S. Tamura, T. Watabiki, Y. Nagakura, Y. Shitaka, S. Hayashibe, S. Kawabata, and M. Okada J. Pharmacol. Exp. Ther. 315 2005 163
28. A. Satoh, Y. Nagatomi, Y. Hirata, S. Ito, G. Suzuki, T. Kimura, S. Maehara, H. Hikichi, A. Satow, M. Hata, H. Ohta, and H. Kawamoto Bioorg. Med. Chem. Lett. 19 2009 5464
29. S. Ito, Y. Hirata, Y. Nagatomi, A. Satoh, G. Suzuki, T. Kimura, A. Satow, S. Maehara, H. Hikichi, M. Hata, H. Ohta, and H. Kawamoto Bioorg. Med. Chem. Lett. 19 2009 5310
30. J.J. Martino, B.A. Wall, E. Mastrantoni, B.J. Wilimczyk, S.N. La Cava, K. Degenhardt, E. White, and S. Chen Oncogene 2012 10.1038/onc.2012.471 advance online publication
31. Y. Ohtani, T. Harada, Y. Funasaka, K. Nakao, C. Takahara, M. Abdel-Daim, N. Sakai, N. Saito, C. Nishigori, and A. Aiba Oncogene 27 2008 7162
32. J. Namkoong, S.-S. Shin, H.J. Lee, Y.E. Marín, B.A. Wall, J.S. Goydos, and S. Chen Cancer Res. 67 2007 2298
33. C.L. Speyer, J.S. Smith, M. Banda, J.A. DeVries, T. Mekani, and D.H. Gorski Breast Cancer Res. Treat. 132 2012 565
34. A.L. Rodriguez, R. Williams, Y. Zhou, S.R. Lindsley, U. Le, M.D. Grier, C.D. Weaver, P.J. Conn, and C.W. Lindsley Bioorg. Med. Chem. Lett. 19 2009 3209
35. D.S. Surry, and S.L. Buchwald Angew. Chem., Int. Ed. 47 2008 6338
36. B. Schlummer, and U. Scholz Adv. Synth. Catal. 346 2004 1599
37. 80 concentration of agonist was added and readings taken for an additional 40 s. Allosteric modulation by the compounds was measured by comparing the amplitude of the responses at the time of glutamate addition plus and minus test compound. For a more detailed description of the assay, see S. Sharma, A.L. Rodriguez, P.J. Conn, and C.W. Lindsley Bioorg. Med. Chem. Lett. 18 2008 4098
38. H. Gunosewoyo, J.L. Guo, M.R. Bennett, M.J. Coster, and M. Kassiou Bioorg. Med. Chem. Lett. 18 2008 3720
39. P.D. Leeson, and B. Springthorpe Nat. Rev. Drug Disc. 6 2007 881
40. Binding to rat plasma proteins and brain homogenates were measured using equilibrium dialysis according to methods similar to those described in J.C. Kalvass, and T.S. Maurer Biopharm. Drug Dispos. 23 2002 327
41. mGlu selectivity assays are described in M.J. Noetzel, J.M. Rook, P.N. Vinson, H. Cho, E. Days, Y. Zhou, A.L. Rodriguez, H. Lavreysen, S.R. Stauffer, C.M. Niswender, Z. Xiang, J.S. Daniels, C.W. Lindsley, C.D. Weaver, and P.J. Conn Mol. Pharmacol. 81 2012 120
42. LeadProfilingScreen®, Eurofins Panlabs, Inc. http://www. eurofinspanlabs.com.