PF-04859989 as a template for structure-based drug design: Identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 7, 2013, Pages 1961-1966

  Dounay, Amy B ^a,b   Anderson, Marie ^a   Bechle, Bruce M ^a   Evrard, Edelweiss ^a   Gan, Xinmin ^a   Kim, Ji Young ^a   McAllister, Laura A ^a   Pandit, Jayvardhan ^a   Rong, Suobao ^a   Salafia, Michelle A ^a   Tuttle, Jamison B ^a   Zawadzke, Laura E ^a   Verhoest, Patrick R ^a  

^a PFIZER INC   (United States)

^b Department of Psychology   (United States)

Author keywords

Irreversible inhibitor; Kynurenic acid; Kynurenine aminotransferase; Kynurenine pathway; Lipophilic efficiency; Mechanism based inactivator; Schizophrenia

Indexed keywords

AMINOTRANSFERASE INHIBITOR; KYNURENINE AMINOTRANSFERASE; PF 04859989; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG BINDING; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; LIPOPHILICITY; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSAMINASES;

EID: 84875229571     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2013.02.039     Document Type: Article

References (29)

1. S. Erhardt, L. Schwieler, L. Nilsson, K. Linderholm, and G. Engberg Physiol. Behav. 92 2007 203
2. S. Erhardt, S.K. Olsson, and G. Engberg CNS Drugs 23 2009 91
3. M.C. Potter, G.I. Elmer, R. Bergeron, E. Albuquerque, P. Guidetti, H.-Q. Wu, and R. Schwarcz Neuropsychopharmacology 35 2010 1734
4. C. Hilmas, E.F. Pereira, M. Alkondon, A. Rassoulpour, R. Schwarcz, and E.X. Albuquerque J. Neurosci. 21 2001 7463
5. M. Kessler, T. Terramani, G. Lynch, and M. Baudry J. Neurochem. 52 1989 1319
6. B.C. Natale, I.A. Murray, J.C. Schroeder, C.A. Flaveny, T.S. Lahoti, E.M. Laurenzana, C.J. Omiecinski, and G.H. Perdew Toxicol. Sci. 115 2010 89
7. S. Erhardt, K. Blennow, C. Nordin, E. Skogh, L.H. Lindstrom, and G. Engberg Neurosci. Lett. 313 2001 96
8. L.K. Nilsson, K.R. Linderholm, G. Engberg, L. Paulson, K. Blennow, L.H. Lindstrom, C. Nordin, A. Karanti, P. Persson, and S. Erhardt Schizophr. Res. 80 2005 315
9. S.K. Olsson, M. Samuelsson, P. Saetre, L. Lindstrom, E.G. Jonsson, C. Nordin, G. Engberg, S. Erhardt, and M. Landen J. Psychiatry Neurosci. 35 2010 195
10. R. Schwarcz, A. Rassoulpour, H.-Q. Wu, D. Medoff, C.A. Tamminga, and R.C. Roberts Biol. Psychiatry 50 2001 521
11. Q. Han, T. Cai, D.A. Tagle, and J. Li Cell. Mol. Life Sci. 67 2010 353
12. F. Rossi, S. Garavaglia, V. Montalbano, M.A. Walsh, and M. Rizzi J. Biol. Chem. 283 2008 3559
13. F. Rossi, C. Valentina, S. Garavaglia, K.V. Sathyasaikumar, R. Schwarz, S. Kojima, K. Okuwaki, S. Ono, Y. Kajii, and M. Rizzi J. Med. Chem. 53 2010 5684
14. R. Pellicciari, R.C. Rizzo, G. Costantino, M. Marinozzi, L. Amori, P. Guidetti, H.-Q. Wu, and R. Schwarcz ChemMedChem 1 2006 528
15. A.B. Dounay, M. Anderson, B.M. Bechle, B.M. Campbell, M.M. Claffey, A. Evdokimov, E. Evrard, K.R. Fonseca, X. Gan, S. Ghosh, M.M. Hayward, W. Horner, J.-Y. Kim, L.A. McAllister, J. Pandit, V. Paradis, V.D. Parikh, M.R. Reese, S. Rong, M.A. Salafia, K. Schuyten, C.A. Strick, J.B. Tuttle, J. Valentine, H. Wang, L.E. Zawadzke, and P.R. Verhoest ACS Med. Chem. Lett. 3 2012 187
16. J.B. Tuttle, M. Anderson, B.M. Bechle, B.M. Campbell, C. Chang, A.B. Dounay, E. Evrard, K.R. Fonseca, X. Gan, S. Ghosh, W. Horner, L.C. James, J.-Y. Kim, L.A. McAllister, J. Pandit, V.D. Parikh, B.J. Rago, M.A. Salafia, C.A. Strick, L.E. Zawadzke, and P.R. Verhoest ACS Med. Chem. Lett. 4 2013 37
17. For X-ray structure of 2 bound to KAT II, see Ref. 16.
18. Full experimental details are contained within the following patent application: Dounay, A. B.; McAllister, L. A.; Parikh, V. D.; Rong, S.; Verhoest, P. R. PCT Int. Appl. 2012, WO 2012073143.
19. E.J. Corey, M.C. Noe, and F. Xu Tetrahedron Lett. 39 1998 5347
20. L.A. McAllister, B.M. Bechle, A.B. Dounay, E. Evrard, X. Gan, S. Ghosh, J.-Y. Kim, V.D. Parikh, J.B. Tuttle, and P.R. Verhoest J. Org. Chem. 76 2011 3484
21. The ester activation step was necessary to prevent over-reduction to a lactam by-product under the reductive cyclization conditions.
22. Y. Xia, S. Chackalamannil, M. Czarniecki, H. Tsai, H. Vaccaro, R. Cleven, J. Cook, A. Fawzi, R. Watkins, and H. Zhang J. Med. Chem. 40 1997 4372
23. T.T. Wager, A. Villalobos, P.R. Verhoest, X. Hou, and C.L. Shaffer Expert Opin. Drug Discov. 6 2011 371
24. Prepared in analogy to compound 18, starting from 3-methyl-5- (trifluoromethyl)-1H-pyrazole as described by Acker, B. A.; Hughes, R. O.; Jacobsen, E. J.; Lu, H.-F.; Rogers, T. E.; Tollefson, M. B.; Walker, J. K. PCT Int. Appl. 2006, WO 2006046135.
25. Prepared from methyl 1-benzyl-4-nitro-1H-pyrazole-5-carboxylate using the general methods described in Schemes 1 and 2. Commercially available 4-nitro-1H-pyrazole-3-carboxylic acid was converted to 1-benzyl-4-nitro-1H- pyrazole-5-carboxylate over two steps.
26. Pyrazole 21 was prepared following the general route shown in Scheme 1. In this case, arylation of methyl 4-nitro-1H-pyrazole-3-carboxylate followed by ester hydrolysis provides 4-nitro-1-phenyl-1H-pyrazole-3-carboxylic acid, following the method of Miller, T. A. Sloman, D. L.; Stanton, M. G.; Wilson, K. J.; Witter, D. J. PCT Int. Appl. 2007, WO 2007087129. Subsequent conversion of the carboxylic acid moiety to a primary bromide may be effected as described in Scheme 1. The resulting 3-(bromomethyl)-4-nitro-1-phenyl-1H-pyrazole was converted to 3-(4-nitro-1-phenyl-1H-pyrazol-3-yl)alanine using chemistry reported by F. Crestey, V. Collot, S. Stiebing, and S. Rault Tetrahedron 62 2006 7772
27. For a description of the use of SF log D and other ADME data sets in a prospective manner, see C.E. Keefer, G. Chang, and G.W. Kauffman Bioorg. Med. Chem. 19 2011 3739
28. M.P. Edwards, and D.A. Price Annu. Rep. Med. Chem. 45 2010 381
29. C.E. Hop, M.J. Cole, R.E. Davidson, D.B. Duignan, J. Federico, J.S. Janiszewski, K. Jenkins, S. Krueger, R. Lebowitz, T.E. Liston, W. Mitchell, M. Snyder, S.J. Steyn, J.R. Soglia, C. Taylor, M.D. Troutman, J. Umland, M. West, K.M. Whalen, V. Zelesky, and S.X. Zhao Curr. Drug Metab. 9 2008 847