Discovery and SAR of a novel series of 2,4,5,6-tetrahydrocyclopenta[c] pyrazoles as N-type calcium channel inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 24, Issue 9, 2014, Pages 2057-2061

  Winters, Michael P ^a   Subasinghe, Nalin ^a   Wall, Mark ^a   Beck, Edward ^a   Brandt, Michael R ^a   Finley, Michael F A ^a   Liu, Yi ^a   Lubin, Mary Lou ^a   Neeper, Michael P ^a   Qin, Ning ^a   Flores, Christopher M ^a   Sui, Zhihua ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

2 4 5 6 Tetrahydrocyclopenta c pyrazoles; N type calcium channel; Pain; Rat CFA model

Indexed keywords

ANALGESIC AGENT; CACNA1B PROTEIN, RAT; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM CHANNEL N TYPE; PYRAZOLE DERIVATIVE; 2,4,5,6 TETRAHYDROCYCLOPENTA[C]PYRAZOLE DERIVATIVE; CALCITONIN GENE RELATED PEPTIDE; UNCLASSIFIED DRUG;

ANIMAL; CHEMISTRY; LIVER MICROSOME; METABOLISM; PAIN; RAT; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CLICK CHEMISTRY; CONTROLLED STUDY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; IC50; IN VIVO STUDY; INFLAMMATORY PAIN; LIVER MICROSOME METABOLISM; NONHUMAN; NUCLEOTIDE SEQUENCE; STRUCTURE ACTIVITY RELATION; TISSUE DISTRIBUTION; VOLUME OF DISTRIBUTION AT STEADY-STATE;

ANALGESICS; ANIMALS; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS, N-TYPE; MICROSOMES, LIVER; PAIN; PYRAZOLES; RATS;

RATTUS;

EID: 84899120957     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2014.03.063     Document Type: Article

References (23)

1. C. Schroeder, C. Doering, G. Zamponi, and R. Lewis Med. Chem. 2 2006 535
2. K. Elmslie J. Neurosci. Res. 75 2004 733
3. F. Belardetti Future Med. Chem. 2 2010 791
4. S. Lee Curr. Neuropharmacol. 11 2013 606
5. McGivern, J. In Peripheral Receptor Targets for Analgesia: Novel Approaches to Pain Management; Cairns, B., Ed.; John Wiley & Sons, Hoboken, NJ 2009, pp. 111-135.
6. J. McGivern, and S. McDonough Curr. Drug Targets CNS Neurol. Disord. 3 2004 457
7. E. Prommer Drugs Today 42 2006 369
8. G. Miljanich Curr. Med. Chem. 11 2004 3029
9. T. Yamamoto, S. Ohno, S. Niwa, M. Tokumasu, M. Hagihara, H. Koganei, S. Fujita, T. Takeda, Y. Saitou, S. Iwayama, A. Takahara, S. Iwata, and M. Shoji Bioorg. Med. Chem. Lett. 21 2011 3317
10. S. Tyagarajan, P. Chakravarty, M. Park, B. Zhou, J. Herrington, K. Ratliff, R. Bugianesi, B. Williams, R. Haedo, A. Swensen, V. Warren, M. Smith, M. Garcia, G. Kaczorowski, O. McManus, K. Lyons, X. Li, M. Madeira, B. Karanam, M. Green, M. Forrest, C. Abbadie, E. McGowan, S. Mistry, N. Jochnowitz, and J. Duffy Bioorg. Med. Chem. Lett. 21 2011 869
11. T. Yamamoto, and A. Takahara Curr. Top. Med. Chem. 9 2009 377
12. H. Pajouhesh, Z. Feng, L. Zhang, H. Pajouhesh, X. Jiang, A. Hendricson, H. Dong, E. Tringham, Y. Ding, T. Vanderah, F. Porreca, F. Belardetti, G. Zamponi, L. Mitscher, and T. Snutch Bioorg. Med. Chem. Lett. 22 2012 4153
13. X. Beebe, C. Yeung, D. Darczak, S. Shekhar, T. Vortherms, L. Miller, I. Milicic, A. Swensen, C. Zhu, P. Banfor, J. Wetter, K. Marsh, M. Jarvis, V. Scott, M. Schrimpf, and C.-H. Lee Bioorg. Med. Chem. Lett. 23 2013 4857
14. M. Finley, M. Lubin, M. Neeper, E. Beck, Y. Liu, C. Flores, and N. Qin Assay Drug Dev. Technol. 8 2010 685
15. M. Winters, C. Teleha, and Z. Sui Tetrahedron Lett. 55 2014 2150
16. J. Leroy Synth. Comm. 22 1992 567
17. A. Padwa, S. Nahm, and E. Sato J. Org. Chem. 43 1978 1664
18. N. Sakai, T. Moriya, and T. Konakahara J. Org. Chem. 72 2007 5920
19. K. Kim, S. Choi, J. Park, Y. Lee, and J. Kim Tetrahedron: Asymmetry 12 2001 2649
20. M. Winters, N. Subasinghe, M. Wall, E. Beck, M. Brandt, M. Finley, Y. Liu, M. Lubin, M. Neeper, N. Qin, C. Flores, and Z. Sui Bioorg. Med. Chem. Lett. 24 2014 2053
21. C. Mathes, S. Friis, M. Finley, and Y. Liu Comb. Chem. High Thr. Screen. 12 2009 78
22. R. Winquist, J. Pan, and V. Gribkoff Biochem. Pharmacol. 70 2005 489
23. A. Malmberg, H. Gilbert, R. McCabe, and A. Basbaum Pain 101 2003 109 More detail on the CFA model