Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 4, 2010, Pages 1378-1383

  Pajouhesh, Hassan ^a   Feng, Zhong Ping ^a,b   Ding, Yanbing ^a   Zhang, Lingyun ^a   Pajouhesh, Hossein ^a   Morrison, Jerrie Lynn ^a   Belardetti, Francesco ^a   Tringham, Elizabeth ^a   Simonson, Eric ^a   Vanderah, Todd W ^c   Porreca, Frank ^c   Zamponi, Gerald W ^b   Mitscher, Lester A ^d   Snutch, Terrance P ^e  

^a Neuromed Pharmaceuticals   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

^c UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^d UNIVERSITY OF KANSAS   (United States)

^e UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Calcium channel; Diphenylpiperazine; L type; N type; Pain

Indexed keywords

[1 (4 BENZHYDRYLPIPERAZIN 1 YL) 3,3 DIPHENYLPROPAN 1 ONE]; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM CHANNEL L TYPE; CALCIUM CHANNEL N TYPE; NP 118809; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CALCIUM TRANSPORT; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG STRUCTURE; NERVE LIGATION; NEUROPATHIC PAIN; NONHUMAN; PAIN ASSESSMENT; PATCH CLAMP; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANALGESICS; ANIMALS; BENZHYDRYL COMPOUNDS; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS, N-TYPE; HUMANS; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; PIPERAZINES; RATS; RATS, SPRAGUE-DAWLEY; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; WATER;

EID: 75449116697     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.008     Document Type: Article

References (38)

1. Maggi C.A., Giuliani S., Santicioli P., Tramontana M., and Meli A. Neuroscience 34 (1990) 243
2. Dubel S.J., Starr T.V.B., Hell J., Ahlijanian M.K., Enyeart J.J., Catterall W.A., and Snutch T.P. Proc. Natl. Acad. Sci. U.S.A. 89 (1992) 5058
3. Westenbroek R.E., Hell J.W., Warner C., Dubel S.J., Snutch T.P., and Catterall W.A. Neuron 9 (1992) 1099
4. Santicioli P., Del Biaanco E., Tramontana M., Geppetti P., and Maggi C.A. Neurosci. Lett. 136 (1992) 161
5. Dunlap K., Luebke J.I., and Turner T.J. Trends Neurosci. 18 (1995) 89
6. Evans A.R., Nicol G.D., and Vasko M.R. Brain Res. 712 (1996) 265
7. Bourinet E., Soong T.-W., Stea A., and Snutch T.P. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 1486
8. Patil P.G., de Leon M., Reed R.R., Dubel S.J., Snutch T.P., and Yue D.T. Biophys. J. 71 (1996) 2509
9. Zamponi G.W., Bourinet E., Nelson D., Nargeot J., and Snutch T.P. Nature 385 (1997) 442
10. Zamponi G.W., and Snutch T.P. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 4035
11. Kerr L.M., Filloux F., Olivera B.M., Jackson H., and Wamsley J.K. Eur. J. Pharmacol. 146 (1998) 181
12. Vanegas H., and Schaible H.-G. Pain 85 (2000) 9
13. Wang Y.-X., Pettus M., Gao D., Phillips C., and Bowersox S.S. Pain 84 (2000) 151
14. Staats P.S., Yearwood T., Charapata S.G., Presley R.W., Wallace M.S., Byas-Smith M., Fisher R., Bryce D., Mangieri E.A., Luther R.R., Mayo M., McGuire D., and Ellis D. J. Am. Med. Assoc. 291 (2004) 63
15. Jain K.K. Expert Opin. Invest. Drugs 9 (2000) 2403
16. Bowersox S., Tich N., Mayo M., and Luther R. Drugs Future 23 (1998) 152
17. Snutch T.P. NeuroRx 2 (2005) 662
18. Hu L.-Y., Ryder T.R., Rafferty M.F., Cody W.L., Lotarski S.M., Miljanich G.P., Millerman E., Rock D.M., Song Y., Stoehr S.J., Taylor C.P., Weber M.L., Szoke B.G., and Vartanian M.G. Bioorg. Med. Chem. Lett. 9 (1999) 907
19. Hu L.-Y., Ryder T.R., Nikam S.S., Millerman E., Szoke B.G., and Rafferty M.F. Bioorg. Med. Chem. Lett. 9 (1999) 1121
20. Knutsen L.J., Hobbs C.J., Earnshaw C.G., Fiumana A., Gilbert J., Mellor S.L., Radford F., Smith N.J., Birch P.J., Ward S.D., Russell Burley J., and James I.F. Bioorg. Med. Chem. Lett. 17 (2007) 662
21. Yamamoto T., Niwa S., Iwayama S., Koganei H., Fujita S., Takeda T., Kito M., Ono Y., Saitou Y., Takahara A., Iwata S., Yamamoto H., and Shoji M. Bioorg. Med. Chem. Lett. 14 (2006) 5333
22. Zamponi G.E., Feng Z.P., Zhang L., Pajouhesh H., Ding Y., Belardetti F., Pajouhesh H., Dolphin D., Mitscher L.A., and Snutch T.P. Bioorg. Med. Chem. Lett. 19 (2009) 6467
23. Jarugu Narasimha M., and Subhas S. J. Org. Chem. 75 (2007) 9786
24. Tan E.S., Miyakawa M., Bunzow J.R., Grandy D.K., and Scanlan T.S. J. Med. Chem. 50 (2007) 2787
25. Denegri B., and Kronja O. J. Org. Chem. 72 (2007) 8427
26. Pajouhesh, H.; Snutch, T. P.; Zamponi, G. W.; Pajouhesh, H., Belardetti, F. U.S. Patent 6951,862, 2007.
27. Pajouhesh, H.; Snutch, T. P.; Zamponi, G. W.; Pajouhesh, H., Belardetti, F. U.S. Patent 2004/0147529, 2004.
28. Pajouhesh, H.; Snutch, T. P.; Pajouhesh, H., Ding, Y. U.S. Patent, U.S. 2006/0063775, 2006.
29. Pajouhesh, H.; Snutch, T. P.; Ding, Y.; Pajouhesh, H. WO 2005/097779 A1, 20 Oct. 2005.
30. Pajouhesh, H.; Snutch, T. P.; Ding, Y.; Pajouhesh, H. WO 2006/024160 A1, 9, March 2006.
31. Bourinet E., Soong T.-W., Sutton K., Slaymaker S., Mathews E., Monteil A., Zamponi G.W., Nargeot J., and Snutch T.P. Nat. Neurosci. 2 (1999) 407
32. Snutch T.P., Tomlinson W.J., Leonard J.P., and Gilbert M.M. Neuron 7 (1991) 45
33. 50 via a single concentration point may be slightly less accurate than fits to entire concentration-dependent response curves.
34. 50 values reflect blockade of channels in the partially inactivated state. In comparison, data obtained from the L-type channel whole-cell patch clamp analyses reflects open/closed state blockade. Selectivity ratios as stated in the text derive from direct comparison of N-type and L-type whole-cell patch clamp data.
35. Orjales A., Mosquera R., Toledo A., Pumar M.C., Garcia N., Cortizo L., and Labeaga L. J. Med. Chem. 46 (2003) 5512
36. Strupczewski J.T., Allen R.C., Gardner B.A., Schmid B.L., Stache U., Glamkowski E., Jones M.C., Ellis D.B., Huger F.P., and Dunn R.W. J. Med. Chem. 28 (1985) 761
37. 6 spinal nerves were not ligated. Thermal hyperalgesia was assessed by the method of Hargreaves and colleagues (Hargreaves, K.; Dubner, R.; Brown, F.; Flores, C.; Joris, J. Pain 1988, 32, 77.) and mechanical hypersensitivity was determined by measuring the paw withdrawal threshold in response to probing with von Frey filaments (Ossipov, M. H.; Lopez, Y.; Nichols, M. L.; Bian, D.; Porreca, F. Neurosci. Lett. 1995, 199, 87.). After baseline assessment compound or vehicle were administered by the oral route (30 mg/kg in 3 ml/kg propylene glycol) and behavioral assessments performed at 30 min intervals post-administration. The percentage activity and the difference between the contralateral and ipsilateral paws were assessed by ANOVA-post-hoc for statistic calculation. The following formula was used to calculate the % anti-allodynic activity: 100% × [(paw withdrawal thresholds after drug treatment - postSNL baseline paw withdrawal thresholds)/(preSNL baseline paw withdrawal thresholds - postSNL baseline paw withdrawal thresholds). The following formula was used to calculate the % anti-hyperalgesic activity: 100% × [(paw withdrawal latencies after drug treatment - postSNL baseline paw withdrawal latencies)/(preSNL baseline paw withdrawal latencies - postSNL baseline paw withdrawal latencies). All surgeries and behavioral testing were performed in accordance with the policies and recommendations of the International Association for the Study of Pain and the National Institutes of Health guidelines for the handling and use of laboratory animal and were approved by the Animal Care and Use Committee of the University of Arizona.
38. Test No. 105: Water Solubility, Organization for Economic Co-Operation and Development (OECD) Guidelines for the Testing of Chemicals, Section 1: Physical and Chemical Properties, 1995.