Preliminary SAR studies on non-apamin-displacing 4-(aminomethylaryl)pyrrazolopyrimidine KCa channel blockers

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 20, 2008, Pages 5694-5697

  Gentles, Robert G ^a   Hu, Shuanghua ^a   Huang, Yazhong ^a   Grant Young, Katherine ^a   Poss, Michael A ^a   Andres, Charles ^a   Fiedler, Tracey ^a   Knox, Ronald ^a   Lodge, Nicholas ^a   Weaver, C David ^a   Harden, David G ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Apamin; Non apamin displacing; Pyrrazolopyrimidine; Small conductance potassium channel

Indexed keywords

4 (AMINOMETHYLARYL)PYRRAZOLOPYRIMIDINE; 5 CHLORO N (THIOPHEN 2 YLMETHYL)PYRAZOLO[1,5 A]PYRIMIDINE 7 AMINE; APAMIN; POTASSIUM CHANNEL BLOCKING AGENT; PYRIMIDINE DERIVATIVE; SMALL CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL; SMALL CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL BLOCKING AGENT; THALLIUM; UNCLASSIFIED DRUG;

ARTICLE; BINDING COMPETITION; DRUG ACTIVITY; DRUG POTENCY; DRUG SELECTIVITY; ELECTROPHORESIS; HUMAN; HUMAN CELL; NERVE CELL EXCITABILITY; POTASSIUM TRANSPORT; REACTION OPTIMIZATION; STRUCTURE ACTIVITY RELATION; WHOLE CELL ELECTROPHYSIOLOGY ASSAY;

APAMIN; BINDING, COMPETITIVE; CELL LINE; ELECTROPHYSIOLOGY; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; POTASSIUM CHANNEL BLOCKERS; POTASSIUM CHANNELS, CALCIUM-ACTIVATED; PROTEIN ISOFORMS; PYRAZOLES; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP; THALLIUM;

EID: 53349162200     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.08.026     Document Type: Article

References (35)

1. Kohler M., Hirschberg B., Bond C.T., Kinzie J.M., Marrion N.V., Maylie J., and Adelman J.P. Science 273 (1996) 1709
2. Keen J.E., Khawaled R., Farrens D.L., Neelands T., Rivard A., Bond C.T., Janowsky A., Fakler B., Adelman J.P., and Maylie J. J. Neurosci. 19 (1999) 8830
3. Schumacher M.A., Rivard A.F., Bichinger H.P., and Adelman J.P. Nature 410 (2001) 1120
4. Wissmann R., Bildl W., Neumann H., Rivard A.F., Klocker N., Weitz D., Schulte U., Adelman J.P., Bentrop D., and Fakler B. J. Biol. Chem. 277 (2002) 4558
5. Xia X.M., Fakler B., Rivard A., Wayman G., Johnson-Pais T., Keen J.E., Ishii T., Hirschberg B., Bond C.T., Lutsenko S., Maylie J., and Adelman J.P. Nature 395 (1998) 503
6. Zhang B.-M., Kohli V., Adachi R., Lopez J.A., Udden M.M., and Sullivan R. Biochemistry 40 (2001) 3189
7. Pedarzani P., Kulik A., Muller M., Ballanyi K., and Stocker M. J. Physiol. 527 (2000) 283
8. Storm J.F. J. Physiol. 409 (1989) 171
9. Stocker M., and Pedarzani P. Mol. Cell. Neurosci. 15 (2000) 476
10. Wolfart J., Neuhoff H., Franz O., and Roeper J. J. Neurosci. 21 (2001) 3443
11. Hosseini R., Benton D.C.H., Dunn P.M., Jenkinson D.H., and Moss G.W.J. J. Physiol. 535 (2001) 323
12. Tacconi S., Carletti R., Bunnemann B., Plumpton C., Pich E.M., and Terstappen G.C. Neuroscience 102 (2001) 209
13. Blank T., Nijholt I., Kye M.-J., and Spiess J. Curr. Drug Targets CNS Neurol. Disord. 3 (2004) 161
14. Waroux O., Massotte L., Alleva L., Graulich A., Thomas E., Liegeois J.-F., Scuvee-Moreau J., and Seutin V. Eur. J. Neurosci. 22 (2005) 3111
15. Dror V., Shamir E., Ghanshani S., Kimhi R., Swartz M., Barak Y., Weizman R., Avivi L., Litmanovitch T., Fantino E., Kalman K., Jones E.G., Chandy K.G., Gargus J.J., Gutman G.A., and Navon R. Mol. Psychiatry 4 (1999) 254
16. Dilly S., Graulich A., Farce A., Seutin V., Liegeois J.-F., and Chavatte P. J. Enzyme Inhib. Med. Chem. 20 (2005) 517
17. Poorheidari G., Stanhope K.J., and Pratt J.A. Psychopharmacology 135 (1998) 242
18. Wulff H., Kolski-Andreaco A., Sankaranarayanan A., Sabatier J.-M., and Shakkottai V. Curr. Med. Chem. 14 (2007) 1437
19. Seutin V., and Liegeois J.F. Br. J. Pharmacol. 151 (2007) 568
20. Turner S.C., and Shieh C.-C. Methods Princ. Med. Chem 29 (2006) 310
21. Schohe-Loop, R.; Seidel, P.-R.; Bullock, W.; Feurer, A.; Terstappen, G.; Schuhmacher, J.; Vander Staay, F.-J.; Schmidt, B.; Fanelli, R. J.; Chisholm, J. C.; McCarthy, R.T. Application US Patent 96-738123 5866562, 1999, 14 p.
22. Graulich A., Dilly S., Farce A., Scuvee-Moreau J., Waroux O., Lamy C., Chavatte P., Seutin V., and Liegeois J.-F. J. Med. Chem. 50 (2007) 5070
23. Graulich, A.; Liegeois, J.-F.; Moreau, J.; Seutin, V. Application: No Patent 2007-EP52029 2007107442, 2007, 59 pp.
24. Graulich A., Mercier F., Scuvee-Moreau J., Seutin V., and Liegeois J.F. Bioorg. Med. Chem. 13 (2005) 1201
25. Scuvee-Moreau J., Boland A., Graulich A., Van Overmeire L., D'Hoedt D., Graulich-Lorge F., Thomas E., Abras A., Stocker M., Liegeois J.-F., and Seutin V. Br. J. Pharmacol. 143 (2004) 753
26. Scuvee-Moreau J., Liegeois J.-F., Massotte L., and Seutin V.J. Pharmacol. Exp. Ther. 302 (2002) 1176
27. Gentles, et al. Bioorg. Med. Chem. Lett. 18 (2008) 5316
28. Stroebaek D., Hougaard C., Johansen T.H., Soerensen U.S., Nielsen E.O., Nielsen K.S., Taylor R.D.T., Pedarzani P., and Christophersen P. Mol. Pharmacol. 70 (2006) 1771
29. Williamson D.S., Parratt M.J., Bower J.F., Moore J.D., Richardson C.M., Dokurno P., Cansfield A.D., Francis G.L., Hebdon R.J., Howes R., Jackson P.S., Lockie A.M., Murray J.B., Nunns C.L., Powles J., Robertson A., Surgenor A.E., and Torrance C. J. Bioorg. Med. Chem. Lett. 15 (2005) 863
30. Robins R.K., Revankar G.R., O'Brien D.E., Springer R.H., Novinson T., Albert A., Senga K., Miller J.P., and Streeter D.G. J. Heterocycl. Chem. 22 (1985) 601
31. Huppatz J.L. Aust. J. Chem. 38 (1985) 221
32. Weaver C.D., Harden D., Dworetzky S.I., Robertson B., and Knox R.J. J. Biomol. Screening 9 (2004) 671
33. Lecomte C., Ferrat G., Fajloun Z., Van Rietschoten J., Rochat H., Martin-Eauclaire M.F., Darbon H., and Sabatier J.M. J. Pept. Res. 54 (1999) 369
34. Hugues M., Romey G., Duval D., Vincent J.P., and Lazdunski M. Proc. Natl. Acad. Sci. U.S.A. 79 (1982) 1308
35. 50 determination was observed to be within one 1/2 log unit as seen with the standard deviations reported.