Design, synthesis and structure-activity relationship of novel [3.3.1] bicyclic sulfonamide-pyrazoles as potent γ-secretase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 19, 2011, Pages 5791-5794

  Aubele, Danielle L ^a   Truong, Anh P ^a   Dressen, Darren B ^a   Probst, Gary D ^a   Bowers, Simeon ^a   Mattson, Matthew N ^a   Semko, Chris M ^a   Sun, Minghua ^a   Garofalo, Albert W ^a   Konradi, Andrei W ^a   Sham, Hing L ^a   Zmolek, Wes ^a   Wong, Karina ^a   Goldbach, Erich ^a   Quinn, Kevin P ^a   Sauer, John Michael ^a   Brigham, Elizabeth F ^a   Wallace, William ^a   Nguyen, Lan ^a   Bova, Michael P ^a   Hemphill, Susanna S ^a   Basi, Guriqbal ^a   more..

^a ELAN PHARMACEUTICALS   (United States)

Author keywords

Secretase inhibitor; Alzheimer's disease; Sulfonamide

Indexed keywords

[3.3.31]BICYCLIC SULFONAMIDE PYRAZOLE DERIVATIVE; AMYLOID BETA PROTEIN; GAMMA SECRETASE INHIBITOR; NOTCH RECEPTOR; PYRAZOLE DERIVATIVE; SULFONAMIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; ENANTIOMER; ENZYME ACTIVITY; ENZYME INHIBITION; MOUSE; NONHUMAN; SINGLE DRUG DOSE; STATISTICAL SIGNIFICANCE; STRUCTURE ACTIVITY RELATION;

AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HETEROCYCLIC COMPOUNDS, 3-RING; INHIBITORY CONCENTRATION 50; MICE; MICE, INBRED STRAINS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

MUS;

EID: 80052564943     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.08.008     Document Type: Article

References (18)

1. D.H. Small, and R. Cappai J. Neurochem. 99 2006 708
2. D.J. Selkoe, and D. Schenk Annu. Rev. Pharmacol. Toxicol. 43 2003 545
3. J. Hardy Neuron 52 2006 3
4. J.R. Hodges Brain 129 2006 2811
5. M. Goedert, and M.G. Spillantini Science 314 2006 777
6. A. Lleo Curr. Top. Med. Chem. 8 2008 9
7. F. Radtke, A. Wilson, J.C. Mancini, and H.R. MacDonal Nat. Immunol. 5 2004 247
8. W.R. Gordon, K.L. Arnett, and S.C. Blacklow J. Cell Sci. 121 2008 3109
9. A.F. Kreft, R. Martone, and A. Porte J. Med. Chem. 52 2009 6169
10. M.N. Mattson, M.L. Neitzel, D.A. Quincy, C.M. Semko, A.W. Garofalo, P.S. Keim, A.W. Konradi, M.A. Pleiss, H.L. Sham, E.F. Brigham, E.G. Goldbach, H. Zhang, J.M. Sauer, and G.S. Basi Bioorg. Med. Chem. Lett. 20 2010 2148
11. Aβx-40 quantified by ELISA as described in: B. Zhao, M. Yu, M. Neitzel, J. Marugg, J. Jagodzinski, M. Lee, K. Hu, D. Schenk, T. Yednock, and G. Basi J. Biol. Chem. 283 2008 2927
12. In vitro potency and metabolism assays performed as described in: A.P. Truong, D.L. Aubele, G.D. Probst, M.L. Neitzel, C.M. Semko, S. Bowers, D. Dressen, R.K. Hom, A.W. Konradi, H.L. Sham, A.W. Garofalo, P.S. Keim, J. Wu, M.S. Dappen, K. Wong, E. Goldbach, K.P. Quinn, J.-M. Sauer, E.F. Brigham, W. Wallace, L. Nguyen, S.S. Hemphill, M.P. Bova, and G. Basi Bioorg. Med. Chem. Lett. 19 2009 4920
13. A.-C. Durand, L. Brahmi, M. Lahrech, S. Hacini, and M. Santelli Synth. Commun. 35 2005 1825
14. S. Kotha, E. Manivannan, T. Ganesh, N. Sreenivasachary, and A. Deb Synlett 1999 1618
15. W.H. Rastetter, and D.P. Phillion J. Org. Chem. 46 1981 3204
16. Y.-L. Zhong, and T.K.M. Shing J. Org. Chem. 62 1997 2622
17. R.H. Mach, R.R. Luedtke, C.D. Unsworth, V.A. Boundy, P.A. Nowak, J.G. Scripko, S.T. Elder, J.R. Jackson, P.L. Hoffman, P.H. Evora, A.V. Rao, P.B. Molinoff, S.R. Childers, and R.L. Ehrenkaufer J. Med. Chem. 36 1993 3707
18. X.M. Ye, A.W. Konradi, J. Smith, D.L. Aubele, A.W. Garofalo, J. Marugg, M.L. Neitzel, C.M. Semko, H.L. Sham, M. Sun, A.P. Truong, J. Wu, H. Zhang, E. Goldbach, J.-M. Sauer, E.F. Brigham, M. Bova, and G.S. Basi Bioorg. Med. Chem. Lett. 20 2010 3502