Design and synthesis of statine-containing BACE inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 24, 2003, Pages 4335-4339

  Hu, Jingdan ^a   Cwi, Cynthia L ^a   Smiley, David L ^a   Timm, David ^a   Erickson, Jon A ^a   McGee, James E ^a   Yang, Hsiu Chiung ^a   Mendel, David ^a   May, Patrick C ^a   Shapiro, Mike ^a   McCarthy, James R ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARAGINYLSTATINE VALYLALANYLGLUTAMINYLPHENYLALANINE; BETA SECRETASE INHIBITOR; ENZYME INHIBITOR; GLUTAMINYLVALYLALANYLSTATINE VALYLALANYLGLUTAMINYLPHENYLALANINE; GLUTAMINYLVALYLASPARAGINYLSTATINE; GLUTAMINYLVALYLASPARAGINYLSTATINE VALINE; GLUTAMINYLVALYLASPARAGINYLSTATINE VALYLALANINE; GLUTAMINYLVALYLASPARAGINYLSTATINE VALYLALANYLGLUTAMIC ACID; GLUTAMINYLVALYLASPARAGINYLSTATINE VALYLALANYLGLUTAMINYLPHENYLALANINE; GLUTAMINYLVALYLMETHIONYLSTATINE ISOLEUCYLALANYLGLUTAMINYLPHENYLALANINE; GLUTAMINYLVALYLMETHIONYLSTATINE LEUCYLALANYLGLUTAMINYLPHENYLALANINE; GLUTAMINYLVALYLMETHIONYLSTATINE VALYLALANYLGLUTAMINYLPHENYLALANINE; HEPTAPEPTIDE; STATINE; UNCLASSIFIED DRUG; VALYLASPARAGINYLSTATINE VALYLALANYLGLUTAMINYLPHENYLALANINE;

AMINO TERMINAL SEQUENCE; ARTICLE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; MATHEMATICAL COMPUTING; PHASE TRANSITION; SOLID; STRUCTURE ACTIVITY RELATION; X RAY ANALYSIS;

EID: 0345358518     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.09.037     Document Type: Article

References (32)

1. Roggo S. Curr. Topics Med. Chem. 2:2002;359.
2. Felsenstein K.M. Ann. N. Y. Acad. Sci. 920:2000;269.
3. Selkoe D.J. Ann. N. Y. Acad. Sci. 924:2000;17.
4. Howlett D.R., Simmons D.L., Dingwall C., Christie G. Trends. Neurosci. 23:2000;565.
5. Wolfe M.S. J. Med. Chem. 44:2001;2039.
6. Tsai J.-Y., Wolfe M.S., Xia W. Curr. Med. Chem. 9:2002;1087.
7. Josien H. Curr. Opin. Drug Discov. Dev. 5:2002;513.
8. Hom R.K., Fang L.Y., Mamo S., Tung J.S., Guinn A.C., Walker D.E., Davis D.L., Gailunas A.F., Thorsett E.D., Sinha S., Knops J.E., Jewett N.E., Anderson J.P., John V. J. Med. Chem. 46:2003;1799.
9. Lin X., Koelsch G., Wu S., Downs D., Dashti A., Tang J. Proc. Natl. Acad. Sci. U.S.A. 97:2000;1456.
10. Vassar R., Bennett B.D., Babu-Khan S., Kahn S., Mendiaz E.A., Denis P., Teplow D.B., Ross S., Amarante P., Loeloff R., Luo Y., Fisher S., Fuller J., Edenson S., Lile J., Jarosinski M.A., Biere A.L., Curran E., Burgess T., Louis J.-C., Collins F., Treanor J., Rogers G., Citron M. Science. 286:1999;735.
11. Yan R., Bienkowski M.J., Shuck M.E., Miao H., Tory M.C., Pauley A.M., Brashler J.R., Stratman N.C., Mathews W.R., Buhl A.E., Carter D.B., Tomasselli A.G., Parodi L.A., Heinrikson R.L., Gurney M.E. Nature. 402:1999;533.
12. Sinha S., Anderson J.P., Barbour R., Basi G.S., Caccavello R., Davis D., Doan M., Dovey H.F., Frigon N., Hong J., Jacobson-Croak K., Jewett N., Keim P., Knops J., Lieberburg I., Power M., Tan H., Tatsuno G., Tung J., Schenk D., Seubert P., Suomensaari S.M., Wang S., Walker D., Zhao J., McConlogue L., John V. Nature. 402:1999;537.
13. Hussain I., Powell D., Howlett D.R., Tew D.G., Meek T.D., Chapman C., Gloger I.S., Murphy K.E., Southan C.D., Ryan D.M., Smith T.S., Simmons D.L., Walsh F.S., Dingwall C., Christie G. Mol. Cell. Neurosci. 14:1999;419.
14. Luo Y., Bolon B., Kahn S., Bennett B.D., Babu-Khan S., Denis P., Fan W., Kha H., Zhang J., Gong Y., Martin L., Louis J.-C., Yan Q., Richards W.G., Citron M., Vassar R. Nat. Neurosci. 4:2001;231.
15. Cai H., Wang Y., McCarthy D., Wen H., Borchelt D.R., Price D.L., Wong P.C. Nat. Neurosci. 4:2001;233.
16. Roberds S.L., Anderson J., Basi G., Bienkowski M.J., Branstetter D.G., Chen K.S., Freedman S.B., Frigon N.L., Games D., Hu K., Johnson-Wood K., Kappenman K.E., Kawabe T.T., Kola I., Kuehn R., Lee M., Liu W., Motter R., Nichols N.F., Power M., Robertson D.W., Schenk D., Schoor M., Shopp G.M., Shuck M.E., Sinha S., Svensson K.A., Tatsuno G., Tintrup H., Wijsman J., Wright S., McConlogue L. Hum. Mol. Genet. 10:2001;1317.
17. Hong L., Koelsch G., Lin X., Wu S., Terzyan S., Ghosh A.K., Zhang X.C., Tang J. Science. 290:2000;150.
18. Turner I.I.I.R.T., Koelsch G., Hong L., Castanheira P., Ghosh A.K., Tang J. Biochemistry. 40:2001;10001.
19. Tung J.S., Davis D.L., Anderson J.P., Walker D.E., Mamo S., Jewett N., Hom R.K., Sinha S., Thorsett E.D., John V. J. Med. Chem. 45:2002;259.
20. Bock M.G., DiPardo R.M., Evans B.E., Rittle K.E., Boger J., Poe M., LaMont B.I., Lynch R.J., Ulm E.H., Vlasuk G.P., Greenlee W. J.; Veber, D. F. J. Med. Chem. 30:1987;1853.
21. Boger J., Payne L.S., Perlow D.S., Lohr N.S., Poe M., Blaine E.H., Ulm E.H., Schorn T.W., LaMont B.I., Lin T.-Y., Kawai M., Rich D.H., Veber D.F. J. Med. Chem. 28:1985;1779.
22. Carroll C.D., Johnson T.O., Tao S., Lauri G., Orlowski M., Gluzman I.Y., Goldberg D.E., Dolle R.E. Bioorg. Med. Chem. Lett. 8:1998;3203.
23. Agarwal N.S., Rich D.H. J. Med. Chem. 29:1986;2519.
24. Hui K.Y., Hermann R.B., Manetta J.V., Gygi T., Angleton E.L. FEBS Lett. 327:1993;355.
25. Kroemer R.T., Ettmayer P., Hecht P. J. Med. Chem. 38:1995;4917.
26. Waller C.L., Oprea T.I., Giolitti A., Marshall G.R. J. Med. Chem. 36:1993;4152.
27. Erickson, J. et al. Manuscript in preparation.
28. (a) . Docking analysis carried out with in-house algorthim, CDOCKER. See: Vieth M., Hirst J.D., Kolinski A., Brooks C.L. III J. Comp. Chem. 19:1998;1612
29. (b) Vieth M., Hirst J.D., Dominy B.N., Daigler H., Brooks C.L. III J. Comp. Chem. 19:1998;1623 (c) Vieth M., Cummins D.J. J. Med. Chem. 43:2000;3020
30. (d) Wu G., Robertson D.H., Brooks C.L. III, Vieth M. J. Comp. Chem. 24:2003;1549.
31. BACE FRET assay uses 20 nM purified recombinant human BACE/Fc. The standard assay format contains 100 mM ELGY-9 (an aminobenzoate based FRET peptide containing Swedish mutation) in 50 mM ammonium acetate, pH 4.6, 1 mg/mL BSA and 1 mM Triton X-100 at room temperature for 4 h. The enzyme activity is determined by an increase in the relative fluorescence of reaction mixture, with umbilliferone excitation/emission filter set.
32. free=0.239) using CNX (Accelyrs, Inc.).