Design, synthesis, and activity of achiral analogs of 2-quinolones and indoles as non-thiol farnesyltransferase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 8, 2005, Pages 2033-2039

  Li, Qun ^a   Woods, Keith W ^a   Wang, Weibo ^a   Lin, Nan Horng ^a   Claiborne, Akiyo ^a   Gu, Wen Zhen ^a   Cohen, Jerry ^a   Stoll, Vincent S ^a   Hutchins, Charles ^a   Frost, David ^a   Rosenberg, Saul H ^a   Sham, Hing L ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Anticancer; Farnesyltransferase inhibitors; R115777; Tipifarnib; Zarnestra

Indexed keywords

INDOLE DERIVATIVE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; QUINOLONE DERIVATIVE; TIPIFARNIB;

ARTICLE; CHIRALITY; DRUG ACTIVITY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY;

EID: 20144388523     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.02.062     Document Type: Article

References (30)

1. For a recent reviews on FTIs see: S.M. Sebti, and A.A. Adjei Semin. Oncol. 31 suppl. I 2004 28 39
2. J. Mazieres, A. Pradines, and G. Favre Cancer Lett. 206 2004 159 167
3. R.J. Doll, P. Kirschmeier, and W.R. Bishop Curr. Opin. Drug Discov. Devel. 7 2004 478 486
4. I.M. Bell J. Med. Chem. 47 2004 1869 1878
5. E. van Cutsem, H. van de Velde, P. Karasek, H. Oettle, W.L. Vervenne, A. Szawlowski, P. Schoffski, S. Post, C. Verslype, H. Neumann, H. Safran, Y. Humblet, J. Perez Ruixo, Y. Ma, and D. von Hoff J. Clin. Oncol. 22 2004 1430 1438
6. M. Venet, D. End, and P. Angibaud Curr. Top. Med. Chem. 3 2003 1095 1102
7. F. Caponigro, M. Casale, and J. Bryce Expert Opin. Investig. Drugs 12 2003 943 954
8. P. Norman Curr. Opin. Invest. Drugs 3 2002 313 319
9. Relevant studies using tipifarnib as a template: P. Angibaud, X. Bourdrez, D.W. End, E. Freyne, M. Janicot, P. Lezouret, Y. Ligny, G. Mannens, S. Daqmsch, L. Mevellec, C. Meyer, P. Muller, I. Pilatte, V. Poncelet, B. Roux, G. Smets, J.V. Dun, P.V. Remoortere, M. Venet, and W. Wouters Bioorg. Med. Chem. Lett. 13 2003 4365 4369
10. P. Angibaud, A.K. Saha, X. Bourdrez, D.W. End, E. Freyne, P. Lezouret, G. Mannens, L. Mevellec, C. Meyer, P. Muller, I. Pilatte, V. Poncelet, B. Roux, G. Smets, J.V. Dun, P.V. Remoortere, M. Venet, and W. Wouters Bioorg. Med. Chem. Lett. 13 2003 4361 4364
11. P. Angibaud, X. Bourdrez, A. Devine, D.W. End, E. Freyne, Y. Ligny, P. Muller, G. Mannens, I. Pilatte, V. Poncelet, S. Skrzat, G. Smets, J.V. Dun, P.V. Remoortere, M. Venet, and W. Wouters Bioorg. Med. Chem. Lett. 13 2003 1543 1547
12. Q. Li, A. Claiborne, T. Li, L. Hasvold, S.V. Stoll, S. Muchmore, C.G. Jakob, W. Gu, J. Cohen, C. Hutchins, D. Frost, S.H. Rosenberg, and H.L. Sham Bioorg. Med. Chem. Lett. 14 2004 5367 5370
13. Q. Li, G.T. Wang, T. Li, S.L. Gwaltney II, K.W. Woods, A. Claiborne, X. Wang, W. Gu, J. Cohen, S.V. Stoll, C. Hutchins, D. Frost, S.H. Rosenberg, and H.L. Sham Bioorg. Med. Chem. Lett. 14 2004 5371 5376
14. T.S. Reid, and L.S. Beese Biochemistry 43 2004 6877 6884
15. R.B. Davis, and L.C. Pizzini J. Org. Chem. 25 1960 1884 1888
16. J.B. Hester, J.H. Ludens, D.E. Emmert, and B.E. West J. Med. Chem. 32 1989 1157 1163
17. G. Mouzin, H. Cousse, and J. Autin Synthesis 6 1981 448 449
18. L. Boymond, M. Rottländer, G. Cahiez, and P. Knochel Angew. Chem., Int. Ed. 37 1998 1701 1703
19. R. Aslanian, J.E. Brown, N.-Y. Shih, M.W. Mutahi, M.J. Green, S. She, M. Del Prado, R. West, and J. Hey Bioorg. Med. Chem. Lett. 8 1998 2263 2268
20. N.J. Anthony, R.P. Gomez, M.D. Schaber, S.D. Mosser, K.A. Hamilton, T.J. O'Neil, K.S. Koblan, S.L. Graham, G.D. Hartman, D. Shah, E. Rands, N.E. Kohl, J.B. Gibbs, and A.I. Oliff J. Med. Chem. 42 1999 3356 3368
21. During the preparation of this manuscript, an alternative method of synthesis of 2a was published by Janssen scientists, see WO03080058
22. T.M. Williams, J.M. Bergman, K. Brashear, M.J. Breslin, C.J. Dinsmore, J.H. Hutchinson, S.C. MacTough, C.A. Stump, D.D. Wei, C.B. Zartman, M.J. Bogusky, J.C. Culberson, C. Buser-Doepner, J. Davide, I.B. Greenberg, K.A. Hamilton, K.S. Koblan, N.E. Kohl, D. Liu, R.B. Lobell, S.D. Mosser, T.J. O'Neill, E. Rands, M.D. Schaber, F. Wilson, E. Senderak, S.L. Motzel, J.B. Gibbs, S.L. Graham, D.C. Heimbrook, G.D. Hartman, A.I. Oliff, and J.R. Huff J. Med. Chem. 42 1999 3779 3784
23. A.R. Katritzky, D. Cheng, and R.P. Musgrave Heterocycles 44 1997 67 70
24. N.P. Pavri, and M.L. Trudell J. Org. Chem. 62 1997 2649 2651
25. H. Lee, J. Lee, S. Lee, Y. Shin, W. Jung, J.H. Kim, K. Park, K. Kim, H.S. Cho, S. Ro, S. Lee, S.W. Jeong, T. Choi, H.H. Chung, and J.S. Koh Bioorg. Med. Chem. Lett. 11 2001 3069 3072
26. Assay methods described in: A. Vogt, Y. Qian, M.A. Blaskovich, R.D. Fossum, A.D. Hamilton, and S.M. Sebti J. Biol. Chem. 270 1995 660 664
27. L. Wang, G.T. Wang, X. Wang, Y. Tong, G. Sullivan, D. Park, N. Leonard, Q. Li, J. Cohen, W.-Z. Gu, H. Zhang, J. Bauch, C.G. Jacob, C.W. Hutchins, S.V. Stoll, K. Marsh, S.H. Rosenberg, H. Sham, and N.-H. Lin J. Med. Chem. 47 2004 612 626
28. S.M. Sebti, and A.D. Hamilton Expert. Opin. Investig. Drugs 9 2000 2767 2782
29. E. Wang, and W.W. Johnson Chemotherapy 49 2003 303 308
30. 16 in which a series of compounds with alky-aminocarbonyl-pyrrole derivative were disclosed