Substituted azoloquinolines and -quinazolines as new potent farnesyl protein transferase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 24, 2003, Pages 4365-4369

  Angibaud, Patrick ^a   Bourdrez, Xavier ^a   End, David W ^b   Freyne, Eddy ^c   Janicot, Michel ^b   Lezouret, Patricia ^a   Ligny, Yannick ^a   Mannens, Geert ^d   Damsch, Siegrid ^e   Mevellec, Laurence ^a   Meyer, Christophe ^a   Muller, Philippe ^a   Pilatte, Isabelle ^a   Poncelet, Virginie ^a   Roux, Bruno ^a   Smets, Gerda ^b,f   Van Dun, Jacky ^c   Van Remoortere, Pieter ^e   Venet, Marc ^a,g   Wouters, Walter ^e  

^a Medicinal Chemistry Department   (France)

^b Drug Discovery   (United States)

^c Oncology Drug Discovery   (Belgium)

^d Preclinical Pharmacokinetics   (Belgium)

^e Drug Evaluation   (Belgium)

^f Centocor   (Netherlands)

^g SERIPHARM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

GERANYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; QUINAZOLINE DERIVATIVE; QUINOLINE DERIVATIVE; TIPIFARNIB;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; TUMOR;

EID: 0344064850     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.08.080     Document Type: Article

References (32)

1. Rodenhuis S. Semin. Cancer Biol. 3:1992;241.
2. Bos J.L. Cancer Res. 49:1989;4682.
3. Barbacid M. Ann. Rev. Biochem. 56:1987;779.
4. Casey P.J., Solski P.A., Der C.J., Buss J.E. Proc. Natl. Acad. Sci. U.S.A. 86:1989;8323.
5. Kato K., Cox A.D., Hisaka M.M., Graham S.M., Buss J.E., Der C.J. Proc. Natl. Acad. Sci. U.S.A. 89:1992;6403.
6. Der C.J., Cox A.D. Cancer Cells. 3:1991;331.
7. Seabra M.C., Reiss Y., Casey P.L., Brown M.S., Goldstein J.L. Cell. 65:1991;429.
8. Rowinsky E.K., Windle J.J., Von Hoff D.D. J. Clin. Oncol. 17:1999;3631.
9. Rowinsky E.K., Patnaik A. Emerg. Drugs. 5:2000;161.
10. End D.W. Invest. New Drugs. 17:1999;241.
11. Johnston S. Lancet Oncol. 2:2001;18.
12. Lebowitz P.F., Casey P.J., Prendergast G.C., Thissen J.A. J. Biol. Chem. 272:1997;15591.
13. Feldkamp M.M., Lau N., Rak J., Kerbel R.S., Guha A. Int. J. Cancer. 81:1999;118.
14. Ashar H.R., James L., Gray K., Carr D., Black S., Armstrong L., Bishop W.R., Kirschmeier P. J. Biol. Chem. 275:2000;30451.
15. Adnane J., Bizouarn F.A., Chen Z., Ohkanda J., Hamilton A.D., Munoz-Antonia T., Sebti S.M. Oncogene. 19:2000;5525.
16. Gibbs R.A. Curr. Opin. Drug Discov. Dev. 5:2000;585.
17. Gibbs R.A., Zahn T.J., Sebolt-Leopold J.S. Curr. Med. Chem. 8:2001;1437.
18. Karp J.E., Kaufmann S.H., Adjei A.A., Lancet J.E., Wright J.J., End D.W. Curr. Opin. Oncol. 13:2001;470.
19. Tamanoi F., Kato-Stankiewicz J., Jiang C., Machado I., Thapar N. J. Cell. Biochem. 37:2001;64.
20. Haluska P., Dy G.K., Adjei A.A. Eur. J. Cancer. 38:2002;1685.
21. Ohkanda J., Knowles D.B., Blaskovich M.A., Sebti S.M., Hamilton A.D. Cur. Top. Med. Chem. 2:2002;303.
22. Ghobrial I.M., Adjei A.A. Hematol. Oncol. Clin. N. Am. 16:2002;1065.
23. End D.W., Smets G., Todd A.V., Applegate T.L., Fuery C.J., Angibaud P., Venet M., Sanz G., Poignet H., Skrzat S., Devine A., Wouters W., Bowden C. Cancer Res. 61:2001;131.
24. Norman P. Curr. Opin. Investing. Drugs. 3:2002;313.
25. Venet, M. G.; Angibaud, P. R.; Muller, P.; Sanz, G. C. W. O patent 97/21701, 1997.
26. Venet, M. Abstract of papers, 222nd National Meeting of the American Chemical Society, Chicago, IL, Aug. 26-30, 2001; American Chemical Society: Washington, DC, 2001; 69BUZP.
27. Venet M., End D.W., Angibaud P. Cur. Top. Med. Chem. 3:2003;1095.
28. Angibaud P., Bourdrez X., Devine A., End D.W., Freyne E., Ligny Y., Muller P., Mannens G., Pilatte I., Poncelet V., Skrzat S., Smets G., Van Dun J., Van Remoortere P., Venet M., Wouters W. Bioorg. Med. Chem. Lett. 13:2003;1543.
29. (a) Angibaud, P. R.; Venet, M. G.; Boudrez, X. M. W. O. patent 00/39082, 2000. (b) Venet, M. G.; Angibaud, P. R.; End, D. W. O patent 01/98302, 2001.
30. (a) Angibaud, P. R.; Venet, M. G.; Boudrez, X. M. W. O. patent 00/39082, 2000. (b) Venet, M. G.; Angibaud, P. R.; End, D. W. O patent 01/98302, 2001.
31. ® (eluent: EtOH 100%). Two pure fractions were collected and the solvent was evaporated. Fraction 1 was converted into the ethanedioic salt (1:1) and crystallized from ethanol. The precipitate was filtered off and dried, yielding 1.59 g (34%) of (A)-5-(3-chlorophenyl)-α- (4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-tetrazolo[1,5-a] quinoline-7-methanamine ethanedioate (1:1) 24a (ee>99% measured by HPLC). Fraction 2 was converted into the ethanedioic salt (1:1) and crystallized from ethanol. The precipitate was filtered off and dried, yielding 1.85 g (39%) of (B)-5-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5- yl)-tetrazolo[1,5-a]quinoline-7-methanamine ethanedioate (1:1) 24b. This compound contains 3% of the (A) enantiomer as measured by HPLC.
32. 3CN/DIPE. The precipitate was filtered off and dried yielding 2.6 g of (+)-5-(3-chlorophenyl)-α-(4-chlorophenyl)-α- (1-methyl-1H-imidazol-5-yl)-tetrazolo[1,5-a]quinazoline-7-methanamine 43b. This compound contains 4% of the (-) enantiomer as measured by HPLC.