Synthesis of N,N′-disubstituted 3-aminobenzo[c] and [d]azepin-2-ones as potent and specific farnesyl transferase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 3, 2004, Pages 767-771

  Le Diguarher, Thierry ^a   Ortuno, Jean Claude ^a   Shanks, David ^a   Guilbaud, Nicolas ^a,b   Pierré, Alain ^a   Raimbaud, Eric ^a   Fauchère, Jean Luc ^a   Hickman, John A ^a   Tucker, Gordon C ^a   Casara, Patrick J ^a  

^a INSTITUT DE RECHERCHES SERVIER   (France)

^b Oncodesign   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AZEPINE DERIVATIVE; PROTEIN FARNESYLTRANSFERASE INHIBITOR;

ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; DRUG POTENCY; DRUG SYNTHESIS; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

EID: 1642493640     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.11.013     Document Type: Article

References (19)

1. Huang C.C., Casey P.J., Fierke C.A. J. Biol. Chem. 272:1997;20.
2. Lerner E.C., Hamilton A.D., Sebti S.M. Anti-Cancer Drug Des. 12:1997;229.
3. Prendergast G.C., Rane N. Expert Opin. Invest. Drugs. 10:2001;2105.
4. Cox A.D., Der C.J. Curr. Opin. Pharm. 2:2002;388.
5. Haluska P., Dy G.K., Adjei A.A. Eur. J. Cancer. 38:2002;1685, and references cited herein.
6. Le Diguarher T., Ortuno J.C., Dorey G., Shanks D., Guilbaud N., Pierré A., Fauchère J.L., Hickman J.A., Tucker G.C., Casara P.J. Bioorg. Med. Chem. 11:2003;3193.
7. Long S.B., Hancock P.J., Kral A.M., Hellinga H.W., Beese L.S. P.NA.S. 98:2001;12948.
8. Strickland C.L., Windsor W.T., Syto R., Wang L., Bond R., Wu Z., Schwartz J., Le H.V., Beese L.S., Weber P.C. Biochemistry. 37:1998;16601.
9. Park H.W., Boduluri S.R., Moomaw J.F., Casey P.J., Beese L.S. Science. 275:1997;1800.
10. Berkowitz W.F., John T.V. J. Org. Chem. 49:1984;5269.
11. Flynn G.A., Burkholder T.P., Huber E.W., Bey P. Bioorg. Med. Chem. Lett. 1:1991;309.
12. Chan D.M. Tetrahedron Lett. 37:1996;9013.
13. Kammermeir B.O.T., Lerch U., Sommer C. Synthesis. 1992;1157.
14. All new compounds 2 and 3 gave spectroscopic data (IR, NMR), elemental analyses (CHN) and/or MS in agreement with the assigned structures.
15. Ben-Ishai D., Sataty I., Peled N., Goldshare R. Tetrahedron. 43:1983;439.
16. Martin A., Gomez-Muñoz A., Waggoner D.W., Stone J.C., Brindley D. J. Biol. Chem. 268:1993;23924.
17. Lamothe M., Perez M. Idrugs. 3:2000;1336, and references cited herein.
18. Bell I.A., Gallicchio S.N., Abrams M., Beese L.S., Beshore D.C., Bhimnathwala H., Bogusky M.J., Buser C.A., Culberson J.C., Davide J., Ellis-Hutchings M., Fernandes C., Gibbs J.B., Graham S.L., Hamilton K.A., Hartman G.D., Heimbrook D.C., Homnick C.F., Huber H.E., Huff J.R., Kassahun K., Koblan K.S., Kohl N.E., Lobell R.B., Lynch J.J., Robinson R., Rodrigues A.D., Taylor J.S., Walsh E.S., Williams T.M., Zartman C.B. J. Med. Chem. 45:2002;2388.
19. All structures were modelled in SYBYL® 6.9. using standard bond lengths and angles. The whole protein, including the zinc and the farnesyl di-phosphate (yellow), was kept fixed in aggregate, except the side chains of some of the hydrophobic amino-acid residues of the beta chain at the active site in close contact with the ligands which were allowed to change their conformations depending on the ligands docked, that is TRP102, TRP106, TYR154, TRP303, TYR361 and TYR365. All the hydrogen atoms were added on the crystal structure pdb1LD8 of the enzyme and their geometries were optimised using the Tripos force field, using Kollman charges on all atom of the residues of the protein and Gasteiger-Hückel charges on the other non-protein molecules. All the water, U49 and acetate molecules were removed before docking.