Synthesis of a C11 spiropiperidino derivative of 8-chloro-6,11- dihydro 5H-benzo[5,6]cyclohepta[1,2-b]pyridine

Tetrahedron Letters

Volumn 39, Issue 42, 1998, Pages 7661-7664

  Afonso, Adriano ^a   Kelly, J ^a   Puar, Mohindar S ^a   McCombie, Stuart ^a   McPhail, Andrew T ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b DUKE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PIPERIDINE DERIVATIVE; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PYRIDINE DERIVATIVE;

ALKYLATION; ARTICLE; ENZYME INHIBITION; PRENYLATION; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

EID: 0032532539     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01714-6     Document Type: Article

References (9)

1. 1. Bishop, R. W.; Bond, R.; Petrin, J.; Wang, L.; Patton, R.; Doll, R.; Njoroge, G.; Cattino, J.; Schwartz, J.; Windsor, W.; Syto, R.; Carr, D.; James, L.; Kirshmeier, P. J. Biological Chem. 1995, 270, 30611.
2. 2. Kelly, J.; Wolin, R.; Connolly, M.; Afonso, A.; James, L.; Kirshmeier, P.; Bishop, W.R.; McPhail, A. T. Biorg. Med. Chem. 1998, 6, 673.
3. 3. Chambers, M. S.; Baker, R.; Billington, D. C.; Knight, A. K.; Middlemiss, D. N.; Wong, E. H. F. J. Med. Chem. 1992, 35, 2033.
4. 4. Villani, F. J.; Daniels, P. J. L.; Ellis, C. A.; Mann, T. A.; Wang, K.-C.; Wefer, E. A.J. Med. Chem. 1972, 15, 750.
5. 5. Martin, A. E.; Ford, T. M.; Bulkowski, J. E. J. Org. Chem. 1982, 47, 412.
6. 6. Crystal structure data may be obtained from the Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB2 1EZ (UK).
7. 7. Compound 8 was resistant to conventional N-detosylation conditions e.g. HBr, electrochemical reduction; use of sodium amalgam/ethanol did provide a detosylated product with concomitant 1,2-reduction of the pyridine ring. Compound 8 was also resistant to LAH reduction.
8. 2): C, 68.47; H, 6.14; N, 8.76. Found: C, 68.27; H, 6.37; N, 8.56.
9. 9. The biological activity of these derivatives will be reported in a forthcoming manuscript.