Efficient one-pot synthesis of biologically active polysubstituted aromatic amines

Bioorganic and Medicinal Chemistry

Volumn 15, Issue 23, 2007, Pages 7311-7317

  Menche, Dirk ^a   Arikan, Fatih ^a   Li, Jun ^a   Rudolph, Sven ^a   Sasse, Florenz ^a  

^a HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

Aromatic amines; Cytotoxicity; Diversity oriented synthesis; One pot synthesis; Reductive amination

Indexed keywords

AROMATIC AMINE;

AMINATION; ARTICLE; BIOLOGICAL ACTIVITY; CHEMICAL STRUCTURE; CONNECTIVE TISSUE; GROWTH INHIBITION; MICROSCOPY; ONE POT SYNTHESIS; SUBSTITUTION REACTION;

AMINES; ANIMALS; CELL LINE; CELL PROLIFERATION; CYTOTOXINS; DRUG EVALUATION, PRECLINICAL; MICE; MOLECULAR STRUCTURE; POTOROIDAE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

MURINAE;

EID: 35148835785     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2007.08.048     Document Type: Article

References (32)

1. For leading references, see:. Evans B.E., Rittle K.E., Bock M.G., DiPrado R.M., Freidinger R.M., Whitter W.L., Lundell G.F., Veber D.F., Anderson P.S., Chang R.S.L., Lotti V.J., Cerino D.J., Chen T.B., Kling P.J., Kunkel K.A., Springer J.P., and Hirshfield J. J. Med. Chem. 31 (1988) 2235
2. Ajay W., Walters P., and Murcko M.A. J. Med. Chem. 41 (1998) 3314
3. Kubinyi, H., Müller, G. (Eds.), Chemogenomics in Drug Discovery-A Medicinal Chemistry Perspective. In Methods and Principles in Medicinal Chemistry; Mannhold, R., Kubinyi, H., Folkers, G., Eds.; Wiley-VCH: Weinheim, Vol. 22, 2004.
4. Recent examples of bioactive tertiary amines, which are structurally closely related to type 4, are described in:. Dinsmore C.J., Williams T.M., O'Neill T.J., Liu D., Rands E., Culberson J.C., Lobell R.B., Koblan K.S., Kohl N.E., Gibbs J.B., Oliff A.I., Graham S.L., and Hartman G.D. Bioorg. Med. Chem. Lett. 9 (1999) 3301
5. Ding C.Z., Hunt J.T., Ricca C., and Manne V. Bioorg. Med. Chem. Lett. 10 (2000) 273
6. Masubuchi K., Taniguchi M., Umeda I., Hattori K., Suda H., Kohchi Y., Isshiki Y., Sakai T., Kohchi M., Shirai M., Okabe H., Sudoh M., Yamazaki T., and Shimma N. Bioorg. Med. Chem. Lett. 10 (2000) 1459
7. Massa M.A., Spangler D.P., Durley R.C., Hickory B.S., Connolly D.T., Witherbee B.J., Smith M.E., and Sikorski J.A. Bioorg. Med. Chem. Lett. 11 (2001) 1625
8. Perez M., Maraval C., Dumond S., Lamothe M., Schambel P., Etiévant C., and Hill B. Bioorg. Med. Chem. Lett. 11 (2003) 1455
9. For leading references, see:. Martens J. In: Helmchen G. (Ed). Methods of Organic Chemistry (Houben-Weyl) Vol. E21d (1995), Thieme, New York 4199
10. Kobayashi S., and Ishitani H. Chem. Rev. 99 (1999) 1069
11. Overman, L. E.; Baxter, E. W.; Reitz, A. B. Organic Reactions; Wiley: New York, 2002; Vol. 59, p. 1-53.
12. For more recent developments, i.e., asymmetric variants, see Refs. 7c,d,f as well as:. Tararov V.I., and Börner A. Synlett (2005) 203
13. Nugent T.C., Ghosh A.K., Wakchaure V.N., and Mohanty R.R. Adv. Synth. Catal. 348 (2006) 1289
14. Menche D., Arikan F., Li J., and Rudolph S. Org. Lett. 9 (2007) 267
15. Notably, all tertiary aromatic amines described in Ref. 2 have been obtained in a non one-pot fashion and the yields where reported for this step-wise process were only moderate
16. Nonaromatic tertiary amines are more readily available by reductive amination, see for example:. Mizuta T., Sakaguchi S., and Ishii Y. J. Org. Chem. 70 (2005) 2195
17. Menche D., Hassfeld J., Li J., Menche G., Ritter A., and Rudolph S. Org. Lett. 8 (2006) 741
18. Menche D., and Arikan F. Synlett 6 (2006) 841
19. Menche D., Böhm S., Li J., Rudolph S., and Zander W. Tetrahedron Lett. 48 (2007) 365
20. Hantzsch-ester mediated reductive aminations in the presence of lewis or Brønsted acids for the synthesis of secondary amines in a non-direct (requiring intermediate formation of the imines, Refs. a-d) or a direct fashion (e,f) have been described by:. Steevens J.B., and Pandit U.K. Tetrahedron 39 (1983) 1395
21. Fujii M., Aida T., Yoshihara M., and Ohno A. Bull. Chem. Soc. Jpn. 62 (1989) 3845
22. Rueping M., Sugiono E., Azap C., Theissmann T., and Bolte M. Org. Lett. 7 (2005) 3781
23. Hoffmann S., Seayad A.M., and List B. Angew. Chem., Int. Ed. 44 (2005) 7424
24. Itoh T., Nagata K., Miyazaki M., Ishikawa H., Kurihara A., and Ohsawa A. Tetrahedron 60 (2004) 6649
25. Storer R.I., Carrera D.E., Ni Y., and MacMillan D.W.C. J. Am. Chem. Soc. 128 (2006) 84
26. For good conversion also in the second step, extended reaction times are beneficial (48 h as compared to 24 h in the first alkylation).
27. 6c
28. The cytotoxicity of simple aromatic amines is suggested to be initiated by nitrogen oxidation to the N-oxides:. Rjosk H.-K., and Neumann H.-G. Zschr. Krebsforsch 75 (1971) 209
29. Hillesheim W., Jaeschke H., and Neumann H.-G. Chem. Biol. Interact. 98 (1995) 85
30. Data for representative primary aromatic amines in the same assay were: para-anisidine: 12 μg/mL (98 μM), para-toluidine: >40 μg/mL.
31. Grube A., Assmann M., Lichte E., Sasse F., Pawlik J.R., and Kock M. J. Nat. Prod. 70 (2007) 504
32. Mosman T. J. Immunol. Methods 65 (1983) 55