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ChemComm
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COMMUNICATION
Journal Name
Compd
IC50 HCT 116
Compd
IC50 HCT 116
(nM)
2007, 27, 209.
nM)b
3000 ± 200
>5000
400 ± 50
>5000
DOI: 10.1039/C6CC07666A
4. C. Mousset, A. Giraud, O. Provot, A. Hamze, J. Bignon, J. M. Liu,
S. Thoret, J. Dubois, J. D. Brion and M. Alami, Bioorg. Med.
Chem. Lett., 2008, 18, 3266.
4a
4k
4l
4m
4n
4o
4r
4aa
5a
5i
6a
6l
7a
7i
isoCA4
>5000
31 ± 0.79
2.3 ± 0.25
>5000
4000 ± 500
100 ± 10
15 ± 0.9
2.2 ± 0.2c
5. S. Messaoudi, B. Treguier, A. Hamze, O. Provot, J. F. Peyrat, J. R.
De Losada, J. M. Liu, J. Bignon, J. Wdzieczak-Bakala, S. Thoret, J.
Dubois, J. D. Brion and M. Alami, J Med Chem, 2009, 52, 4538.
6. (a) A. Hamze, A. Giraud, S. Messaoudi, O. Provot, J.-F. Peyrat, J.
Bignon, J.-M. Liu, J. Wdzieczak-Bakala, S. Thoret, J. Dubois, J.-D.
Brion and M. Alami, ChemMedChem, 2009, 4, 1912; (b) A.
Hamze, J.-D. Brion and M. Alami, Org. Lett., 2012, 14, 2782; (c)
J. Aziz, E. Brachet, A. Hamze, J.-F. Peyrat, G. Bernadat, E.
Morvan, J. Bignon, J. Wdzieczak-Bakala, D. Desravines, J.
Dubois, M. Tueni, A. Yassine, J.-D. Brion and M. Alami, Org.
Biomol. Chem., 2013, 11, 430; (d) A. Maksimenko, M. Alami, F.
Zouhiri, J. D. Brion, A. Pruvost, J. Mougin, A. Hamze, T.
Boissenot, O. Provot, D. Desmaele and P. Couvreur, Acs Nano,
2014, 8, 2018.
>5000
>5000
>5000
80 ± 1
4z
a
b
HCT-116 human colon carcinoma cells. Compound concentration required to
decrease cell growth by 50%; values represent the average SD of three
experiments. c The IC50 values for isoCA-4 was determined in this study.
In summary, we developed an efficient one-pot method
involving a palladium-catalyzed reaction of N-tosylhydrazones
with ortho-nitro-haloarenes and reductive cyclization in the
presence of PPh3 for the synthesis of arylated free indoles as
well as (1-arylvinyl)carbazole derivatives.
7. A. Penoni, J. Volkmann and K. M. Nicholas, Org. Lett., 2002, 4,
699.
This new process based on simple starting materials permits
the formation of 1 C-C, and, 1 C-N bond in a single step
reaction. A broad scope of functionalization on the C3 aryl
substituent is tolerated. In addition, this method allowed the
access to 2,3-disubstituted aryl-indoles, which are difficult to
obtain using traditional pathways. Among evaluated
derivatives, compound 5i exhibited the highest cytotoxic
activity (IC50 = 2.3 nM) against human colon cancer cell lines.
8. (a) T. Sakamoto, Y. Kondo, N. Takazawa and H. Yamanaka,
Tetrahedron Lett., 1993, 34, 5955; (b) L.-Z. Gong and P. Knochel,
Synlett, 2005, 2005, 267.
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Tetrahedron Lett., 2007, 48, 2415; (b) B. S. Lane, M. A. Brown
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Notes and references
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product obtained can be contaminated by the N-ethylated
derivatives, most likely from the alkylation of the product by the
triethyl phosphate byproduct generated in the reaction mixture.
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Selective N1-, C2- or C3-arylation of the indole nucleus, see: L.
Joucla and L. Djakovitch, Adv. Synth. Catal., 2009, 351, 673.
‡ T. Bzeih thanks Lebanese University for her Ph.D grant. The
authors gratefully acknowledge support of this project by
CNRS, University Paris-Sud and “La Ligue Contre le Cancer”
throughout an “Equipe Labellisée 2014” grant.
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4 | J. Name., 2012, 00, 1-3
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