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. Hz, 66 (s, 1H : y), 9.88 (s, 1H : p), 10.33 (s, 1H : z)

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?. Kbr, 3055 (C Ar - H stretch), 2962, 2866 (C Alk -H stretch), pp.1508-1261

O. @bullet, (4-hydroxyphényl)-2-phénylbut-1-èn-1-yl]phényl}subéramide Une solution méthanolique de C-PhAm est versée dans une solution aqueuse concentrée de NaOH. Le mélange est mis sous agitation pendant une nuit à température ambiante. Puis, la solution est acidifiée à l'HCl et le produit est extrait à l'AcOEt. La phase organique est séchée sur MgSO 4 , filtrée et évaporée. Le brut de la réaction est purifié sur une colonne de gel de silice

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M. Görmen, . Plazuk, . Pigeon, M. Hillard, . Plamont et al., Comparative toxicity of [3]ferrocenophane and ferrocene moieties on breast cancer cells, Tetrahedron Letters, vol.51, issue.1, pp.118-120, 2010.
DOI : 10.1016/j.tetlet.2009.10.102

2. Hz and J. =. , 1H : z), 2H : n), 7.38 (t, J = 7.2 Hz, 2H : g), 9.74 et 9.91 pour l'isomère E (s, 1H : p), p.97, 1930.

?. Kbr, 1701 (OC=O stretch), 1662 (NC=O stretch), 1593 (C Ar =C Ar stretch), 1520 (N-H bend) SM (IC, C Alk -H stretch) HPLC (R T, vol.3089, issue.2927, pp.3313-3051

?. Kbr, 1666 (NC=O stretch), 1593 (C Ar =C Ar stretch), 1520 (N-H bend) SM (IC, R F : (AcOEt): 0.92, pp.3321-3086

. Hz, 2H : b), 3.56 (s, 3H : z), 3.95 (t, J = 1.8 Hz, 2H : ?'), 4.01 (s, 4H : ? et ?), 2H : g), 9.76 et 9.93 pour E (s, 1H : p), pp.2726-2728

F. @bullet, {[3]ferrocénophan-1-ylidène(phényl)méthyl}phényl)subéramide Réactifs et conditions : FnTAM-OPOA (1 mmol, 0.56 g), THF (10 mL, ClCO 2 Et (2 mmol, 0.19 mL), Et 3 N (2.5 mmol, 0.35 mL), NaNH 2 (excès). Eluant pour la colonne : mélanges hexane/AcOEt. 36% (0.20 g) de produit est obtenu. Solide jaune. Z/E = 96

?. Kbr, 3093 (C Ar -H stretch), 2927, 2854 (C Alk -H stretch), 1662 (NC=O stretch), 1597 (C Ar =C Ar stretch), 1519 (N-H bend) SM (IC, pp.578-561

S. Cohen and S. Lippard, Cisplatin: From DNA damage to cancer chemotherapy, Prog Nucleic Acid Res Mol Biol, vol.67, pp.93-130, 2001.
DOI : 10.1016/S0079-6603(01)67026-0

S. Top, . Vessières, . Leclercq, . Quivy, . Tang et al., Synthesis, Biochemical Properties and Molecular Modelling Studies of Organometallic Specific Estrogen Receptor Modulators (SERMs), the Ferrocifens and Hydroxyferrocifens: Evidence for an Antiproliferative Effect of Hydroxyferrocifens on both Hormone-Dependent and Hormone-Independent Breast Cancer Cell Lines, Chemistry - A European Journal, vol.9, issue.21, pp.5223-5236, 2003.
DOI : 10.1002/chem.200305024

A. Vessières, . Top, . Pigeon, . Hillard, . Boubeker et al., Modification of the Estrogenic Properties of Diphenols by the Incorporation of Ferrocene. Generation of Antiproliferative Effects in Vitro, Journal of Medicinal Chemistry, vol.48, issue.12, pp.3997-3940, 2005.
DOI : 10.1021/jm050251o

W. Wlassoff, . Cd-albright, . Sivashinski, . Ivanova, R. Appelbaum et al., Hydrogen peroxide overproduced in breast cancer cells can serve as an anticancer prodrug generating apoptosis-stimulating hydroxyl radicals under the effect of tamoxifen-ferrocene conjugate, Journal of Pharmacy and Pharmacology, vol.41, issue.639, pp.1549-1553, 2007.
DOI : 10.1211/jpp.59.11.0013

E. Hillard, . Vessières, . Thouin, C. Jaouen, and . Amatore, Ferrocene-Mediated Proton-Coupled Electron Transfer in a Series of Ferrocifen-Type Breast-Cancer Drug Candidates, Angewandte Chemie International Edition, vol.44, issue.2, pp.285-290, 2006.
DOI : 10.1002/anie.200502925

E. Hillard, . Pigeon, C. Vessières, G. Amatore, and . Jaouen, The influence of phenolic hydroxy substitution on the electron transfer and anti-cancer properties of compounds based on the 2-ferrocenyl-1-phenyl-but-1-ene motif, Dalton Transactions, vol.5, issue.43, pp.5073-5081, 2007.
DOI : 10.1039/b705030e

URL : https://hal.archives-ouvertes.fr/hal-01230399

P. Pigeon, . Top, . Zekri, . Hillard, M. Vessières et al., The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-l-ene compounds against breast cancer cells, Journal of Organometallic Chemistry, vol.694, issue.6, pp.895-901, 2009.
DOI : 10.1016/j.jorganchem.2008.11.035

O. Zekri, . Hillard, . Top, . Vessières, . Pigeon et al., Role of aromatic substituents on the antiproliferative effects of diphenyl ferrocenyl butane compounds, Dalton Trans, vol.22, pp.4318-4326, 2009.

O. Buriez, . Labbé, . Pigeon, C. Jaouen, and . Amatore, Electrochemical attachment of a conjugated amino???ferrocifen complex onto carbon and metal surfaces, Journal of Electroanalytical Chemistry, vol.619, issue.620, pp.169-175, 2008.
DOI : 10.1016/j.jelechem.2008.04.012

URL : https://hal.archives-ouvertes.fr/hal-01230398

W. Lai, J. Zahid, and . Uetrecht, Metabolism of trimethoprim to a reactive iminoquinone methide by activated human neutrophils and hepatic microsomes, J Pharm Exp Ther, vol.291, pp.292-299, 1999.

. Mc-damsten, . Jsb-de-vlieger, . Wma-niessen, N. Irth, . Vermeulen et al., Trimethoprim: Novel Reactive Intermediates and Bioactivation Pathways by Cytochrome P450s, Chemical Research in Toxicology, vol.21, issue.11, pp.2181-2187, 2008.
DOI : 10.1021/tx8002593

G. Bucher, A Laser Flash Photolysis Study on 2-Azido-N,N-diethylbenzylamine ??? The Reactivity of Iminoquinone Methides in Solution, European Journal of Organic Chemistry, vol.2001, issue.13, pp.2463-2475, 2001.
DOI : 10.1002/1099-0690(200107)2001:13<2463::AID-EJOC2463>3.0.CO;2-6

. Par, Schéma 3) ?qui a également révélé une activité antiproliférative contre les cellules MDA-MB-231? ne subit pas une séquence d'oxydation stimulée par une base dans les mêmes conditions que pour l'amine Fc-aline ou le diphénol Fc-diphol. Dès lors, nous avons proposé que le mécanisme d'activation redox pouvait se produire une fois que l'amide Fc-alide était convertie in vitro en l'amine Fc

. Schéma-3, Oxydation du 4-(2-ferrocényl-1-phénylbut-1-én-1-yl)acétanilide Fc-alide non observable et sa valeur d

K. Sakano, Y. Oikawa, S. Hiraku, and . Kawanishi, Mechanism of metal-mediated DNA damage induced by a metabolite of carcinogenic acetamide, Chemico-Biological Interactions, vol.149, issue.1, pp.51-59, 2004.
DOI : 10.1016/j.cbi.2004.06.005

D. Plazuk, . Vessieres, . Hillard, . Buriez, . Labbé et al., A [3]Ferrocenophane Polyphenol Showing a Remarkable Antiproliferative Activity on Breast and Prostate Cancer Cell Lines, Journal of Medicinal Chemistry, vol.52, issue.15, pp.4964-4967, 2009.
DOI : 10.1021/jm900297x

URL : https://hal.archives-ouvertes.fr/hal-00448988

M. Görmen, . Plazuk, . Pigeon, M. Hillard, . Plamont et al., Comparative toxicity of [3]ferrocenophane and ferrocene moieties on breast cancer cells, Tetrahedron Letters, vol.51, issue.1, pp.118-120, 2010.
DOI : 10.1016/j.tetlet.2009.10.102

M. Görmen, . Pigeon, . Top, . Hillard, C. Huché et al., Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and [3]Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells, ChemMedChem, vol.693, issue.639, pp.2039-2050, 2010.
DOI : 10.1002/cmdc.201000286

. Synthèse-de-diamides-fn-dibut, N. Fn-dihex-et-fn-dioct-les, and N. , -[([3]ferrocénophan-1-ylidèneméthylene)bis(4,1-phénylène)]dialkanamides dérivés de la dianiline Fn-dialine et les chlorures de butyryle (bu), hexanoyle (he) et octanoyle (oc) peuvent être préparés selon deux voies. La voie-A implique, dans un premier temps, la réaction d'amidation de la 4,4'-diaminobenzophénone avec les chlorures d'acyle correspondants en présence de la triéthylamine Les produits sont obtenus avec d'excellents rendements

. Dans-un-deuxième-temps, une réaction d'hétérocouplage entre la [3]ferrocénophan-1- one et les N,N'-[carbonylbis(4,1-phénylène)]dialkanamides formés préalablement a été réalisée (Schéma 6) Les produits ont été obtenus avec des rendements supérieurs à ceux que l'on attendrait pour une réaction d

. De-la-même-manière, les analogues tétraméthylés des deux anilines primaires : (i) l'organique Ph-dialine et (ii) l'inexistante organométallique 4,4'-(2-ferrocénylbut-1-éne-1,1- diyl)dianiline ont été aussi préparés. Ainsi, la propiophénone et le propionylferrocène ont réagi indépendamment avec la cétone de Michler selon la réaction de McMurry

P. Messina, . Labbé, . Buriez, . Hillard, D. Vessières et al., Deciphering the Activation Sequence of Ferrociphenol Anticancer Drug Candidates, Chemistry - A European Journal, vol.28, issue.21, pp.6581-6587, 2012.
DOI : 10.1002/chem.201103378

Y. Tan, . Pigeon, . Top, . Labbé, . Buriez et al., Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells, Dalton Transactions, vol.46, issue.639, pp.7537-7549, 2012.
DOI : 10.1002/chem.201103378

URL : https://hal.archives-ouvertes.fr/hal-01230385

L. Voltammogrames-ont-Été-enregistrés-d, une solution 0.5 mM d'analyte dans une solution 0.1 M de Bu 4 NBF 4 dans le MeOH Électrode de travail : Pt (? = 0.5 mm), électrode auxiliaire : baguette d'acière inoxydable

L. Voltammogrames-ont-Été-enregistrés-d, une solution 0.5 mM d'analyte dans une solution 0.1 M de Bu 4 NBF 4 dans le MeOH Électrode de travail : Pt (? = 0.5 mm), électrode auxiliaire : baguette d'acière inoxydable

@. N. Fn-dibut, 1-phénylène)]dibutyramide Réactifs et quantités : Fn-dialine (2.36 mmol, 0.99 g) Eluant pour la colonne: CHCl 3 /AcOEt/AcOH: 2/1/1. La première fraction a été identifié comme le produit désiré, la deuxième était le produit de monoamidation et la troisième

. Hz, 1H : i), 2H : l'), 2.27 (t, J = 7.4 Hz, 2H : k), 2.35 (t, J = 7.4 Hz, 2H : k'), pp.9632-9634

?. Kbr, 1662 (N=CO stretch), 1597 (C Ar =C Ar stretch) 1523 (N-H bend), 1400 (C-N stretch) SM (IC, Macherey-Nagel C18, MeOH). pf, pp.3298-3101

B. Voie, . Réactifs, and . Quantités, Fn-dialine (0.59 mmol, 0.25 g) THF (15 mL), chlorure d'octanoyle (1.18 mmol, 0.2 mL) Et 3 N (1.43 mmol, 0.2 mL) Éluant pour la colonne: CHCl 3 /AcOEt /AcOH: 2/1/1. La première fraction est le produit désiré, la seconde est le produit de monoamidation et la troisième

3. Hz, 3H : q), 1.21-1.45 (m, 16H : p', p, o', o, n', n, m' et m), 1.55-1.78 (m, 4H : l' et l), '), 2.37 (t, J = 7.4 Hz, 2H : k) 2H : ?), p.88299802

2. Hz, 1H : i), pp.98-107

?. Kbr, 3101 (C Ar -H stretch), 2924, 2854 (C Alk -H stretch), 1662 (NC=O stretch, 1400 (C-N stretch). SM (IC Calc. pour C 42 H 52 FeN 2 O 2 (%): C, 74.99; H, pp.3298-1597

@. N. Fn-dihex, 1-phénylène)]dihexanamide Réactifs and quantités: Zn (24 mmol, 1.57 g) TiCl 4 (12 mmol, 1.3 mL), THF (30 mL), dihex (2.4 mmol, 0.98 g), Fn-dialine (2.4 mmol, 0.58 g), THF (20 mL) Le mélange est agité pendant 15 min après l'addition des cétones

I. Kbr, (C Ar -H stretch), 2927, 2858 (C Alk -H stretch), 1662 (NC=O stretch, 1400 (C-N stretch). SM (IC, pp.3298-3043

. Anal and . Calc, C, 74.02; H, 7.19; N, 4.54. Trouvé : C, 73, Macherey-Nagel, C18, 5 µm, 4.6 x 250 mm, MeOH, pp.38-44

@. Ph-dialine, -phénylbut-1-éne-1,1-diyl)dianiline Réactifs et quantités : Zn (48 mmol, 3.14 g), TiCl 4 (24 mmol, 2.6 mL), THF (80 mL)

. Propiophénone, 78 mmol, 0.91 g), 4,4'-diaminobenzophénone (5.09 mmol, 1.08 g), THF (40 mL), DMSO (1 mL) Temps de réaction : 5 min

?. Kbr, (C Alk -H stretch), 1616 (NH 2 scissoring), 1508 (C Ar =C Ar stretch), 1280 (C Ar -N stretch) MS (IC, pp.3432-3024, 2870.

@. Ph-dialinetm, -phénylbut-1-éne-1,1-diyl)bis(N

Q. Réactifs, Zn (72 mmol, 4.71 g), TiCl 4 (36 mmol, 3.9 mL), THF (100 mL)

. Propiophénone, 6 mmol, 1.02 g), bis[(4-(diméthylamino)phényl]méthanone (7.6 mmol, 2.04 g), THF (60 mL) Temps de réaction : 20 min

?. Kbr, 2962, 2877 (C Alk -H stretch), 1608, 1515 (C Ar =C Ar stretch), 1342 (C Ar -N stretch) SM (IE, pp.370-373

Q. Réactifs, Zn (72 mmol, 4.71 g) TiCl 4 (36 mmol, 3.9 mL), THF (100 mL), bis

C. Au-comportement-dans-l-'acétone and D. Dans-le, Spectre 2) nous n'avons pas observé de changements notables