References
- 1
Bagshawe KD.
Tumor Marker Update.
1997,
34:
220
- 2
Melton RG.
Sherwood RF.
J. Natl. Cancer Inst.
1996,
21:
153
- 3
Niculescu-Duvaz I.
Springer CJ.
Adv. Drug Delivery Rev.
1997,
26:
151
- 4
Jungheim LN.
Shepherd TA.
Chem. Rev.
1994,
94:
1553
-
5a
Jacquesy J.-C.
Gesson J.-P.
Monneret C.
Mondon M.
Renoux B.
Florent J.-C.
Koch M.
Tillequin F.
Sedlacek HH.
Gerken M.
Kolar C.
Gaudel G.
Bosslet K.
Czech J.
Hoffmann D.
Seemann G.
Eur. Pat. Appl.
1992,
EP 511:
917 ; Chem. Abstr. 1994, 120, 271070S
-
5b
Florent J.-C.
Dong X.
Gaudel G.
Mitaku S.
Monneret C.
Gesson J.-P.
Jacquesy J.-C.
Mondon M.
Renoux B.
Andrianomenjanahary S.
Michel S.
Koch M.
Tillequin F.
Gerken M.
Czech J.
Straub R.
Bossley K.
J. Med. Chem.
1998,
41:
3572
- 6
Bosslet K.
Czech J.
Lorenz P.
Sedlacek HH.
Schuermann M.
Seemann G.
Br. J. Cancer
1992,
65:
234
- 7
Bosslet K.
Czech J.
Hoffmann D.
Tumor Targeting
1995,
1:
45
- 8
Bosslet K.
Czech J.
Hoffmann D.
Cancer Res.
1994,
54:
2151
- 9
Schmidt F.
Florent J.-C.
Monneret C.
Straub R.
Czech J.
Gerken M.
Bosslet K.
Bioorg. Med. Chem. Lett.
1997,
7:
1071
- 10
Lougerstay-Madec R.
Florent J.-C.
Monneret C.
Nemati F.
Poupon MF.
Anti-Cancer Drug Design.
1998,
13:
995
- 11
Tietze LF.
Lieb M.
Herzig T.
Haunert F.
Schuberth I.
Bioorg. Med. Chem.
2001,
9:
1929
-
12a
Schmidt F.
Ugureanu I.
Duval R.
Poupon A.
Monneret C.
Eur. J. Org. Chem.
2001,
2129
-
12b
Desbene S.
Van Dufat-Trinh H.
Michel S.
Tillequin F.
Koch M.
Schmidt F.
Florent J.-C.
Monneret C.
Straub R.
Czech M.
Gerken M.
Bosslet K.
Anti-cancer Drug Design
1999,
14:
93
- 13
Papot S.
Bachmann C.
Combaud D.
Gesson J.-P.
Tetrahedron
1999,
55:
4699
-
14a
Bergman J.
Brynolf A.
Vuorinen E.
Tetrahedron
1986,
42:
3689
-
14b
Bergman J.
Norrby PO.
Sand P.
Tetrahedron
1990,
46:
6113
- 15
Coyne WE.
Cusic JW.
J. Med. Chem.
1968,
11:
1208
- 19 We have recently shown that 2-nitro-quinone-methides are not irreversible inhibitors of bovine β-glucuronidase: Azoulay M.
Chalard F.
Gesson J.-P.
Florent J.-C.
Monneret C.
Carbohydr. Res.
2001,
332:
151
16 Preparation of 8: 6-Nitroveratryl chloroformate (85 mg, 0.30 mmol) and pyridine (0.075 mL, 0.9 mmol) were added to a stirred solution of 7 (100 mg, 0.15 mmol) in CH2Cl2 (0.65 mL) at r.t. After 3 h the mixture was worked up with a saturated solution of NaHCO3 and the aqueous layer was washed with CH2Cl2. The combined organic layers were dried (MgSO4), filtered, concentrated to dryness and the remaining yellow solid was purified by flash chromatography (petroleum ether-EtOAc 1:1) to give 8 (116 mg, 0.13 mmol, 87%). 1H NMR (300 MHz, CD3COCD3), δ: 2.04, 2.05, 2.07 (3 × s, 9 H, CH3COO), 3.26
(s, 3 H, CH3N), 3.50 (s, 3 H, OCH3), 3.70 (s, 3 H, COOCH3), 3.87 (s, 6 H, OCH3), 4.37 (d, 2 H, J = 6 Hz, CH2N), 4.65
(d, 1 H, J = 9.5 Hz, H-5), 5.00 (s, 2 H, CH2O), 5.18-5.69 (m, 6 H, H-1,2,3,4, CH2O), 6.48 (s, 1 H, Harom), 7.02 (s, 1 H, NH), 7.30-7.84 (m, 8 H, Harom) ppm; 13C NMR (75 MHz, CD3COCD3), δ: 37.9 (CH3N), 41.3 (CH2N), 53.0 (COOCH3), 56.6 (OCH3), 65.0-65.1 (CH2O), 69.9, 71.1, 72.1, 72.8 (C-2,3,4,5), 100.0 (C-1), 121.2-149.6 (Carom), 155.0-156.1 (Carom), 167.7 (COOMe), 169.5, 170.0, 170.2 (CH3CO) ppm; mp 100 °C.
17 Data for 9: [αD] = +6,4 (c 0.95, CHCl3); 1H NMR (300 MHz, CD3COCD3), δ: 3.51 (s, 3 H, CH3N), 3.59-3.62 (m, 3 H,
H-2,3,4), 3.71 (s, 3 H, COOCH3), 3.87 (s, 6 H, OCH3), 4.20 (d, 1 H, J = 9.5 Hz, H-5), 4.37 (d, 2 H, J = 6 Hz, CH2N), 5.00 (s, 2 H, CH2O), 5.33 (s, 2 H, CH2O), 5.51 (d, 1 H, J = 16 Hz, H-1), 7.00 (broad s, 1 H, HNH), 7.31-7.83 (m, 9 H, Harom) ppm; 13C NMR (75 MHz, CD3COCD3), δ: 37.9 (CH3N), 41.3 (CH2N), 52.5 (COOCH3), 56.5, 56.6 (OCH3), 65.0, 65.1 (CH2O), 72.3, 74.1, 76.4, 76.9 (C-2,3,4,5), 101.9 (C-1), 118.1-150.0 (Carom), 155.2, 157.1 (Ccarbamate), 169.5 (COOMe) ppm; mp 90 °C. The highly polar compound 10 does not lead to well resolved NMR spectra (this is observed for all glucuronylated prodrugs).
18 HPLC conditions : C-16 reverse phase column : Discovery RP amide, 5 m (15 cm × 4.6 mm) and pre-column Discovery, 5 µm, UV detection (λ 254 nm), mobile phase (acetonitrile-0.065 M acetate ammonium solution, 30:70, 1 mL min-1). Retention time: 10: 7.8 min; 4-hydroxy-3-nitrobenzyl alcohol: 3.6 min; 3 (R1 = CH3, R2 = H): 4.1 min; 6-nitroveratryl alcohol: 5.2 min; 1 (R1 = CH3, R2 = H, R3 = 6-nitroveratryl alcohol): 6.3 min.