Development of new hetero-steroid hybrids with antiproliferative activity against MCF-7…
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temperature for 20–24 h, and the residue was extracted with
CH2Cl2 (3×10 cm3). The organic layer was washed twice
with water, brine, and dried over anhydrous Na2SO4.
7.42 (app. d, J=9 Hz, 2H, ArH), 7.06 (app. d, J=6.5 Hz,
2H, ArH), 6.91 (d, J=8.5 Hz, 1H, H-1), 6.44 (dd, J=3 Hz,
8.5 Hz, 1H, H-2), 6.39 (d, J=3 Hz, 1H, H-4), 5.34 (s, 1H),
2.67–2.63 (m, 2H, H-6), 2.38 (m, 1H), 2.10–1.98 (m, 2H),
1.84–1.78 (m, 3H), 1.62–1.20 (m, 6H), 1.05–1.03 (m,
1H), 0.94 (s, 3H, CH3, H-18) ppm; 13C NMR (DMSO-d6,
125 MHz): δ = 155.9 (C-3), 154.9, 139.7, 138.6, 137.2,
136.8, 132.5 (2 CHAr), 130.5, 128.7 (2 CHAr), 126.5, 122.3
(2 CHAr), 121.0, 120.2 (2 CHAr), 116.7, 114.9, 112.7, 81.1
(C-17), 47.8, 46.9, 43.1, 37.3, 32.8, 29.3, 27.2, 26.1, 23.6,
18.6, 14.4 (CH3, C-18) ppm; HRMS (ESI+): m/z calcd. for
C32H33BrN4O4S ([M+H]+) 648.1406, found 648.1413.
4‑[4‑(17α‑1,3,5(10)‑Estratrien‑3,17β‑diol)‑1H‑1,2,3‑triazol‑1
‑yl]‑N‑phenylbenzenesulfonamide (15a, C32H34N4O4S) Puri-
fcation was achieved using fash chromatography (ethyl
acetate/hexane, 1:3) which provided white solid (88%)
1
15a. M.p.: 212–214 °C; H NMR (DMSO-d6, 500 MHz):
δ=10.40 (brs, 1H, –NHSO2–), 8.96 (brs, 1H, ArOH), 8.65
(s, 1H, triazole = CH), 8.11 (d, J = 9 Hz, 2H, ArH), 7.91
(d, J = 9 Hz, 2H, ArH), 7.21 (t, J = 8 Hz, 2H, ArH), 7.07
(d, J=7.5 Hz, 2H, ArH), 7.01 (t, J=7 Hz, 1H, ArH), 6.91
(d, J=8.5 Hz, 1H, H-1), 6.44 (dd, J=2.5 Hz, 8.5 Hz, 1H,
H-2), 6.39 (d, J=2.5 Hz, 1H, H-4), 5.31 (s, 1H), 2.67 (m,
2H, H-6), 2.38 (m, 1H), 2.10–1.98 (m, 2H), 1.84–1.78 (m,
3H), 1.63–1.61 (m, 1H), 1.54–1.45 (m, 2H), 1.35–1.1.20 (m,
4‑[4‑(17α‑1,3,5(10)‑Estratrien‑3,17β‑diol)‑1H‑1,2,3‑
triazol‑1‑yl]‑N‑(4‑nitrophenyl)benzenesulfonamide (15d,
C32H33N5O6S) Purifcation was achieved using fash chro-
matography (ethyl acetate/hexane, 1:3) which provided
3H), 1.06–1.01 (m, 1H), 0.94 (s, 3H, CH3, H-18) ppm; 13
C
white solid (73%) 15d. M.p.: 223–224 °C; H NMR
1
NMR (DMSO-d6, 125 MHz): δ=155.8 (C-3), 154.8, 139.3,
139, 137.1, 130.4, 129.2 (2 CHAr), 128.6 (2 CHAr), 125.9,
120.9, 120.5 (2 CHAr), 120 (2 CHAr), 116.7, 114.9, 112.7,
81 (C-17), 47.7, 46.8, 43.1, 37.3, 32.7, 29.2, 27.1, 26.0, 21.8,
18.3, 14.3 (CH3, C-18) ppm; HRMS (ESI+): m/z calcd. for
C32H34N4O4S ([M+H]+) 570.2301, found 570.2309.
(DMSO-d6, 500 MHz): δ = 11.4 (s, 1H, –NHSO2–), 8.98
(brs, 1H, ArOH), 8.65 (s, 1H, triazole = CH), 8.14 (dd,
J = 9 Hz, 9 Hz, 4H, ArH), 8.05 (d, J = 8.5 Hz, 2H, ArH),
7.31 (d, J=9.5 Hz, 2H, ArH), 6.90 (d, J=8.5 Hz, 1H, H-1),
6.44–6.38 (m, 2H, H-2, H-4), 5.34 (s, 1H), 2.67 (m, 2H,
H-6), 2.40–2.25 (m, 2H), 2.10–1.78 (m, 4H), 1.63–1.12
(m, 7H), 1.08–0.93 (m, 4H) ppm; 13C NMR (DMSO-d6,
125 MHz): δ=167.1 (C–NO2), 155.9 (C-3), 139.9, 137.2,
132.0, 130.4, 128.8 (2 CHAr), 126.0, 125.5 (2 CHAr), 121.1,
120.4 (2 CHAr), 118.3 (2 CHAr), 116.4, 114.9, 112.7, 81.1
(C-17), 47.8, 46.9, 43.1, 37.3, 32.2, 29.3, 27.4, 23.3, 22.4,
18.6, 14.4 (CH3, C-18) ppm; HRMS (ESI+): m/z calcd. for
C32H33N5O6S ([M+H]+) 615.2152, found 615.2155.
4‑[4‑(17α‑1,3,5(10)‑Estratrien‑3,17β‑diol)‑1H‑1,2,3‑
triazol‑1‑yl]‑N‑(4‑chlorophenyl)benzenesulfonamide (15b,
C32H33ClN4O4S) Purifcation was achieved using fash chro-
matography (ethyl acetate/hexane, 1:3) which provided white
solid (77%) 15b. M.p.: 203–205 °C; 1H NMR (DMSO-d6,
500 MHz): δ = 10.55 (brs, 1H, –NHSO2–), 9.00 (brs, 1H,
ArOH), 8.61 (s, 1H, triazole =CH), 8.07 (d, J=9 Hz, 2H,
ArH), 7.88 (d, J = 9 Hz, 2H, ArH), 7.24 (t, J = 5 Hz, 2H,
ArH), 7.04 (t, J=8.5 Hz, 2H, ArH), 6.91 (d, J=8 Hz, 1H,
H-1), 6.44–6.39 (m, 2H, H-2, H-4), 5.34 (s, 1H), 2.66 (m,
2H, H-6), 2.38 (m, 1H), 2.15–1.77 (m, 5H), 1.62–1.20 (m,
4‑[4‑(17α‑1,3,5(10)‑Estratrien‑3,17β‑diol)‑1H‑1,2,3‑
triazol‑1‑yl]‑N‑(4‑methoxyphenyl)benzenesulfonamide
(15e, C33H36N4O5S) Purifcation was achieved using fash
chromatography (ethyl acetate/hexane, 1:3) which provided
white solid (68%) 15e. M.p.: 178–180 °C; 1H NMR (DMSO-
d6, 500 MHz): δ=10.01 (s, 1H, –NHSO2–), 8.97 (brs, 1H,
ArOH), 8.66 (s, 1H, triazole = CH), 8.11 (t, J = 7 Hz, 2H,
ArH), 7.82 (d, J = 9 Hz, 2H, ArH), 7.72 (dd, J = 9 Hz,
1.5 Hz, 2H, ArH), 6.90 (dd, J=2.5 Hz, 7.0 Hz, 2H, ArH),
6.80 (dd, J = 1.5 Hz, 9 Hz, 1H, H-1), 6.45–6.39 (m, 2H,
H-2, H-4), 5.32 (s, 1H), 3.66 (s, 3H, OCH3), 2.67 (m, 2H,
H-6), 2.40–2.25 (m, 2H), 2.10–1.75 (m, 5H), 1.62–1.15
(m, 7H), 0.94 (s, 3H, CH3, H-18) ppm; 13C NMR (DMSO-
d6, 125 MHz): δ=156.8 (C-3), 154.9, 144.6, 139.3, 138.6,
137.1, 136.1, 128.9, 128.6, 126.5, 124.0 (4 CHAr), 116.8,
114.9, 114.3 (4 CHAr), 112.7, 81.1 (C-17), 56.1 (OCH3),
47.8, 46.9, 43.1, 37.5, 32.4, 29.1, 27.3, 26.1, 22.4, 18.1,
13.9 (CH3, C-18) ppm; HRMS (ESI+): m/z calcd. for
C33H36N4O5S ([M+H]+) 600.2406, found 600.2415.
7H), 1.05–1.03 (m, 1H), 0.93 (s, 3H, CH3, H-18) ppm; 13
C
NMR (DMSO-d6, 125 MHz): δ=155.8 (C-3), 154.9, 139.7,
137.2, 131.6, 130.5, 129.0 (2 CHAr), 128.6 (2 CHAr), 126.1,
122.1 (2 CHAr), 121.0, 120.1 (2 CHAr), 116.7, 114.9, 112.7,
81.1 (C-17), 47.8, 46.9, 43.1, 37.8, 32.8, 29.3, 27.2, 26.1,
23.6, 20.3, 17.8, 14.4 (CH3, C-18) ppm; HRMS (ESI+):
m/z calcd. for C32H33ClN4O4S ([M+H]+) 604.1911, found
604.2001.
4‑[4‑(17α‑1,3,5(10)‑Estratrien‑3,17β‑diol)‑1H‑1,2,3‑
triazol‑1‑yl]‑N‑(4‑bromophenyl)benzenesulfonamide (15c,
C32H33BrN4O4S) Purification was achieved using flash
chromatography (ethyl acetate/hexane, 1:3) which pro-
1
vided white solid (91%) 15c. M.p.: 225–226 °C; H NMR
(DMSO-d6, 500 MHz): δ=10.56 (br s, 1H, –NHSO2–), 8.98
(br s, 1H, ArOH), 8.64 (s, 1H, triazole = CH), 8.13 (app.
d, J = 9 Hz, 2H, ArH), 7.92 (app. d, J = 7 Hz, 2H, ArH),
1 3