Syntheses and Antitumor Activities of Phenylpiperazine Derivatives†

doi:10.7503/cjcu20150397

Abstract

Abstract:

The structure of phenylpiperazine as an important pharmacophore could generate wide pharmacological activities. In this work, a series of novel phenylpiperazine derivatives was designed, synthesized and their preliminary antiproliferative activities against tumor cell lines were evaluated using MTT assay. Results indicated that the most active target compound 4t had the substitution of benzenesulfonamides and benzofuran on N1 and N4 position of piperazine respectively. Furthermore, IC₅₀ values of compound 4t against five tumor cell lines in vitro were determined. Compound 4t could inhibit the growth of some tumor cell lines and showed similar inhibitory activities against MDA-MB-231 tumor cell line(IC₅₀=3.50 μmol/L) compared with Gossypol(IC₅₀=1.40 μmol/L). These results provided useful information for designing new phenylpiperazine derivatives with higher antitumor activity.

Key words: Phenylpiperazine derivatives, Antitumor activity in vitro, Structure-activity relationship

CLC Number:

O625

TrendMD:

WANG Gang, HAN Leiqiang, FANG Hao. Syntheses and Antitumor Activities of Phenylpiperazine Derivatives^†[J]. Chem. J. Chinese Universities, 2015, 36(12): 2435.

Figures/Tables 5

References 20

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Compd.	Appearance	Yield(%)	m. p./℃	HRMS(calcd.), m/z [M+H]⁺
4a	Yellow solid	72	>250	530.0977(530.0976)
4b	Yellow solid	72	248—250	530.0979(530.0976)
4c	Yellow solid	88	220—221	519.0736(519.0736)
4d	Slightly yellow solid	74	>250	515.1231(515.1231)
4e	Yellow solid	69	164—166	485.1125(485.1125)
4f	Yellow solid	83	214—216	485.1125(485.1125)
4g	Yellow solid	78	174—176	474.0884(474.0885)
4h	Slightly yellow solid	95	182—184	470.1384(470.1380)
4i	Yellow solid	43	238—240	536.1234(536.1234)
4j	Yellow solid	67	202—204	536.1237(536.1234)
4k	Slightly yellow solid	89	212—214	525.0994(525.0994)
4l	Off-white solid	90	224—226	521.1486(521.1489)
4m	Yellow solid	72	242—244	530.0974(530.0976)
4n	Yellow solid	98	164—166	485.1121(485.1125)
4o	Slightly yellow solid	77	188—189	536.1236(536.1234)
4q	Slightly brown solid	73	64—66	470.1992(470.1994)
4r	Slightly brown solid	44	84—86	644.1536(644.1540)
4s	Slightly yellow solid	67	84—86	475.1786(475.1783)
4t	Off-white solid	56	202—204	449.0930(449.0932)

Compd.	Appearance	Yield(%)	m. p./℃	HRMS(calcd.), m/z [M+H]⁺
4a	Yellow solid	72	>250	530.0977(530.0976)
4b	Yellow solid	72	248—250	530.0979(530.0976)
4c	Yellow solid	88	220—221	519.0736(519.0736)
4d	Slightly yellow solid	74	>250	515.1231(515.1231)
4e	Yellow solid	69	164—166	485.1125(485.1125)
4f	Yellow solid	83	214—216	485.1125(485.1125)
4g	Yellow solid	78	174—176	474.0884(474.0885)
4h	Slightly yellow solid	95	182—184	470.1384(470.1380)
4i	Yellow solid	43	238—240	536.1234(536.1234)
4j	Yellow solid	67	202—204	536.1237(536.1234)
4k	Slightly yellow solid	89	212—214	525.0994(525.0994)
4l	Off-white solid	90	224—226	521.1486(521.1489)
4m	Yellow solid	72	242—244	530.0974(530.0976)
4n	Yellow solid	98	164—166	485.1121(485.1125)
4o	Slightly yellow solid	77	188—189	536.1236(536.1234)
4q	Slightly brown solid	73	64—66	470.1992(470.1994)
4r	Slightly brown solid	44	84—86	644.1536(644.1540)
4s	Slightly yellow solid	67	84—86	475.1786(475.1783)
4t	Off-white solid	56	202—204	449.0930(449.0932)

Compd.	¹H NMR(300 MHz), δ
4a	8.57(d, J=8.8 Hz, 1H, ArH), 8.39(s, 1H, ArH), 8.20—8.24(m, 3H, ArH), 8.10(d, J=9.2 Hz, 1H, ArH), 7.96(t, J=8.4 Hz, 1H, ArH), 7.07(d, J=9.2 Hz, 2H, ArH), 6.96(dd, J=2.4, 9.6 Hz, 1H, ArH), 6.87(d, J=2.4 Hz, 1H, ArH), 3.60(t, J=4.4 Hz, 4H, piperazine), 3.11(t, J=4.4 Hz, 4H, piperazine)
4b	8.44(d, J=5.6 Hz, 2H, ArH), 8.22(d, J=5.6 Hz, 2H, ArH), 8.10(d, J=6.4 Hz, 1H, ArH), 8.04(d, J=5.6 Hz, 2H, ArH), 7.07(d, J=5.6 Hz, 2H, ArH), 6.96(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.87(d, J=1.6 Hz, 1H, ArH), 3.59(d, J=2.8 Hz, 4H, piperazine), 3.10(d, J=2.8 Hz, 4H, piperazine)
4c	8.22(d, J=6.0 Hz, 2H, ArH), 8.10(d, J=6.4 Hz, 1H, ArH), 7.75(dd, J=6.0, 17.6 Hz, 4H, ArH), 7.08(d, J=6.0 Hz, 2H, ArH), 6.97(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.87(d, J=1.6 Hz, 1H, ArH), 3.58(s, 4H, piperazine), 3.07(s, 4H, piperazine)
4d	8.23(d, J=9.2 Hz, 2H, ArH), 8.10(d, J=9.6 Hz, 1H, ArH), 7.69(d, J=8.8 Hz, 2H, ArH), 7.17(d, J=8.8 Hz, 2H, ArH), 7.08(d, J=9.2 Hz, 2H, ArH), 6.96(dd, J=2.8, 9.6 Hz, 1H, ArH), 6.87(d, J=2.8 Hz, 1H, ArH), 3.85(s, 3H, OCH₃), 3.58(t, J=4.8 Hz, 4H, piperazine), 2.95(t, J=4.8 Hz, 4H, piperazine)
4e	8.55(dd, J=0.8, 5.6 Hz, 1H, ArH), 8.37(s, 1H, ArH), 8.19(d, J=6.0 Hz, 1H, ArH), 8.02(d, J=6.4 Hz, 1H, ArH), 7.95(t, J=5.2 Hz, 1H, ArH), 7.34(t, J=5.2 Hz, 2H, ArH), 7.10(t, J=5.2 Hz, 1H, ArH), 6.90(d, J=5.2 Hz, 2H, ArH), 6.84(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.57(d, J=1.6 Hz, 1H, ArH), 3.50(t, J=3.2 Hz, 4H, piperazine), 3.08(t, J=3.2 Hz, 4H, piperazine)
4f	8.43(d, J=5.6 Hz, 2H, ArH), 8.02(dd, J=1.2, 6.0 Hz, 3H, ArH), 7.34(t, J=5.6 Hz, 2H, ArH), 7.10(t, J=4.8 Hz, 1H, ArH), 6.90(d, J=4.8 Hz, 2H, ArH), 6.85(dd, J=2.0, 6.4 Hz, 1H, ArH), 6.58(d, J=1.6 Hz, 1H, ArH), 3.49(t, J=3.2 Hz, 4H, piperazine), 3.08(t, J=3.2 Hz, 4H, piperazine)
4g	8.03(d, J=6.4 Hz, 1H, ArH), 7.75(dd, J=5.6, 14.8 Hz, 4H, ArH), 7.35(t, J=5.6 Hz, 2H, ArH), 7.10(t, J=5.2 Hz, 1H, ArH), 6.91(d, J=5.2 Hz, 2H, ArH), 6.85(dd, J=2.0, 6.0 Hz, 1H, ArH), 6.59(d, J=2.0 Hz, 1H, ArH), 3.48(t, J=3.2 Hz, 4H, piperazine), 3.00(t, J=3.2 Hz, 4H, piperazine)
4h	8.03(d, J=9.2 Hz, 1H, ArH), 7.68(d, J=8.8 Hz, 2H, ArH), 7.35(t, J=7.6 Hz, 2H, ArH), 7.17(d, J=8.8 Hz, 2H, ArH), 7.10(t, J=7.2 Hz, 1H, ArH), 6.91(d, J=8.4 Hz, 2H, ArH), 6.86(dd, J=2.4, 9.2 Hz, 1H, ArH), 6.59(d, J=2.4 Hz, 1H, ArH), 3.85(s, 3H, OCH₃), 3.48(t, J=4.8 Hz, 4H, piperazine), 2.94(t, J=4.8 Hz, 4H, piperazine)
4i	8.85(dd, J=1.6, 4.4 Hz, 1H, ArH), 8.55(td, J=0.8, 8.4 Hz, 1H, ArH), 8.44(dd, J=1.2, 8.4 Hz, 1H, ArH), 8.34(d, J=1.2 Hz, 1H, ArH), 8.16(d, J=7.6 Hz, 1H, ArH), 8.06(d, J=9.6 Hz, 1H, ArH), 7.94(t, J=8.0 Hz, 1H, ArH), 7.79(d, J=8.0 Hz, 1H, ArH), 7.60(dd, J=4.0, 8.0 Hz, 1H, ArH), 7.54(t, J=8.0 Hz, 1H, ArH), 7.17(d, J=8.0 Hz, 1H, ArH), 6.81(dd, J=2.4, 9.2 Hz, 1H, ArH), 6.36(d, J=2.4 Hz, 1H, ArH), 3.38(t, J=4.8 Hz, 4H, piperazine), 3.02(t, J=4.8 Hz, 4H, piperazine)
4j	8.84(dd, J=0.8, 2.4 Hz, 1H, ArH), 8.41—8.44(m, 3H, ArH), 8.05(d, J=6.4 Hz, 1H, ArH), 7.98(d, J=5.6 Hz, 2H, ArH), 7.78(d, J=5.6 Hz, 1H, ArH), 7.60(dd, J=2.8, 5.6 Hz, 1H, ArH), 7.53(t, J=5.2 Hz, 1H, ArH), 7.16(d, J=4.8 Hz, 1H, ArH), 6.80(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.37(d, J=1.6 Hz, 1H, ArH), 3.37(t, J=3.2 Hz, 4H, piperazine), 3.00(t, J=3.2 Hz, 4H, piperazine)
4k	8.85(dd, J=0.8, 2.4 Hz, 1H, ArH), 8.44(dd, J=0.8, 5.2 Hz, 1H, ArH), 8.06(d, J=6.0 Hz, 1H, ArH), 7.79(d, J=5.2 Hz, 2H, ArH), 7.72(d, J=0.8 Hz, 4H, ArH), 7.60(dd, J=2.8, 5.6 Hz, 1H, ArH), 7.54(t, J=5.2 Hz, 1H, ArH), 7.16(d, J=5.2 Hz, 1H, ArH), 6.81(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.38(d, J=1.6 Hz, 1H, ArH), 2.93(t, J=3.2 Hz, 8H, piperazine)
4l	8.84(dd, J=0.8, 2.4 Hz, 1H, ArH), 8.43(dd, J=1.2, 5.6 Hz, 1H, ArH), 8.06(d, J=6.4 Hz, 1H, ArH), 7.79(d, J=5.2 Hz, 1H, ArH), 7.64(d, J=6.0 Hz, 2H, ArH), 7.60(dd, J=2.8, 5.6 Hz, 1H, ArH), 7.53(t, J=5.2 Hz, 1H, ArH), 7.13—7.17(m, 3H, ArH), 6.81(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.37(d, J=2.0 Hz, 1H, ArH), 3.84(s, 3H, OCH₃), 3.34(t, J=3.2 Hz, 4H, piperazine), 2.86(t, J=3.2 Hz, 4H, piperazine)
4m	8.58(d, J=5.6 Hz, 1H, ArH), 8.41(s, 1H, ArH), 8.29(d, J=6.0 Hz, 2H, ArH), 8.23(d, J=5.2 Hz, 1H, ArH), 7.96—8.01(m, 2H), 7.30(d, J=5.6 Hz, 2H, ArH), 7.09(d, J=0.8 Hz, 1H, ArH), 6.84(dd, J=0.8, 6.0 Hz, 1H, ArH), 3.12(s, 8H, piperazine)
4n	8.58(d, J=5.6 Hz, 1H, ArH), 8.41(s, 1H, ArH), 8.23(d, J=4.8 Hz, 1H, ArH), 8.00(t, J=5.6 Hz, 1H, ArH), 7.92(d, J=6.0 Hz, 1H, ArH), 7.47(t, J=5.6 Hz, 2H, ArH), 7.28(t, J=5.2 Hz, 1H, ArH), 7.15(d, J=5.6 Hz, 2H, ArH), 6.89(d, J=1.6 Hz, 1H, ArH), 6.54(dd, J=1.6, 6.0 Hz, 1H, ArH), 3.11(d, J=6.4 Hz, 8H, piperazine)
4o	8.84(d, J=2.4 Hz, 1H, ArH), 8.59(d, J=5.2 Hz, 1H, ArH), 8.48(d, J=5.2 Hz, 1H, ArH), 8.42(s, 1H, ArH), 8.23(d, J=5.2 Hz, 1H, ArH), 8.00(t, J=5.2 Hz, 1H, ArH), 7.97(d, J=5.6 Hz, 1H, ArH), 7.82(d, J=6.4 Hz, 1H, ArH), 7.68(t, J=5.6 Hz, 1H, ArH), 7.60—7.62(m, 2H, ArH), 6.94(d, J=1.2 Hz, 1H, ArH), 6.27(dd, J=1.6, 6.0 Hz, 1H, ArH), 3.11(d, J=2.4 Hz, 8H, piperazine)
4q	7.46—7.50(m, 5H, ArH), 7.28—7.36(m, 4H, ArH), 7.22(dd, J=0.8, 4.8 Hz, 1H, ArH), 7.01(t, J=4.8 Hz, 1H, ArH), 6.86(d, J=5.2 Hz, 2H, ArH), 6.73(d, J=5.6 Hz, 1H, ArH), 6.59(dd, J=1.6, 5.6 Hz, 1H, ArH), 6.42(d, J=1.6 Hz, 1H, ArH), 4.39(s, 2H, NH₂), 3.35(s, 2H, CH₂), 2.84(s, 4H, piperazine), 2.36(s, 4H, piperazine)
4r	7.57(dd, J=2.4, 8.8 Hz, 3H, ArH), 7.33—7.36(m, 6H, ArH), 7.22—7.30(m, 5H, ArH), 7.09(t, J=6.4 Hz, 1H, ArH), 6.63—6.66(m, 2H, ArH), 6.50(d, J=8.0 Hz, 2H, ArH), 6.20(d, J=2.0 Hz, 1H, ArH), 3.39(s, 2H, CH₂), 3.00(s, 4H, piperazine), 2.45(s, 4H, piperazine)
4s	7.60(d, J=0.8 Hz, 1H, ArH), 7.55(d, J=6.4 Hz, 1H, ArH), 7.52(d, J=4.8 Hz, 1H, ArH), 7.49(s, 4H, ArH), 7.36—7.40(m, 2H, ArH), 7.22—7.26(m, 2H, ArH), 7.14(d, J=1.2 Hz, 1H, ArH), 4.34(q, J=4.8 Hz, 2H, OCH₂), 3.40(s, 2H, ArCH₂), 3.07(s, 4H, piperazine), 2.45(s, 4H, piperazine), 1.33(t, J=4.8 Hz, 3H, CH₃)
4t	7.78(dd, J=5.6, 18.0 Hz, 4H, ArH), 7.62(s, 1H, ArH), 7.58(d, J=6.4 Hz, 1H, ArH), 7.22(dd, J=1.2, 6.0 Hz, 1H, ArH), 7.18(d, J=1.2 Hz, 1H, ArH), 4.34(q, J=4.8 Hz, 2H, OCH₂), 3.19(s, 4H, piperazine), 3.07(s, 4H, piperazine), 1.33(t, J=4.8 Hz, 3H, CH₃)

Compd.	¹H NMR(300 MHz), δ
4a	8.57(d, J=8.8 Hz, 1H, ArH), 8.39(s, 1H, ArH), 8.20—8.24(m, 3H, ArH), 8.10(d, J=9.2 Hz, 1H, ArH), 7.96(t, J=8.4 Hz, 1H, ArH), 7.07(d, J=9.2 Hz, 2H, ArH), 6.96(dd, J=2.4, 9.6 Hz, 1H, ArH), 6.87(d, J=2.4 Hz, 1H, ArH), 3.60(t, J=4.4 Hz, 4H, piperazine), 3.11(t, J=4.4 Hz, 4H, piperazine)
4b	8.44(d, J=5.6 Hz, 2H, ArH), 8.22(d, J=5.6 Hz, 2H, ArH), 8.10(d, J=6.4 Hz, 1H, ArH), 8.04(d, J=5.6 Hz, 2H, ArH), 7.07(d, J=5.6 Hz, 2H, ArH), 6.96(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.87(d, J=1.6 Hz, 1H, ArH), 3.59(d, J=2.8 Hz, 4H, piperazine), 3.10(d, J=2.8 Hz, 4H, piperazine)
4c	8.22(d, J=6.0 Hz, 2H, ArH), 8.10(d, J=6.4 Hz, 1H, ArH), 7.75(dd, J=6.0, 17.6 Hz, 4H, ArH), 7.08(d, J=6.0 Hz, 2H, ArH), 6.97(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.87(d, J=1.6 Hz, 1H, ArH), 3.58(s, 4H, piperazine), 3.07(s, 4H, piperazine)
4d	8.23(d, J=9.2 Hz, 2H, ArH), 8.10(d, J=9.6 Hz, 1H, ArH), 7.69(d, J=8.8 Hz, 2H, ArH), 7.17(d, J=8.8 Hz, 2H, ArH), 7.08(d, J=9.2 Hz, 2H, ArH), 6.96(dd, J=2.8, 9.6 Hz, 1H, ArH), 6.87(d, J=2.8 Hz, 1H, ArH), 3.85(s, 3H, OCH₃), 3.58(t, J=4.8 Hz, 4H, piperazine), 2.95(t, J=4.8 Hz, 4H, piperazine)
4e	8.55(dd, J=0.8, 5.6 Hz, 1H, ArH), 8.37(s, 1H, ArH), 8.19(d, J=6.0 Hz, 1H, ArH), 8.02(d, J=6.4 Hz, 1H, ArH), 7.95(t, J=5.2 Hz, 1H, ArH), 7.34(t, J=5.2 Hz, 2H, ArH), 7.10(t, J=5.2 Hz, 1H, ArH), 6.90(d, J=5.2 Hz, 2H, ArH), 6.84(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.57(d, J=1.6 Hz, 1H, ArH), 3.50(t, J=3.2 Hz, 4H, piperazine), 3.08(t, J=3.2 Hz, 4H, piperazine)
4f	8.43(d, J=5.6 Hz, 2H, ArH), 8.02(dd, J=1.2, 6.0 Hz, 3H, ArH), 7.34(t, J=5.6 Hz, 2H, ArH), 7.10(t, J=4.8 Hz, 1H, ArH), 6.90(d, J=4.8 Hz, 2H, ArH), 6.85(dd, J=2.0, 6.4 Hz, 1H, ArH), 6.58(d, J=1.6 Hz, 1H, ArH), 3.49(t, J=3.2 Hz, 4H, piperazine), 3.08(t, J=3.2 Hz, 4H, piperazine)
4g	8.03(d, J=6.4 Hz, 1H, ArH), 7.75(dd, J=5.6, 14.8 Hz, 4H, ArH), 7.35(t, J=5.6 Hz, 2H, ArH), 7.10(t, J=5.2 Hz, 1H, ArH), 6.91(d, J=5.2 Hz, 2H, ArH), 6.85(dd, J=2.0, 6.0 Hz, 1H, ArH), 6.59(d, J=2.0 Hz, 1H, ArH), 3.48(t, J=3.2 Hz, 4H, piperazine), 3.00(t, J=3.2 Hz, 4H, piperazine)
4h	8.03(d, J=9.2 Hz, 1H, ArH), 7.68(d, J=8.8 Hz, 2H, ArH), 7.35(t, J=7.6 Hz, 2H, ArH), 7.17(d, J=8.8 Hz, 2H, ArH), 7.10(t, J=7.2 Hz, 1H, ArH), 6.91(d, J=8.4 Hz, 2H, ArH), 6.86(dd, J=2.4, 9.2 Hz, 1H, ArH), 6.59(d, J=2.4 Hz, 1H, ArH), 3.85(s, 3H, OCH₃), 3.48(t, J=4.8 Hz, 4H, piperazine), 2.94(t, J=4.8 Hz, 4H, piperazine)
4i	8.85(dd, J=1.6, 4.4 Hz, 1H, ArH), 8.55(td, J=0.8, 8.4 Hz, 1H, ArH), 8.44(dd, J=1.2, 8.4 Hz, 1H, ArH), 8.34(d, J=1.2 Hz, 1H, ArH), 8.16(d, J=7.6 Hz, 1H, ArH), 8.06(d, J=9.6 Hz, 1H, ArH), 7.94(t, J=8.0 Hz, 1H, ArH), 7.79(d, J=8.0 Hz, 1H, ArH), 7.60(dd, J=4.0, 8.0 Hz, 1H, ArH), 7.54(t, J=8.0 Hz, 1H, ArH), 7.17(d, J=8.0 Hz, 1H, ArH), 6.81(dd, J=2.4, 9.2 Hz, 1H, ArH), 6.36(d, J=2.4 Hz, 1H, ArH), 3.38(t, J=4.8 Hz, 4H, piperazine), 3.02(t, J=4.8 Hz, 4H, piperazine)
4j	8.84(dd, J=0.8, 2.4 Hz, 1H, ArH), 8.41—8.44(m, 3H, ArH), 8.05(d, J=6.4 Hz, 1H, ArH), 7.98(d, J=5.6 Hz, 2H, ArH), 7.78(d, J=5.6 Hz, 1H, ArH), 7.60(dd, J=2.8, 5.6 Hz, 1H, ArH), 7.53(t, J=5.2 Hz, 1H, ArH), 7.16(d, J=4.8 Hz, 1H, ArH), 6.80(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.37(d, J=1.6 Hz, 1H, ArH), 3.37(t, J=3.2 Hz, 4H, piperazine), 3.00(t, J=3.2 Hz, 4H, piperazine)
4k	8.85(dd, J=0.8, 2.4 Hz, 1H, ArH), 8.44(dd, J=0.8, 5.2 Hz, 1H, ArH), 8.06(d, J=6.0 Hz, 1H, ArH), 7.79(d, J=5.2 Hz, 2H, ArH), 7.72(d, J=0.8 Hz, 4H, ArH), 7.60(dd, J=2.8, 5.6 Hz, 1H, ArH), 7.54(t, J=5.2 Hz, 1H, ArH), 7.16(d, J=5.2 Hz, 1H, ArH), 6.81(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.38(d, J=1.6 Hz, 1H, ArH), 2.93(t, J=3.2 Hz, 8H, piperazine)
4l	8.84(dd, J=0.8, 2.4 Hz, 1H, ArH), 8.43(dd, J=1.2, 5.6 Hz, 1H, ArH), 8.06(d, J=6.4 Hz, 1H, ArH), 7.79(d, J=5.2 Hz, 1H, ArH), 7.64(d, J=6.0 Hz, 2H, ArH), 7.60(dd, J=2.8, 5.6 Hz, 1H, ArH), 7.53(t, J=5.2 Hz, 1H, ArH), 7.13—7.17(m, 3H, ArH), 6.81(dd, J=1.6, 6.4 Hz, 1H, ArH), 6.37(d, J=2.0 Hz, 1H, ArH), 3.84(s, 3H, OCH₃), 3.34(t, J=3.2 Hz, 4H, piperazine), 2.86(t, J=3.2 Hz, 4H, piperazine)
4m	8.58(d, J=5.6 Hz, 1H, ArH), 8.41(s, 1H, ArH), 8.29(d, J=6.0 Hz, 2H, ArH), 8.23(d, J=5.2 Hz, 1H, ArH), 7.96—8.01(m, 2H), 7.30(d, J=5.6 Hz, 2H, ArH), 7.09(d, J=0.8 Hz, 1H, ArH), 6.84(dd, J=0.8, 6.0 Hz, 1H, ArH), 3.12(s, 8H, piperazine)
4n	8.58(d, J=5.6 Hz, 1H, ArH), 8.41(s, 1H, ArH), 8.23(d, J=4.8 Hz, 1H, ArH), 8.00(t, J=5.6 Hz, 1H, ArH), 7.92(d, J=6.0 Hz, 1H, ArH), 7.47(t, J=5.6 Hz, 2H, ArH), 7.28(t, J=5.2 Hz, 1H, ArH), 7.15(d, J=5.6 Hz, 2H, ArH), 6.89(d, J=1.6 Hz, 1H, ArH), 6.54(dd, J=1.6, 6.0 Hz, 1H, ArH), 3.11(d, J=6.4 Hz, 8H, piperazine)
4o	8.84(d, J=2.4 Hz, 1H, ArH), 8.59(d, J=5.2 Hz, 1H, ArH), 8.48(d, J=5.2 Hz, 1H, ArH), 8.42(s, 1H, ArH), 8.23(d, J=5.2 Hz, 1H, ArH), 8.00(t, J=5.2 Hz, 1H, ArH), 7.97(d, J=5.6 Hz, 1H, ArH), 7.82(d, J=6.4 Hz, 1H, ArH), 7.68(t, J=5.6 Hz, 1H, ArH), 7.60—7.62(m, 2H, ArH), 6.94(d, J=1.2 Hz, 1H, ArH), 6.27(dd, J=1.6, 6.0 Hz, 1H, ArH), 3.11(d, J=2.4 Hz, 8H, piperazine)
4q	7.46—7.50(m, 5H, ArH), 7.28—7.36(m, 4H, ArH), 7.22(dd, J=0.8, 4.8 Hz, 1H, ArH), 7.01(t, J=4.8 Hz, 1H, ArH), 6.86(d, J=5.2 Hz, 2H, ArH), 6.73(d, J=5.6 Hz, 1H, ArH), 6.59(dd, J=1.6, 5.6 Hz, 1H, ArH), 6.42(d, J=1.6 Hz, 1H, ArH), 4.39(s, 2H, NH₂), 3.35(s, 2H, CH₂), 2.84(s, 4H, piperazine), 2.36(s, 4H, piperazine)
4r	7.57(dd, J=2.4, 8.8 Hz, 3H, ArH), 7.33—7.36(m, 6H, ArH), 7.22—7.30(m, 5H, ArH), 7.09(t, J=6.4 Hz, 1H, ArH), 6.63—6.66(m, 2H, ArH), 6.50(d, J=8.0 Hz, 2H, ArH), 6.20(d, J=2.0 Hz, 1H, ArH), 3.39(s, 2H, CH₂), 3.00(s, 4H, piperazine), 2.45(s, 4H, piperazine)
4s	7.60(d, J=0.8 Hz, 1H, ArH), 7.55(d, J=6.4 Hz, 1H, ArH), 7.52(d, J=4.8 Hz, 1H, ArH), 7.49(s, 4H, ArH), 7.36—7.40(m, 2H, ArH), 7.22—7.26(m, 2H, ArH), 7.14(d, J=1.2 Hz, 1H, ArH), 4.34(q, J=4.8 Hz, 2H, OCH₂), 3.40(s, 2H, ArCH₂), 3.07(s, 4H, piperazine), 2.45(s, 4H, piperazine), 1.33(t, J=4.8 Hz, 3H, CH₃)
4t	7.78(dd, J=5.6, 18.0 Hz, 4H, ArH), 7.62(s, 1H, ArH), 7.58(d, J=6.4 Hz, 1H, ArH), 7.22(dd, J=1.2, 6.0 Hz, 1H, ArH), 7.18(d, J=1.2 Hz, 1H, ArH), 4.34(q, J=4.8 Hz, 2H, OCH₂), 3.19(s, 4H, piperazine), 3.07(s, 4H, piperazine), 1.33(t, J=4.8 Hz, 3H, CH₃)

Compd.	IC₅₀/(μmol·L^-1)
Compd.	MDA-MB-231	A549	MCF-7	Hela	KG1
4t	3.50±0.68	25.9±7.9	20.9±3.9	> 42	17.3±0.4
Gossypol	1.40±0.24	4.02±0.41	3.00±0.87	8.81±1.22	2.87±0.77