一種具有α,β‑不飽和酮結構片段的孕烯醇酮衍生物及其用途的製作方法

2023-09-13 08:14:55 2

本發明涉及一種具有α,β-不飽和酮結構片段的孕烯醇酮衍生物及其在製備預防和/或治療乳腺癌的用途。

背景技術：

腫瘤是機體在各種致瘤因素作用下，局部組織的細胞在基因水平上失去對其生長的正常調控導致異常增生與分化而形成的新生物。惡性腫瘤的病因尚未完全了解，其中乳腺癌是由於癌細胞親潤並破壞正常乳房組織形成的一種惡性腫瘤，是全世界女性最常見的癌症。據資料統計，乳腺癌發病率佔全身各種惡性腫瘤的7-10％，在婦女僅次於子宮癌，嚴重影響婦女身心健康甚至危及生命。與發達國家相比，中國雖屬乳腺癌的低發區，但近年來乳腺癌發病率增長趨勢明顯，目前約有47萬名乳腺癌患者。針對乳腺癌藥物這一市場，近年來製藥公司的研發投入明顯增強，儘管抗乳腺癌的化療藥物已不在少數，但是乳腺癌對於化療藥物的低敏感性及化療藥物造成的副作用均已引起了醫學界的關注。

甾體類化合物廣泛存在於動植物體內，是一類具有顯著生理活性的物質，它們對細胞具有高度的滲透能力和對細胞核及細胞膜的結合能力，在醫藥化學中被廣泛的應用。近年來，藥物化學家一直致力通過不同的方式對甾體化合物進行結構改造，進而發現潛在藥用價值的抗腫瘤藥物先導物，然後進一步探索它們在臨床上的應用，希望尋找到更好的高效低毒抗腫瘤藥物。

本發明公開了一種具有α,β-不飽和酮結構片段的孕烯醇酮衍生物，可用於製備抗乳腺癌藥物。

技術實現要素：

本發明人經過對大量實驗室合成化合物及其結構衍生物的篩選，發現了一類結構相對簡單、對乳腺癌mcf-7細胞具有一定的抑制活性的通式i所示的新化合物，由此可能具有預防和/或治療乳腺癌的作用，從而在製藥領域具有潛在的用途。迄今為止，未見關於式i所示化合物的結構、製備方法及用途的報導。

本發明採用以下技術方案：

一種具有α,β-不飽和酮結構片段的孕烯醇酮衍生物，其特徵在於，它具有如下通式i所示的結構：

其中，r1、r2和r3為芳環上鄰位、間位及對位取代基團，r1、r2或r3可分別或同時為氫、甲基、甲氧基、乙氧基、羥基、硝基、二甲胺基、二乙胺基、異丙基、氟、氯、溴、腈基。

本發明還提供了一種上述的衍生物在製備抗乳腺癌藥物中的應用。

本發明還提供了一種用於預防和/或治療乳腺癌的藥物，它是由上述通式i所示的衍生物為活性成分或主要活性成分，輔以藥學上可接受的輔料製成。

本發明所涉及衍生物的製備方法，包括以下步驟：

a)孕烯醇酮(式1)和對硝基氯甲酸苯酯反應得到式2化合物。其中，所用縛酸劑為吡啶、三乙胺、二異丙基乙胺、碳酸鈉和碳酸鉀中至少一種；反應溶劑為n,n-二甲基甲醯胺、三乙胺、二異丙胺、二異丙基乙胺、四氫呋喃、二氯甲烷、1,4-二氧六環及甲苯中至少一種；該反應溫度為0℃～100℃，反應時間為1～36小時。

b)式2化合物與n-boc-乙二胺反應得到式3化合物。其中，所用催化劑為三乙胺、二異丙基乙胺、二氮雜二環辛烷、吡啶、4-二甲氨基吡啶、碳酸鈉、碳酸銫或碳酸鉀；該反應所用溶劑為二氯甲烷、四氫呋喃、n,n-二甲基甲醯胺、四氫呋喃、1,4-二氧六環或水，該反應溫度為0℃～100℃，反應時間為1～24小時。

c)式3化合物經脫boc保護基後得到在式4化合物。其中，去保護基試劑為鹽酸、三氟乙酸、苯磺酸、硫酸、三氟化硼或乙酸；所用溶劑為二氯甲烷、乙酸乙酯、甲醇、四氫呋喃、三氯甲烷及水中至少一種；該反應溫度為0℃～100℃，反應時間為1～48小時。

d)式4化合物與氰乙酸在縮合劑作用下，得到式5化合物。其中，所用的縮合劑為n,n'-二環己基碳二亞胺、n,n'-二異丙基碳二亞胺、1-乙基-(3-二甲基氨基丙基)碳醯二亞胺鹽酸鹽、偶氮二甲酸二乙酯、偶氮二甲酸二異丙酯、1-羥基-7-偶氮苯並三氮唑、1-羥基苯並三氮唑、o-(7-氮苯並三氮唑)-n,n,n',n'-四甲基脲六氟磷酸酯和苯並三氮唑-n,n,n',n'-四甲基脲六氟磷酸酯中的一種或兩種以上的組合；所用溶劑為甲醇、乙醇、丙醇、異丙醇、乙腈、1,4-二氧六環、二氯乙烷、n,n-二異丙基乙胺和水中的一種或一種以上；反應溫度為0℃～100℃；反應時間為6～36小時；

e)式5化合物與式6化合物在鹼催化作用下反應，得到通式i化合物。其中，所述鹼可為三乙胺、n,n-二異丙基乙胺、哌啶、吡啶、碳酸鈉、碳酸鉀、氫氧化鈉、氫氧化鉀或1-4個碳的醇鉀及醇鈉；所用溶劑為甲醇、乙醇、丙醇、異丙醇、水和四氫呋喃中的一種或一種以上；反應溫度為0℃～100℃；反應時間為6～24小時。

所述式6化合物結構如下：其中：

其中，r1、r2和r3為芳環上鄰位、間位及對位取代基團，r1、r2或r3可分別或同時為氫、甲基、甲氧基、乙氧基、羥基、硝基、二甲胺基、二乙胺基、異丙基、氟、氯、溴、腈基。

本發明提供了上述衍生物化合物在製備抗乳腺癌藥物中的應用。

本發明還提供了一種用於預防和/或治療乳腺癌的藥物組合物，其特徵在於，以上述通式i所示的衍生物為活性成分或主要活性成分，輔以藥學上可接受的輔料。

本發明的有益效果是：本發明的化合物為首次合成的一類具有α,β-不飽和酮結構片段的孕烯醇酮衍生物，在對合成化合物細胞測試實驗中，首次發現該類化合物對mcf-7細胞具有較強的抑制活性，因而它們在製備預防和/或治療乳腺癌的藥物中具有潛在的應用前景。

具體實施方式

下面結合具體實施例對本發明做進一步的詳細說明。這些實施例僅用於說明本發明而不用於限制本發明的範圍。

實施例1：式2化合物的製備

將3.16g式1化合物溶於30ml二氯甲烷中，隨後加入1.82g吡啶和3.015g對硝基氯甲酸苯酯，氮氣保護，室溫下攪拌24小時。之後將反應液濃縮，二氯甲烷/水萃取有機相。有機相依次用飽和碳酸鈉溶液、水和飽和食鹽水洗滌，濃縮。殘餘物經柱層析純化後得到3.80g無色油狀化合物式2，產率79％。1hnmr(400mhz,cdcl3)δ8.29(s,1h),8.27(s,1h),7.40(s,1h),7.37(s,1h),5.43(d,j＝5.2hz,1h),4.68–4.55(m,1h),2.54(t,j＝8.9hz,3h),2.19(dd,j＝9.5,7.7hz,1h),2.13(s,3h),2.09–1.98(m,3h),1.94(dt,j＝13.4,3.5hz,1h),1.78–1.72(m,1h),1.69(d,j＝5.9hz,2h),1.68–1.59(m,1h),1.60(s,2h),1.51(d,j＝4.0hz,1h),1.49–1.44(m,2h),1.31–1.08(m,3h),1.05(s,3h),0.64(s,3h).13cnmr(151mhz,cdcl3)δ209.53,155.61,151.79,145.29,138.84,125.29,123.22,121.80,79.59,63.64,56.80,49.82,43.97,38.74,37.80,36.79,36.56,31.78,31.76,31.57,27.54,24.48,22.83,21.05,19.27,13.24.esi-msm/z:482[m+h]+.

實施例2：式3化合物的製備

將3.80g式2化合物溶於50ml二氯甲烷中，加入2.4g三乙胺和3.79gn-boc-乙二胺，氮氣保護，室溫攪拌30小時。反應液減壓濃縮後，加入100ml水，乙酸乙酯萃取三次。有機相依次用飽和碳酸鈉溶液、飽和食鹽水洗滌，用飽和碳酸鈉溶液洗至溶液為中性，無水硫酸鎂乾燥。最後經過濾、有機相濃縮，柱層析得到2.667g淡黃色固體化合物式3，產率84％。1hnmr(400mhz,cdcl3)δ5.42–5.33(m,1h),4.91(d,j＝54.1hz,2h),4.49(t,j＝11.4hz,1h),3.26(s,4h),2.53(t,j＝8.9hz,1h),2.39–2.32(m,1h),2.31–2.24(m,1h),2.20–2.15(m,1h),2.12(s,3h),2.06–1.94(m,2h),1.92–1.82(m,2h),1.67(d,j＝7.8hz,1h),1.63(s,3h),1.60(d,j＝2.5hz,1h),1.55–1.51(m,1h),1.49(d,j＝3.9hz,1h),1.46(s,1h),1.44(s,9h),1.28–1.21(m,1h),1.17(dd,j＝9.8,5.8hz,2h),1.00(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.64,156.48,139.80,122.20,79.56,74.33,63.69,56.84,49.86,44.00,41.28,40.74,38.79,38.48,36.98,36.57,31.82,31.76,31.58,28.38,28.09,24.48,22.81,21.04,19.32,13.23.esi-msm/z:525[m+na]+.

實施例3：式4化合物的製備

將2.667g式3化合物溶於30ml二氯甲烷中，冰浴至0℃後加入10ml三氟乙酸，氮氣保護，攪拌30小時。反應結束後，反應液並濃縮，得到2.19g油狀的式4化合物，未純化，直接用於下一步反應。

實施例4：式5化合物的製備

將924mg氰乙酸、1.597gedci、147mg的hobt溶於30ml二氯甲烷中，後加入2.103gn,n-二異丙基乙胺，氮氣保護，攪拌半小時後，加入2.19g式4化合物後，室溫攪拌36小時。反應液濃縮，殘餘物經柱層析純化後得到1.98g的式5化合物，產率84％。1hnmr(400mhz,cdcl3)δ7.22(s,1h),5.36(d,j＝5.0hz,1h),5.23(t,j＝5.6hz,1h),4.51–4.41(m,1h),3.45–3.40(m,2h),3.39(s,3h),3.36–3.29(m,2h),2.53(t,j＝8.9hz,1h),2.36(d,j＝4.4hz,1h),2.28(d,j＝12.4hz,1h),2.20–2.13(m,1h),2.11(s,3h),2.05–1.94(m,3h),1.90–1.82(m,3h),1.66(d,j＝8.0hz,2h),1.62–1.51(m,3h),1.44(d,j＝8.9hz,3h),1.23(s,2h),1.17(d,j＝5.8hz,1h),1.13(d,j＝4.2hz,1h),0.99(s,3h),0.61(s,3h).13cnmr(151mhz,cdcl3)δ209.71,161.72,157.36,139.60,122.42,114.48,74.92,63.68,56.82,49.84,44.00,41.70,40.14,38.77,38.42,36.94,36.56,31.81,31.75,31.59,28.05,25.92,24.48,22.82,21.04,19.32,13.23.esi-msm/z:492[m+na]+.

實施例5：通式i化合物的製備

室溫下，在3ml乙醇中加入155mg的式5化合物(1equiv)，加入相應式6化合物(1.1equiv)和200μl哌啶，氮氣保護，室溫攪拌16小時。濃縮反應液得殘餘物，經柱層析純化後得到相應的通式i化合物。化合物編號、具體結構式以及原料如下表1所示。

表1化合物編號、具體結構式、所用原料以及活性結果

化合物i-1，淡黃色固體(147mg,76％).1hnmr(400mhz,cdcl3)δ8.22(s,1h),7.95(s,1h),7.92(s,1h),6.99(s,1h),6.96(s,1h),5.34(d,j＝5.0hz,1h),5.12(t,j＝5.6hz,1h),4.57–4.45(m,1h),3.88(s,3h),3.58–3.52(m,2h),3.48(s,2h),3.40(d,j＝5.4hz,2h),2.53(t,j＝8.8hz,1h),2.41–2.32(m,1h),2.27(d,j＝11.3hz,1h),2.17(s,1h),2.12(s,3h),2.03(d,j＝7.4hz,1h),1.66(d,j＝8.1hz,1h),1.59(s,1h),1.56(s,1h),1.52(s,1h),1.44(s,1h),1.42(s,1h),1.22–1.18(m,1h),1.17(d,j＝5.9hz,1h),1.13(s,1h),0.98(s,3h),0.61(s,3h).13cnmr(151mhz,cdcl3)δ209.69,163.39,161.77,156.82,152.43,139.73,133.18,124.62,122.27,117.44,114.72,100.36,74.65,63.70,56.84,55.61,49.84,44.01,41.27,40.60,38.80,38.43,36.96,36.55,31.82,31.76,31.59,28.06,24.49,22.82,21.04,19.32,13.24.esi-msm/z:610[m+na]+.

化合物i-2，淡黃色固體(139mg,70％).1hnmr(600mhz,cdcl3)δ8.20(s,1h),7.70(s,1h),7.41(s,1h),7.00(s,1h),6.90(s,1h),6.32(s,1h),5.35(s,1h),5.09(s,1h),4.53(s,1h),3.97(s,3h),3.57(s,2h),3.42(s,2h),2.54(s,1h),2.37(s,1h),2.27(s,1h),2.18(d,j＝9.7hz,1h),2.13(s,3h),2.05(s,1h),1.98(d,j＝15.3hz,1h),1.90(s,1h),1.85(d,j＝12.5hz,1h),1.69(s,3h),1.63–1.52(m,3h),1.46(s,2h),1.26(s,2h),1.15(d,j＝10.2hz,2h),1.00(s,3h),0.63(s,3h).13cnmr(151mhz,cdcl3)δ209.74,161.78,156.86,152.89,150.43,146.82,139.72,127.92,124.47,122.28,117.62,115.02,111.20,100.02,74.64,63.70,56.84,56.11,49.85,44.01,41.29,40.62,38.79,38.43,36.95,36.55,31.82,31.76,31.59,28.07,24.49,22.82,21.04,19.32,13.24.esi-msm/z:604[m+h]+.

化合物i-3，淡黃色固體(79mg,38％).1hnmr(600mhz,dmso)δ9.65(s,1h),8.24(t,j＝5.6hz,1h),8.04(s,1h),7.35(s,2h),7.13(t,j＝5.6hz,1h),5.29–5.25(m,1h),4.30(ddd,j＝15.9,11.4,4.5hz,1h),3.79(s,6h),3.27–3.23(m,2h),3.13–3.08(m,2h),2.54(t,j＝9.0hz,1h),2.30–2.25(m,1h),2.18(t,j＝11.3hz,1h),2.04(s,3h),1.97(d,j＝11.3hz,1h),1.92–1.85(m,1h),1.79(dd,j＝21.7,9.6hz,2h),1.56–1.50(m,3h),1.47(d,j＝13.7hz,1h),1.40–1.36(m,2h),1.22(dq,j＝13.3,7.1hz,2h),1.14–1.10(m,2h),1.06–1.00(m,1h),0.93(s,3h),0.84(dd,j＝11.5,4.4hz,1h),0.80(t,j＝7.3hz,1h),0.50(s,3h).13cnmr(151mhz,dmso)δ208.99,162.06,156.35,151.57,148.34,141.09,140.21,122.43,122.21,117.85,108.86,101.87,73.48,63.47,63.02,56.47,49.78,43.72,41.96,38.76,38.34,37.04,36.55,31.77,31.68,30.25,29.11,28.33,24.48,22.68,21.03,19.45,13.40.esi-msm/z:656[m+na]+.

化合物i-4，淡黃色固體(79mg,38％).1hnmr(600mhz,dmso)δ9.70(s,1h),8.33(t,j＝5.6hz,1h),7.96(s,1h),7.15(d,j＝1.9hz,1h),7.12(t,j＝5.8hz,1h),7.09(d,j＝1.8hz,1h),5.27–5.24(m,1h),4.28(ddd,j＝16.1,11.4,4.7hz,1h),3.77(s,3h),3.72(s,3h),3.22(dt,j＝7.7,6.3hz,2h),3.11–3.06(m,2h),2.53(t,j＝9.0hz,1h),2.27–2.23(m,1h),2.17(d,j＝11.1hz,1h),2.03(s,3h),2.01–1.95(m,2h),1.88(ddd,j＝12.3,5.1,2.5hz,1h),1.77(dd,j＝7.6,3.0hz,1h),1.74(s,1h),1.55–1.50(m,3h),1.49–1.44(m,1h),1.39–1.35(m,2h),1.10(d,j＝3.3hz,2h),1.05–0.99(m,1h),0.92(s,3h),0.49(s,3h).13cnmr(151mhz,dmso)δ207.94,160.73,155.29,152.52,150.26,149.94,139.46,139.12,126.43,121.14,115.98,110.60,105.77,103.74,72.41,61.95,59.48,55.39,55.21,48.71,42.65,37.69,37.26,35.96,35.48,30.70,30.61,27.25,23.40,21.60,19.95,18.38,12.32.esi-msm/z:656[m+na]+.

化合物i-5，褐色固體(37mg,19％).1hnmr(600mhz,cdcl3)δ8.31(s,1h),8.00(s,2h),7.78(s,2h),7.22(s,1h),5.35(s,1h),5.01(s,1h),4.53(s,1h),3.58(s,2h),3.44(s,2h),2.53(s,1h),2.37(s,1h),2.27(s,1h),2.17(d,j＝9.5hz,1h),2.12(s,3h),2.04(s,1h),1.98(d,j＝17.1hz,1h),1.90(s,1h),1.85(d,j＝12.9hz,1h),1.67(s,1h),1.61(s,4h),1.57(s,1h),1.46(s,3h),1.23(dd,j＝14.2,8.9hz,2h),1.16(d,j＝10.9hz,2h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.65,159.98,157.18,150.17,139.61,135.71,132.84,130.68,122.38,117.81,115.75,115.52,107.84,99.99,74.89,63.67,56.81,49.83,43.99,42.08,40.19,38.77,38.39,36.92,36.54,31.80,31.75,31.58,28.04,24.48,22.81,21.03,19.31,13.23.esi-msm/z:612[m+na]+.

化合物i-6，黃色固體(90mg,47％).1hnmr(600mhz,cdcl3)δ8.30(s,1h),8.00(d,j＝7.7hz,2h),7.78(d,j＝7.7hz,2h),5.35(d,j＝2.5hz,1h),5.02(s,1h),4.53(t,j＝11.1hz,1h),3.57(d,j＝5.0hz,2h),3.43(d,j＝4.2hz,2h),2.53(t,j＝8.7hz,1h),2.38(d,j＝9.4hz,1h),2.27(t,j＝12.0hz,1h),2.18(t,j＝10.3hz,1h),2.12(s,3h),2.04(s,1h),1.98(d,j＝17.5hz,1h),1.90(d,j＝11.4hz,1h),1.85(d,j＝13.4hz,1h),1.67(s,1h),1.64(s,3h),1.59(s,1h),1.57(s,1h),1.54(s,1h),1.45(d,j＝8.9hz,2h),1.26–1.20(m,2h),1.15(d,j＝12.3hz,2h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ207.81,158.14,155.33,148.33,137.77,133.87,131.00,128.84,120.54,115.97,113.91,113.67,106.00,73.04,61.83,54.97,47.99,42.15,40.23,38.35,36.93,36.55,35.08,34.70,29.96,29.91,29.74,26.20,22.64,20.97,19.19,17.47,11.39.esi-msm/z:605[m+na]+.

化合物i-7，白色固體(82mg,42％).1hnmr(600mhz,cdcl3)δ8.26(s,1h),7.87(s,2h),7.46(s,2h),7.05(s,1h),5.34(s,1h),5.03(s,1h),4.52(s,1h),3.56(s,2h),3.42(s,2h),2.53(d,j＝6.7hz,1h),2.36(s,1h),2.26(s,1h),2.17(d,j＝8.9hz,1h),2.12(s,3h),2.04(s,1h),1.97(d,j＝16.9hz,1h),1.90(s,1h),1.84(d,j＝12.9hz,1h),1.65(s,3h),1.62–1.52(m,3h),1.45(s,3h),1.15(d,j＝10.5hz,2h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.66,160.78,156.98,151.37,139.64,139.01,131.84,130.21,129.63,122.32,116.45,104.48,74.75,63.68,56.82,49.82,43.99,41.65,40.36,38.78,38.41,36.93,36.54,31.80,31.75,31.58,28.04,24.48,22.81,21.03,19.31,13.23.esi-msm/z:614[m+na]+.

化合物i-8，白色固體(53mg,28％).1hnmr(600mhz,cdcl3)δ8.28(s,1h),8.18(s,1h),8.13(s,1h),7.80(s,1h),7.64(d,j＝6.6hz,1h),7.20(s,1h),5.36(s,1h),5.00(s,1h),4.53(s,1h),3.58(s,2h),3.44(s,2h),2.53(s,1h),2.37(s,1h),2.28(s,1h),2.17(d,j＝8.9hz,1h),2.12(s,3h),2.04(s,1h),1.98(d,j＝17.2hz,1h),1.90(s,1h),1.86(d,j＝12.6hz,1h),1.67(s,1h),1.59(s,5h),1.46(s,2h),1.25(s,1h),1.22(d,j＝5.0hz,1h),1.16(d,j＝11.7hz,2h),1.00(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.67,160.03,157.19,149.88,139.61,135.28,133.83,133.74,133.01,130.24,122.40,117.56,115.75,113.92,107.27,74.90,63.68,56.82,49.82,43.99,42.06,40.20,38.78,38.40,36.93,36.55,31.81,31.75,31.58,28.04,24.48,22.81,21.03,19.31,13.23.esi-msm/z:605[m+na]+.

化合物i-9，淡黃色固體(81mg,40％).1hnmr(600mhz,cdcl3)δ8.22(s,1h),7.70(d,j＝1.3hz,1h),7.46(dd,j＝8.5,2.0hz,1h),6.96–6.92(m,1h),6.87(s,1h),5.37–5.33(m,1h),5.02(s,1h),4.56–4.49(m,1h),3.96(s,3h),3.95(s,3h),3.59–3.54(m,2h),3.42(d,j＝5.2hz,2h),2.53(dd,j＝11.3,6.7hz,1h),2.38(dd,j＝12.7,2.8hz,1h),2.27(t,j＝11.6hz,1h),2.21–2.15(m,1h),2.12(s,3h),2.04(dd,j＝7.9,2.8hz,1h),1.97(dtd,j＝17.4,5.2,2.8hz,1h),1.90(d,j＝11.7hz,1h),1.87–1.82(m,1h),1.68–1.66(m,1h),1.57(dd,j＝9.7,2.7hz,2h),1.45(d,j＝9.7hz,2h),1.32–1.26(m,1h),1.24–1.19(m,1h),1.18–1.15(m,1h),1.13(dd,j＝13.2,4.3hz,1h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.62,161.68,156.83,156.79,153.23,152.71,149.22,139.71,127.22,124.83,122.26,117.55,111.45,110.98,100.40,74.61,63.68,56.83,56.14,56.01,49.84,43.99,41.32,40.61,38.79,38.42,36.94,36.55,31.81,31.75,31.58,28.05,24.48,22.81,21.03,19.31,13.23.esi-msm/z:640[m+na]+.

化合物i-10，白色固體(66mg,31％).1hnmr(600mhz,cdcl3)δ8.24(s,1h),7.80(s,2h),7.63(s,2h),7.05(s,1h),5.34(s,1h),5.02(s,1h),4.52(s,1h),3.56(s,2h),3.42(s,2h),2.53(d,j＝7.0hz,1h),2.36(s,1h),2.27(s,1h),2.17(d,j＝6.9hz,1h),2.12(s,3h),2.04(s,1h),1.97(d,j＝16.7hz,1h),1.90(s,1h),1.84(d,j＝12.3hz,1h),1.67(s,1h),1.63(s,3h),1.56(s,1h),1.45(s,3h),1.27–1.23(m,1h),1.14(s,2h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.66,160.77,156.99,151.47,139.64,132.62,131.90,130.61,127.63,122.33,116.44,104.64,74.77,63.69,56.83,49.83,44.00,41.68,40.35,38.79,38.41,36.93,36.54,31.81,31.75,31.59,28.04,24.49,22.82,21.04,19.31,13.23.esi-msm/z:658[m+na]+.

化合物i-11，淡黃色固體(61mg,31％).1hnmr(600mhz,cdcl3)δ8.36(s,1h),8.34(s,1h),8.33(s,1h),8.08(s,1h),8.06(s,1h),5.35(d,j＝3.1hz,1h),5.05(d,j＝6.9hz,1h),4.52(dd,j＝13.5,8.8hz,1h),3.60–3.56(m,2h),3.48(d,j＝4.5hz,1h),3.44(d,j＝4.5hz,2h),2.53(t,j＝8.9hz,1h),2.41–2.35(m,1h),2.26(t,j＝11.8hz,1h),2.17(s,1h),2.12(s,3h),2.06–2.02(m,1h),1.97(dd,j＝17.5,2.3hz,1h),1.90(d,j＝10.3hz,1h),1.87–1.83(m,1h),1.68(s,1h),1.65(s,1h),1.62–1.53(m,3h),1.44(d,j＝9.8hz,3h),1.27–1.18(m,2h),1.15(dt,j＝17.1,9.1hz,2h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.68,159.87,157.22,149.68,149.44,139.60,137.43,131.15,124.32,122.39,115.66,108.48,74.90,63.67,56.81,49.82,43.99,42.12,40.17,38.76,38.40,36.92,36.55,31.80,31.75,31.58,28.04,24.47,22.81,21.03,19.31,13.23.esi-msm/z:610[m+na]+.

化合物i-b12，淡黃色固體(70mg,38％).1hnmr(600mhz,cdcl3)δ8.31(s,1h),7.93(d,j＝7.3hz,2h),7.53(dd,j＝8.6,6.0hz,1h),7.49(dd,j＝10.1,4.6hz,2h),7.00(s,1h),5.36–5.34(m,1h),5.05(s,1h),4.53(td,j＝11.2,5.5hz,1h),3.59–3.54(m,2h),3.45–3.40(m,2h),2.53(dd,j＝11.2,6.7hz,1h),2.38(dd,j＝12.7,2.9hz,1h),2.27(t,j＝11.6hz,1h),2.20–2.15(m,1h),2.12(s,3h),2.04(dd,j＝8.2,2.4hz,1h),1.97(dtd,j＝17.4,5.2,2.8hz,1h),1.91(d,j＝12.1hz,1h),1.84(dt,j＝13.3,3.4hz,1h),1.68–1.65(m,1h),1.64(d,j＝3.2hz,1h),1.64–1.61(m,1h),1.61–1.57(m,1h),1.56(d,j＝2.6hz,1h),1.54(d,j＝2.2hz,1h),1.48(dd,j＝10.6,4.8hz,1h),1.44(d,j＝9.4hz,2h),1.24–1.19(m,1h),1.18–1.15(m,1h),1.14(d,j＝4.0hz,1h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.63,161.06,156.89,152.99,139.68,132.81,131.78,130.69,129.24,122.28,116.71,103.96,74.69,63.68,56.82,49.82,43.99,41.49,40.45,38.78,38.41,36.94,36.53,31.80,31.74,31.58,28.05,24.48,22.80,21.03,19.30,13.22.esi-msm/z:580[m+na]+.

化合物i-13，白色固體(70mg,38％).1hnmr(600mhz,cdcl3)δ8.28(s,1h),7.53–7.46(m,2h),7.39(t,j＝7.9hz,1h),7.08(d,j＝8.1hz,1h),7.01(s,1h),5.35(d,j＝3.5hz,1h),5.06(s,1h),4.52(dd,j＝13.5,9.0hz,1h),3.86(s,3h),3.57(d,j＝4.4hz,2h),3.42(d,j＝5.1hz,2h),2.53(t,j＝8.9hz,1h),2.37(d,j＝9.1hz,1h),2.27(t,j＝12.0hz,1h),2.20–2.15(m,1h),2.12(s,3h),2.04(s,1h),1.97(d,j＝17.5hz,1h),1.90(d,j＝11.2hz,1h),1.84(d,j＝13.4hz,1h),1.70–1.65(m,2h),1.60(dd,j＝11.8,6.2hz,2h),1.56(s,1h),1.48–1.41(m,3h),1.24–1.19(m,1h),1.18–1.11(m,2h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.70,161.07,159.93,156.91,153.01,139.67,132.96,130.22,123.68,122.29,119.41,116.74,114.48,104.11,74.70,63.69,56.82,55.43,49.83,44.00,41.47,40.45,38.78,38.41,36.93,36.54,31.80,31.75,31.58,28.05,24.48,22.81,21.03,19.31,13.23.esi-msm/z:610[m+na]+.

化合物i-14，白色固體(50mg,26％).1hnmr(600mhz,cdcl3)δ8.23(s,1h),7.89–7.80(m,2h),7.49(d,j＝7.5hz,1h),7.43(d,j＝7.7hz,1h),7.13(s,1h),5.34(s,1h),5.11(s,1h),4.51(s,1h),3.56(s,2h),3.42(s,2h),2.52(t,j＝8.5hz,1h),2.36(d,j＝9.0hz,1h),2.25(s,1h),2.18–2.14(m,1h),2.11(s,3h),2.03(d,j＝6.0hz,1h),1.96(d,j＝16.8hz,1h),1.89(d,j＝8.8hz,1h),1.83(d,j＝13.2hz,1h),1.66(s,2h),1.61–1.51(m,3h),1.44(t,j＝8.5hz,3h),1.24(s,2h),1.14(d,j＝11.5hz,2h),0.98(s,3h),0.61(s,3h).13cnmr(151mhz,cdcl3)δ209.71,160.58,157.03,151.16,139.65,135.30,133.44,132.56,130.50,130.40,128.38,122.34,116.14,105.72,74.75,63.69,56.82,49.82,44.00,41.67,40.34,38.78,38.43,36.94,36.55,31.81,31.75,31.59,28.06,24.49,22.82,21.04,19.31,13.24.esi-msm/z:614[m+na]+.

化合物i-15，白色固體(100mg,53％).1hnmr(600mhz,cdcl3)δ8.27(s,1h),7.69(d,j＝7.7hz,1h),7.66(d,j＝9.3hz,1h),7.47(dd,j＝14.4,7.1hz,1h),7.23(d,j＝8.2hz,1h),7.07(s,1h),5.36(d,j＝2.7hz,1h),5.02(s,1h),4.53(t,j＝11.3hz,1h),3.57(d,j＝4.8hz,2h),3.43(d,j＝4.9hz,2h),2.53(t,j＝8.8hz,1h),2.38(d,j＝9.4hz,1h),2.27(t,j＝11.6hz,1h),2.17(d,j＝11.4hz,1h),2.12(s,3h),2.04(s,1h),1.98(d,j＝17.4hz,1h),1.91(d,j＝11.4hz,1h),1.85(d,j＝13.4hz,1h),1.67(d,j＝3.0hz,1h),1.62–1.59(m,2h),1.56(d,j＝15.0hz,2h),1.47–1.41(m,3h),1.25(s,1h),1.16(dd,j＝10.9,5.0hz,2h),0.99(s,3h),0.86(d,j＝7.6hz,1h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.67,163.59,161.94,160.59,151.38,139.64,130.90,130.85,126.66,126.64,122.35,116.89,116.74,116.19,105.55,74.79,63.69,56.82,49.83,44.00,41.72,40.33,38.78,38.40,36.93,36.54,31.81,31.75,31.58,28.05,24.48,22.81,21.03,19.31,13.23.esi-msm/z:598[m+na]+.

化合物i-16，白色固體(60mg,28％).1hnmr(600mhz,cdcl3)δ8.23(s,1h),8.01(s,1h),7.90(d,j＝7.6hz,1h),7.66(d,j＝7.9hz,1h),7.38(t,j＝7.8hz,1h),7.06(s,1h),5.36(s,1h),4.99(s,1h),4.53(s,1h),3.57(s,2h),3.43(d,j＝4.0hz,2h),2.54(t,j＝8.7hz,1h),2.38(d,j＝10.6hz,1h),2.27(t,j＝11.7hz,1h),2.19–2.14(m,1h),2.12(s,2h),2.05(s,1h),1.98(d,j＝17.2hz,1h),1.91(d,j＝10.7hz,1h),1.85(d,j＝13.1hz,1h),1.67(d,j＝2.8hz,1h),1.58(s,5h),1.45(dd,j＝21.2,12.4hz,3h),1.28–1.20(m,2h),1.15(t,j＝12.9hz,2h),1.00(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.65,160.5,160.49,157.04,156.99,151.08,151.04,139.63,135.48,133.72,133.67,133.39,130.71,128.70,123.27,122.36,116.15–116.10(m),105.71–105.66(m),74.79,63.69,56.83,49.83,44.00,41.75,40.33,38.79,38.41,36.93,36.55,31.81,31.76,31.58,28.05,24.48,22.81,21.04,19.31,13.23.esi-msm/z:658[m+na]+.

化合物i-17，白色固體(89mg,47％).1hnmr(600mhz,cdcl3)δ8.27(s,1h),7.97(dd,j＝8.6,5.3hz,2h),7.18(t,j＝8.5hz,2h),7.01(s,1h),5.37–5.34(m,1h),5.02(s,1h),4.55–4.50(m,1h),3.56(d,j＝5.2hz,2h),3.42(d,j＝5.3hz,2h),2.53(t,j＝8.9hz,1h),2.40–2.36(m,1h),2.28(d,j＝11.0hz,1h),2.17(dd,j＝9.3,2.5hz,1h),2.12(s,3h),2.04(dd,j＝7.6,2.8hz,1h),2.00–1.95(m,1h),1.91(d,j＝11.4hz,1h),1.87–1.83(m,1h),1.67(dd,j＝6.4,2.8hz,1h),1.61(s,3h),1.57(d,j＝3.4hz,1h),1.45(d,j＝9.7hz,2h),1.25(s,1h),1.23(d,j＝5.9hz,1h),1.20(s,1h),1.18–1.16(m,1h),1.15(s,1h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.66,164.26,160.95,156.95,151.49,139.67,133.17,133.11,128.14,122.32,116.72,116.64,116.57,103.6,103.53,74.75,63.69,56.83,49.84,44.00,41.61,40.41,38.79,38.41,36.94,36.55,31.81,31.76,31.59,28.05,24.48,22.81,21.04,19.31,13.23.esi-msm/z:598[m+na]+.

化合物i-18，黃色固體(80mg,40％).1hnmr(600mhz,cdcl3)δ8.18(s,1h),7.62(s,1h),7.47(d,j＝7.8hz,1h),6.93(d,j＝8.5hz,1h),5.96(s,1h),5.35(d,j＝5.0hz,1h),5.05(d,j＝5.1hz,1h),4.55–4.48(m,1h),3.97(s,2h),3.55(s,2h),3.41(d,j＝5.5hz,2h),2.53(t,j＝8.9hz,1h),2.37(d,j＝9.5hz,1h),2.30–2.23(m,1h),2.20–2.15(m,1h),2.12(s,3h),2.05–2.02(m,1h),1.99–1.95(m,1h),1.90(d,j＝11.9hz,1h),1.86–1.82(m,1h),1.63(s,3h),1.56(d,j＝2.7hz,1h),1.45(d,j＝9.5hz,2h),1.28(dd,j＝12.5,4.8hz,1h),1.22(ddd,j＝14.8,10.7,4.8hz,2h),1.18–1.13(m,2h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.70,161.68,156.81,152.64,150.67,145.99,139.69,125.54,125.36,122.27,117.26–117.21(m),115.84,110.70,100.95,74.66,63.69,56.83,56.15,49.83,44.00,41.97,40.57,38.79,38.42,36.94,36.54,31.81,31.75,31.58,28.06,24.48,22.81,21.03,19.31,13.23.esi-msm/z:626[m+na]+.

化合物i-19，白色固體(60mg,30％).1hnmr(600mhz,cdcl3)δ8.71(s,1h),8.37(s,2h),8.29(d,j＝7.8hz,1h),7.72(t,j＝8.0hz,1h),7.22(s,1h),5.38–5.34(m,1h),5.02(s,1h),4.53(td,j＝11.3,5.6hz,1h),3.59(d,j＝4.5hz,2h),3.45(d,j＝5.2hz,2h),2.54(t,j＝8.9hz,1h),2.42–2.36(m,1h),2.28(t,j＝11.6hz,1h),2.21–2.16(m,1h),2.13(s,3h),2.07–2.03(m,1h),2.01–1.95(m,1h),1.91(d,j＝11.6hz,1h),1.86(d,j＝13.4hz,1h),1.67(dd,j＝7.8,3.5hz,1h),1.61(s,3h),1.57(s,1h),1.55(d,j＝4.6hz,1h),1.45(d,j＝9.8hz,2h),1.27–1.20(m,2h),1.19–1.12(m,2h),1.00(s,3h),0.63(s,3h).13cnmr(151mhz,cdcl3)δ207.46,157.75,154.98,147.61,146.43,137.41,132.97,131.12,128.26,124.42,123.11,120.20,113.48,105.51,72.68,61.48,54.62,47.63,41.80,39.86,38.03,36.58,36.21,34.73,34.35,29.61,29.56,29.39,25.85,22.29,20.62,18.84,17.12,11.04.esi-msm/z:625[m+na]+.

化合物i-20，黃色固體(80mg,39％).1hnmr(600mhz,cdcl3)δ8.16(s,1h),7.53(d,j＝2.1hz,1h),7.48(dd,j＝8.5,2.0hz,1h),6.94(d,j＝8.5hz,1h),6.87(s,1h),5.36–5.34(m,1h),5.04(d,j＝5.3hz,1h),4.54–4.49(m,1h),4.35–4.33(m,2h),4.30–4.28(m,2h),3.54(d,j＝2.3hz,2h),3.40(d,j＝5.4hz,2h),2.53(t,j＝9.0hz,1h),2.39–2.35(m,1h),2.26(t,j＝11.6hz,1h),2.17(dd,j＝8.9,3.0hz,1h),2.12(s,3h),2.05–2.02(m,1h),2.00–1.95(m,1h),1.90(d,j＝11.6hz,1h),1.86–1.82(m,1h),1.68–1.66(m,1h),1.63(s,3h),1.61(d,j＝8.3hz,1h),1.57(dd,j＝6.5,3.0hz,1h),1.45(d,j＝9.5hz,2h),1.24–1.19(m,1h),1.18–1.15(m,1h),1.14(d,j＝4.0hz,1h),1.02(d,j＝5.5hz,1h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.70,161.62,156.80,152.34,147.98,143.76,139.71,125.49,125.38,122.27,119.70,118.06,117.19,101.08,74.65,64.80,64.05,63.70,56.84,49.84,44.01,41.27,40.58,38.80,38.42,36.95,36.55,31.82,31.76,31.59,28.06,24.49,22.81,21.04,19.31,13.24.esi-msm/z:638[m+na]+.

化合物i-21，黃色固體(80mg,39％).1hnmr(600mhz,cdcl3)δ8.11(s,1h),7.87(s,1h),7.85(s,1h),6.67(s,1h),6.66(s,1h),5.37–5.34(m,1h),5.07(d,j＝5.2hz,1h),4.55–4.48(m,1h),3.54(s,2h),3.44(q,j＝7.1hz,4h),3.41–3.37(m,2h),2.53(dd,j＝11.3,6.7hz,1h),2.40–2.34(m,1h),2.30–2.24(m,1h),2.19–2.15(m,1h),2.12(s,3h),2.04(s,1h),1.97(dtd,j＝17.4,5.2,2.9hz,1h),1.90(d,j＝12.4hz,1h),1.84(d,j＝13.4hz,1h),1.68–1.65(m,2h),1.61(s,4h),1.56(dd,j＝5.9,3.4hz,1h),1.45(d,j＝9.0hz,3h),1.23(s,2h),1.22(s,3h),1.21(s,2h),1.18–1.15(m,1h),1.14(d,j＝3.9hz,1h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.66,163.20,156.6,156.5,152.50,151.23,139.80,133.92,122.16,118.94,111.11,110.7,110.65,94.33,74.47,63.70,56.84,49.84,44.72,44.00,40.95,40.81,38.80,38.43,36.97,36.54,31.82,31.76,31.58,28.06,24.49,22.81,21.04,19.31,13.23,12.55.esi-msm/z:629[m+na]+.

化合物i-22，黃色固體(90mg,45％).1hnmr(600mhz,cdcl3)δ8.14(s,1h),7.89(s,1h),7.88(s,1h),6.70(s,1h),6.69(s,1h),5.38–5.34(m,1h),5.06(d,j＝5.3hz,1h),4.55–4.49(m,1h),3.54(s,2h),3.49(d,j＝5.4hz,1h),3.40(d,j＝5.4hz,2h),3.10(s,4h),2.54(dd,j＝11.3,6.6hz,1h),2.40–2.35(m,1h),2.27(t,j＝11.3hz,1h),2.19–2.16(m,1h),2.13(s,3h),2.06–2.03(m,1h),1.98(ddd,j＝12.2,5.0,2.6hz,1h),1.91(d,j＝12.2hz,1h),1.85(d,j＝13.4hz,1h),1.69–1.66(m,1h),1.64(dd,j＝9.1,5.7hz,1h),1.60(s,3h),1.57(dd,j＝5.7,3.4hz,1h),1.45(d,j＝9.6hz,2h),1.26–1.22(m,1h),1.19–1.16(m,1h),1.14(d,j＝3.8hz,1h),0.99(s,3h),0.63(s,3h).13cnmr(151mhz,cdcl3)δ209.67,162.99,156.62,153.26,152.67,139.78,133.55,122.18,119.53,118.74,111.49,95.17,74.50,63.70,56.84,49.84,44.01,40.91,40.03,38.80,38.43,36.97,36.55,31.82,31.76,31.59,28.06,24.49,22.81,21.04,19.31,13.23.esi-msm/z:601[m+na]+.

化合物i-23，淡黃色固體(70mg,36％).1hnmr(600mhz,cdcl3)δ8.78(s,1h),8.15(d,j＝7.7hz,1h),7.53–7.47(m,1h),7.04(q,j＝7.7hz,1h),6.95(t,j＝7.5hz,1h),6.88(s,1h),5.37–5.33(m,1h),5.03(d,j＝5.2hz,1h),4.58–4.48(m,1h),3.89(s,3h),3.56(d,j＝4.6hz,2h),3.49(d,j＝4.3hz,1h),3.42(d,j＝5.3hz,2h),2.53(dd,j＝11.3,6.7hz,1h),2.38(dd,j＝12.7,3.2hz,1h),2.27(t,j＝11.3hz,1h),2.21–2.14(m,1h),2.12(s,3h),2.04(dd,j＝7.9,2.8hz,1h),2.01–1.95(m,1h),1.91(dd,j＝9.7,2.3hz,1h),1.87–1.82(m,1h),1.59(s,3h),1.58–1.53(m,2h),1.45(d,j＝9.7hz,2h),1.26–1.24(m,1h),1.24–1.20(m,1h),1.18–1.13(m,2h),1.00(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.66,161.50,159.15,156.78,148.03,139.73,134.44,129.07,122.25,121.05,120.84,117.2,117.1,111.17,103.5,103.4,74.63,63.69,56.84,55.67,49.84,44.00,41.27,40.59,38.79,38.41,36.96,36.55,31.82,31.76,31.58,28.06,24.49,22.81,21.04,19.31,13.23.esi-msm/z:610[m+na]+.

化合物i-24，白色固體(82mg,42％).1hnmr(600mhz,cdcl3)δ8.28(s,1h),7.89(s,1h),7.88(s,1h),7.35(s,1h),7.34(s,1h),6.91(s,1h),5.37–5.34(m,1h),5.01(d,j＝5.2hz,1h),4.56–4.49(m,1h),3.56(s,2h),3.42(d,j＝5.4hz,2h),2.97(dt,j＝13.8,6.9hz,1h),2.53(t,j＝9.0hz,1h),2.40–2.35(m,1h),2.27(t,j＝11.5hz,1h),2.17(s,1h),2.12(s,3h),2.04(dd,j＝8.2,2.5hz,1h),2.00–1.95(m,1h),1.91(d,j＝10.4hz,1h),1.87–1.82(m,1h),1.68–1.66(m,1h),1.66–1.62(m,1h),1.59(s,3h),1.58–1.53(m,2h),1.45(d,j＝9.2hz,2h),1.28(s,3h),1.27(s,3h),1.22(dd,j＝12.2,5.7hz,1h),1.17(dd,j＝6.5,4.0hz,1h),1.14(d,j＝4.2hz,1h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ209.65,161.40,156.84,154.74,152.98,139.69,131.04,129.47,127.41,122.27,117.04,102.54,74.67,63.69,56.83,49.84,44.00,41.39,40.52,38.79,38.41,36.94,36.54,34.37,31.81,31.76,31.58,28.05,24.48,23.60,22.81,21.04,19.31,13.23.esi-msm/z:622[m+na]+.

化合物i-25，白色固體(82mg,42％).1hnmr(600mhz,cdcl3)δ8.16(s,1h),7.85(s,1h),7.84(s,1h),6.94(s,1h),6.93(s,1h),5.35(s,1h),5.12(t,j＝5.5hz,1h),4.55–4.49(m,1h),3.57–3.54(m,2h),3.50(s,1h),3.42(d,j＝5.3hz,2h),2.54(t,j＝8.9hz,1h),2.38(d,j＝9.9hz,1h),2.27(t,j＝12.3hz,1h),2.18(s,1h),2.13(s,3h),2.03(dd,j＝8.1,2.5hz,1h),1.99–1.95(m,1h),1.91(d,j＝10.7hz,1h),1.84(d,j＝13.3hz,1h),1.69(d,j＝2.8hz,1h),1.68–1.66(m,2h),1.59(s,1h),1.56(d,j＝2.6hz,1h),1.46–1.42(m,3h),1.30–1.27(m,1h),1.26(dd,j＝5.9,2.3hz,1h),1.23–1.20(m,1h),1.15(dd,j＝6.5,1.9hz,1h),1.14–1.12(m,1h),0.99(s,3h),0.62(s,3h).13cnmr(151mhz,cdcl3)δ210.11,162.02,160.83,157.08,152.64,139.60,133.50,124.20,122.35,117.44,116.42,99.70,74.92,63.70,56.81,49.80,44.06,41.32,40.61,38.76,38.40,36.92,36.53,31.80,31.74,31.59,28.05,24.48,22.83,21.03,19.31,13.24.esi-msm/z:596[m+na]+.

實施例6：化合物對乳腺癌細胞mcf-7的抑制作用測定

mtt比色法：根據細胞生長速率，將處於對數生長期的mcf-7細胞以100μl/孔接種於96孔板中，貼壁生長24小時再加濃度梯度藥物，設5個梯度(0,3.125,6.25,12.5,25,50,100μm/孔)，每個濃度設三個復孔。在37℃、5％co2條件下培養48h，然後棄去培養液，每孔加入100μl含10％mtt的培養液，繼續培養4h後吸去培養液。最後每孔加入100μl的二甲基亞碸，在全自動多功能酶標儀檢測od值為490nm波長下測定，計算細胞的存活率。

通過graphpadprism5軟體計算存活率達50％時的藥物濃度即ic50值。對乳腺癌細胞mcf-7的抑制活性測定，結果如表1所示。

表1說明：各化合物對乳腺癌細胞mcf-7具有不同程度的抑制作用。其中化合物i-7,i-8,i-10,i-12,i-14,i-15,i-16,i-17,i-19,i-20對乳腺癌細胞mcf-7的ic50值分別達到了6.21,8.81,6.27,6.64,6.02,6.12,6.10,6.03,6.52,6.50μm。結果表明，這些化合物對乳腺癌細胞mcf-7具有較強的抑制作用，是抗乳腺癌的潛在藥物。