CN105732755B - 3β‑羟基‑16‑芳基雄甾‑5(6),8(14),15(16)‑三烯‑17‑酮 - Google Patents
3β‑羟基‑16‑芳基雄甾‑5(6),8(14),15(16)‑三烯‑17‑酮 Download PDFInfo
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- CN105732755B CN105732755B CN201610093315.4A CN201610093315A CN105732755B CN 105732755 B CN105732755 B CN 105732755B CN 201610093315 A CN201610093315 A CN 201610093315A CN 105732755 B CN105732755 B CN 105732755B
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- androstane
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
本发明涉及一种化合物，包括：3β‑羟基‑16‑芳基雄甾‑5(6),8(14),15(16)‑三烯‑17‑酮，其结构式如下：其中，Ar‑选自下列结构中的一种：其化合物有如下8个：
Description
技术领域
本发明属于化学合成领域，涉及到3β-羟基-16-芳基雄甾-5(6),8(14),15(16)-三烯-17-酮，具体是3β-羟基-16-芳基雄甾-5(6),8(14),15(16)-三烯-17-酮8个化合物。
背景技术
天然甾体的改造和修饰已经越来越受到人们的关注，经过某些特定的修饰，如甾体环、侧链的修饰，可以得到一些重要的优于母体生物活性甾体化合物衍生物【Levina,I.S.；Pokrovskaya,E.V.；Kulikova,L.E.；Kamernitzky,A.V.；Kachala,V.V.；Smirnov,A.N.Steroids.2008,73,815】。如已经用于临床的醋酸阿比特龙酯(abirateroneacetate,)，化学名为17-(3-吡啶基)雄甾-5,16-二烯-3β-乙酸酯，是由Centocor Ortho公司开发的口服有效的CYP 17酶不可逆抑制剂，通过转化成阿比特龙对睾丸及身体其它部位如肾上腺等产生的雄激素起抑制作用。2011年4月28日经美国FDA批准上市，与泼尼松联用治疗前列腺癌【G.A.Potter,S.E.Barrie,M.Jarman and M.G.Rowlands,J.Med.Chem.,1995，38,2463.】。
许多研究发现，甾体D环修饰时，如果能够保留甾体C-17位的羰基，而在羰基的邻位C-16位上引入一些特征侧链，同样能够获得优于母体化合物的生理功能【Chattopadhaya,R.；Jindal,D.P.；Minu,M.；Gupta,R.Arzneim.Forsch.2004,54,551；Bansal,R.；Guleria,S.Steroids.2008,73,1391；Dubey,S.；Kaur,P.；Jindal,D.P.；Satyanarayan,Y.D.；Piplani,P.Med.Chem.2008,4,229；Guo,H.；Wu,H.；Yang,J.；Xiao,Y.；Altenbach,H.；Qiu,G.；Hu,H.；Wu,Z.；He,X.；Zhou,D.；Hu,X.Steroids.2011,76,709；Moreira,V.M.；Salvador,J.A.R.；Bejad,A.M.；Paixaod,J.A.Steroids.2011,76,582.】。如2004年，Dubey等人通过多步合成了一系列16-(4-取代的苯乙烯基)-雄甾-5-烯衍生物，细胞活性测试表明这是一类新型的细胞毒性药物，通过对人体的三种癌症细胞：乳癌细胞MCF-7，肺癌细胞NCI-H460和中枢神经肿瘤细胞SF-268这三种人癌细胞的体外抗肿瘤实验，发现这些化合物可以诱导人体的癌细胞凋亡，从而抑制肿瘤细胞的增殖【Dubey,S.；Piplani,P.；Jindal,D.P.Chem Biodiver.2004,1,1529.】。2007年，Gamal课题组报道了在表雄酮D-环保留17-位羰基的情况下键连了一个杂环结构，获得了很好的抗菌活性【Mervat,M.；Abdelhalim.；Manal,M.T.；Samira,T.；Rabie.；Gamal,A.Steroids.2007,72,459.】。2012年，Bansa等人以雄甾去氢表雄酮为原料，在甾体D环的16位的碳原子上，在保留17-位羰基的基础上键连了一个咪唑基，生物活性测试表明具有很强的抑制癌症细胞的作用【Ranju,B.；Sheetal,G.；Sridhar,T.；Subhash,L.；Patwar,R.Steroids.2012,77,621.】。
近来研究发现甾体环中如存在多个烯基，更能够强化甾体化合物的生理活性。如2015年Gabriele M.等人从海绵Callyspongia cf.C.flammea中分离到三个多烯基甾体化合物，尤其值得注意的是这些甾体化合物中存在一般甾体衍生物不常形成的C(8)＝C(14)的烯基。这些化合物具有抑制Aftin-5细胞产生Ab-42而用于治疗老年痴呆症。
发明内容
针对以上所述缺陷，本发明提供了3β-羟基-16-芳基雄甾-5(6),8(14),15(16)-三烯-17-酮，结构式如下：
其中，Ar-选自下列结构中的一种：
其化合物有如下8个：
本发明结构式中C3为3β-羟基；C8与C14之间为双键；C5与C6之间为双键；C15与C16之间为双键。
本发明中除了保留了甾体应有的活性结构，同时在甾体D环上保留17-位羰基的，在甾体刚性骨架上构建α,β-不饱和羰基结构单元，能与多种受体结合,呈现出广泛的生物活性。
进一步，3β-羟基-16-芳基雄甾-5(6),8(14),15(16)-三烯-17-酮在抗癌活性中的应用。
本发明3β-羟基-16-芳基雄甾-5(6),8(14),15(16)-三烯-17-酮可以作为药物前体，作为临床药物筛选化合物，进一步研究可以与一种或多种药用辅料职称药学上可接受的任一剂型。
具体实施方式
本发明3β-羟基-16-芳基雄甾-5(6),8(14),15(16)-三烯-17-酮，其结构式如下：
其中，Ar-选自下列结构中的一种：
其化合物有如下8个：
本发明结构式中C3为3β-羟基；C8与C14之间为双键；C5与C6之间为双键；C15与C16之间为双键。
测试仪器
红外光谱分析：Bruker tensor 27红外光谱仪，KBr压片法，检测范围为4000～400cm-1；熔点测量：WRR熔点仪(上海精密科学仪器有限公司)，数据未经校正。1H-NMR及13C-NMR分析：Bruker Advance 600(德国Bruker公司)；反应进程用TLC跟踪检测。
实施例1：关键中间体(3β)-羟基-雄甾-5(6),8(14),15(16)-三烯-17-酮(3)的合成
取化合物(6)3.67g(0.01mol)，一水溴化锂3.67g(0.035mol)，碳酸锂2.96g(0.04mol)，30mL DMF，回流，氮气保护。8h后停止反应，冷却后逐滴加到碎冰中，搅拌，有固体析出，抽滤，得到黄色固体。用DCM溶解，依次用水洗，饱和食盐水洗1-2遍，然后收集有机相，无水硫酸钠干燥，旋干得黄色粘稠状固体，柱层析，DCM:EA＝20:1，收集第二个点得0.88g，产率31.0％；IR(KBr,cm-1):3312,2930,2858,1709,1643,1519,1453,1219,1108,1009,940,865,700；13C-NMR(150MHz,CDCl3)δ(ppm):212.2,152.69,141.65,139.34,133.78,128.06,118.87,70.98,48.28,45.75,41.59,38.87,36.34,31.50,28.97,27.63,22.95,19.50,18.82；Mp:194-195℃；1H NMR(600MHz,CDCl3)δ(ppm):7.81(d,J＝5.7Hz,1H),5.94(d,J＝5.7Hz,1H),5.28(s,1H),3.52(m,1H),1.12(s,3H),0.95(s,3H)；MS(EI)(m/z):285.43[(M+1)+](100％).
实施例2：(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮(4)的合成
取化合物(7)0.50g(1.74mmol)，碘0.89g(3.48mmol),DMAP 0.01g(0.087mmol)，吡啶6mL(0.07mmol)，CCl4 15mL于0℃下搅拌，搅拌过夜。反应结束后旋干溶剂后，用DCM萃取之后，用饱和的硫代硫酸钠的溶液洗1-2遍，20％稀盐酸洗1-2遍之后，饱和食盐水洗一遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝20:1，得到浅棕色产品，产率80％。1H-NMR(600MHz,CDCl3)δ(ppm):8.16(s,1H),5.28(s,1H),3.68-3.39(m,1H),1.15(s,3H),0.94(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):204.62,158.00,140.59,138.94,133.13,117.62,97.47,69.95,47.06,43.82,40.52,37.88,35.24,30.46,28.06,26.81,22.11,18.52,17.70.IR(KBr):3468,2929,2858,1700,1657,1513,1450,1370,1276,1211,1062,1004,937,918,846,734；HRMS(ESI)calcd for C19H23IO2[M+H]412.0822；Found 411.0818；Mp:135-136℃(PE/AcOEt).
实施例3：(3β)-羟基-16-苯基雄甾-5(6),8(14),15(16)-三烯-17-酮(5a)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，苯硼酸0.26g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到淡黄色固体产品，产率：91％。Mp:175-176℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):7.96(s,1H),7.77(d,J＝7.7Hz,2H),7.31(t,J＝7.6Hz,2H),7.24(t,J＝7.3Hz,1H),5.31(s,1H),3.53(m,1H),1.19(s,3H),0.96(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):209.53,146.57,141.62,137.77,136.78,133.70,132.22,128.49,128.29,127.12,119.04,71.05,48.53,47.50,41.61,38.98,36.33,31.52,29.11,27.87,23.36,19.58,18.87；IR(KBr,cm-1):3462,2929,2856,1684,1450,1339,1292,1176,1059,927,795,750,654；HRMS(ESI)calcd for C25H28O2[M+H]361.2168；Found 361.2164.
Pd催化剂可选Pd(dppf)Cl2，Pd(PPh3)4,Pd(acac)2,PdCl2(DPPE),Pd/C或Pd(CH3CN)Cl2。
实施例4：(3β)-羟基-16-(3-吡啶基)雄甾-5(6),8(14),15(16)-三烯-17-酮(5b)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，吡啶-3-硼酸0.26g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到淡黄色固体产品,产率:85％,Mp:167-168℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.91(s,1H),8.46(d,J＝4.4Hz,1H),8.17(d,J＝7.9Hz,1H),8.06(s,1H),7.28–7.23(m,1H),5.32(s,1H),3.58–3.51(m,1H),1.98(s,1H),1.20(s,3H),0.98(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):208.10,147.92,147.00,146.13,140.75,136.75,134.59,133.43,132.83,122.32,119.83,117.80,69.99,47.61,46.25,40.57,38.05,35.31,30.49,29.90,26.80,22.26,18.57,17.80；IR(KBr,cm-1):3472,2928,2857,1697,1647,1458,1415,1376,1299,1066,933,808；HRMS(ESI)calcd forC24H27NO2[M+H]362.2121；Found 362.2112.
实施例5：(3β)-羟基-16-(2-氟苯基)雄甾-5(6),8(14),15(16)-三烯-17-酮(5c)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，2-氟苯硼酸0.30g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到淡黄色固体产品,产率:86％,Mp:164-165℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.17(s,1H),8.01(t,J＝7.2Hz,1H),7.22–7.17(m,2H),7.10(dd,J＝13.5,6.1Hz,1H),5.31(s,1H),3.53(m,1H),1.20(s,3H),0.97(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):209.43,159.53(d,J＝249.6Hz),149.42(d,J＝10.2Hz),140.49,137.02,133.70,130.16,129.91,128.32(d,J＝8.5Hz),123.03(d,J＝3.3Hz),119.13(d,J＝12.3Hz),118.02,114.62(d,J＝22.3Hz),70.02,47.58,45.45,40.58,37.98,35.32,30.49,28.05,26.82,22.31,18.54,17.84；IR(KBr,cm-1):3491,3043,2930,2859,1691,1562,1480,1449,1274,1213,1110,1055,930,875,800,758,722；HRMS(ESI)calcd for C25H27FO2[M+H]379.2074；Found 379.2074.
实施例6：(3β)-羟基-16-(3-氟苯基)雄甾-5(6),8(14),15(16)-三烯-17-酮(5d)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，3-氟苯硼酸0.30g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到淡黄色固体产品,产率:84％,Mp:190-191℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):7.97(s,1H),7.55(t,J＝7.7Hz,2H),7.27(dd,J＝14.3,7.8Hz,1H),6.93(t,J＝7.6Hz,1H),5.32(s,1H),3.53(m,1H),1.19(s,3H),0.97(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):207.90,161.88(d,J＝245.6Hz),146.03,140.69,136.62,134.57(d,J＝2.1Hz),133.75,133.32,128.89(d,J＝8.1Hz),121.69(d,J＝2.8Hz),117.90,114.04(d,J＝21.3Hz),112.96(d,J＝22.8Hz),70.05,47.64,46.57,40.63,38.02,35.35,30.56,28.13,26.88,22.32,18.56,17.84；IR(KBr,cm-1):3500,3075,2928,2857,1679,1577,1426,1340,1263,1185,1058,886,790,681；HRMS(ESI)calcd for C25H27FO2[M+H]379.2074；Found 379.2074.
实施例7：(3β)-羟基-16-(4-氟-3-吡啶)雄甾-5(6),8(14),15(16)-三烯-17-酮(5e)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，4-氟-3-吡啶硼酸0.30g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到淡黄色固体产品,产率:90％,Mp:180-181℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.56(s,1H),8.26(t,J＝7.2Hz,1H),8.02(s,1H),6.89(d,J＝6.6Hz,1H),5.32(s,1H),3.54(m,1H),1.20(s,3H),0.98(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):207.92,162.11(d,J＝238.5Hz),145.84,145.04(d,J＝14.7Hz),140.67,138.64(d,J＝8.0Hz),136.54,134.65,131.76(d,J＝2.9Hz),125.34,117.74,108.24(d,J＝37.3Hz),70.00,47.61,46.19,40.57,38.05,35.31,30.49,28.17,26.78,22.25,18.56,17.79；IR(KBr,cm-1):3497,2696,2930,2851,2818,1680,1587,1472,1376,1297,1176,1120,1069,1022,928,834,744,670；HRMS(ESI)calcdfor C24H26FNO2[M+H]380.2027；Found 380.2012.
实施例8：(3β)-羟基-16-(5-嘧啶)雄甾-5(6),8(14),15(16)-三烯-17-酮(5f)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，5-嘧啶硼酸0.26g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到淡黄色固体产品,产率:87％,Mp:203-204℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):9.11(s,2H),9.07(s,1H),8.13(s,1H),5.32(s,1H),3.59–3.50(m,1H),1.21(s,3H),0.98(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):207.56,156.63,153.76,146.98,140.77,136.67,136.43,129.91,125.53,117.52,69.89,47.69,46.10,40.54,38.16,35.32,30.46,28.26,26.73,22.19,18.60,17.75；IR(KBr,cm-1):3487,3034,2940,2861,2799,1701,1644,1558,1406,1299,1144,1009,932,721；HRMS(ESI)calcd for C23H26N2O2[M+H]363.2073；Found 363.2068.
实施例9：(3β)-羟基-16-(3-三氟甲基苯基)雄甾-5(6),8(14),15(16)-三烯-17-酮(5g)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，3-三氟甲基苯硼酸0.40g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到淡黄色固体产品,产率:93％,Mp:195-196℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.04(s,1H),8.02(s,1H),7.99(d,J＝7.8Hz,1H),7.49(d,J＝7.7Hz,1H),7.43(t,J＝7.8Hz,1H),5.32(s,1H),3.56-3.52(m,1H),1.20(s,3H),0.98(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):207.94,146.41,140.64,136.56,134.31(d,J＝8.5Hz),131.99,129.87(q,J＝32.6Hz),129.28,127.91,123.98,123.69(q,J＝3.7Hz),123.07(q,J＝271.5Hz),122.74(q,J＝3.5Hz),117.83,70.02,47.63,46.50,40.58,38.03,35.31,30.50,28.17,26.82,22.28,18.56,17.81；IR(KBr,cm-1):3489,3032,2939,2894,2827,1680,1587,1475,1419,1322,1123,1006,805；HRMS(ESI)calcd for C26H27F3O2[M+H]429.2042；Found 429.2039.
实施例10：(3β)-羟基-16-(5-甲氧基-3-吡啶)雄甾-5(6),8(14),15(16)-三烯-17-酮(5h)的合成
取化合物(3β)-羟基-16-碘-雄甾-5(6),8(14),15(16)-三烯-17-酮0.50g(1.2mmol)，5-甲氧基吡啶-3-硼酸0.36g(2.13mmol)，双三苯基膦二氯化钯0.017g(0.024mmol)，碘化亚铜0.0024g(0.013mmol),THF20mL，甲醇4mL，随后加入2M碳酸钠溶液2.4mL，升温至回流。10h后原料消耗完毕。反应结束，旋干溶剂后，用DCM萃取，之后，用水洗1-2遍，饱和食盐水洗1-2遍，收集有机相，无水硫酸钠干燥。柱层析，DCM:EA＝10:1，得到深黄色固体产品,产率:74％,Mp:193-194℃(PE/AcOEt)；1H-NMR(600MHz,CDCl3)δ(ppm):8.49(s,1H),8.16(s,1H),8.07(s,1H),7.79(s,1H),5.32(s,1H),3.82(s,3H),3.57-3.50(m,1H),1.20(s,3H),0.97(s,3H)；13C-NMR(150MHz,CDCl3)δ(ppm):208.27,154.50,146.50,140.67,139.05,136.60,136.17,134.84,132.37,127.83,117.76,117.45,69.95,54.57,47.64,46.32,40.57,38.07,35.32,30.48,28.19,26.80,22.26,18.57,17.80；IR(KBr,cm-1):3488,2930,2872,1686,1610,1521,1450,1370,1296,1119,1008,940；HRMS(ESI)calcdfor C25H29NO3[M+H]392.2226；Found 392.2229.
从CH2Cl2溶剂中得到5a的晶体和从CHCl3溶剂中得到5b的晶体，通过X-射线单晶衍射进行表征，晶体数据信息列于表2中。晶体结构进一步验证了目标化合物的结构，并且可以看出甾体8(14)位上的双键的存在。
化合物5a的分子结构(含CH2Cl2)
化合物5b的分子结构(含CHCl3)
表1 化合物5a和5b的晶体参数
实施例11：抗癌活性的测试
所合成化合物5a-h对A549人肺癌细胞，SKOV3人卵巢癌细胞，MKN45人胃癌细胞和MDA-MB-435人乳腺癌高转移细胞体外增殖的抑制作用进行了测试。
测试结果表明所合成化合物5a-h对A549人肺癌细胞，SKOV3人卵巢癌细胞，MKN45人胃癌细胞和MDA-MB-435人乳腺癌高转移细胞等都具有抑制作用，所有化合物对SKOV3人卵巢癌细胞抑制作用优于对其它三类人癌细胞。而芳基上具有氟取代基的化合物5c,5d,5e和5g抑制效果最好。
表2 化合物5a-h对人癌细胞株体外增殖的抑制作用(半数抑制浓度)a
a 实验结果取八次实验数据平均值±标准偏差
b A549:人肺癌细胞,SKOV3:人卵巢癌细胞,MKN-45:人胃癌细胞,
MDA-MB-435:人乳腺癌高转移细胞。
Claims (1)
1.3β-羟基-16-芳基雄甾-5(6),8(14),15(16)-三烯-17-酮，其特征在于其结构式如下：
其中，Ar-选自下列结构中的一种
。
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| US5001119A (en) * | 1987-11-25 | 1991-03-19 | Schwartz Arthur G | 16-substituted androstanes and 16-substituted androstenes |
| CN103073607A (zh) * | 2013-02-26 | 2013-05-01 | 昆明理工大学 | 12β-羟基雄甾-4,6,8（9）,13（14）-四烯-3,11,16-三酮及其应用 |
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| US5001119A (en) * | 1987-11-25 | 1991-03-19 | Schwartz Arthur G | 16-substituted androstanes and 16-substituted androstenes |
| CN103073607A (zh) * | 2013-02-26 | 2013-05-01 | 昆明理工大学 | 12β-羟基雄甾-4,6,8（9）,13（14）-四烯-3,11,16-三酮及其应用 |
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