Ferrocene-bridged bicyclic-[2.2.1]-heptyl diene compound

A ferrocene and compound technology, applied in the field of ferrocene-oxo bridge bicyclo-[2.2.1]-heptene compounds, can solve the problems of increasing the risk of endometrial cancer due to drug resistance

Active Publication Date: 2015-12-02
铱诺(武汉)药业有限公司
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AI-Extracted Technical Summary

Problems solved by technology

In addition, although SERMs have been successful in the treatment of breast cancer, the problem of drug resistance and problems such...
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Abstract

The invention discloses a ferrocene-bridged bicyclic-[2.2.1]-heptyl diene compound that contains N-hydroxy-(i)N-benzene succinic amide or a similar structure. 3-(4-hydroxyphenyl)-4-suberic nonacylanilino-furan or similar analogs and a ferrocene vinyl sulfonate derivative are used as raw materials, and a solvent and a catalyst are not needed; the raw materials are reacted for 3 hours at 90 DEG C through one step to obtain a ferrocene-bridged bicyclic-[2.2.1]-heptyl diene compound that contains a suberic nonacylanilino group. According to an in vitro experiment, compared with a current anti-cancer drug Tamoxifen, the novel ferrocene-bridged bicyclic-[2.2.1]-heptyl diene compound has stronger inhibitory activity on hormone-dependent breast cancer MCF-7 cells and non-hormone-dependent breast cancer MDA-MB-231 cells, and has no toxicity on normal VERO cells while the current anti-cancer drug Tamoxifen has toxicity on normal VERO cells.

Application Domain

Organic active ingredientsAntineoplastic agents +1

Technology Topic

BenzenePerylene derivatives +23

Image

  • Ferrocene-bridged bicyclic-[2.2.1]-heptyl diene compound
  • Ferrocene-bridged bicyclic-[2.2.1]-heptyl diene compound
  • Ferrocene-bridged bicyclic-[2.2.1]-heptyl diene compound

Examples

  • Experimental program(10)

Example Embodiment

[0063] Example 1: 3-(4-hydroxyphenyl)-4-pimelic acid monoanilide-7-oxo bridge bicyclo[2.2.1]-5-heptene-2-sulfonic acid-(3-ferrocene Preparation of carbonylphenyl)-ester (TC1)
[0064]
[0065] Weigh 3-(4-hydroxyphenyl)-4-pimelic acid anilide-furan (200mg, 0.509mmol) and ethylenesulfonic acid-3-(ferrocenecarbonylphenyl)-ester (241.7mg, 0.160 mmol) is placed in a two-necked round-bottomed bottle of 50mL and then slowly warmed up to 90°C, spin-dried after 3 hours of reaction, and directly separated and purified by column chromatography, the eluent ratio is dichloromethane:methanol=60:1, to obtain 374.5mg red solid, yield 93.2%, m.p.111-114°C; 1 HNMR (400MHz, Acetone- d 6 ) δ 9.34(s,1H),8.01(s,1H),7.86(d, J =7.6Hz,1H),7.65(t, J =7.2Hz,2H),7.55(m,1H),7.47(t, J =8.0Hz,1H),7.35(t, J =8.8Hz,2H),7.27(t, J =8.8Hz,2H),6.86(t, J =8.4Hz,2H),5.78(s,1H),5.51(s,1H),4.89(s,2H),4.66(s,2H),4.24(s,5H),3.98(m,1H),2.52 (m,1H),2.40(m,3H),2.29(t, J =6.8Hz,2H),1.71(t, J =6.8Hz,2H),1.62(t, J =7.2Hz,2H),1.41(m,2H). 13 CNMR (100MHz, Acetone- d 6 ) δ 197.45,175.10,172.50,158.66,158.59,149.98,143.61,142.30,141.97,140.15,139.23,137.53,131.12,130.19,129.80,128.98,128.59,127.58,125.99.124.61,122.98,120.40,116.56,85.19,83.82, 78.71, 73.91, 72.16, 71.17, 62.11, 37.64, 34.18, 31.68, 31.47, 26.02, 25.42; HRMS (ESI) calcdforC 42 h 38 54 FeNO 9 S[M-H] - ,786.6621;found786.6624.

Example Embodiment

[0066] Example 2: 3-(4-hydroxyphenyl)-4-pimelic acid monoanilide-7-oxo bridge bicyclo[2.2.1]-5-heptene-2-sulfonic acid-(4-ferrocene Preparation of carbonylphenyl)-ester (TC2)
[0067]
[0068] The preparation method is as in Example 1, and the product is a red solid with a yield of 90.6%, m.p.108-110°C. 1 HNMR (400MHz, Acetone- d 6 ) δ 9.31(s,1H),8.00(d, J =8.0Hz,2H),7.67(d, J =8.4Hz,1H),7.63(d, J =8.4Hz,1H),7.43(t, J =8.0Hz,2H),7.36(d, J =8.0Hz,1H),7.32(t, J =7.6Hz,2H),7.26(d, J =8.0Hz,1H),6.88(d, J =8.0Hz,1H),6.83(d, J=8.0Hz,1H),5.76(s,1H),5.50(s,1H),4.84(s,2H),4.66(s,2H),4.23(s,5H),3.95(m,1H),2.51 (m,1H),2.39(m,3H),2.32(t, J =7.2Hz,2H),1.70(m,2H),1.62(t, J =7.2Hz,2H),1.41(m,2H). 13 CNMR (100MHz, Acetone- d 6 ) δ 197.40,174.90,172.30,158.70,158.56,152.60,143.55,142.00,140.35,140.21,139.32,137.54,130.92,130.34,129.78,129.12,128.47,127.94,123.87.123.03,120.29,120.10,116.71,116.51,85.28, 83.73,78.93,73.66,72.17,71.07,61.81,37.61,34.12,31.57,31.36,25.98,25.41;HRMS(ESI)calcdforC 42 h 38 54 FeNO 9 S[M-H] - ,786.6627;found786.6624.

Example Embodiment

[0069] Example 3: 3-(4-hydroxyphenyl)-4-pimelic acid monoanilide-7-oxo bridge bicyclo[2.2.1]-5-heptene-2-sulfonic acid-(4-ferrocene Preparation of benzyl)-ester (TC3)
[0070]
[0071] The preparation method was as in Example 1, and the product was a red solid with a yield of 85.2%, m.p.96-98°C. 1 HNMR (400MHz, Acetone- d 6 ) δ 9.14(s,1H),7.53(t, J =8.8Hz,2H),7.17(d, J =7.6Hz,1H),7.15(d, J =7.2Hz,1H),7.11(d, J =7.6Hz,1H),7.09(d, J =7.6Hz,1H),7.05(d, J =8.8Hz,2H),7.00(d, J =7.2Hz,1H),6.99(d, J =7.2Hz,1H),6.71(d, J =8.8Hz,1H),6.68(d, J =8.8Hz,1H),5.53(s,1H),5.31(t, J =3.2Hz,1H),3.97(s,7H),3.92(s,2H),3.64(m,1H),3.60(m,2H),2.27(m,3H),2.17(m,3H),1.58 (t, J =7.6Hz,2H),1.46(t, J =7.6Hz,2H),1.30(m,2H). 13 CNMR (100MHz, Acetone- d 6 ) δ 174.83,172.18,158.56,158.42,148.63,142.13,141.90,140.21,140.09,139.24,137.59,130.60,130.29,129.11,128.46,127.95,124.71,123.90,122.84,120.23,116.40,88.54,85.22,83.64,69.43, 69.36, 68.39, 61.21, 37.55, 35.90, 34.08, 31.51, 31.31, 25.98, 25.39; HRMS (ESI) calcdforC 42 h 40 54 FeNO 8 S[M-H] - ,772.1820;found772.1824.

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