CN101094844A - 苯并二氢吡喃衍生物,药物及其在治疗中的应用 - Google Patents
苯并二氢吡喃衍生物,药物及其在治疗中的应用 Download PDFInfo
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- CN101094844A CN101094844A CN200580038015.6A CN200580038015A CN101094844A CN 101094844 A CN101094844 A CN 101094844A CN 200580038015 A CN200580038015 A CN 200580038015A CN 101094844 A CN101094844 A CN 101094844A
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Abstract
Description
H | δppm | 峰形 | J Hz | 积分 | 注释 |
C2平伏 | 4.14 | Dd | 10.98 | 1 | |
C2直立 | 4.35 | Dd | 1 | Dd是重叠的 | |
C3 | 3.47 | Ddd | 1 | ||
C4 | 4.20 | Dd | 5.12 | 1 | |
C5 | 6.71 | D | 8.05 | 1 | |
C6 | 6.36 | Dd | 2.56,8.42 | 1 | |
C8 | 6.41 | D | 2.20 | 1 | |
C9 | 3.71 | S | - | 3 | |
C2’,C6’ | 6.61 | D | - | 2 | C2’、C3’、C2”和C3”的双重峰重叠总积分是8 |
C3’,C5’ | 6.61 | D | - | 2 | |
C2”,C6” | 6.61 | D | - | 2 | |
C3”,C5” | 6.61 | D | - | 2 |
组织/细胞类型 | 名称 | 类似物(IC50 uM) | 抗肿瘤(IC50 uM) | ||
DHE | HMC | HHC | 顺式铂氨 | ||
成纤维细胞 | 新生儿包皮成纤维细胞(人,NFF) | >150 | 86.12±7.6 | 60.8 | 9.85±5 |
肾脏 | 家兔肾脏(细胞) | >150 | 61±4.3 | >150 | 未测试 |
适应症 | 名称 | 类似物(IC50 uM) | 抗肿瘤(IC50 uM) | |
DHE | HMC | 顺式铂氨 | ||
卵巢(癌) | A2780 | 1.7±0.61 | 1.58±0.59 | 2.10 |
CP70 | 1.69±0.62 | 1.21±0.29 | 10.30 | |
SKOV-3 | 21.83±4.65 | 2.26 | 5.40 | |
前列腺(癌) | PC3 | 9.09±8.12 | 2.9±0.92 | 2.11 |
LNCaP | 4.8±3.8 | 4.52 | >10 | |
DU145 | 5.95±1.5 | 3.78 | 2.07 | |
乳腺(癌) | MCF-7 | 21.5±13.2 | 7.15±7 | 3.69 |
MDA-MB-468 | 7.9±3.5 | 1.1±0.35 | 0.58 | |
胶质瘤 | HTB-138 | 7.35±0.89 | 1.9±0.27 | 42.30 |
胰腺(癌) | CRL-2119 | 56.62±16.8 | 14.1±1.16 | 9.36 |
白血病 | RPMI-8226 | 3.72±0.08 | NT | NT |
CCRF-CEM | 1.7±0.68 | 1.90 | NT | |
肺(癌) | NCI-H23 | 8.75±7.2 | 3.75±2.5 | NT |
NCI-H460 | 10.6±3.8 | 2.23±0.15 | 22.29 | |
结肠直肠(癌) | HT-29 | 50.45±21.9 | 3.7±1.4 | 22.7±35 |
HCT-15 | 24.4±12.57 | 37.8±33 | 129.9±39 | |
黑色素瘤 | MM200 | 2.90 | 0.7±.03 | 8.3±0.7 |
A2058 | NT | 1.2±0.65 | 5.73±2.3 | |
IGR-3 | NT | 0.53±0.02 | NT |
适应症 | 细胞系 | 化合物(IC50 uM) | |||||
HMC1 | 2 | 6 | HHC 11 | 14-烯 | 14 | ||
卵巢(癌) | CP70 | 2.1 | 3±1.2 | >100 | 1.1±0.9 | >100 | >100 |
前列腺(癌) | PC3 | 2.5±1 | 4.2±0.02 | 116±57 | 0.88±0.4 | 46.2±7 | 32.5±2.1 |
乳腺(癌) | MDA-MB-468 | 2.8±4.2 | 1.9 | 28.7±3.6 | 1±0.1 | NT | 56.6 |
胶质瘤 | HTB-138 | 1.9±0.3 | 3.77 | >100 | 0.52±0.1 | 82±10 | 53.5±14 |
胰腺(癌) | HPAC | 2.8±0.9 | 24.4±12 | >100 | 31.6±27 | 81.5±59 | 79±56 |
白血病 | CCRF-CEM | 2±0.97 | 4.02 | 92±81.6 | 0.6±0.01 | >100 | 73±51.6 |
NSC肺(癌) | NCI-H460 | 2.8±2 | 5.4±2.1 | NT | 0.5±0.1 | >100 | 65 |
结肠直肠(癌) | HT-29 | 5.4±1.8 | 59.4 | >100 | 2.5±1 | 97.5±30 | 45±4.7 |
黑色素瘤 | MM200 | 1.07±0.5 | 7.34 | >100 | 0.6±0.3 | 58±2.7 | 93±2.9 |
时间 | HMC(uM) | DHE(uM) | ||
总的 | 游离的 | 总的 | 游离的 | |
0.25 | 72±4.4 | 0.38±0.04 | 511.5±99 | 3.3±0.13 |
0.5 | 122±18.4 | 1.3±0.2 | 357±82 | 2.9±0.05 |
1 | 141±45.8 | 0.95±0.4 | 387±22.8 | 1.5±0.11 |
4 | 33.9±12.7 | 0.19±0.08 | 117.6±42 | 1.3±0.07 |
24 | 0 | 0 | 0.13±0.1 | 0.15±0.04 |
化合物 | Cmax(ng/mL) | Tmax(小时) | t1/2(小时) |
HMC(1) | 513 | 2.17 | 3.99 |
HHC(11) | 341 | 2.67 | 3.26 |
时间(小时) | 血清HMC(uM) | |
静脉内 | 腹膜内 | |
0.25 | 1069.75 | 131.37 |
0.50 | 198.66 | 31.78 |
1 | 3.98 | 18.74 |
4 | 0.07 | 0.15 |
24 | 0.05 | 0.17 |
样品 | 描述 | 坏死评分 0-5 |
4/04&1/8 | 载体对照 | 0.5 |
4/04&2/8 | HMC | 2 |
4/04&4/8 | 2 | |
4/04&5/8 | 2 | |
4/04&1/11 | 无治疗对照 | 0.5 |
样品 | 组 | 临床标记(小鼠) | |||
ALP | ALT | Cre | 脲 | ||
U/L | U/L | μM | mM | ||
对照 | 1/11 | 116 | 713 | 7 | 6.92 |
载体 | 1/8 | 152 | 441 | 26 | 9.81 |
HMC治疗(100mg/kg) | 2/8 | 74 | 505 | 17 | 7.27 |
4/8 | 111 | 482 | 8 | 8.11 | |
5/8 | 100 | 494 | 8 | 7.79 | |
正常范围 | 86-246 | 84-143 | 1.5-6 | 6.3-8* |
药物浓度(uM) | 凋亡百分比 | ||
TRAIL敏感 | Trail-耐受 | Trail+ve/胱冬酶8-ve |
MEL-RM | ME4405 | IGR3 | Mel-AT | ||||||
DHE | HMC | DHE | HMC | DHE | HMC | DHE | HMC | ||
触接时小42 | 对照 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
1 | 0 | 0 | 0 | 0 | 0 | 8 | 0 | 0 | |
2 | 0 | 8 | 2 | 8 | 0 | 11 | 3 | 6 | |
4 | 0 | 25 | 2 | 9 | 1 | 39 | 4 | 9 | |
8 | 2 | 39 | 6 | 11 | 3 | 41 | 8 | 23 | |
20 | 5 | 38 | 11 | 19 | 4 | 32 | 10 | 24 | |
触接时小84 | 对照 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
1 | 1 | 1.5 | 1 | 1.5 | 1 | 1 | 1.5 | 1 | |
2 | 1.5 | 8 | 3 | 8 | 1 | 9 | 5 | 7 | |
4 | 3 | 22 | 14 | 42 | 2 | 21 | 15 | 25 | |
8 | 10 | 38 | 40 | 20 | 8 | 38 | 43 | 59 | |
20 | 12 | 30 | 35 | 18 | 8 | 38 | 40 | 35 |
药物 | 处理(IC50 uM) | ||||
联用 | 改变系数 | 24小时 | 先用HMC | 改变系数 | |
顺式铂氨 | 8.82 | -- | 6.32 | -- | -- |
HMC | 0.72 | -- | 20.64 | -- | -- |
HMC 10uM | 1.00E-06 | HMC效力 | -- | 1.28E-05 | >10000 |
HMC 5uM | 1.00E-06 | HMC效力 | -- | 2.71E-05 | >10000 |
HMC 2uM | 1.00E-06 | HMC效力 | -- | 1.00E-06 | >10000 |
HMC 1uM | 0.45 | HMC效力 | -- | 8.29 | -1.31 |
药物 | 处理(IC50 uM) | ||||
联用 | 改变系数 | 24小时 | 先用HMC | 改变系数 | |
HMC | 0.51 | -- | 27.79 | -- | -- |
HMC 1uM | 1.00E-06 | ?HMC效力 | -- | 1.76E-03 | >1000 |
HMC 2uM | 1.00E-06 | ?HMC效力 | -- | 1.00E-06 | >1000 |
吉西他滨 | 3.88E-03 | -- | 4.67E-03 | -- | -- |
HMC | 0.51 | -- | 27.79 | -- | -- |
HMC 1uM | 1.00E-06 | ?HMC效力 | -- | 1.00E-06 | >1000 |
HMC 2uM | 1.00E-06 | ?HMC效力 | -- | 3.89E-05 | >100 |
药物 | 处理(IC50 uM) | ||||
联用 | 改变系数 | 24小时 | 先用HMC | 改变系数 | |
HMC 1uM | 0.006 | 1.00 | -- | 0.03 | -4.44 |
HMC 2uM | 1.00E-06 | 5964.400 | -- | 0.01 | -1.035 |
紫杉醇 | 1.25E-07 | -- | 5.84E-04 | -- | -- |
HMC | 1.26 | -- | 55.50 | -- | -- |
HMC 1uM | 4.12E-09 | 30.36 | -- | 5.31E-05 | 11.00 |
HMC 2uM | 3.91E-10 | ?HMC效力 | -- | 5.48E-09 | 106633.75 |
药物 | 处理(IC50 uM) | ||||
联用 | 改变系数 | 24小时 | 先用HMC | 改变系数 | |
HMC 1uM | 0.115 | -14.145 | -- | 0.009 | 9.304 |
HMC 2uM | 1.00E-06 | ?HMC效力 | -- | 7.85E-05 | >1000 |
拓扑替康 | 0.095 | -- | 2.216 | -- | -- |
HMC | 0.702 | -- | 17.952 | -- | -- |
HMC 1uM | 0.000 | ?HMC效力 | -- | 0.044 | 50.656 |
HMC 2uM | 1.00E-06 | ?HCM效力 | -- | 1.00E-06 | >10000 |
药物 | 处理(IC50 uM) | ||||
联用 | 改变系数 | 24小时 | 先用HMC | 改变系数 | |
阿霉素 | 0.19 | -- | 0.100 | -- | -- |
HMC | 0.54 | -- | 50.515 | -- | -- |
HMC 1uM | 0.40 | -2.06 | -- | 0.062 | 1.62 |
HMC 2uM | 0.18 | ?HMC效力 | -- | 8.16E-03 | 12.22 |
浓度(μM) | 化合物6 | 化合物7 | 化合物4 |
10 | -48.7 | -26.2 | -6.1 |
1 | -13.0 | -25.4 | -11.9 |
0.1 | -10.4 | -1.4 | -6.3 |
0.001 | 1.0 | 19.2 | -14.3 |
0.01 | - | - | -11.3 |
药物 | 癌症适应症 | |||||
卵巢(癌) | 前列腺(癌) | 乳腺(癌) | 黑色素瘤 | 胶质瘤 | 胰腺(癌) | |
CP70 | PC3 | MDA-468 | MM96L | HTB-138 | HPAC | |
顺式铂氨 | SSSSS | SSSSS | - | SSSSS | n.o. | n.o. |
- | SSSSS | - | - | n.o. | - | |
- | - | - | - | - | - | |
吉西他滨 | SSSSS | SSSSS | SSSSS | - | SSSSS | SSSSS |
- | - | - | - | SSSSS | - | |
- | - | - | - | - | - | |
紫杉醇 | n.o. | n.o. | MS | - | MS | n.o. |
MS | - | - | - | n.o. | - | |
- | - | - | - | n.o. | - | |
脱羧铂氨 | - | - | - | SSSSS | - | - |
氮烯唑胺 | - | - | - | SSSSS | - | - |
类似物 | 黑色素瘤细胞系(IC50μM) | ||||||
MM200 | A2058 | IgR3 | RM | 4405 | MM96L | SKMel28 | |
DHE | 4.77±4 | NT | NT | NT | NT | 4.76 | 4.40 |
HMC | 1.13±0.52 | 1.42±0.48 | 0.51±0.08 | 1.4±1.6 | 1.46±0.18 | 1.31±0.38 | 0.68±0.16 |
HHC | 0.66±0.28 | 0.34 | 0.20 | 0.39±0.28 | 0.50 | 0.2±0.09 | 0.36±0.34 |
化合物 | PGE2 | TXB2 |
1 | -33.8 | 0 |
2 | -12.6 | 16 |
6 | -37.7 | -16.4 |
11 | 27.2 | 51.4 |
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JP4976649B2 (ja) * | 2004-09-21 | 2012-07-18 | マーシャル エドワーズ,インク. | 化合物 |
US8080675B2 (en) | 2004-09-21 | 2011-12-20 | Marshall Edwards, Inc. | Chroman derivatives, medicaments and use in therapy |
CN101056868B (zh) | 2004-09-21 | 2012-05-02 | 马休爱德华兹股份有限公司 | 取代的苯并二氢吡喃衍生物、药物及其在治疗中的应用 |
JP6013349B2 (ja) | 2010-11-01 | 2016-10-25 | メイ ファーマ, インク.Mei Pharma, Inc. | 癌の処置のためのイソフラボノイド化合物および方法 |
JP6218680B2 (ja) * | 2014-06-11 | 2017-10-25 | 三菱電機株式会社 | ネットワーク解析支援装置、ネットワーク解析支援方法、および、プログラム |
HUE054998T2 (hu) | 2015-02-02 | 2021-10-28 | Mei Pharma Inc | Kombinációs terápiák emlõrák kezelésében való alkalmazásra |
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US5883118A (en) * | 1996-01-11 | 1999-03-16 | Nova Nordisk A/S | Prostatic carcinoma |
CA2269936A1 (en) * | 1996-10-28 | 1998-05-07 | Lise Brown Christiansen | Novel trans-3,4-chroman derivatives useful in the prevention or treatment of estrogen related diseases or syndromes |
AU4772397A (en) * | 1996-10-28 | 1998-05-22 | Novo Nordisk A/S | Novel (cis)-3,4-chroman derivatives useful in the prevention or treatment of estrogen related diseases or syndromes |
KR20000001793A (ko) * | 1998-06-13 | 2000-01-15 | 이경하 | 신규한 벤조피란 또는 티오벤조피란 유도체 |
MXPA03006505A (es) * | 2001-01-24 | 2004-04-21 | Chiesi Farma Spa | Derivados de 2h-1-benzopirano, procedimiento para su preparacion y sus composiciones farmaceuticas. |
JP4976649B2 (ja) * | 2004-09-21 | 2012-07-18 | マーシャル エドワーズ,インク. | 化合物 |
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2005
- 2005-09-21 CN CN2005800380156A patent/CN101094844B/zh active Active
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CN103224481A (zh) * | 2013-05-20 | 2013-07-31 | 黑龙江大学 | 一种去氢雌马酚的制备方法 |
CN105980372A (zh) * | 2014-02-07 | 2016-09-28 | 诺沃根有限公司 | 官能化的苯并吡喃化合物及其用途 |
CN105980372B (zh) * | 2014-02-07 | 2018-05-08 | 凯捷治疗有限公司 | 官能化的苯并吡喃化合物及其用途 |
WO2018145342A1 (zh) * | 2017-02-10 | 2018-08-16 | 山东康迈祺生物科技有限公司 | 一种二氢大豆苷元的制备方法 |
CN108409701A (zh) * | 2017-02-10 | 2018-08-17 | 山东康迈祺生物科技有限公司 | 一种二氢大豆苷元的制备方法 |
CN108409701B (zh) * | 2017-02-10 | 2020-09-25 | 山东康迈祺生物科技有限公司 | 一种二氢大豆苷元的制备方法 |
CN112920173A (zh) * | 2021-01-25 | 2021-06-08 | 江苏师范大学 | 一种手性苯并二氢吡喃化合物及其合成方法 |
Also Published As
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JP2006096734A (ja) | 2006-04-13 |
JP5816868B2 (ja) | 2015-11-18 |
JP2012144537A (ja) | 2012-08-02 |
CN101094844B (zh) | 2012-07-25 |
JP4976649B2 (ja) | 2012-07-18 |
JP2014237638A (ja) | 2014-12-18 |
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