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Arylpiperazine compound as well as preparation method and application thereof

A compound, cyano technology, applied in the field of medicine, can solve the problems of incurable prostate cancer, inability to improve treatment results or survival rate, etc.

Active Publication Date: 2018-01-12
袁牧
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, metastatic prostate cancer is not curable and androgen ablation therapy becomes standard therapy
None of the conventional cancer treatments for prostate cancer have been very successful, although various chemotherapeutic drugs alone or in combination with radiation therapy are used to treat patients with advanced disease
Other studies have shown that once tumor cells become hormone-resistant, standard cytotoxic agents do little to improve treatment outcomes or survival in hormone-insensitive prostate cancer, although they do provide some pain relief for patients

Method used

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  • Arylpiperazine compound as well as preparation method and application thereof
  • Arylpiperazine compound as well as preparation method and application thereof
  • Arylpiperazine compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Embodiment 1: the preparation of intermediate 5

[0084]

[0085] Add 100mg (0.22mmol) intermediate 4, 59.8mg (0.26mmol) 1-(4-trifluoromethylphenyl) piperazine, 182mg (1.32mmol) potassium carbonate, 15mL acetonitrile in 25mL round bottom flask, at 86 The reaction was carried out at ℃ for 16 h, and TLC showed that the reaction of the starting material was complete. The reaction was stopped, filtered and concentrated. The crude product was purified by silica gel column chromatography, eluent: V (ethyl acetate): V (petroleum ether) = 1:3, to obtain 35.2 mg of white solid, yield: 33%. M.p.:165-166℃; MS(ESI,m / z):509.2[M+1] + ; 8.01(d, J=8.7Hz, 1H), 7.35(d, J=8.0Hz, 2H), 7.26(d, J=3.6Hz, 2H), 7.00–6.94(m, 2H), 6.90(d, J=4.3Hz, 2H), 6.88(dd, J=4.7, 1.9Hz, 1H), 6.78(d, J=2.3Hz, 1H), 5.08(s, 2H), 3.16(t, J=4.9Hz, 4H), 2.92(t, J=6.0Hz, 2H), 2.87(dd, J=9.7, 6.5Hz, 2H), 2.71(t, J=4.9Hz, 4H), 2.68(dd, J=9.8, 6.6 Hz, 2H), 2.61(t, J=6.5Hz, 2H), 2.11(t, J=6.4Hz, 2H); 13 C NMR ...

Embodiment 2

[0086] Embodiment 2: the preparation of compound 6

[0087]

[0088] The reaction of intermediate 4 with 1-(2,5-dimethylphenyl)piperazine, the synthesis process and test conditions are the same as in Example 1. 41.2 mg of white solid was obtained, yield: 40%. M.p.:145-146℃; MS(ESI,m / z):469.2[M+1] + ; 1 HNMR (500MHz, CDCl 3 )δinppm: 8.01(d, J=8.7Hz, 1H), 7.35(d, J=8.0Hz, 2H), 7.26(d, J=3.6Hz, 2H), 7.00–6.94(m, 2H), 6.90( d, J=4.3Hz, 2H), 6.88(dd, J=4.7, 1.9Hz, 1H), 5.08(s, 2H), 3.16(t, J=4.9Hz, 4H), 2.92(t, J=6.0 Hz, 2H), 2.87(dd, J=9.7, 6.5Hz, 2H), 2.71(t, J=4.9Hz, 4H), 2.68(dd, J=9.8, 6.6Hz, 2H), 2.61(t, J =6.5Hz, 2H), 2.11(t, J=6.4Hz, 2H), 1.67(m, 6H); 13 C NMR (126MHz, CDCl 3 )δin ppm:197.21,175.15,162.73,150.96,146.95,139.92,136.18,134.14,130.8,129.69,129.22,129.08,127.80,126.51,123.97,119.81,113.68,113.59,77.28,77.02,76.77,69.91,59.98, 53.35, 51.09, 38.90, 32.62, 30.16, 23.36, 21.74, 21.18, 17.43.

Embodiment 3

[0089] Embodiment 3: the preparation of compound 7

[0090]

[0091] The reaction of intermediate 4 with 1-(3-methylphenyl)piperazine, the synthesis process and test conditions are the same as in Example 1. 64.9 mg of white solid was obtained, yield: 65%. M.p.:132-133℃; MS(ESI,m / z):455.1[M+1] + ; 1 H NMR (500MHz, CDCl 3 )δinppm: 8.01(d, J=8.7Hz, 1H), 7.35(d, J=8.0Hz, 2H), 7.26(d, J=3.6Hz, 2H), 7.00–6.94(m, 2H), 6.90( d, J=4.3Hz, 2H), 6.88(dd, J=4.7, 1.9Hz, 1H), 6.78(d, J=2.3Hz, 1H), 5.08(s, 2H), 3.16(t, J=4.9 Hz, 4H), 2.92(t, J=6.0Hz, 2H), 2.87(dd, J=9.7, 6.5Hz, 2H), 2.71(t, J=4.9Hz, 4H), 2.68(dd, J=9.8 , 6.6Hz, 2H), 2.61(t, J=6.5Hz, 2H), 2.11(t, J=6.4Hz, 2H), 1.62(m, 3H); 13 C NMR (126MHz, CDCl 3 )δin ppm:197.16,162.73,151.31,146.93,140.36,138.80,134.01,129.68,129.06,128.96,127.74,126.51,120.70,116.95,113.67,113.59,113.22,77.28,77.23,77.03,76.77,69.93,60.33, 53.25, 49.19, 38.90, 33.25, 30.16, 23.36, 21.78.

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PUM

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Abstract

The invention provides a novel arylpiperazine compound as well as a preparation method and application thereof. The invention provides the compound shown as a general formula (I). Compared with a control compound, namely Naftopidil, the representative compound shown as the general formula (I) is equivalent and even higher in in-vitro anti-tumor cell activity and has higher selectivity.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a novel arylpiperazine compound and its preparation method and application. technical background [0002] Prostate cancer (PCa) is a very common disease in men, and ranks second among the lethal cancers in men, and its morbidity and mortality are second only to lung cancer. The incidence of PCa in European and American countries is much higher than that in China, Japan and other East Asian countries, and now the incidence of prostate cancer in my country is also showing an increasing trend, and prostate cancer has become a global problem. [0003] Clinically, localized disease can be cured by surgery or radiation therapy to remove or destroy cancer cells. However, metastatic prostate cancer is not curable and androgen ablation therapy has become the standard therapy. Despite the use of various chemotherapeutic drugs alone or in combination with radiation therapy to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/096C07D295/155A61K31/495A61P35/00A61P13/08
Inventor 袁牧陈洪叶碧波杨宗琳
Owner 袁牧