KR100466168B1 - 1,3-dihydroxybenzene derivatives, a process for the preparation thereof, and a composition as a anticancer agent comprising them - Google Patents

1,3-dihydroxybenzene derivatives, a process for the preparation thereof, and a composition as a anticancer agent comprising them Download PDF

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KR100466168B1
KR100466168B1 KR10-2001-0074621A KR20010074621A KR100466168B1 KR 100466168 B1 KR100466168 B1 KR 100466168B1 KR 20010074621 A KR20010074621 A KR 20010074621A KR 100466168 B1 KR100466168 B1 KR 100466168B1
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dihydroxyphenyl
propen
phenyl
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안병준
위엥하이남
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충남대학교산학협력단
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    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/02—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with no unsaturation outside the aromatic ring
    • C07C39/08—Dihydroxy benzenes; Alkylated derivatives thereof
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Abstract

본발명은 아래 일반식(I)의 1,4-디히드록시벤젠 유도체 및 약제학적으로 허용가능한 그의 염 및 이의 제조방법에 관한 것으로서, 일반식(I)의 1,4-디히드록시벤젠 유도체를 포함하는 조성물은 항암제로서 유용하다.The present invention relates to a 1,4-dihydroxybenzene derivative of the general formula (I) and a pharmaceutically acceptable salt thereof and a preparation method thereof, wherein the 1,4-dihydroxybenzene derivative of the general formula (I) The composition comprising is useful as an anticancer agent.

(I)(I)

[식 중, Y는 -CH=CH-CO-, -CO-CH=CH-, 또는 -CO-CR2=CH-;X는 페닐 또는 하나 이상의 치환기 R1으로 치환된 페닐; 또는 Y는 -COCH=CH-이고 X는[Wherein Y is -CH = CH-CO-, -CO-CH = CH-, or -CO-CR 2 = CH-; X is phenyl or phenyl substituted with one or more substituents R 1 ; Or Y is -COCH = CH- and X is

;R1은 수소, 할로겐, 히드록시, 치환되거나 치환되지 않은 알킬, 알콕시, 알킬티오, 니트로, 아미노, 알킬설포닐, 페닐 또는 알킬렌디옥시, 또는 이들의 조합; R2는 시아노, 할로겐 또는 알킬, 또는 이들의 조합; R3는 수소, 할로겐, 알콕시, 알킬, 아미노 또는 니트로, 또는 이들의 조합; 및 R4는 수소 또는 알콕시, 또는 이들의 조합임. R 1 is hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, alkoxy, alkylthio, nitro, amino, alkylsulfonyl, phenyl or alkylenedioxy, or a combination thereof; R 2 is cyano, halogen or alkyl, or a combination thereof; R 3 is hydrogen, halogen, alkoxy, alkyl, amino or nitro, or a combination thereof; And R 4 is hydrogen or alkoxy, or a combination thereof.

Description

1,4-디히드록시벤젠 유도체, 이의 제조방법 및 이를 포함하는 항암제조성물{1,3-DIHYDROXYBENZENE DERIVATIVES, A PROCESS FOR THE PREPARATION THEREOF, AND A COMPOSITION AS A ANTICANCER AGENT COMPRISING THEM}1,4-dihydroxybenzene derivative, a method for preparing the same and an anticancer composition comprising the same {1,3-DIHYDROXYBENZENE DERIVATIVES, A PROCESS FOR THE PREPARATION THEREOF, AND A COMPOSITION AS A ANTICANCER AGENT COMPRISING THEM}

본발명은 신규의 1,4-디히드록시벤젠 유도체에 관한 것으로서, 더욱 상세하게는 하기 일반식(I)로 나타내어지는 1,4-디히드록시벤젠 유도체 및 약제학적으로 허용가능한 그의 염, 이들의 제조방법 및 이들을 유효성분으로 함유하는 약제학적 조성물에 관한 것이다.The present invention relates to novel 1,4-dihydroxybenzene derivatives, more particularly 1,4-dihydroxybenzene derivatives represented by the following general formula (I) and pharmaceutically acceptable salts thereof, these It relates to a method for preparing and a pharmaceutical composition containing these as an active ingredient.

(I)(I)

[식 중, Y는 -CH=CH-CO-, -CO-CH=CH-, 또는 -CO-CR2=CH-;[Wherein Y is -CH = CH-CO-, -CO-CH = CH-, or -CO-CR 2 = CH-;

X는 페닐 또는 하나 이상의 치환기 R1으로 치환된 페닐; 또는 Y는 -CO-CH=CH-이고 X는X is phenyl or phenyl substituted with one or more substituents R 1 ; Or Y is -CO-CH = CH- and X is

; ;

R1은 수소, 할로겐, 히드록시, 치환되거나 치환되지 않은 알킬, 알콕시, 알킬티오, 니트로, 아미노, 알킬설포닐, 페닐 또는 알킬렌디옥시, 또는 이들의 조합; R2는 시아노, 할로겐 또는 알킬, 또는 이들의 조합; R3는 수소, 할로겐, 알콕시, 알킬, 아미노 또는 니트로 또는 이들의 조합; 및 R4는 수소 또는 알콕시, 또는 이들의 조합임.R 1 is hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, alkoxy, alkylthio, nitro, amino, alkylsulfonyl, phenyl or alkylenedioxy, or a combination thereof; R 2 is cyano, halogen or alkyl, or a combination thereof; R 3 is hydrogen, halogen, alkoxy, alkyl, amino or nitro or a combination thereof; And R 4 is hydrogen or alkoxy, or a combination thereof.

아래의 화학식1로 나타내어지는 1,3-디페닐-2-프로펜-1-온 부분(chalcone)의 구조는 천연에 널리 그리고 다양하게 분포되어 있는 플라보노이드의 근간 구조로서 플라보노이드 화합물은 최근까지 항암제로서는 각광을 받지 못하다가 최근 합성 플라보노이드인 플라본 아세트산 ( Finlay, G. J.; Smith, G. P.; Fray, L. M.; Baguley, B. C. Effects of flavone acetic acid on Lewis lung carcinoma: evidence for an indirect effect. J. Natl. Cancer Inst. 80, 241, 1988)이 좋은 항암성을 보임이 밝혀지면서 다시 주목을 끌게 되었다.The structure of the 1,3-diphenyl-2-propen-1-one chalcone represented by the following formula (1) is a backbone structure of flavonoids widely and variously distributed in nature. Flavonoid compounds have recently been used as anticancer agents. Recently, flavon acetic acid (Finlay, GJ; Smith, GP; Fray, LM; Baguley, BC Effects of flavone acetic acid on Lewis lung carcinoma: evidence for an indirect effect.J. Natl. Cancer Inst. 80, 241, 1988) again attracted attention as it turned out to be good anti-cancer.

또한, 새로운 항암제의 개발 방법 중 암세포의 혈관신생(angiogenesis)을 억제시켜 암세포의 전이와 증식을 억제시키는 약제들이 주목을 받고 있다. 혈관신생은 암세포의 초기 증식과정에서 반드시 일어나며 생성된 혈관들이 암세포의 필수적인 산소와 영양분을 공급함으로써 암세포의 지속적인 성장을 가능하게 한다. 또한이렇게 생성된 혈관들은 악성 암세포들이 다른 기관으로 전이되는 통로로 사용되어 암치료를 불가능하게 하는 원인이 되기도 한다.In addition, among the development methods of new anticancer drugs, drugs that inhibit cancer cell angiogenesis (angiogenesis) to inhibit the metastasis and proliferation of cancer cells are attracting attention. Angiogenesis necessarily occurs during the initial growth of cancer cells, and the resulting blood vessels provide the necessary oxygen and nutrients for the cancer cells, enabling the cancer cells to continue to grow. These blood vessels are also used as a path for malignant cancer cells to spread to other organs, making cancer treatment impossible.

암(특히 고형암)의 성장 및 전이에는 혈관신생이 필수 불가결한 현상이다. 고형암의 크기가 약 1-2 mm3까지는 성장에 필요한 성장인자(growth factor), 산소,영양분 등을 확산(diffusion)에 의해 공급받을 수 있으나, 그 이상 성장하기 위해서는 암세포는 새로운 혈관형성을 통해서 성장에 필요한 성장인자, 산소, 영양분 등을 계속 공급받아야 한다. 따라서 암세포에 의한 혈관형성을 차단함으로써 암의 성장을 효과적으로 막을 수 있는 것이다.Angiogenesis is indispensable for the growth and metastasis of cancer, especially solid cancer. Solid tumors up to about 1-2 mm 3 can be supplied with diffusion factors such as growth factor, oxygen, and nutrients for growth, but in order to grow further, cancer cells grow through new angiogenesis. You must continue to receive growth factors, oxygen, and nutrients. Therefore, by blocking the angiogenesis by cancer cells can effectively prevent the growth of cancer.

혈관신생억제제의 개발연구는 1971년 미국의 Judah Folkman박사에 의해 암의 성장에 혈관형성이 필수적이라는 가설(Folkman, J. New England J. Medicine, 285, 1182, 1971)이 제창된 이후, 1990년 미국 Harvard 의과대학의 Folkman 박사에 의해 개발된 최초의 천연물유래의 혈관신생 저해제인 fumagillin 및 TNP-470 (Ingber, D., Nature 348, 555, 1990)가 발표되었으며, 그후 혈관신생에 대한 연구의 발전과 더불어 수많은 혈관형성 저해제가 개발되어 현재 임상실험을 하고 있는 것으로 알려져 있다. 그후 1994년에 보고된 angiostatin (0'Reilly, M.S.,. et al, Cell 79, 315, 1994)은 최초로 발견된 내인성 혈관신생저해제로서 Lewis Lung Carcinoma를 이식한 C57BL/J마우스의 뇨에서 분리된 plasminogen의 37 kDa 단편으로 혈관 내피세포의 증식을 강력히 억제하는 것으로 알려져 있다. 이후 마우스 hemangioendothelioma 세포주인 EOMA로 부터 collagen 18의 20 kDa fragment인 endostatin (O'Reilly, M.S.. et al, Cell 88, 277, 1997)이 발견되었는데endostatin, angiostatin 모두 in vivo 및 in vivo에서 강력한 혈관신생저해작용과 더불어 동물모델에서 내성을 보이지 않고 우수한 항암효과를 나타내는 것으로 알려져 있다. 최근 들어 제니스테인(genistein), 루테올린(luteolin), 다이드제인The research on the development of angiogenesis inhibitors was carried out in 1990 by Dr. Judah Folkman of the United States in 1990. The first natural product-derived angiogenesis inhibitors, fumagillin and TNP-470 (Ingber, D., Nature 348, 555, 1990), developed by Dr. Folkman of Harvard Medical School in the United States, have since been developed. In addition, numerous angiogenesis inhibitors have been developed and are currently known to be in clinical trials. Angiostatin (0'Reilly, MS ,. et al, Cell 79, 315, 1994), subsequently reported in 1994, was the first endogenous angiogenesis inhibitor found in plasminogen isolated from the urine of C57BL / J mice implanted with Lewis Lung Carcinoma. 37 kDa fragment is known to strongly inhibit the proliferation of vascular endothelial cells. Endostatin (O'Reilly, MS. Et al, Cell 88, 277, 1997), a 20 kDa fragment of collagen 18, was found from EOMA, a mouse hemangioendothelioma cell line. Both endostatin and angiostatin were potent angiogenesis in vivo and in vivo. In addition to its activity, it is known to exhibit excellent anticancer effects without showing resistance in animal models. Recently, genistein, luteolin, and dyedzein

(daidzein) 등이 신생혈관 저해작용을 보인다는 연구 결과(Fotsis, T.; Pepper, M.; Adlerereutz, H. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Pro. Natl. Acd. Sci. USA. 2690, 1993)가 나오자 플라보노이드 화합물의 항암제로서의 가능성이 더욱 높아졌다. 또한 찰콘(chalcone) 유도체가 강력한 유사분열 억제 활성 및 티로신 키나제 저해작용을 보인다고 보고하고 있다 ( Edwards, M. L.; Stemmerick, D. M.; Sunkara, P. S. Chalcones: A new class of antimitotic agents. J. Med. Chem. 33, 1948, 1990., Ducki, S.; Forrest, R.; Hadfield, J. A.; Kendall, A.; Lawrence, N. J.; McGown, A. T.; Reninison, D. Potent antimitotic and cell growth inhibitory properties of substituted chalcones.Bioorg. Med. Chem. Lett.8, 1051-1056, 1998.). 이러한 활성 저지는 항암 작용의 중요한 타깃임을 감안할 때 항암제로서의 찰콘의 연구는 중요하다.(Daidzein) et al. (Fotsis, T .; Pepper, M .; Adlerereutz, H. Genistein, a dietary-derived inhibitor of in vitro angiogenesis.Pro. Natl. Acd. Sci. USA) 2690, 1993), the possibility of the flavonoid compound as an anticancer agent was increased. It has also been reported that chalcone derivatives exhibit potent mitotic inhibitory activity and tyrosine kinase inhibitory activity (Edwards, ML; Stemmerick, DM; Sunkara, PS Chalcones: A new class of antimitotic agents. J. Med. Chem. 33 , 1948, 1990., Ducki, S .; Forrest, R .; Hadfield, JA; Kendall, A .; Lawrence, NJ; McGown, AT; Reninison, D. Potent antimitotic and cell growth inhibitory properties of substituted chalcones.Bioorg . Med. Chem. Lett . 8 , 1051-1056, 1998.). Considering that such inhibition of activity is an important target of anticancer action, the study of Chalcone as an anticancer agent is important.

화학식 1:찰콘Formula 1: Chalcone

한편, 강활(羌活)에 함유되어 있는 메칠 카페에이트(methyl caffeate, 화학식 2)는 몇 종의 암세포에 대하여 좋은 세포독성을 보인다는 사실이 공지되어있다(Nguyen Hai Nam, Ha Thi Huong, Hwan Mook Kim and Byung-Zun Ahn. Cytotoxic Constituents from Notopterygium incisum.Kor.J.Pharmcogn. 31, 77-81, 2000). 본 발명자는 메칠 카페에이트의 구조를 기준으로 여러 가지 유도체를 합성하였던 바, 메칠 2,5-디히드록시 신나메이트 (methyl 2,5-dihydroxy cinnamate, 화학식 3)가 메틸 카페에이트 보다 10배 이상의 강한 세포독성을 나타냄을 발견하였다.On the other hand, methyl caffeate (Formula 2) contained in the actives is known to show good cytotoxicity against several types of cancer cells (Nguyen Hai Nam, Ha Thi Huong, Hwan Mook Kim) and Byung-Zun Ahn.Cytotoxic Constituents from Notopterygium incisum.Kor. J. Pharmcogn . 31, 77-81, 2000). The present inventors synthesized various derivatives based on the structure of methyl caffeate, and methyl 2,5-dihydroxy cinnamate (Formula 3) is 10 times stronger than methyl caffeate. It was found to be cytotoxic.

화학식 2: 메틸 카페에이트Formula 2: Methyl Caffeate

화학식 3: 2,5-디하이드록시 신나메이트Formula 3: 2,5-dihydroxy cinnamate

이 물질의 세포독성은 구조 중 p-히드로퀴논(1,4-디히드록시벤젠)이 암세포 내에서 p-퀴논으로 변화한 후 효소, 수용체, 핵산 등과 반응함으로써 발현된다고 추정된다. 더욱이 a,b-불포화 카보닐기 (a,b-unsaturated carbonyl)는 하나의 마이클 수용체(Michael acceptor)로서 역시 효소, 핵산, 기타 수용체들과 공유결함을 함으로써 세포독성을 일으킨다.The cytotoxicity of this substance is estimated to be expressed by the reaction of p-hydroquinone (1,4-dihydroxybenzene) in the structure with p-quinone in cancer cells, followed by enzymes, receptors, and nucleic acids. Furthermore, a, b-unsaturated carbonyl is a Michael acceptor that also causes cytotoxicity by covalent defects with enzymes, nucleic acids, and other receptors.

따라서 본 발명자는 메틸 2,5-디히드록시신나메이트를 선도물질 (lead compound)로 하여 유도체를 합성하여 이들이 강한 세포독성 및 항암 작용을 가짐을발견하고 본발명을 완성하기에 이르렀다.Therefore, the present inventors synthesized derivatives using methyl 2,5-dihydroxycinnamate as a lead compound, and discovered that they had strong cytotoxic and anticancer effects and completed the present invention.

상기 화학식 2 및 3에서, 세포독성을 나타내는 정확한 구조 및 메카니즘을 밝히진 못하였으나, p-히드로퀴논(1,4-디히드록시벤젠)와 a,b-불포화 에논(enone)이 세포독성을 나타내는 기본구조로 추정된다.In Formulas 2 and 3, although the exact structure and mechanism of cytotoxicity was not revealed, p-hydroquinone (1,4-dihydroxybenzene) and a, b-unsaturated enone are the basics of cytotoxicity. It is estimated to be a structure.

본발명의 첫번째 양상에서, 본발명은 아래 일반식(I)의 1,4-디히드록시벤젠 유도체 및 약제학적으로 허용가능한 그의 염을 제공한다:In a first aspect of the present invention, the present invention provides 1,4-dihydroxybenzene derivatives of the general formula (I) below and pharmaceutically acceptable salts thereof:

(I)(I)

[식 중, Y는 -CH=CH-CO-, -CO-CH=CH-, 또는 -CO-CR2=CH-;[Wherein Y is -CH = CH-CO-, -CO-CH = CH-, or -CO-CR 2 = CH-;

X는 페닐 또는 하나 이상의 치환기 R1으로 치환된 페닐; 또는 Y는 -CO-CH=CH-이고 X는X is phenyl or phenyl substituted with one or more substituents R 1 ; Or Y is -CO-CH = CH- and X is

; ;

R1은 수소, 할로겐, 히드록시, 치환되거나 치환되지 않은 알킬, 알콕시, 알킬티오, 니트로, 아미노, 알킬설포닐, 페닐 또는 알킬렌디옥시, 또는 이들의 조합;R2는 수소, 시아노, 할로겐 또는 알킬, 또는 이들의 조합; R3는 수소, 할로겐, 알콕시, 알킬, 아미노 또는 니트로 또는 이들의 조합; 및 R4는 수소 또는 알콕시, 또는 이들의 조합임.R 1 is hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, alkoxy, alkylthio, nitro, amino, alkylsulfonyl, phenyl or alkylenedioxy, or a combination thereof; R 2 is hydrogen, cyano, halogen Or alkyl, or a combination thereof; R 3 is hydrogen, halogen, alkoxy, alkyl, amino or nitro or a combination thereof; And R 4 is hydrogen or alkoxy, or a combination thereof.

보다 상세하게는, 본발명은 일반식(Ia)의 3-(2,5-디히드록시페닐)-1-(치환-페닐)-2-프로펜-1-온 유도체, 일반식(Ib)의 1-(2,5-디히드록시페닐)-3-(치환-페닐)More specifically, the present invention is a 3- (2,5-dihydroxyphenyl) -1- (substituted-phenyl) -2-propen-1-one derivative of general formula (Ia), general formula (Ib) 1- (2,5-Dihydroxyphenyl) -3- (substituted-phenyl)

-2-프로펜-1-온 유도체, 일반식(Ic)의 1-(2,5-디히드록시페닐)-3-페닐-2-치환-2-프로펜-1-온 유도체 및 일반식(Id)의 1,4,5-트리페닐-2,4-펜타디엔-1-온 유도체에 관한 것이다.-2-propen-1-one derivative, 1- (2,5-dihydroxyphenyl) -3-phenyl-2-substituted-2-propen-1-one derivative of general formula (Ic) and general formula 1,4,5-triphenyl-2,4-pentadien-1-one derivative of (Id).

일반식(Ia)Formula (Ia)

일반식(Ib)Formula (Ib)

일반식(Ic)Formula (Ic)

일반식(Id)Formula (Id)

[식 중, R1,R2,R3및 R4는 상기에서 정의된 바와 같다.[Wherein, R 1, R 2, R 3 and R 4 are as defined above.

일반식(I)의 화합물은 바람직하게는 R1이 수소, 클로로, 브로모, 플루오로, 메틸, 메톡시 또는 히드록시, R2는 클로로, 메틸 또는 시아노이고 R3및 R4는 메톡시인 화합물이다.Compounds of formula (I) are preferably those in which R 1 is hydrogen, chloro, bromo, fluoro, methyl, methoxy or hydroxy, R 2 is chloro, methyl or cyano and R 3 and R 4 are methoxy Phosphorus compound.

본발명에 따른 일반식(Ia) 내지 (Id)의 화합물의 예는 다음의 표 1 내지 표 4에 나타내었다.Examples of compounds of general formulas (Ia) to (Id) according to the present invention are shown in Tables 1 to 4 below.

표 1: 일반식(Ia)의 화합물의 예Table 1: Examples of Compounds of Formula (Ia)

R1 R 1 화합물명(화합물 번호)Compound name (compound number) HH (E)-3-(2,5-디히드록시페닐)-1-페닐-2-프로펜-1-온 (1-1).(E) -3- (2,5-dihydroxyphenyl) -1-phenyl-2-propen-1-one (1-1). 2-F2-F (E)-3-(2,5-디히드록시페닐)-1-(2-플루오로페닐)-2-프로펜-1-온 (1-2).(E) -3- (2,5-dihydroxyphenyl) -1- (2-fluorophenyl) -2-propen-1-one (1-2). 2-Cl2-Cl (E)-1-(2-클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-3).(E) -1- (2-chlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-3). 3-Cl3-Cl (E)-1-(3-클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-4).(E) -1- (3-chlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-4). 4-Cl4-Cl (E)-1-(4-클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-5).(E) -1- (4-chlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-5). 2-Br2-Br (E)-1-(2-브로모페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-6).(E) -1- (2-bromophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-6). 4-Br4-Br (E)-1-(4-브로모페닐)-3-(2,5-디히드록시페닐)- 2-프로펜-1-온 (1-7).(E) -1- (4-bromophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-7). 2,3,4,5,6-F5 2,3,4,5,6-F 5 (E)-3-(2,5-디히드록시페닐)-1-(2,3,4,5,6-펜타플루오로페닐)-2-프로펜-1-온 (1-8).(E) -3- (2,5-dihydroxyphenyl) -1- (2,3,4,5,6-pentafluorophenyl) -2-propen-1-one (1-8). 4-NO2 4-NO 2 (E)-3-(2,5-디히드록시페닐)-1-(4-니트로페닐)-2-프로펜-1-온 (1-9).(E) -3- (2,5-dihydroxyphenyl) -1- (4-nitrophenyl) -2-propen-1-one (1-9).

2,5-F2 2,5-F 2 (E)-1-(2,5-디플루오로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-10).(E) -1- (2,5-difluorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-10). 3,5-F2 3,5-F 2 (E)-1-(3,5-디플루오로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-11).(E) -1- (3,5-difluorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-11). 2,3-Cl2 2,3-Cl 2 (E)-1-(2,3-디클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-12).(E) -1- (2,3-dichlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-12). 3,4-Cl2 3,4-Cl 2 (E)-1-(3,4-디클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-13).(E) -1- (3,4-dichlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-13). 3,5-Cl2 3,5-Cl 2 (E)-1-(3,5-디클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-14).(E) -1- (3,5-dichlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-14). 2-OCH3-5-Br2-OCH 3 -5-Br (E)-1-[(5-브로모-2-메톡시)페닐]-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-15).(E) -1-[(5-bromo-2-methoxy) phenyl] -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1-15). 2-CH3 2-CH 3 (E)-3-(2,5-디히드록시페닐)-1-(2-메틸페닐)-2-프로펜-1-온 (1-16).(E) -3- (2,5-dihydroxyphenyl) -1- (2-methylphenyl) -2-propen-1-one (1-16). 4-CH3 4-CH 3 (E)-3-(2,5-디히드록시페닐)-1-(4-메틸페닐)-2-프로펜-1-온 (1-17).(E) -3- (2,5-dihydroxyphenyl) -1- (4-methylphenyl) -2-propen-1-one (1-17). 2-OCH3 2-OCH 3 (E)-3-(2,5-디히드록시페닐)-1-(2-메톡시페닐)-2-프로펜-1-온 (1-18).(E) -3- (2,5-dihydroxyphenyl) -1- (2-methoxyphenyl) -2-propen-1-one (1-18). 3-OCH3 3-OCH 3 (E)-3-(2,5-디히드록시페닐)-1-(3-메톡시페닐)-2-프로펜-1-온 (1-19).(E) -3- (2,5-dihydroxyphenyl) -1- (3-methoxyphenyl) -2-propen-1-one (1-19). 4-OCH3 4-OCH 3 (E)-3-(2,5-디히드록시페닐)-1-(4-메톡시페닐)-2-프로펜-1-온 (1-20).(E) -3- (2,5-dihydroxyphenyl) -1- (4-methoxyphenyl) -2-propen-1-one (1-20). 4-SCH3 4-SCH 3 (E)-3-(2,5-디히드록시페닐)-1-(4-티오메틸페닐)-2-프로펜-1-온 (1-21).(E) -3- (2,5-dihydroxyphenyl) -1- (4-thiomethylphenyl) -2-propen-1-one (1-21). 2,3-(OCH3)2 2,3- (OCH 3 ) 2 (E)-3-(2,5-디히드록시페닐)-1-(2,3-디메톡시페닐)-2-프로펜-1-온 (1-22).(E) -3- (2,5-dihydroxyphenyl) -1- (2,3-dimethoxyphenyl) -2-propen-1-one (1-22). 2,4-(OCH3)2 2,4- (OCH 3 ) 2 (E)-3-(2,5-디히드록시페닐)-1-(2,4-디메톡시페닐)-2-프로펜-1-온 (1-23).(E) -3- (2,5-dihydroxyphenyl) -1- (2,4-dimethoxyphenyl) -2-propen-1-one (1-23). 2,5-(OCH3)2 2,5- (OCH 3 ) 2 (E)-3-(2,5-디히드록시페닐)-1-(2,5-디메톡시페닐)-2-프로펜-1-온 (1-24).(E) -3- (2,5-dihydroxyphenyl) -1- (2,5-dimethoxyphenyl) -2-propen-1-one (1-24). 3,4-(OCH3)2 3,4- (OCH 3 ) 2 (E)-3-(2,5-디히드록시페닐)-1-(3,4-디메톡시페닐)-2-프로펜-1-온 (1-25).(E) -3- (2,5-dihydroxyphenyl) -1- (3,4-dimethoxyphenyl) -2-propen-1-one (1-25). 3,5-(OCH3)2 3,5- (OCH 3 ) 2 (E)-3-(2,5-디히드록시페닐)-1-(3,5-디메톡시페닐)-2-프로펜-1-온 (1-26).(E) -3- (2,5-dihydroxyphenyl) -1- (3,5-dimethoxyphenyl) -2-propen-1-one (1-26). 2,3,4-(OCH3)3 2,3,4- (OCH 3 ) 3 (E)-3-(2,5-디히드록시페닐)-1-(2,3,4-트리메톡시페닐)-2-프로펜-1-온 (1-27).(E) -3- (2,5-dihydroxyphenyl) -1- (2,3,4-trimethoxyphenyl) -2-propen-1-one (1-27). 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 (E)-3-(2,5-디히드록시페닐)-1-(2,4,5-트리메톡시페닐)-2-프로펜-1-온 (1-28).(E) -3- (2,5-dihydroxyphenyl) -1- (2,4,5-trimethoxyphenyl) -2-propen-1-one (1-28).

2,4,6-(OCH3)3 2,4,6- (OCH 3 ) 3 (E)-3-(2,5-디히드록시페닐)-1-(2,4,6-트리메톡시페닐)-2-프로펜-1-온 (1-29).(E) -3- (2,5-dihydroxyphenyl) -1- (2,4,6-trimethoxyphenyl) -2-propen-1-one (1-29). 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 (E)-3-(2,5-디히드록시페닐)-1-(3,4,5-트리메톡시페닐)-2-프로펜-1-온 (1-30).(E) -3- (2,5-dihydroxyphenyl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (1-30). 2-OH2-OH (E)-3-(2,5-디히드록시페닐)-1-(2-히드록시페닐)-2-프로펜-1-온 (1-31).(E) -3- (2,5-dihydroxyphenyl) -1- (2-hydroxyphenyl) -2-propen-1-one (1-31). 3-OH3-OH (E)-3-(2,5-디히드록시페닐)-1-(3-히드록시페닐)-2-프로펜-1-온 (1-32).(E) -3- (2,5-dihydroxyphenyl) -1- (3-hydroxyphenyl) -2-propen-1-one (1-32). 4-OH4-OH (E)-3-(2,5-디히드록시페닐)-1-(4-히드록시페닐)-2-프로펜-1-온 (1-33).(E) -3- (2,5-dihydroxyphenyl) -1- (4-hydroxyphenyl) -2-propen-1-one (1-33). 2-OH-5-OCH3 2-OH-5-OCH 3 (E)-3-(2,5-디히드록시페닐)-1-[(2-히드록시-5-메톡시)페닐]-2-프로펜-1-온 (1-34).(E) -3- (2,5-dihydroxyphenyl) -1-[(2-hydroxy-5-methoxy) phenyl] -2-propen-1-one (1-34). 2-OH-6-OCH3 2-OH-6-OCH 3 (E)-3-(2,5-디히드록시페닐)-1-[(2-히드록시-6-메톡시)페닐]-2-프로펜-1-온 (1-35).(E) -3- (2,5-dihydroxyphenyl) -1-[(2-hydroxy-6-methoxy) phenyl] -2-propen-1-one (1-35). 2,3-(OH)2 2,3- (OH) 2 (E)-3-(2,5-디히드록시페닐)-1-(2,3-디히드록시페닐)-2-프로펜-1-온 (1-36).(E) -3- (2,5-dihydroxyphenyl) -1- (2,3-dihydroxyphenyl) -2-propen-1-one (1-36). 2,4-(OH)2 2,4- (OH) 2 (E)-3-(2,5-디히드록시페닐)-1-(2,4-디히드록시페닐)-2-프로펜-1-온 (1-37).(E) -3- (2,5-dihydroxyphenyl) -1- (2,4-dihydroxyphenyl) -2-propen-1-one (1-37). 2,5-(OH)2 2,5- (OH) 2 (E)-3-(2,5-디히드록시페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (1-38).(E) -3- (2,5-dihydroxyphenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (1-38). 3,4-(OH)2 3,4- (OH) 2 (E)-3-(2,5-디히드록시페닐)-1-(3,4-디히드록시페닐)-2-프로펜-1-온 (1-39).(E) -3- (2,5-dihydroxyphenyl) -1- (3,4-dihydroxyphenyl) -2-propen-1-one (1-39). 3,5-(OH)2 3,5- (OH) 2 (E)-3-(2,5-디히드록시페닐)-1-(3,5-디히드록시페닐)-2-프로펜-1-온 (1-40).(E) -3- (2,5-dihydroxyphenyl) -1- (3,5-dihydroxyphenyl) -2-propen-1-one (1-40). 3,4-OCH2O3,4-OCH 2 O (E)-3-(2,5-디히드록시페닐)-1-(3,4-메틸렌디옥시페닐)-2-프로펜-1-온 (1-41).(E) -3- (2,5-dihydroxyphenyl) -1- (3,4-methylenedioxyphenyl) -2-propen-1-one (1-41). 4-비스페닐4-bisphenyl (E)-3-(2,5-디히드록시페닐)-1-(4-페닐페닐)-2-프로펜-1-온 (1-42).(E) -3- (2,5-dihydroxyphenyl) -1- (4-phenylphenyl) -2-propen-1-one (1-42). 4-SO2CH3 4-SO 2 CH 3 (E)-3-(2,5-디히드록시페닐)-1-(4-메틸설포닐페닐)-2-프로펜-1-온 (1-43).(E) -3- (2,5-dihydroxyphenyl) -1- (4-methylsulfonylphenyl) -2-propen-1-one (1-43).

표 2: 일반식(Ib)의 화합물의 예Table 2: Examples of Compounds of Formula (Ib)

R1 R 1 화합물명(화합물 번호)Compound name (compound number) HH 1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온(2-1)1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one (2-1) 2-F2-F (E)-1-(2,5-디히드록시페닐)-3-(2-플루오로페닐)-2-프로펜-1-온 (2-2).(E) -1- (2,5-dihydroxyphenyl) -3- (2-fluorophenyl) -2-propen-1-one (2-2). 2-Cl2-Cl (E)-3-(2-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-3).(E) -3- (2-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-3). 3-Cl3-Cl (E)-3-(3-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-4).(E) -3- (3-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-4). 4-Cl4-Cl (E)-3-(4-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-5).(E) -3- (4-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-5). 4-Br4-Br (E)-3-(4-브로모페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-6).(E) -3- (4-bromophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-6). 4-NO2 4-NO 2 (E)-1-(2,5-디히드록시페닐)-3-(4-니트로페닐)-2-프로펜-1-온 (2-7).(E) -1- (2,5-dihydroxyphenyl) -3- (4-nitrophenyl) -2-propen-1-one (2-7). 2,3,4,5,6-F5 2,3,4,5,6-F 5 (E)-1-(2,5-디히드록시페닐)-3-(2,3,4,5,6-펜타플루오로페닐)-2-프로펜-1-온 (2-8).(E) -1- (2,5-dihydroxyphenyl) -3- (2,3,4,5,6-pentafluorophenyl) -2-propen-1-one (2-8). 2,5-F2 2,5-F 2 (E)-3-(2,5-디플루오로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-9).(E) -3- (2,5-difluorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-9). 2,5(CF3)2 2,5 (CF 3 ) 2 (E)-3-[2,5-비스(트리플루오로메틸)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-10).(E) -3- [2,5-bis (trifluoromethyl) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-10). 2-Br-5-O-CH3 2-Br-5-O-CH 3 (E)-3-[(2-브로모-5-메톡시)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-11).(E) -3-[(2-bromo-5-methoxy) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-11). 2-OCH3-5-Br2-OCH3-5-Br (E)-3-[(5-브로모-2-메톡시)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온(2-12).(E) -3-[(5-bromo-2-methoxy) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-12). 2-Br-5-OH2-Br-5-OH (E)-1-(2,5-디히드록시페닐)-3-(2-메틸페닐)-2-프로펜-1-온 (2-13).(E) -1- (2,5-dihydroxyphenyl) -3- (2-methylphenyl) -2-propen-1-one (2-13).

2-CH3 2-CH 3 (E)-3-[(5-브로모-2-히드록시)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-14).(E) -3-[(5-bromo-2-hydroxy) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2-14). 2-OCH3 2-OCH 3 (E)-1-(2,5-디히드록시페닐)-3-(2-메톡시페닐)-2-프로펜-1-온 (2-15).(E) -1- (2,5-dihydroxyphenyl) -3- (2-methoxyphenyl) -2-propen-1-one (2-15). 3-OCH3 3-OCH 3 (E)-1-(2,5-디히드록시페닐)-3-(3-메톡시페닐)-2-프로펜-1-온 (2-16).(E) -1- (2,5-dihydroxyphenyl) -3- (3-methoxyphenyl) -2-propen-1-one (2-16). 4-OCH3 4-OCH 3 (E)-1-(2,5-디히드록시페닐)-3-(4-메톡시페닐)-2-프로펜-1-온 (2-17).(E) -1- (2,5-dihydroxyphenyl) -3- (4-methoxyphenyl) -2-propen-1-one (2-17). 2-OH2-OH (E)-1-(2,5-디히드록시페닐)-3-(2-히드록시페닐)-2-프로펜-1-온 (2-18).(E) -1- (2,5-dihydroxyphenyl) -3- (2-hydroxyphenyl) -2-propen-1-one (2-18). 3-OH3-OH (E)-1-(2,5-디히드록시페닐)-3-(3-히드록시페닐)-2-프로펜-1-온 (2-19).(E) -1- (2,5-dihydroxyphenyl) -3- (3-hydroxyphenyl) -2-propen-1-one (2-19). 4-OH4-OH (E)-1-(2,5-디히드록시페닐)-3-(4-히드록시페닐)-2-프로펜-1-온 (2-20).(E) -1- (2,5-dihydroxyphenyl) -3- (4-hydroxyphenyl) -2-propen-1-one (2-20). 4-N(CH3)2 4-N (CH 3 ) 2 (E)-1-(2,5-디히드록시페닐)-3-(4-디메틸아미노페닐)-2-프로펜-1-온 (2-21).(E) -1- (2,5-dihydroxyphenyl) -3- (4-dimethylaminophenyl) -2-propen-1-one (2-21). 4-SCH3 4-SCH 3 (E)-1-(2,5-디히드록시페닐)-3-(4-메틸페닐)-2-프로펜-1-온 (2-22).(E) -1- (2,5-dihydroxyphenyl) -3- (4-methylphenyl) -2-propen-1-one (2-22). 2,5-(CH3)2 2,5- (CH 3 ) 2 (E)-1-(2,5-디히드록시페닐)-3-(2,5-디메틸페닐)-2-프로펜-1-온 (2-23).(E) -1- (2,5-dihydroxyphenyl) -3- (2,5-dimethylphenyl) -2-propen-1-one (2-23). 2,3-(OCH3)2 2,3- (OCH 3 ) 2 (E)-1-(2,5-디히드록시페닐)-3-(2,3-디메톡시페닐)-2-프로펜-1-온 (2-24).(E) -1- (2,5-dihydroxyphenyl) -3- (2,3-dimethoxyphenyl) -2-propen-1-one (2-24). 2,4-(OCH3)2 2,4- (OCH 3 ) 2 (E)-1-(2,5-디히드록시페닐)-3-(2,4-디메톡시페닐)-2-프로펜-1-온 (2-25).(E) -1- (2,5-dihydroxyphenyl) -3- (2,4-dimethoxyphenyl) -2-propen-1-one (2-25). 2,5-(OCH3)2 2,5- (OCH 3 ) 2 (E)-1-(2,5-디히드록시페닐)-3-(2,5-디메톡시페닐)-2-프로펜-1-온 (2-26).(E) -1- (2,5-dihydroxyphenyl) -3- (2,5-dimethoxyphenyl) -2-propen-1-one (2-26).

3,5-(OCH3)2 3,5- (OCH 3 ) 2 (E)-1-(2,5-디히드록시페닐)-3-(3,5-디메톡시페닐)-2-프로펜-1-온 (2-27).(E) -1- (2,5-dihydroxyphenyl) -3- (3,5-dimethoxyphenyl) -2-propen-1-one (2-27). 3,4-(OCH3)2 3,4- (OCH 3 ) 2 (E)-1-(2,5-디히드록시페닐)-3-(3,4-디메톡시페닐)-2-프로펜-1-온 (2-28).(E) -1- (2,5-dihydroxyphenyl) -3- (3,4-dimethoxyphenyl) -2-propen-1-one (2-28). 2,3,4-(OCH3)3 2,3,4- (OCH 3 ) 3 (E)-1-(2,5-디히드록시페닐)-3-(2,3,4-트리메톡시페닐)-2-프로펜-1-온 (2-29).(E) -1- (2,5-dihydroxyphenyl) -3- (2,3,4-trimethoxyphenyl) -2-propen-1-one (2-29). 2,4,5-(OCH3)3 2,4,5- (OCH 3 ) 3 (E)-1-(2,5-디히드록시페닐)-3-(2,4,5-트리메톡시페닐)-2-프로펜-1-온 (2-30).(E) -1- (2,5-dihydroxyphenyl) -3- (2,4,5-trimethoxyphenyl) -2-propen-1-one (2-30). 2,4,6-(OCH3)3 2,4,6- (OCH 3 ) 3 (E)-1-(2,5-디히드록시페닐)-3-(2,4,6-트리메톡시페닐)-2-프로펜-1-온 (2-31).(E) -1- (2,5-dihydroxyphenyl) -3- (2,4,6-trimethoxyphenyl) -2-propen-1-one (2-31). 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 (E)-1-(2,5-디히드록시페닐)-3-(3,4,5-트리메톡시페닐)-2-프로펜-1-온 (2-32).(E) -1- (2,5-dihydroxyphenyl) -3- (3,4,5-trimethoxyphenyl) -2-propen-1-one (2-32). 2,3-(OH)2 2,3- (OH) 2 (E)-1-(2,5-디히드록시페닐)-3-(2,3-디히드록시페닐)-2-프로펜-1-온 (2-33).(E) -1- (2,5-dihydroxyphenyl) -3- (2,3-dihydroxyphenyl) -2-propen-1-one (2-33). 2,4-(OH)2 2,4- (OH) 2 (E)-1-(2,5-디히드록시페닐)-3-(2,4-디히드록시페닐)-2-프로펜-1-온 (2-34).(E) -1- (2,5-dihydroxyphenyl) -3- (2,4-dihydroxyphenyl) -2-propen-1-one (2-34). 2,5-(OH)2 2,5- (OH) 2 (E)-1-(2,5-디히드록시페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (2-35).(E) -1- (2,5-dihydroxyphenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (2-35). 3,4-(OH)2 3,4- (OH) 2 (E)-1-(2,5-디히드록시페닐)-3-(3,4-디히드록시페닐)-2-프로펜-1-온 (2-36).(E) -1- (2,5-dihydroxyphenyl) -3- (3,4-dihydroxyphenyl) -2-propen-1-one (2-36). 3,5-(OH)2 3,5- (OH) 2 (E)-1-(2,5-디히드록시페닐)-3-(3,5-디히드록시페닐)-2-프로펜-1-온 (2-37).(E) -1- (2,5-dihydroxyphenyl) -3- (3,5-dihydroxyphenyl) -2-propen-1-one (2-37). 2-OH-5-OCH3 2-OH-5-OCH 3 (E)-1-(2,5-디히드록시페닐)-3-[(2-히드록시-5-메톡시)페닐]-2-프로펜-1-온 (2-38).(E) -1- (2,5-dihydroxyphenyl) -3-[(2-hydroxy-5-methoxy) phenyl] -2-propen-1-one (2-38). 4-OH-3-OCH3 4-OH-3-OCH 3 (E)-1-(2,5-디히드록시페닐)-3-[(4-히드록시-3-메톡시)페닐]-2-프로펜-1-온 (2-39).(E) -1- (2,5-dihydroxyphenyl) -3-[(4-hydroxy-3-methoxy) phenyl] -2-propen-1-one (2-39). 3,4-OCH2O3,4-OCH 2 O (E)-1-(2,5-디히드록시페닐)-3-(3,4-메틸렌디옥시페닐)-2-프로펜-1-온 (2-40).(E) -1- (2,5-dihydroxyphenyl) -3- (3,4-methylenedioxyphenyl) -2-propen-1-one (2-40). 4-비스페닐4-bisphenyl (E)-1-(2,5-디히드록시페닐)-3-(4-페닐페닐)-2-프로펜-1-온 (2-41).(E) -1- (2,5-dihydroxyphenyl) -3- (4-phenylphenyl) -2-propen-1-one (2-41). 4-SO2CH3 4-SO 2 CH 3 (E)-1-(2,5-디히드록시페닐)-3-(4-메틸설포닐페닐)-2-프로펜-1-온 (2-42).(E) -1- (2,5-dihydroxyphenyl) -3- (4-methylsulfonylphenyl) -2-propen-1-one (2-42).

표 3: 일반식(Ic) 화합물의 예Table 3: Examples of Formula (Ic) Compounds

R1 R 1 R2 R 2 화합물명(화합물 번호)Compound name (compound number) 2-Cl2-Cl BrBr (Z)-2-브로모-3-(2-플루오로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (3-1).(Z) -2-bromo-3- (2-fluorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (3-1). 3-Cl3-Cl (Z)-2-브로모-3-(3-플루오로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (3-2).(Z) -2-bromo-3- (3-fluorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (3-2). 4-Cl4-Cl (Z)-2-브로모-3-(4-플루오로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (3-3).(Z) -2-bromo-3- (4-fluorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (3-3). 2-Cl2-Cl CNCN (Z)-3-(2-플루오로페닐)-2-시아노-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (4-1).(Z) -3- (2-fluorophenyl) -2-cyano-1- (2,5-dihydroxyphenyl) -2-propen-1-one (4-1). 3-Cl3-Cl (Z)-3-(3-플루오로페닐)-2-시아노-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (4-2).(Z) -3- (3-fluorophenyl) -2-cyano-1- (2,5-dihydroxyphenyl) -2-propen-1-one (4-2). 4-Cl4-Cl (Z)-3-(4-플루오로페닐)-2-시아노-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (4-3).(Z) -3- (4-fluorophenyl) -2-cyano-1- (2,5-dihydroxyphenyl) -2-propen-1-one (4-3). 2-Cl2-Cl CH3 CH 3 (E)-3-(2-플루오로페닐)-1-(2,5-디히드록시페닐)-2-메틸-2-프로펜-1-온 (5-1).(E) -3- (2-fluorophenyl) -1- (2,5-dihydroxyphenyl) -2-methyl-2-propen-1-one (5-1). 3-Cl3-Cl (E)-3-(3-플루오로페닐)-1-(2,5-디히드록시페닐)-2-메틸-2-프로펜-1-온 (5-2).(E) -3- (3-fluorophenyl) -1- (2,5-dihydroxyphenyl) -2-methyl-2-propen-1-one (5-2). 4-Cl4-Cl (E)-3-(4-플루오로페닐)-1-(2,5-디히드록시페닐)-2-메틸-2-프로펜-1-온 (5-3).(E) -3- (4-fluorophenyl) -1- (2,5-dihydroxyphenyl) -2-methyl-2-propen-1-one (5-3).

표 4: 일반식(Id) 화합물의 예Table 4: Examples of Formula (Id) Compounds

R3 R 3 R4 R 4 화합물명(화합물 번호)Compound name (compound number) 4-OCH3 4-OCH 3 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-1-(2,5-디히드록시페닐)-5-(6-메톡시페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-1).all-trans-1- (2,5-dihydroxyphenyl) -5- (6-methoxyphenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1 -On (6-1). 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 4-OCH3 4-OCH 3 all-트랜스-1-(2,5-디히드록시페닐)-4-(6-메톡시페닐)-5-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-2).all-trans-1- (2,5-dihydroxyphenyl) -4- (6-methoxyphenyl) -5- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1 -On (6-2). 4-OCH3 4-OCH 3 3,4-(OCH3)2 3,4- (OCH 3 ) 2 all-트랜스-1-(2,5-디히드록시페닐)-4-(3,4-디메톡시페닐)-5-(6-메톡시페닐)-2,4-펜탄디엔-1-온 (6-3).all-trans-1- (2,5-dihydroxyphenyl) -4- (3,4-dimethoxyphenyl) -5- (6-methoxyphenyl) -2,4-pentanedien-1-one ( 6-3). 4-OCH3 4-OCH 3 HH all-트랜스-1-(2,5-디히드록시페닐)-4-(6-메톡시페닐)-5-(6-메톡시페닐)-2,4-펜탄디엔-1-온 (6-4)all-trans-1- (2,5-dihydroxyphenyl) -4- (6-methoxyphenyl) -5- (6-methoxyphenyl) -2,4-pentanedien-1-one (6- 4) 4-OCH3 4-OCH 3 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-1-(2,5-디히드록시페닐)-5-(6-메톡시페닐)-4-페닐-2,4-펜탄디엔-1-온 (6-5).all-trans-1- (2,5-dihydroxyphenyl) -5- (6-methoxyphenyl) -4-phenyl-2,4-pentanedien-1-one (6-5). HH HH all-트랜스-1-(2,5-디히드록시페닐)-5-페닐-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-6).all-trans-1- (2,5-dihydroxyphenyl) -5-phenyl-4- (3,4,5-trimethoxyphenyl) -2,4-pentanedien-1-one (6-6 ). HH 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-1-(2,5-디히드록시페닐)-4-페닐-5-페닐-2,4-펜탄디엔-1-온 (6-7).all-trans-1- (2,5-dihydroxyphenyl) -4-phenyl-5-phenyl-2,4-pentanedien-1-one (6-7). 4-OCH2CH3 4-OCH 2 CH 3 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-1-(2,5-디히드록시페닐)-5-(6-에톡시페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-8).all-trans-1- (2,5-dihydroxyphenyl) -5- (6-ethoxyphenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1 -On (6-8). 4-Cl4-Cl 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-1-(2,5-디히드록시페닐)-5-(6-플루오로페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-9).all-trans-1- (2,5-dihydroxyphenyl) -5- (6-fluorophenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1 -On (6-9). 4-CH3 4-CH 3 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-1-(2,5-디히드록시페닐)-5-(6-메틸페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-10).all-trans-1- (2,5-dihydroxyphenyl) -5- (6-methylphenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanedien-1-one (6-10). 4-OCH3-3-NO2 4-OCH 3 -3-NO 2 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-1-(2,5-디히드록시페닐)-5-[(3-니트로-4-메톡시)페닐]-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-11).all-trans-1- (2,5-dihydroxyphenyl) -5-[(3-nitro-4-methoxy) phenyl] -4- (3,4,5-trimethoxyphenyl) -2, 4-pentanedien-1-one (6-11). 4-OCH3-3-NH2 4-OCH 3 -3-NH 2 3,4,5-(OCH3)3 3,4,5- (OCH 3 ) 3 all-트랜스-5-[(3-아미노-4-메톡시)페닐]-1-(2,5-디히드록시페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-12).all-trans-5-[(3-amino-4-methoxy) phenyl] -1- (2,5-dihydroxyphenyl) -4- (3,4,5-trimethoxyphenyl) -2, 4-pentanedien-1-one (6-12).

일반식(I)의 화합물 중 더욱 바람직한 화합물은 다음과 같다:More preferred among the compounds of formula (I) are as follows:

(E)-3-(2,5-디히드록시페닐)-1-(2-클로로페닐)-2-프로펜-1-온(1-3),( E ) -3- (2,5-dihydroxyphenyl) -1- (2-chlorophenyl) -2-propen-1-one (1-3),

(E)-3-(2,5-디히드록시페닐)-1-[(5-브로모-2-메톡시)페닐]-2-프로펜-1-온(1-15),( E ) -3- (2,5-dihydroxyphenyl) -1-[(5-bromo-2-methoxy) phenyl] -2-propen-1-one (1-15),

(E)-3-(2,5-디히드록시페닐)-1-(4-티오메틸페닐)-2-프로펜-1-온(1-21),( E ) -3- (2,5-dihydroxyphenyl) -1- (4-thiomethylphenyl) -2-propen-1-one (1-21),

(E)-3-(2,5-디히드록시페닐)-1-(2,4-디메톡시페닐)-2-프로펜-1-온(1-23),( E ) -3- (2,5-dihydroxyphenyl) -1- (2,4-dimethoxyphenyl) -2-propen-1-one (1-23),

(E)-3-(2,5-디히드록시페닐)-1-(3,4-디메톡시페닐)-2-프로펜-1-온(1-27),( E ) -3- (2,5-dihydroxyphenyl) -1- (3,4-dimethoxyphenyl) -2-propen-1-one (1-27),

(E)-3-(2,5-디히드록시페닐)-1-(2,4,6-트리메톡시페닐)-2-프로펜-1-온(1-29),( E ) -3- (2,5-dihydroxyphenyl) -1- (2,4,6-trimethoxyphenyl) -2-propen-1-one (1-29),

(E)-3-(2,5-디히드록시페닐)-1-(3,4,5-트리메톡시페닐)-2-프로펜-1-온(1-30),( E ) -3- (2,5-dihydroxyphenyl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (1-30),

(E)-3-(2,5-디히드록시페닐)-1-(2-히드록시페닐)-2-프로펜-1-온(1-31),( E ) -3- (2,5-dihydroxyphenyl) -1- (2-hydroxyphenyl) -2-propen-1-one (1-31),

(E)-3-(2,5-디히드록시페닐)-1-(3-히드록시페닐)-2-프로펜-1-온(1-32),( E ) -3- (2,5-dihydroxyphenyl) -1- (3-hydroxyphenyl) -2-propen-1-one (1-32),

(E)-3-(2,5-디히드록시페닐)-1-(3,4-디히드록시페닐)-2-프로펜-1-온(1-39),( E ) -3- (2,5-dihydroxyphenyl) -1- (3,4-dihydroxyphenyl) -2-propen-1-one (1-39),

(E)-1-(2,5-디히드록시페닐)-3-(2-클로로페닐)-2-프로펜-1-온(2-3),( E ) -1- (2,5-dihydroxyphenyl) -3- (2-chlorophenyl) -2-propen-1-one (2-3),

(E)-1-(2,5-디히드록시페닐)-3-(2,4-디메톡시페닐)-2-프로펜-1-온(2-25),(E) -1- (2,5-dihydroxyphenyl) -3- (2,4-dimethoxyphenyl) -2-propen-1-one (2-25),

(E)-1-(2,5-디히드록시페닐)-3-(3,5-디메톡시페닐)-2-프로펜-1-온(2-27),(E) -1- (2,5-dihydroxyphenyl) -3- (3,5-dimethoxyphenyl) -2-propen-1-one (2-27),

(E)-1-(2,5-디히드록시페닐)-3-(3,4-디메톡시페닐)-2-프로펜-1-온(2-28),( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4-dimethoxyphenyl) -2-propen-1-one (2-28),

(E)-1-(2,5-디히드록시페닐)-3-(2,3,4-트리메톡시페닐)-2-프로펜-1-온(2-( E ) -1- (2,5-dihydroxyphenyl) -3- (2,3,4-trimethoxyphenyl) -2-propen-1-one (2-

29),29),

(E)-1-(2,5-디히드록시페닐)-3-(3,4,5-트리메톡시페닐)-2-프로펜-1-온(2-32),( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4,5-trimethoxyphenyl) -2-propen-1-one (2-32),

(E)-1-(2,5-디히드록시페닐)-3-(2,3-디히드록시페닐)-2-프로펜-1-온(2-33),( E ) -1- (2,5-dihydroxyphenyl) -3- (2,3-dihydroxyphenyl) -2-propen-1-one (2-33),

(E)-1-(2,5-디히드록시페닐)-3-(3,4-디히드록시페닐)-2-프로펜-1-온(2-36),( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4-dihydroxyphenyl) -2-propen-1-one (2-36),

(E)-1-(2,5-디히드록시페닐)-3-(3,5-디히드록시페닐)-2-프로펜-1-온(2-37),( E ) -1- (2,5-dihydroxyphenyl) -3- (3,5-dihydroxyphenyl) -2-propen-1-one (2-37),

(E)-1-(2,5-디히드록시페닐)-3-(3,4-메틸렌디옥시페닐)-2-프로펜-1-온(2-40),( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4-methylenedioxyphenyl) -2-propen-1-one (2-40),

(E)-1-(2,5-디히드록시페닐)-3-(4-페닐페닐)-2-프로펜-1-온(2-41),( E ) -1- (2,5-dihydroxyphenyl) -3- (4-phenylphenyl) -2-propen-1-one (2-41),

(E)-1-(2,5-디히드록시페닐)-3-(4-메틸설포닐페닐)-2-프로펜-1-온(2-42)인 화합물.( E ) -1- (2,5-dihydroxyphenyl) -3- (4-methylsulfonylphenyl) -2-propen-1-one (2-42).

일반식(I)의 화합물 중 가장 바람직한 것은 (E)-1-(2,5-디히드록시페닐)-3-(2-클로로페닐)-2-프로펜-1-온(2-3)이다.Most preferred among the compounds of formula (I) are ( E ) -1- (2,5-dihydroxyphenyl) -3- (2-chlorophenyl) -2-propen-1-one (2-3) to be.

본발명의 두번째 양상에서, 본발명은 일반식(I)의 화합물을 제조하는 방법을 제공한다. 일반식(I)의 속하는 일반식(Ia) 내지 (Id)의 화합물의 제조방법은 다음과 같다.In a second aspect of the invention, the invention provides a method for preparing a compound of formula (I). The manufacturing method of the compound of general formula (Ia)-(Id) which belongs to general formula (I) is as follows.

(1) 일반식(Ia)의 3-(2,5-디히드록시페닐)-1-페닐-2-프로펜-1-온 유도체를 제조 방법(1) Method of producing 3- (2,5-dihydroxyphenyl) -1-phenyl-2-propen-1-one derivative of general formula (Ia)

2,5-디히드록시벤즈알데히드를 3,4-디히드로-2H-피란과 반응시켜 일반식(II)의 화합물을 얻고 이를 R1(R1은 제 1항에서 정의된 바와 같음)으로 치환된 아세토페논과 염기 존재 하에서 축합시켜 일반식(III)의 화합물을 얻고, 산촉매 존재하에서 3,4-디히드로-2H-피란기를 제거하여 일반식(Ia)의 3-(2,5-디히드록시페닐)-1-페닐-2-프로펜-1-온을 제조한다.2,5-dihydroxybenzaldehyde is reacted with 3,4-dihydro-2H-pyran to obtain a compound of formula II, which is substituted with R 1 (R 1 is as defined in claim 1). Condensation with acetophenone in the presence of a base to obtain a compound of formula (III), and 3,4-dihydro-2H-pyrane group in the presence of an acid catalyst to remove 3- (2,5-dihydroxy of formula (Ia) Phenyl) -1-phenyl-2-propen-1-one is prepared.

일반식(Ia)의 화합물의 제조방법을 도식화하여 나타내면 반응식 1과 같다.Scheme 1 shows a method for preparing a compound of formula (Ia).

반응식 1Scheme 1

(2) 일반식(Ib)의 1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온 유도체를 제조하는 방법(2) A method for producing the 1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one derivative of general formula (lb)

2,5-디히드록시아세토페논을 3,4-디히드로-2H-피란과 반응시켜 일반식(II)의 화합물을 얻고 이를 R1(R1은 제 1항에서 정의한 바와 같음)으로 치환된 벤즈알데히드와 염기 존재하에서 축합시켜 일반식(IV)의 화합물을 얻고 산촉매 존재 하에서 3,4-디히드로-2H-피란기를 제거하여 일반식(Ib)의 1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온을 제조한다.2,5-dihydroxyacetophenone is reacted with 3,4-dihydro-2H-pyran to give a compound of formula II, which is substituted with R 1 (R 1 is as defined in claim 1). Condensation with benzaldehyde in the presence of a base to obtain a compound of formula (IV), and 3,4-dihydro-2H-pyrane group in the presence of an acid catalyst to remove 1- (2,5-dihydroxyphenyl) of formula (Ib) Prepare 3-phenyl-2-propen-1-one.

일반식(Ib)의 화합물의 제조방법을 도식화하여 나타내면 반응식 2와 같다.Scheme 2 shows a method for preparing a compound of formula (Ib).

반응식 2Scheme 2

(3) 일반식(Ic)의 2-치환-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온을 제조하는 방법(3) A method for producing 2-substituted-1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one of formula (Ic)

(i) 일반식(Ib)의 화합물을 브롬화시켜 2,3-디브로모 화합물을 얻고, 이를 알칼리로 처리하여 일반식(Ic1)의 2-브로모-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온을 제조하거나,(i) bromination of the compound of general formula (Ib) to give a 2,3-dibromo compound, which is treated with alkali to give 2-bromo-1- (2,5-dihydroxy of general formula (Ic1) Phenyl) -3-phenyl-2-propen-1-one, or

(ii) 2',5'-디벤질옥시페닐-2-시아노아세토페논과 R1(R1은 제 1항에서 정의된 바와 같음)으로 치환된 벤즈알데히드를 Knoevenagel 축합반응시켜 일반식(V)의 2-시아노-1-2',5'-디벤질옥시페닐-3-페닐-2-프로펜-1-온을 얻고 이를 탈벤질화제를 사용하여 탈벤질화시켜 일반식(Ic2)의 2-시아노-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온을 제조하거나,(ii) Knoevenagel condensation reaction of benzaldehyde substituted with 2 ', 5'-dibenzyloxyphenyl-2-cyanoacetophenone with R 1 (R 1 is as defined in claim 1) to formula (V). 2-cyano-1-2 ', 5'-dibenzyloxyphenyl-3-phenyl-2-propen-1-one was obtained and debenzylated using a debenzylating agent to yield a compound of formula (Ic2). 2-cyano-1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one, or

(iii) 2',5'-디히드록시프로피오페논과 R1(R1은 제 1항에서 정의된 바와 같음)으로 치환된 벤즈알데히드를 축합시켜 2-메틸-3-페닐-1-(2,5-디테트라히드로푸라닐옥시)-2-프로펜-1-온을 얻고 이를 산존재 하에서 반응시켜 일반식(Ic3)의 1-(2,5-디히드록시페닐)-2-메틸-3-페닐-2-프로펜-1-온을 제조한다.(iii) condensation of 2 ', 5'-dihydroxypropiophenone with benzaldehyde substituted with R 1 (R 1 is as defined in claim 1) to form 2-methyl-3-phenyl-1- (2, 5-Ditetrahydrofuranyloxy) -2-propen-1-one was obtained and reacted in the presence of acid to yield 1- (2,5-dihydroxyphenyl) -2-methyl-3 of formula (Ic3). Prepare -phenyl-2-propen-1-one.

일반식(Ic)의 화합물의 제조방법을 도식화하여 나타내면 반응식3과 같다.Scheme 3 shows a method for preparing a compound of formula (Ic).

반응식 3Scheme 3

(4) 일반식(Id)의 1,4,5-트리페닐-2,4-펜탄디엔-1-온 유도체를 제조하는 방법(4) A method for producing a 1,4,5-triphenyl-2,4-pentanedien-1-one derivative of formula (Id)

일반식(VI)의 페닐아세트산을 일반식(VII)의 벤즈알데히드와 축합시켜 일반식(VIII)의 2,3-디아릴프로펜산을 얻고 이를 메틸 에스터화시켜 일반식(IX)의 화합물을 얻고 이를 수소화시켜 일반식(X)의 알콜을 얻고 이를 산화시켜 일반식(XI)의 알데히드를 얻고 이 알데히드를 아세토페논과 축합하여 일반식(Id)의 1,4,5-트리페닐-2,4-펜탄디엔-1-온 유도체를 제조한다.The phenylacetic acid of formula (VI) is condensed with benzaldehyde of formula (VII) to give 2,3-diarylpropenic acid of formula (VIII), which is methyl esterified to obtain a compound of formula (IX). Hydrogenation yields an alcohol of general formula (X), oxidizes it to obtain an aldehyde of general formula (XI) and condenses this aldehyde with acetophenone to yield 1,4,5-triphenyl-2,4- of general formula (Id). To prepare a pentaneden-1-one derivative.

일반식(Id)의 화합물의 제조방법을 도식화하여 나타내면 반응식4와 같다.Scheme 4 shows a method for preparing a compound of formula (Id).

본발명의 세번째 양상에서, 본발명은 약제학적으로 허용되는 담체와 함께 일반식(I)의 화합물을 유효성분으로 포함하는 것을 특징으로 하는 항암제 조성물을 제공한다.In a third aspect of the present invention, the present invention provides an anticancer composition comprising a compound of formula (I) as an active ingredient together with a pharmaceutically acceptable carrier.

본발명에 따르는 일반식(I)의 1,4-디히드록시벤젠 유도체는 다양한 양에서 강력한 항암효과를 가지고 있어 임상적으로 유용한 항암제로 사용될 수 있다.The 1,4-dihydroxybenzene derivative of general formula (I) according to the present invention has a strong anticancer effect in various amounts and can be used as clinically useful anticancer agent.

본발명에 따른 화합물을 유효성분으로 함유하는 항암제 조성물은 임상적으로 이용 시에 약제학적 분야에서 통상적으로 사용되는 담체와 함께 배합하여, 약제학적 분야에서 통상적인 제제, 예를 들면, 정제, 캅셉제, 트로키제, 액제, 현탁제 등의 경구투여용 제제, 주사용 용액 또는 현탁액, 또는 주사 시에 주사용 증류수로 제조하여 사용할 수 있는 즉시 사용형 주사용 건조 분말 등의 형태인 주사용 제제, 연고제, 크림제, 액제 등의 국소적용형 제제 등의 다양한 제제로 제형화할 수 있다.The anticancer composition containing the compound according to the present invention as an active ingredient is combined with a carrier which is commonly used in the pharmaceutical field at the time of clinical use, and is a conventional agent in the pharmaceutical field, for example, a tablet, a capsule , Ointments, in the form of oral preparations such as troches, solutions, suspensions, injectable solutions or suspensions, or ready-to-use injectable dry powders which can be prepared and used as injection distilled water for injection. It can be formulated into various preparations such as topical preparations such as creams and liquids.

본 발명의 조성물 내에서 사용될 수 있는 담체는 약제학적 분야에서 통상적인 것으로, 예를 들면 경구투여용 제제의 경우에는 결합제, 활택제, 붕해제, 부형제, 가용화제, 안정화제 등이 있고, 국소투여용 제제의 경우에는 기제, 부형제, 윤활제, 보존제 등이 있다. 이렇게 제조된 약제학적 제제는 경구적으로 투여하거나, 비경구적으로, 예를 들면, 정맥 내, 피하, 복강 내 또는 국소 적용할 수 있다. 또한 경구투여시에 약제가 위산에 의해 분해되는 것을 방지하기 위하여 제산제를 병용하거나 정제 등의 경구투여용 고형 제제를 장용피로 피복된 제제로 제형화하여 투여할 수 있다.Carriers that can be used in the composition of the present invention are conventional in the pharmaceutical field, for example, in the case of oral preparations, there are binders, lubricants, disintegrants, excipients, solubilizers, stabilizers, and the like. In the case of a solvent preparation, there are a base, an excipient, a lubricant, and a preservative. Pharmaceutical preparations thus prepared can be administered orally or parenterally, eg, intravenously, subcutaneously, intraperitoneally or topically. In addition, in order to prevent the decomposition of the drug by gastric acid during oral administration, an antacid may be used in combination or a solid preparation for oral administration such as tablets may be formulated into a formulation coated with enteric skin.

본발명에 따른 일반식(I)의 1,4-디히드록시벤젠 유도체의 인체에 대한 투여량은 체내에서 활성 성분의 흡수도, 불활성화율 및 배설속도, 환자의 연령, 성별 및 상태, 치료할 질병의 증등도 등에 따라 적절히 선택되나, 일반적으로 성인에게 1일에 180mg내지 300mg으로, 바람직하게는 200mg의 양으로 투여될 수 있다. 따라서 본발명의 조성물을 단위투여형으로 제조시에 각각의 단위투여형은 상기 언급된 유효 용량 범위를 고려하여 일반식(I)의 화합물을 180mg 내지 300mg, 바람직하게는 200mg을 함유하도록 제형화시켜 복강 또는 정맥투여할 수 있다. 이렇게 제형화된 단위투여형은 필요에 따라 약제의 투여를 감시하거나 관할하는 전문가의 판단과 개인의 요구에 따라 전문화된 투약법을 사용하거나, 일정 시간 간격으로 수회, 바람직하게는 1회 내지 6회 투여할 수 있다.The dosage of the 1,4-dihydroxybenzene derivative of general formula (I) according to the present invention to the human body is determined by the absorption rate, inactivation rate and excretion rate of the active ingredient in the body, the age, sex and condition of the patient, the disease to be treated. Although appropriately selected depending on the degree of increase, etc., it is generally administered to adults in an amount of 180 mg to 300 mg per day, preferably in an amount of 200 mg. Therefore, when preparing the composition of the present invention in unit dosage form, each unit dosage form is formulated to contain 180 mg to 300 mg, preferably 200 mg of the compound of general formula (I) in view of the above-mentioned effective dosage range It may be intraperitoneally or intravenously. The unit dosage forms thus formulated may use specialized dosing regimens, preferably one to six times at regular time intervals, according to the judgment of the expert who monitors or governs the administration of the drug as needed and the needs of the individual. May be administered.

[실시예]EXAMPLE

본발명은 하기의 실시예에 의해 더욱 구체적으로 설명된다. 그러나, 이들실시예는 본발명의 이해를 돕기 위해 예시한 것으로 본발명이 이들에 의해 어떤 식으로든 제한되는 것은 아니다.The present invention is explained in more detail by the following examples. However, these examples are illustrated to aid the understanding of the present invention and the present invention is not limited in any way by these.

실시예 1: 일반식 (Ia)의 3-(2,5-디히드록시페닐)-1-페닐-2-프로펜-1-온 유도체의 제조(공통적 제조법)Example 1: Preparation of 3- (2,5-dihydroxyphenyl) -1-phenyl-2-propen-1-one derivative of general formula (Ia) (common method)

2,5-디히드록시벤즈알데히드(25 mmol) 및 피리디움p-톨루엔 설포네이트 (0.15 g, 0.6 mmol)를 메치렌클로라이드 100ml가 들어있는 반응기에 가하고 실온에서 30분 교반한다. 3,4-디히드로-2H-피란 13 ml를 메칠렌 클로라이드 20 mL와 혼합하고 이 용액을 상기 혼합물에 한방울씩 적가한다. 이 반응 혼합물을 실온에서 4시간 반응시킨 후 물을 가하여 2 번 헹구고 메칠렌 클로라이드 용액은 건조용 망초로 탈수한 후 감압 하에 증발 건조시켜 중간체인 2,5-비스(테트라히드로피란-2-일옥시)아세토페논을 얻었다.2,5-Dihydroxybenzaldehyde (25 mmol) and pyridium p -toluene sulfonate (0.15 g, 0.6 mmol) are added to a reactor containing 100 ml of methylene chloride and stirred at room temperature for 30 minutes. 13 ml of 3,4-dihydro-2H-pyran are mixed with 20 mL of methylene chloride and the solution is added dropwise to the mixture dropwise. The reaction mixture was allowed to react at room temperature for 4 hours, and then rinsed twice with water. The methylene chloride solution was dehydrated with a drying forget-me-not and evaporated to dryness under reduced pressure to obtain an intermediate 2,5-bis (tetrahydropyran-2-yloxy). Acetophenone was obtained.

위에서 얻은 중간체(대략 25 mmol), 치환된 아세토페논 (2.6 g, 25 mmol) 및 수산화 바륨 옥타하이드레이트(8.15 g, 25 mmol)를 메탄올(100 mL) 내에 용해시키고 12시간 40℃에서 교반한다. 반응물은 감압 하에서 농축한 다음 물 100 ml를 가하고 혼화한 후 1N-HCl로 중화하였다. 이 수용액을 메칠렌클로라이드 100ml 씩으로 3회 추출하여 얻은 추출물은 건조용 망초로 탈수한 후 감압 하에 농축 건조하였다. 잔류물은 (E)-3-[2,5-비스(테트라히드로피란-2-일옥시)페닐]-1-페닐-2-프로펜-1-온을 85% 이상 함유하고 있었다.The intermediate obtained above (approximately 25 mmol), substituted acetophenone (2.6 g, 25 mmol) and barium hydroxide octahydrate (8.15 g, 25 mmol) are dissolved in methanol (100 mL) and stirred at 40 ° C. for 12 h. The reaction was concentrated under reduced pressure, then 100 ml of water was added, mixed, and neutralized with 1N-HCl. The extract obtained by extracting this aqueous solution three times with 100 ml of methylene chloride was dehydrated with a drying forget-me-not and concentrated to dryness under reduced pressure. The residue contained 85% or more of ( E ) -3- [2,5-bis (tetrahydropyran-2-yloxy) phenyl] -1-phenyl-2-propen-1-one.

(E)-3-[2,5-비스(테트라히드로피란-2-일옥시)페닐]-1-페닐-2-프로펜-1-온 및p-톨루엔 설폰산(0.2 g, 1.05 mmol)을 메탄올(100 mL)에 용해시킨 후 실온에서4시간 반응시켰다. 반응물로부터 메탄올을 날려 보내고 남은 잔사에 물(100 mL)을 가한 다음 5% 중조로 중화시킨 후 초산에칠(EA) 100 ml씩으로 3회 추출하였다. 초산에칠 층은 무수망초로 탈수 한 후 감압 하에서 건조하였다. 잔사는 물성에 따라 직접 재결정하든지 실리카겔 칼럼 상에서 정제하였다.( E ) -3- [2,5-bis (tetrahydropyran-2-yloxy) phenyl] -1-phenyl-2-propen-1-one and p -toluene sulfonic acid (0.2 g, 1.05 mmol) Was dissolved in methanol (100 mL) and reacted at room temperature for 4 hours. Methanol was blown from the reaction, water (100 mL) was added to the residue, and the mixture was neutralized with 5% sodium bicarbonate and extracted three times with 100 ml of ethyl acetate (EA). The ethyl acetate layer was dehydrated with anhydrous forget-me-not and dried under reduced pressure. The residue was directly recrystallized according to physical properties or purified on a silica gel column.

실시예 1에 의하여 합성한 물질과 그들의 물성은 다음과 같았다.The materials synthesized according to Example 1 and their physical properties were as follows.

(E)-3-(2,5-디히드록시페닐)-1-페닐-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1-phenyl-2-propen-1-one (1 -1-One ).).

담황색 결정, 수율 4.2 g (45%), m.p. 187-190 ℃; IR (KBr) 3340, 1680, 1640, 1580 cm-1; MS (CIMS)m/z240 (M+);1H-NMR (DMSO-d 6, 90 MHz) 8.17 (1H, d,J= 16.50 Hz), 7.55~7.89 (5H, m), 7.39 (1H, d,J= 16.50 Hz), 6.58~6.85 (3H, m); Anal. (C15H12O3) C, H.Light yellow crystals, yield 4.2 g (45%), mp 187-190 ° C; IR (KBr) 3340, 1680, 1640, 1580 cm −1 ; MS (CIMS) m / z 240 (M < + >); 1 H-NMR (DMSO- d 6 , 90 MHz) 8.17 (1H, d, J = 16.50 Hz), 7.55-7.89 (5H, m), 7.39 (1H, d, J = 16.50 Hz), 6.58-6.85 ( 3H, m); Anal. (C 15 H 12 O 3 ) C, H.

(E)-3-(2,5-디히드록시페닐)-1-(2-플루오로페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2-fluorophenyl) -2-propen-1-one (1 -2-2 ).).

황색 결정, 수율 51%; m.p. 135-137 ℃; IR (KBr) 3350, 1680, 1630, 1580 cm-1; 1H-NMR (DMSO-d 6, 90 MHz) 8.24 (1H, d,J= 16.00 Hz), 7.51~7.97 (2H, m), 7.56 (1H, d,J= 16.00 Hz), 7.15~7.32 (2H, m), 6.61~6.83 (3H, m); Anal. (C15H11FO3) C, H.Yellow crystals, yield 51%; mp 135-137 ° C; IR (KBr) 3350, 1680, 1630, 1580 cm -1; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.24 (1H, d, J = 16.00 Hz), 7.51-7.97 (2H, m), 7.56 (1H, d, J = 16.00 Hz), 7.15-7.32 ( 2H, m), 6.61-66.83 (3H, m); Anal. (C 15 H 11 FO 3 ) C, H.

(E)-1-(2-클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (2-chlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -3-3 )) ..

황색 결정, 수율 36%; m.p. 113-115 ℃; IR (KBr) 3320, 1680, 1620, 1580cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.21 (1H, d,J= 16.00 Hz), 7.49~7.95 (2H, m), 7.43 (1H, d,J= 16.00 Hz), 7.21~7.37 (2H, m), 6.55~6.78 (3H, m); Anal. (C15H11ClO3) C, H.Yellow crystals, yield 36%; mp 113-115 ° C .; IR (KBr) 3320, 1680, 1620, 1580 cm -1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.21 (1H, d, J = 16.00 Hz), 7.49-7.95 (2H, m), 7.43 (1H, d, J = 16.00 Hz), 7.21-7.37 ( 2H, m), 6.55-6.78 (3H, m); Anal. (C 15 H 11 ClO 3 ) C, H.

(E)-1-(3-클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (3-chlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -4-4 ).).

황색 결정, 수율 47%; m.p. 125-127 ℃; IR (KBr) 3330, 1680, 1640, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.17 (1H, d,J= 16.21 Hz), 7.40~7.85 (5H, m), 6.76~6.97 (3H, m); Anal. (C15H11ClO3) C, H.Yellow crystals, yield 47%; mp 125-127 ° C; IR (KBr) 3330, 1680, 1640, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.17 (1H, d, J = 16.21 Hz), 7.40 ~ 7.85 (5H, m), 6.76 ~ 6.97 (3H, m); Anal. (C 15 H 11 ClO 3 ) C, H.

(E)-1-(4-클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (4-chlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -5-5 ).).

황색 결정, 수율 43%; m.p. 151-152 ℃; IR (KBr) 3340, 1675, 1635, 1580 cm-1; 1H-NMR (DMSO-d 6, 300 MHz) 8.08 (1H, d,J= 16.30 Hz), 7.81 (2H, d,J= 8.70 Hz), 7.45 (2H, d,J= 8.70 Hz), 7.41 (1H, d,J= 16.30 Hz), 6.69~6.95 (3H, m); Anal. (C15H11ClO3) C, H.Yellow crystals, yield 43%; mp 151-152 ° C; IR (KBr) 3340, 1675, 1635, 1580 cm −1; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.08 (1H, d, J = 16.30 Hz), 7.81 (2H, d, J = 8.70 Hz), 7.45 (2H, d, J = 8.70 Hz), 7.41 (1H, doublet, J = 16.30 Hz), 6.69-6.95 (3H, m); Anal. (C 15 H 11 ClO 3 ) C, H.

(E)-1-(2-브로모페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (2-bromophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -6-6 ).).

적색 결정, 수율 42%; m.p. 113-115 ℃; IR (KBr) 3320, 1680, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.15 (1H, d,J= 16.50 Hz), 7.51~7.86 (2H, m), 7.41 (1H, d,J= 16.50 Hz), 7.15~7.41 (2H, m), 6.50~6.99 (3H, m).Red crystals, yield 42%; mp 113-115 ° C .; IR (KBr) 3320, 1680, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.15 (1H, d, J = 16.50 Hz), 7.51-7.86 (2H, m), 7.41 (1H, d, J = 16.50 Hz), 7.15-7.41 ( 2H, m), 6.50-6.99 (3H, m).

(E)-1-(4-브로모페닐)-3-(2,5-디히드록시페닐)- 2-프로펜-1-온 (1(E) -1- (4-bromophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -7-7 ).).

적색 결정, 수율 45%; m.p. 143-145 ℃; IR (KBr) 3330, 1680, 16340 1580 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.18 (1H, d,J= 16.30 Hz), 7.75 (2H, d,J= 9.40 Hz), 7.40 (2H, d,J= 9.40 Hz), 7.39 (1H, d,J= 16.30 Hz), 6.73~6.99 (3H, m).Red crystals, yield 45%; mp 143-145 ° C; IR (KBr) 3330, 1680, 16340 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.18 (1H, d, J = 16.30 Hz), 7.75 (2H, d, J = 9.40 Hz), 7.40 (2H, d, J = 9.40 Hz), 7.39 (1H, doublet, J = 16.30 Hz), 6.73-6.99 (3H, m).

(( EE )-3-(2,5-디히드록시페닐)-1-(2,3,4,5,6-펜타플루오로페닐)-2-프로펜-1-온) -3- (2,5-dihydroxyphenyl) -1- (2,3,4,5,6-pentafluorophenyl) -2-propen-1-one (1(One -8-8 ).).

적색 결정; 수율 37%; m.p. 157-159 ℃; IR (KBr) 3350, 1660, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.18 (1H, d,J= 16.30 Hz), 7.39 (1H, d,J= 16.30 Hz), 6.66~6.87 (3H, m).Red crystals; Yield 37%; mp 157-159 ° C; IR (KBr) 3350, 1660, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.18 (1H, d, J = 16.30 Hz), 7.39 (1H, d, J = 16.30 Hz), 6.66-6.87 (3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(4-니트로페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (4-nitrophenyl) -2-propen-1-one (1 -9-9 ).).

적색 결정, 수율 41%; m.p. 139-141 ℃; IR (KBr) 3350, 1680, 1630, 1575 cm-1;1H-NMR (DMSO-d6, 300 MHz) 8.06 (1H, d,J= 16.11 Hz), 7.84 (2H, d,J= 8.41 Hz), 7.45 (2H, d,J= 8.41 Hz), 7.41 (1H, d,J= 16.11 Hz), 6.67~6.89 (3H, m); Anal. (C15H11NO5) C, H, N.Red crystals, yield 41%; mp 139-141 ° C; IR (KBr) 3350, 1680, 1630, 1575 cm −1 ; 1 H-NMR (DMSO- d 6, 300 MHz) 8.06 (1H, d, J = 16.11 Hz), 7.84 (2H, d, J = 8.41 Hz), 7.45 (2H, d, J = 8.41 Hz), 7.41 (1H, doublet, J = 16.11 Hz), 6.67-6.89 (3H, m); Anal. (C 15 H 11 NO 5 ) C, H, N.

(E)-1-(2,5-디플루오로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (2,5-difluorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -10-10 ).).

적색 결정, 수율 44%; m.p. 127-129 ℃; IR (KBr) 3330, 1680, 1615, 1590cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.07 (1H, d,J= 16.01 Hz), 7.47~7.85 (2H, m), 7.41(1H, d,J= 16.01 Hz), 6.65~6.89 (4H, m).Red crystals, yield 44%; mp 127-129 ° C; IR (KBr) 3330, 1680, 1615, 1590 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.07 (1H, d, J = 16.01 Hz), 7.47-7.85 (2H, m), 7.41 (1H, d, J = 16.01 Hz), 6.65-6.89 ( 4H, m).

(E)-1-(3,5-디플루오로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (3,5-difluorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -11-11 ).).

적색 결정, 수율 41%; m.p. 115-117 ℃; IR (KBr) 3340, 1680, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.03 (1H, d,J= 16.02 Hz), 7.67 (2H, d,J= 2.15 Hz), 7.40(1H, d,J= 16.02 Hz), 7.01 (1H, d,J= 2.15 Hz ), 6.47~6.74 (3H, m).Red crystals, yield 41%; mp 115-117 ° C; IR (KBr) 3340, 1680, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.03 (1H, d, J = 16.02 Hz), 7.67 (2H, d, J = 2.15 Hz), 7.40 (1H, d, J = 16.02 Hz), 7.01 (1H, doublet, J = 2.15 Hz), 6.47-6.74 (3H, m).

(E)-1-(2,3-디클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (2,3-dichlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -12-12 ).).

적색 결정, 수율 37%; m.p. 148-149 ℃; IR (KBr) 3345, 1680, 1610, 1590 cm-1; 1H-NMR (DMSO-d 6, 90 MHz) 8.17 (1H, d,J= 16.01 Hz), 7.25~7.56 (4H, m), 6.51~6.82 (3H, m).Red crystals, yield 37%; mp 148-149 ° C; IR (KBr) 3345, 1680, 1610, 1590 cm −1; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.17 (1H, d, J = 16.01 Hz), 7.25-7.56 (4H, m), 6.51-6.82 (3H, m).

(E)-1-(3,4-디클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (3,4-dichlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -13-13 )) ..

적색 결정, 수율 42%; m.p. 131-132 ℃; IR (KBr) 3350, 1680, 1640, 1580 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.11 (1H, d,J= 15.80 Hz), 7.38~7.55 (3H, m),7.14 (1H, d,J= 9.41 Hz ), 6.56~6.84 (3H, m).Red crystals, yield 42%; mp 131-132 ° C; IR (KBr) 3350, 1680, 1640, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.11 (1H, d, J = 15.80 Hz), 7.38-7.55 (3H, m), 7.14 (1H, d, J = 9.41 Hz), 6.56-6.84 ( 3H, m).

(E)-1-(3,5-디클로로페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1- (3,5-dichlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -14-14 ).).

적색 결정, 수율 45%; m.p. 124-126 ℃; IR (KBr) 3340, 1680, 1630, 1580 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.07 (1H, d,J= 16.10 Hz), 7.65 (2H, d,J= 2.30 Hz), 7.42(1H, d,J= 16.10 Hz), 7.11 (1H, d,J= 2.30 Hz ), 6.51~6.79 (3H, m).Red crystals, yield 45%; mp 124-126 ° C; IR (KBr) 3340, 1680, 1630, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.07 (1H, d, J = 16.10 Hz), 7.65 (2H, d, J = 2.30 Hz), 7.42 (1H, d, J = 16.10 Hz), 7.11 (1H, d, J = 2.30 Hz), 6.51-6.69 (3H, m).

(E)-1-[(5-브로모-2-메톡시)페닐]-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -1-[(5-bromo-2-methoxy) phenyl] -3- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -15-15 ).).

적색 결정, 수율 64%; m.p. 163-164 ℃; IR (KBr) 3340, 2910, 1670, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.03 (1H, d,J= 15.87 Hz), 7.21~7.52 (3H, m), 6.41~6.84 (4H, m).Red crystals, yield 64%; mp 163-164 ° C; IR (KBr) 3340, 2910, 1670, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.03 (1H, d, J = 15.87 Hz), 7.21-7.52 (3H, m), 6.41-6.84 (4H, m).

(E)-3-(2,5-디히드록시페닐)-1-(2-메틸페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2-methylphenyl) -2-propen-1-one (1 -16-16 ).).

황색 결정, 수율 57%; m.p. 171-173 ℃; IR (KBr) 3340, 2910, 1680, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.19 (1H, d,J= 16.00 Hz), 7.39~7.71 (5H, m), 6.63~6.84 (3H, m). Yellow crystals, yield 57%; mp 171-173 ° C; IR (KBr) 3340, 2910, 1680, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.19 (1H, d, J = 16.00 Hz), 7.39-7.71 (5H, m), 6.63-6.84 (3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(4-메틸페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (4-methylphenyl) -2-propen-1-one (1 -17-17 ).).

황색 결정, 수율 65%; m.p. 168-170 ℃; IR (KBr) 3320, 2915, 1680, 1620,1575 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.01 (1H, d,J= 16.33 Hz), 7.71 (2H, d,J= 8.7 Hz), 7.43 (1H, d,J= 16.33 Hz), 7.29 (2H, d,J= 8.71 Hz), 6.59~6.87 (3H, m). Yellow crystals, yield 65%; mp 168-170 ° C; IR (KBr) 3320, 2915, 1680, 1620,1575 cm -1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.01 (1H, d, J = 16.33 Hz), 7.71 (2H, d, J = 8.7 Hz), 7.43 (1H, d, J = 16.33 Hz), 7.29 (2H, doublet, J = 8.71 Hz), 6.59-6.87 (3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(2-메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2-methoxyphenyl) -2-propen-1-one (1 -18-18 ).).

적색 결정, 수율 68%; m.p. 154-155 ℃; IR (KBr) 3340, 2920, 1680, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.27 (1H, d,J= 15.9 Hz), 7.40~7.74 (4H, m), 6.63~6.92 (4H, m), 3.91 (3H, s).Red crystals, yield 68%; mp 154-155 ° C; IR (KBr) 3340, 2920, 1680, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.27 (1H, d, J = 15.9 Hz), 7.40 ~ 7.74 (4H, m), 6.63 ~ 6.92 (4H, m), 3.91 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(3-메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (3-methoxyphenyl) -2-propen-1-one (1 -19-19 ).).

적색 결정, 수율 71%; m.p. 137-139 ℃; IR (KBr) 3350, 2915, 1675, 1615, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.31 (1H, d,J= 16.54 Hz), 7.01~7.38 (4H, m), 7.41(1H, d,J= 16.54 Hz), 6.47~6.71 (3H, m), 3.89 (3H, s).Red crystals, yield 71%; mp 137-139 ° C; IR (KBr) 3350, 2915, 1675, 1615, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.31 (1H, d, J = 16.54 Hz), 7.01-7.38 (4H, m), 7.41 (1H, d, J = 16.54 Hz), 6.47-6.71 ( 3H, m), 3.89 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(4-메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (4-methoxyphenyl) -2-propen-1-one (1 -20-20 ).).

적색 결정, 수율69%; m.p. 157-159 ℃; IR (KBr) 3330, 2920, 1680, 1610, 1580 cm-1;1H-NMR (DMSO-d 6,300 MHz) 8.11 (1H, d,J= 16.22 Hz), 7.68 (2H, d,J= 8.51 Hz), 7.41 (1H, d,J= 16.22 Hz), 6.97 (2H, d,J= 8.51 Hz), 6.54~6.85 (3H, m), 3.89 (3H, s). Red crystals, yield 69%; mp 157-159 ° C; IR (KBr) 3330, 2920, 1680, 1610, 1580 cm −1 ; 1 H-NMR (DMSO- d 6, 300 MHz) 8.11 (1H, d, J = 16.22 Hz), 7.68 (2H, d, J = 8.51 Hz), 7.41 (1H, d, J = 16.22 Hz), 6.97 (2H, d, J = 8.51 Hz), 6.54-6.85 (3H, m), 3.89 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(4-티오메틸페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (4-thiomethylphenyl) -2-propen-1-one (1 -21-21 ).).

적색 결정, 수율 60%; m.p. 119-120 ℃; IR (KBr) 3340, 2915, 1675, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.01 (1H, d,J= 15.70 Hz), 7.59 (2H, d,J= 8.20 Hz), 7.39 (1H, d,J= 15.70 Hz), 6.87 (2H, d,J= 8.20 Hz), 6.55~6.87 (3H, m), 3.98 (3H, s); Anal. (C17H14O3S) C, H. Red crystals, yield 60%; mp 119-120 ° C; IR (KBr) 3340, 2915, 1675, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.01 (1H, d, J = 15.70 Hz), 7.59 (2H, d, J = 8.20 Hz), 7.39 (1H, d, J = 15.70 Hz), 6.87 (2H, d, J = 8.20 Hz), 6.55-6.67 (3H, m), 3.98 (3H, s); Anal. (C 17 H 14 O 3 S) C, H.

(E)-3-(2,5-디히드록시페닐)-1-(2,3-디메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,3-dimethoxyphenyl) -2-propen-1-one (1 -22-22 ).).

황색 결정, 수율 58%; m.p. 114-115 ℃; IR (KBr) 3340, 2900, 1670, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 7.97 (1H, d,J= 15.81 Hz), 7.41 (1H, d,J= 15.82 Hz), 6.94~7.25 (3H, m), 6.45~6.79 (3H, m), 3.95 (3H, s), 3.84 (3H, s).Yellow crystals, yield 58%; mp 114-115 ° C; IR (KBr) 3340, 2900, 1670, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.97 (1H, d, J = 15.81 Hz), 7.41 (1H, d, J = 15.82 Hz), 6.94-7.25 (3H, m), 6.45-6.69 ( 3H, m), 3.95 (3H, s), 3.84 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(2,4-디메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,4-dimethoxyphenyl) -2-propen-1-one (1 -23-23 ).).

황색 결정, 수율 67%; m.p. 158-160 ℃; IR (KBr) 3330, 2910, 1680, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.00 (1H, d,J= 16.40 Hz), 57.61 (1H, m), 7.38 (1H, d,J= 16.40 Hz), 6.39~6.75 (5H, m), 3.91 (3H, s), 3.89 (3H, s).Yellow crystals, yield 67%; mp 158-160 ° C; IR (KBr) 3330, 2910, 1680, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.00 (1H, d, J = 16.40 Hz), 57.61 (1H, m), 7.38 (1H, d, J = 16.40 Hz), 6.39-6.75 (5H, m), 3.91 (3H, s), 3.89 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(2,5-디메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,5-dimethoxyphenyl) -2-propen-1-one (1 -24-24 ).).

황색 결정, 수율 71%; m.p. 138-141 ℃; IR (KBr) 3320, 2915, 1690, 1610, 1590 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.99 (1H, d,J= 16.00 Hz), 7.37 (1H, d,J= 16.00 Hz), 7.25 (1H, m), 6.51~6.82 (5H, m), 3.92 (3H, s), 3.90 (3H, s).Yellow crystals, 71% yield; mp 138-141 ° C; IR (KBr) 3320, 2915, 1690, 1610, 1590 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.99 (1H, d, J = 16.00 Hz), 7.37 (1H, d, J = 16.00 Hz), 7.25 (1H, m), 6.51-6.82 (5H, m), 3.92 (3H, s), 3.90 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(3,4-디메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (3,4-dimethoxyphenyl) -2-propen-1-one (1 -25-25 ).).

황색 결정, 수율 77%; m.p. 155-156 ℃; IR (KBr) 3340, 2920, 1690, 1620, 1580 cm-1;1H-NMR (DMSO-d6, 90 MHz) 8.01 (1H, d,J= 16.11 Hz), 7.38 (1H, d,J= 16.11 Hz), 7.29 (1H, d, J = 2.73 Hz), 7.26 (1H, dd,J= 2.73, 8.41 Hz), 6.94 (1H, d,J= 8.41 Hz), 6.51~6.82 (3H, m), 3.93 (3H, s) 3.92 (3H, s); Anal. (C17H16O5) C, H.Yellow crystals, yield 77%; mp 155-156 ° C; IR (KBr) 3340, 2920, 1690, 1620, 1580 cm −1 ; 1 H-NMR (DMSO-d 6 , 90 MHz) 8.01 (1H, d, J = 16.11 Hz), 7.38 (1H, d, J = 16.11 Hz), 7.29 (1H, d, J = 2.73 Hz), 7.26 (1H, doublet of doublets, J = 2.73, 8.41 Hz), 6.94 (1H, d, J = 8.41 Hz), 6.51-6.82 (3H, m), 3.93 (3H, s) 3.92 (3H, s); Anal. (C 17 H 16 O 5 ) C, H.

(E)-3-(2,5-디히드록시페닐)-1-(3,5-디메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (3,5-dimethoxyphenyl) -2-propen-1-one (1 -26-26 ).).

황색 결정, 수율 71%; m.p. 171-172 ℃; IR (KBr) 3320, 2915, 1680, 1625, 1575 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.00 (1H, d,J= 16.00 Hz), 7.45 (1H, d,J= 16.00 Hz), 7.28 (2H, d,J= 2.50 Hz), 6.84 (1H, t,J= 2.50 Hz), 6.53~6.82 (3H, m), 3.91 (6H, s).Yellow crystals, 71% yield; mp 171-172 ° C; IR (KBr) 3320, 2915, 1680, 1625, 1575 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.00 (1H, d, J = 16.00 Hz), 7.45 (1H, d, J = 16.00 Hz), 7.28 (2H, d, J = 2.50 Hz), 6.84 (1H, t, J = 2.50 Hz), 6.53-6.82 (3H, m), 3.91 (6H, s).

(E)-3-(2,5-디히드록시페닐)-1-(2,3,4-트리메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,3,4-trimethoxyphenyl) -2-propen-1-one (1 -27-27 ).).

황색 결정, 수율 59%; m.p. 128-130 ℃; IR (KBr) 3340, 2910, 1670, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 7.95 (1H, d,J= 15.59 Hz), 7.58 (1H, d,J= 15.59 Hz), 7.29 (1H, d,J= 8.6 Hz), 6.66 (1H, dd,J= 7.82, 2.40 Hz), 6.51 (1H, d,J= 8.61 Hz), 6.44 (1H, d,J= 7.82 Hz), 6.41 (1H, d,J= 2.40 Hz), 3.95 (3H, s), 3.89 (3H, s), 3.88 (3H, s).Yellow crystals, yield 59%; mp 128-130 ° C; IR (KBr) 3340, 2910, 1670, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.95 (1H, d, J = 15.59 Hz), 7.58 (1H, d, J = 15.59 Hz), 7.29 (1H, d, J = 8.6 Hz), 6.66 (1H, dd, J = 7.82, 2.40 Hz), 6.51 (1H, d, J = 8.61 Hz), 6.44 (1H, d, J = 7.82 Hz), 6.41 (1H, d, J = 2.40 Hz), 3.95 (3H, s), 3.89 (3H, s), 3.88 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(2,4,5-트리메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,4,5-trimethoxyphenyl) -2-propen-1-one (1 -28-28 ).).

황색 결정, 수율 77%; m.p. 149-151 ℃; IR (KBr) 3330, 2920, 1680, 1610, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.84 (1H, d,J= 16.10 Hz), 7.47 (1H, d,J= 16.10 Hz), 7.27 (1H, s), 6.72 (1H, d,J= 2.51 Hz), 6.61 (1H, dd,J= 8.11, 2.51 Hz), 6.51 (1H, s), 6.44 (1H, d,J= 8.11 Hz), 3.94 (3H, s), 3.90 (3H, s), 3.89 (3H, s).Yellow crystals, yield 77%; mp 149-151 ° C; IR (KBr) 3330, 2920, 1680, 1610, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.84 (1H, d, J = 16.10 Hz), 7.47 (1H, d, J = 16.10 Hz), 7.27 (1H, s), 6.72 (1H, d, J = 2.51 Hz), 6.61 (1H, dd, J = 8.11, 2.51 Hz), 6.51 (1H, s), 6.44 (1H, d, J = 8.11 Hz), 3.94 (3H, s), 3.90 (3H, s), 3.89 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(2,4,6-트리메톡시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,4,6-trimethoxyphenyl) -2-propen-1-one (1 -29-29 ).).

황색 결정, 수율 66%; m.p. 171-173 ℃; IR (KBr) 3350, 1680, 1620, 1575 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.85 (1H, d,J= 16.00 Hz), 7.51 (1H, d,J= 16.00 Hz), 6.67 (2H, s), 6.39~6.65 (3H, m), 3.87 (6H, s), 3.85 (3H, s).Yellow crystals, yield 66%; mp 171-173 ° C; IR (KBr) 3350, 1680, 1620, 1575 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.85 (1H, d, J = 16.00 Hz), 7.51 (1H, d, J = 16.00 Hz), 6.67 (2H, s), 6.39-6.65 (3H, m), 3.87 (6H, s), 3.85 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(3,4,5-트리메톡시페닐)-2-프로펜-1-온(1(E) -3- (2,5-dihydroxyphenyl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one (1 -30-30 ).).

황색 결정, 수율66%; m.p. 171-173 ℃; IR (KBr) 3350, 1680, 1620, 1575 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.85 (1H, d,J= 16.01 Hz), 7.51 (1H, d,J= 16.01 Hz), 6.67 (2H, s), 6.39~6.65 (3H, m), 3.87 (6H, s), 3.85 (3H, s).Yellow crystals, yield 66%; mp 171-173 ° C; IR (KBr) 3350, 1680, 1620, 1575 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.85 (1H, d, J = 16.01 Hz), 7.51 (1H, d, J = 16.01 Hz), 6.67 (2H, s), 6.39-6.65 (3H, m), 3.87 (6H, s), 3.85 (3H, s).

(E)-3-(2,5-디히드록시페닐)-1-(2-히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2-hydroxyphenyl) -2-propen-1-one (1 -31-31 ).).

적색 결정, 수율 45%; m.p. 159-161 ℃; IR (KBr) 3360, 1680, 1625, 1590 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 7.84 (1H, d,J= 15.82 Hz), 7.44 (1H, d,J= 15.82 Hz), 6.84~7.42 (4H, m), 6.66 (1H, d,J= 2.11 Hz), 6.52 (1H, d,J= 8.51 Hz), 6.43 (1H, dd,J= 8.51, 2.11 Hz).Red crystals, yield 45%; mp 159-161 ° C; IR (KBr) 3360, 1680, 1625, 1590 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.84 (1H, d, J = 15.82 Hz), 7.44 (1H, d, J = 15.82 Hz), 6.84-7.42 (4H, m), 6.66 (1H, d, J = 2.11 Hz), 6.52 (1H, d, J = 8.51 Hz), 6.43 (1H, dd, J = 8.51, 2.11 Hz).

(E)-3-(2,5-디히드록시페닐)-1-(3-히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (3-hydroxyphenyl) -2-propen-1-one (1 -32-32 ).).

적색 결정, 수율 37%; m.p. 145-147 ℃; IR (KBr) 3340, 1680, 1610, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.78 (1H, d,J= 16.00 Hz), 7.41 (1H, d,J= 16.00 Hz), 7.32 (1H, s), 7.00~7.38 (3H, m), 6.45~6.75 (3H, m).Red crystals, yield 37%; mp 145-147 ° C; IR (KBr) 3340, 1680, 1610, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.78 (1H, d, J = 16.00 Hz), 7.41 (1H, d, J = 16.00 Hz), 7.32 (1H, s), 7.00-7.38 (3H, m), 6.45-6.75 (3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(4-히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (4-hydroxyphenyl) -2-propen-1-one (1 -33-33 ).).

적색 결정, 수율 41%; m.p. 127-129 ℃; IR (KBr) 3350, 1680, 1610, 1580cm-1;1H-NMR (DMSO-d 6, 300 MHz) 7.84 (1H, d,J= 16.21 Hz), 7.55 (2H, d, J = 7.9 Hz), 7.39 (1H, d,J= 16.21 Hz), 6.94 (2H, d,J= 7.9 Hz), 6.53~6.79 (3H, m).Red crystals, yield 41%; mp 127-129 ° C; IR (KBr) 3350, 1680, 1610, 1580 cm -1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.84 (1H, d, J = 16.21 Hz), 7.55 (2H, d, J = 7.9 Hz), 7.39 (1H, d, J = 16.21 Hz), 6.94 (2H, d, J = 7.9 Hz), 6.53-6.69 (3H, m).

(E)-3-(2,5-디히드록시페닐)-1-[(2-히드록시-5-메톡시)페닐]-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1-[(2-hydroxy-5-methoxy) phenyl] -2-propen-1-one (1 -34-34 ).).

황색 결정, 수율 41%; m.p. 119-121 ℃; IR (KBr) 3340, 2910, 1680, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.00 (1H, d,J= 16.12 Hz), 7.39 (1H, d,J= 16.12 Hz), 6.88~7.21 (3H, m), 6.44~6.75 (3H, m), 3.94 (3H, m).Yellow crystals, 41% yield; mp 119-121 ° C; IR (KBr) 3340, 2910, 1680, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.00 (1H, d, J = 16.12 Hz), 7.39 (1H, d, J = 16.12 Hz), 6.88-7.71 (3H, m), 6.44-6.75 ( 3H, m), 3.94 (3H, m).

(E)-3-(2,5-디히드록시페닐)-1-[(2-히드록시-6-메톡시)페닐]-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1-[(2-hydroxy-6-methoxy) phenyl] -2-propen-1-one (1 -35-35 ).).

황색 결정, 수율 57%; m.p. 140-141 ℃; IR (KBr) 3345, 2915, 1680, 1625, 1575 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.01 (1H, d,J= 15.91 Hz), 7.42 (1H, d,J= 15.90 Hz), 6.76~7.00 (3H, m), 6.43~6.75 (3H, m), 3.89 (3H, m).Yellow crystals, yield 57%; mp 140-141 ° C; IR (KBr) 3345, 2915, 1680, 1625, 1575 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.01 (1H, d, J = 15.91 Hz), 7.42 (1H, d, J = 15.90 Hz), 6.76-7.00 (3H, m), 6.43-6.75 ( 3H, m), 3.89 (3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(2,3-디히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,3-dihydroxyphenyl) -2-propen-1-one (1 -36-36 ).).

황색 결정, 수율 29%; m.p. 125-127 ℃; IR (KBr) 3350, 1680, 1620, 1580 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.11 (1H, d,J= 16.00 Hz), 7.35 (1H, d,J=16.00 Hz), 6.85~7.21 (3H, m), 6.51~6.82 (3H, m).Yellow crystals, yield 29%; mp 125-127 ° C; IR (KBr) 3350, 1680, 1620, 1580 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.11 (1H, d, J = 16.00 Hz), 7.35 (1H, d, J = 16.00 Hz), 6.85-7.21 (3H, m), 6.51-6.82 ( 3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(2,4-디히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,4-dihydroxyphenyl) -2-propen-1-one (1 -37-37 ).).

황색 결정, 수율 38%; m.p. 141-142 ℃; IR (KBr) 3340, 1680, 1620, 1575 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.02 (1H, d,J= 16.01 Hz), 7.51 (1H, d,J= 8.22 Hz), 7.41 (1H, d,J= 16.01 Hz), 6.39~6.82 (5H, m).Yellow crystals, yield 38%; mp 141-142 ° C; IR (KBr) 3340, 1680, 1620, 1575 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.02 (1H, d, J = 16.01 Hz), 7.51 (1H, d, J = 8.22 Hz), 7.41 (1H, d, J = 16.01 Hz), 6.39 ˜6.82 (5H, m).

(E)-3-(2,5-디히드록시페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (1 -38-38 ).).

황색 결정, 수율 35%; m.p. 144-145 ℃; IR (KBr) 3345, 1680, 1610, 1590 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.99 (1H, d,J= 16.11 Hz), 7.41 (1H, d,J= 16.11 Hz), 6.88~7.02 (3H, m), 6.44~6.75 (3H, m).Yellow crystals, yield 35%; mp 144-145 ° C; IR (KBr) 3345, 1680, 1610, 1590 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.99 (1H, d, J = 16.11 Hz), 7.41 (1H, d, J = 16.11 Hz), 6.88-7.02 (3H, m), 6.44-6.75 ( 3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(3,4-디히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (3,4-dihydroxyphenyl) -2-propen-1-one (1 -39-39 ).).

황색 결정, 수율 28%; m.p. 111-113 ℃; IR (KBr) 3350, 1680, 1615, 1585 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.10 (1H, d,J= 16.23 Hz), 7.45 (1H, d,J= 16.22 Hz), 6.88~7.11 (3H, m), 6.51~6.87 (3H, m).Yellow crystals, yield 28%; mp 111-113 ° C; IR (KBr) 3350, 1680, 1615, 1585 cm -1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.10 (1H, d, J = 16.23 Hz), 7.45 (1H, d, J = 16.22 Hz), 6.88-7.11 (3H, m), 6.51-6.07 ( 3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(3,5-디히드록시페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (3,5-dihydroxyphenyl) -2-propen-1-one (1 -40-40 ).).

황색 결정, 수율 31%; m.p. 131-132 ℃; IR (KBr) 3340, 1680, 1610, 1590 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.05 (1H, d,J= 15.4 Hz), 7.40 (1H, d,J= 15.4 Hz), 6.71 (2H, s), 6.50~6.82 (4H, m).Yellow crystals, yield 31%; mp 131-132 ° C; IR (KBr) 3340, 1680, 1610, 1590 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.05 (1H, d, J = 15.4 Hz), 7.40 (1H, d, J = 15.4 Hz), 6.71 (2H, s), 6.50-6.82 (4H, m).

(( E)-3-(2,5-디히드록시페닐)-1-(3,4-메틸렌디옥시페닐)-2-프로펜-1-온 (1E) -3- (2,5-dihydroxyphenyl) -1- (3,4-methylenedioxyphenyl) -2-propen-1-one (1 -41-41 ).).

황색 결정, 수율 68%; m.p. 111-113 ℃; IR (KBr) 3350, 1680, 1615, 1585 cm-1;1H-NMR (DMSO-d6) 8.00 (1H, d,J= 16.10 Hz), 7.42 (1H, d,J= 16.10 Hz), 5.91 (2H, s), 6.84~7.10 (3H, m), 6.51~6.83 (3H, m); Anal. (C16H12O5) C, H.Yellow crystals, yield 68%; mp 111-113 ° C; IR (KBr) 3350, 1680, 1615, 1585 cm -1 ; 1 H-NMR (DMSO-d 6 ) 8.00 (1H, d, J = 16.10 Hz), 7.42 (1H, d, J = 16.10 Hz), 5.91 (2H, s), 6.84-7.10 (3H, m), 6.51-6.63 (3H, m); Anal. (C 16 H 12 O 5 ) C, H.

(E)-3-(2,5-디히드록시페닐)-1-(4-페닐페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (4-phenylphenyl) -2-propen-1-one (1 -42-42 ).).

황색 결정, 수율 57%; m.p. 145-146 ℃; IR (KBr) 3340, 1680, 1610, 1590 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.99 (1H, d,J= 16.04 Hz), 7.42 (1H, d,J= 16.04 Hz), 6.79~7.40 (9H, m), 6.50~6.78 (3H, m).Yellow crystals, yield 57%; mp 145-146 ° C; IR (KBr) 3340, 1680, 1610, 1590 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.99 (1H, d, J = 16.04 Hz), 7.42 (1H, d, J = 16.04 Hz), 6.79-7.40 (9H, m), 6.50-6.78 ( 3H, m).

(E)-3-(2,5-디히드록시페닐)-1-(4-메틸설포닐페닐)-2-프로펜-1-온 (1(E) -3- (2,5-dihydroxyphenyl) -1- (4-methylsulfonylphenyl) -2-propen-1-one (1 -43-43 ).).

적색 결정, 수율 80%; m.p. 145-147 ℃; IR (KBr) 3330, 2920, 1680, 1620, 1580, 1380 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.12 (1H, d,J= 16.11 Hz), 7.63 (2H, d,J= 7.81 Hz), 7.42 (1H, d,J= 16.11 Hz), 6.99 (2H, d,J= 7.81 Hz),6.48~6.84 (3H, m), 3.23 (3H, s); Anal. (C17H14O5S) C, H. Red crystals, yield 80%; mp 145-147 ° C; IR (KBr) 3330, 2920, 1680, 1620, 1580, 1380 cm -1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.12 (1H, d, J = 16.11 Hz), 7.63 (2H, d, J = 7.81 Hz), 7.42 (1H, d, J = 16.11 Hz), 6.99 (2H, d, J = 7.81 Hz), 6.68-6.84 (3H, m), 3.23 (3H, s); Anal. (C 17 H 14 O 5 S) C, H.

실시예 2: 일반식(Ib)의 1-(2,5-디히드록시페닐)-3-(치환) 페닐-2-프로펜-1-온 유도체의 제조(공통적 제조법)Example 2: Preparation of 1- (2,5-dihydroxyphenyl) -3- (substituted) phenyl-2-propen-1-one derivative of general formula (lb) (common method)

별도로 합성한 2,5-비스(테트라히드로피란-2-일옥시)아세토페논), 치환된 벤즈알데히드 유도체(25 mmol) 및 수산화 바륨 옥타하이드레이트(8.15 g, 25 mmol) 을 메탄올(100 mL)에 용해시키고 40 ℃에서 12시간 교반한다. 반응이 끝나면 물 100 mL를 가하여 흔들어 준 다음 1-N HCl 으로 중화한다. 중화용액은 MC 100 ml 씩으로 3번 추출한다. 추출액은 무수망초로 탈수한다음 증발 건조한다. 건조물의 80% 이상이 (E)-1-[2,5-비스(테트라히드로피란-2-일옥시)페닐]-3-페닐-2-프로펜-1-온로 구성되어 있었으므로 이 건조물을 다음 반응에 그대로 사용하였다.Separately synthesized 2,5-bis (tetrahydropyran-2-yloxy) acetophenone), substituted benzaldehyde derivatives (25 mmol) and barium hydroxide octahydrate (8.15 g, 25 mmol) were dissolved in methanol (100 mL) And stirred at 40 ° C. for 12 hours. After the reaction, add 100 mL of water, shake, and neutralize with 1-N HCl. Neutralizing solution is extracted three times with 100 ml each MC. The extract is dehydrated with anhydrous forget-me-not and evaporated to dryness. 80% or more of the dry matter consisted of ( E ) -1- [2,5-bis (tetrahydropyran-2-yloxy) phenyl] -3-phenyl-2-propen-1-one. It was used as it is for the next reaction.

위 건조물과p-톨루엔 설폰산(0.2 g, 1.05 mmol)을 메탄올(100 mL)에 용해시키고 실온에서 4시간 교반하였다. 반응 후 물(100 mL) 을 가한 다음 5% 중조로 중화시켰다. 중화된 용액은 초산에칠 50ml씩으로 3회 추출하였다. 초산에칠 추출물은 무수 망초로 탈수한 다음 증발 건조하였다. 건조물은 물성에 따라 직접 메탄올 등 알코올에서 재결정하든지 실리카겔 칼럼 상에서 초산에칠-헥산 혼합용매를 사용하여 정제하였다.The above dried product and p -toluene sulfonic acid (0.2 g, 1.05 mmol) were dissolved in methanol (100 mL) and stirred at room temperature for 4 hours. After the reaction was added water (100 mL) and neutralized with 5% sodium bicarbonate. The neutralized solution was extracted three times with 50 ml each of ethyl acetate. The ethyl acetate extract was dehydrated with anhydrous forget-me-not and then evaporated to dryness. The dried product was directly recrystallized from an alcohol such as methanol or purified on an silica gel column using an ethyl acetate-hexane mixed solvent according to physical properties.

실시예 2에 의하여 합성한 물질과 그들의 물성을 다음과 같았다.The materials synthesized according to Example 2 and their physical properties were as follows.

(E)-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one (2 -1-One ))

담황색 결정, 수율 65%; m.p. 187-190 ℃; IR (KBr) 3340, 1640 cm-1; MS(CIMS) m/z 240;1H-NMR (DMSO-d6, 90 MHz) 11.89 (1H, s), 9.58 (1H, s), 7.98 (1H, d,J= 15.12 Hz), 7.71-7.32 (5H, m), 7.15 (1H, d,J= 2.12 Hz), 7.07-6.91 (2H, m), 6.79 (1H, d,J= 15.10 Hz). .Pale yellow crystals, yield 65%; mp 187-190 ° C; IR (KBr) 3340, 1640 cm −1 ; MS (CIMS) m / z 240; 1 H-NMR (DMSO-d 6 , 90 MHz) 11.89 (1H, s), 9.58 (1H, s), 7.98 (1H, d, J = 15.12 Hz), 7.71-7.32 (5H, m), 7.15 ( 1H, d, J = 2.12 Hz), 7.07-6.91 (2H, m), 6.79 (1H, d, J = 15.10 Hz). .

(E)-1-(2,5-디히드록시페닐)-3-(2-플루오로페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2-fluorophenyl) -2-propen-1-one (2 -2-2 ).).

적색 결정; 수율 81%;1H-NMR (DMSO-d6, 90 MHz) 12.00 (1H, s), 10.18 (1H, s), 8.11 (1H, s,J= 15.21 Hz), 7.42 (1H, s,J= 15.21 Hz), 7.32-6.91 (4H, m), 6.88-6.73 (3H, m).Red crystals; Yield 81%; 1 H-NMR (DMSO-d 6 , 90 MHz) 12.00 (1H, s), 10.18 (1H, s), 8.11 (1H, s, J = 15.21 Hz), 7.42 (1H, s, J = 15.21 Hz) , 7.32-6.91 (4H, m), 6.88-6.73 (3H, m).

(E)-3-(2-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3- (2-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -3-3 ).).

적색 결정; 수율 76%;1H-NMR (DMSO-d 6, 90 MHz) 12.27 (1H, s), 9.98 (1H, s), 8.08 (1H, s,J= 14.39 Hz), 7.45 (1H, s,J= 14.42 Hz), 7.27-7.11 (4H, m), 6.85-6.73 (2H, m), 6.70 (1H, d,J= 8.21 Hz).Red crystals; Yield 76%; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.27 (1H, s), 9.98 (1H, s), 8.08 (1H, s, J = 14.39 Hz), 7.45 (1H, s, J = 14.42 Hz) , 7.27-7.11 (4H, m), 6.85-6.73 (2H, m), 6.70 (1H, d, J = 8.21 Hz).

(E)-3-(3-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3- (3-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -4-4 ).).

적색 결정; 수율 59%;1H-NMR (DMSO-d 6, 90 MHz) 11.79 (1H, s), 9.37 (1H, s), 8.01 (1H, s,J= 15.87 Hz), 7.41 (1H, s,J= 15.87 Hz), 7.31 (1H, d,J= 7.89 Hz), 7.29-7.02 (2H, m), 6.98 (1H, d,J= 8.12 Hz), 6.86-6.71 (2H, m).Red crystals; Yield 59%; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.79 (1H, s), 9.37 (1H, s), 8.01 (1H, s, J = 15.87 Hz), 7.41 (1H, s, J = 15.87 Hz) , 7.31 (1H, d, J = 7.89 Hz), 7.29-7.02 (2H, m), 6.98 (1H, d, J = 8.12 Hz), 6.86-6.71 (2H, m).

(E)-3-(4-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3- (4-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -5-5 ).).

적색 결정; 수율 65%; m.p. 208-210 ℃; MS (CIMS)m/z274.5; IR (KBr)3340, 1640 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 7.85 (H-, d,J= 16.3 Hz), 7.78 (H-, d,J= 16.3 Hz), 7.71-7.75 (H-2, H-6, m), 7.42~7.48 (H-6, H-3, H-5, m), 7.05 (H-4, dd,J= 8.12 Hz), 6.84 (H-3, d,J= 8.12 Hz).Red crystals; Yield 65%; mp 208-210 ° C; MS (CIMS) m / z 274.5; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.85 (H-, d, J = 16.3 Hz), 7.78 (H-, d, J = 16.3 Hz), 7.71-7.75 (H-2, H-6 , m), 7.42-7.48 (H-6, H-3, H-5, m), 7.05 (H-4, dd, J = 8.12 Hz), 6.84 (H-3, d, J = 8.12 Hz) .

(E)-3-(4-브로모페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3- (4-bromophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -6-6 ).).

적색 결정s; 수율 43%; m.p. 220-221 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 7.94 (H-, d,J= 16.10 Hz), 7.93 (H-, d,J= 16.10 Hz), 7.73~7.91 (H-2, H-6, m), 7.23~7.42 (H-6, H-3, H-5, m), 7.12 (H-4, dd,J= 2.50, 8.41 Hz), 6.83 (H-3, d,J= 8.41 Hz).Red crystals; Yield 43%; mp 220-221 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.94 (H-, d, J = 16.10 Hz), 7.93 (H-, d, J = 16.10 Hz), 7.73-7.91 (H-2, H-6 , m), 7.23-7.42 (H-6, H-3, H-5, m), 7.12 (H-4, dd, J = 2.50, 8.41 Hz), 6.83 (H-3, d, J = 8.41 Hz).

(E)-1-(2,5-디히드록시페닐)-3-(4-니트로페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (4-nitrophenyl) -2-propen-1-one (2 -7-7 ).).

적색 결정; 수율 70%; m.p. 161-163 m.p. 152-154 oC; ; IR (KBr) 3350, 1650 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.02 (H-, d,J= 16.00 Hz), 7.91 (H-, d,J= 16.00 Hz), 7.65~7.84 (H-2, H-6, m), 7.27~7.45 (H-6, H-3, H-5, m), 7.07 (H-4, dd,J= 2.50, 8.41 Hz), 6.85 (H-3, d,J= 7.89 Hz).Red crystals; Yield 70%; mp 161-163 mp 152-154 oC; ; IR (KBr) 3350, 1650 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.02 (H-, d, J = 16.00 Hz), 7.91 (H-, d, J = 16.00 Hz), 7.65-7.84 (H-2, H-6 , m), 7.27-7.45 (H-6, H-3, H-5, m), 7.07 (H-4, dd, J = 2.50, 8.41 Hz), 6.85 (H-3, d, J = 7.89 Hz).

(E)-1-(2,5-디히드록시페닐)-3-(2,3,4,5,6-펜타플루오로페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,3,4,5,6-pentafluorophenyl) -2-propen-1-one (2 -8-8 ).).

적색 결정; 수율 78%; IR (KBr) 3350, 1660 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.03 (1H, s), 9.22 (1H, s), 7.88 (1H, d,J= 15.93 Hz), 7.50 (1H, d,J=15.93 Hz), 7.18 (1H, d,J= 2.70 Hz), 7.02 (1H, dd,J= 2.70, 8.82 Hz), 6.82 (1H, d,J= 8.82 Hz); Anal. (CnHnOn) C, H.Red crystals; Yield 78%; IR (KBr) 3350, 1660 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.03 (1H, s), 9.22 (1H, s), 7.88 (1H, d, J = 15.93 Hz), 7.50 (1H, d, J = 15.93 Hz) , 7.18 (1H, d, J = 2.70 Hz), 7.02 (1H, dd, J = 2.70, 8.82 Hz), 6.82 (1H, d, J = 8.82 Hz); Anal. (C n H n 0 n ) C, H.

(( EE )-3-(2,5-디플루오로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온) -3- (2,5-difluorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2(2 -9-9 ).).

적색 결정; 수율 57%; IR (KBr) 3520, 1680 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.17 (1H, s), 10.27 (1H, s), 8.12 (H, d,J= 15.38 Hz), 7.96 (H, d,J= 2.24 Hz), 7.87 (H, d,J= 15.38 Hz), 7.55-7.41 (2H, m), 7.46-6.99 (3H, m).Red crystals; Yield 57%; IR (KBr) 3520, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.17 (1H, s), 10.27 (1H, s), 8.12 (H, d, J = 15.38 Hz), 7.96 (H, d, J = 2.24 Hz) , 7.87 (H, d, J = 15.38 Hz), 7.55-7.41 (2H, m), 7.46-6.99 (3H, m).

(E)-3-[2,5-비스(트리플루오로메틸)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3- [2,5-bis (trifluoromethyl) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -10-10 ).).

적색 결정; 수율 42%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.98 (1H, s), 9.71 (1H, s), 8.03 (H, d,J= 14.49 Hz), 7.84 (H, d,J= 2.21 Hz), 7.73 (H, d,J= 14.50 Hz), 7.56-6.87 (5H, m).Red crystals; Yield 42%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.98 (1H, s), 9.71 (1H, s), 8.03 (H, d, J = 14.49 Hz), 7.84 (H, d, J = 2.21 Hz) , 7.73 (H, d, J = 14.50 Hz), 7.56-6.87 (5H, m).

(E)-3-[(2-브로모-5-메톡시)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3-[(2-bromo-5-methoxy) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -11-11 ).).

적색 결정; 수율 81%; IR (KBr) 3420, 1670 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.41 (1H, s), 10.06 (1H, s), 8.01 (H, d,J= 16.15 Hz), 7.75-7.56 (3H, m), 7.27-6.85 (5H, m), 3.91 (3H, s).Red crystals; Yield 81%; IR (KBr) 3420, 1670 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.41 (1H, s), 10.06 (1H, s), 8.01 (H, d, J = 16.15 Hz), 7.75-7.56 (3H, m), 7.27- 6.85 (5H, m), 3.91 (3H, s).

(E)-3-[(5-브로모-2-메톡시)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3-[(5-bromo-2-methoxy) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -12-12 ).).

적색 결정; 수율 69%; IR (KBr) 3400, 1680 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.07 (1H, s), 10.06 (1H, s), 8.02 (H, d,J= 15.75 Hz), 7.91 (H, d,J= 2.43 Hz), 7.83 (H, d,J= 15.75 Hz), 7.71-7.59 (1H, m), 7.35-6.85 (4H, m), 3.98 (3H, s).Red crystals; Yield 69%; IR (KBr) 3400, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.07 (1H, s), 10.06 (1H, s), 8.02 (H, d, J = 15.75 Hz), 7.91 (H, d, J = 2.43 Hz) , 7.83 (H, d, J = 15.75 Hz), 7.71-7.59 (1H, m), 7.35-6.85 (4H, m), 3.98 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(2-메틸페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2-methylphenyl) -2-propen-1-one (2 -13-13 ).).

적색 결정; 수율 85%; IR (KBr) 3400, 1670 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.94 (H, d,J= 15.88 Hz), 7.65-7.45 (2H, m), 7.33-7.11 (4H, m), 7.02-6.96 (2H, m), 2.34 (3H, s).Red crystals; Yield 85%; IR (KBr) 3400, 1670 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.94 (H, d, J = 15.88 Hz), 7.65-7.45 (2H, m), 7.33-7.11 (4H, m), 7.02-6.96 (2H, m ), 2.34 (3H, s).

(E)-3-[(5-브로모-2-히드록시)페닐]-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -3-[(5-bromo-2-hydroxy) phenyl] -1- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -14-14 ).).

적색 결정; 수율 48%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.31 (1H, s), 10.12 (1H, s), 9.21 (1H, s), 8.07 (1H, d,J= 14.57 Hz), 7.63-7.25 (3H, m), 7.05-6.75 (4H, m).Red crystals; Yield 48%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.31 (1H, s), 10.12 (1H, s), 9.21 (1H, s), 8.07 (1H, d, J = 14.57 Hz), 7.63-7.25 ( 3H, m), 7.05-6.75 (4H, m).

(E)-1-(2,5-디히드록시페닐)-3-(2-메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2-methoxyphenyl) -2-propen-1-one (2 -15-15 ).).

노란색 결정; 수율 82%; m.p. 152-154 oC; IR (KBr) 3340, 1640 cm-1;1H-NMR(DMSO-d 6, 90 MHz) 11.81 (1H, s), 9.22 (1H, s), 8.21-7.75 (3H, m), 7.55-7.35 (2H, m), 7.18-6.78 (4H, m), 3.90 (3H, s).Yellow crystals; Yield 82%; mp 152-154 oC; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.81 (1H, s), 9.22 (1H, s), 8.21-7.75 (3H, m), 7.55-7.35 (2H, m), 7.18-6.78 (4H , m), 3.90 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(3-메톡시페닐)-2-프로펜-1-온(E) -1- (2,5-dihydroxyphenyl) -3- (3-methoxyphenyl) -2-propen-1-one (2(2 -16-16 ).).

노란색 결정; 수율 86%; IR (KBr) 3420, 1680 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.85 (1H, s), 9.21 (1H, s), 7.86 (1H, d,J= 15.21 Hz), 7.82-7.35 (4H, m), 7.17-6.84 (3H, m), 6.75 (1H, d,J= 2.75 Hz), 3.84 (3H, s).Yellow crystals; Yield 86%; IR (KBr) 3420, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.85 (1H, s), 9.21 (1H, s), 7.86 (1H, d, J = 15.21 Hz), 7.82-7.35 (4H, m), 7.17- 6.84 (3H, m), 6.75 (1H, doublet, J = 2.75 Hz), 3.84 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(4-메톡시페닐)-2-프로펜-1-온(E) -1- (2,5-dihydroxyphenyl) -3- (4-methoxyphenyl) -2-propen-1-one (2(2 -17-17 ).).

노란색 결정; 수율 83%; IR (KBr) 3380, 1670 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.06 (1H, s), 9.28 (1H, s), 8.02-7.90 (4H, m), 7.63 (1H, d,J= 2.70 Hz), 7.18-7.09 (3H, m), 6.93 (1H, d,J= 8.82 Hz), 3.88 (3H, s).Yellow crystals; Yield 83%; IR (KBr) 3380, 1670 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.06 (1H, s), 9.28 (1H, s), 8.02-7.90 (4H, m), 7.63 (1H, d, J = 2.70 Hz), 7.18- 7.09 (3H, m), 6.93 (1H, doublet, J = 8.82 Hz), 3.88 (3H, s).

(( EE )-1-(2,5-디히드록시페닐)-3-(2-히드록시페닐)-2-프로펜-1-온) -1- (2,5-dihydroxyphenyl) -3- (2-hydroxyphenyl) -2-propen-1-one (2(2 -18-18 ).).

노란색 결정; 수율 37%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.11 (1H, s), 10.48 (1H, s), 9.32 (1H, s), 7.99 (1H, d,J= 15.49 Hz), 7.65-7.12 (4H, m), 7.03-6.71 (4H, m).Yellow crystals; Yield 37%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.11 (1H, s), 10.48 (1H, s), 9.32 (1H, s), 7.99 (1H, d, J = 15.49 Hz), 7.65-7.12 ( 4H, m), 7.03-6.71 (4H, m).

(E)-1-(2,5-디히드록시페닐)-3-(3-히드록시페닐)-2-프로펜-1-온(E) -1- (2,5-dihydroxyphenyl) -3- (3-hydroxyphenyl) -2-propen-1-one (2(2 -19-19 ).).

노란색 결정; 수율 72%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.07 (1H, s), 10.38 (1H, s), 9.12 (1H, s), 7.88 (1H, d,J= 14.51 Hz), 7.68-7.21 (4H, m), 7.11-6.68 (4H, m).Yellow crystals; Yield 72%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.07 (1H, s), 10.38 (1H, s), 9.12 (1H, s), 7.88 (1H, d, J = 14.51 Hz), 7.68-7.21 ( 4H, m), 7.11-6.68 (4H, m).

(E)-1-(2,5-디히드록시페닐)-3-(4-히드록시페닐)-2-프로펜-1-온(E) -1- (2,5-dihydroxyphenyl) -3- (4-hydroxyphenyl) -2-propen-1-one (2(2 -20-20 ).).

노란색 결정; 수율 47%; m.p. 121-125 ℃; IR (KBr) 3540, 1680 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.01 (1H, s, br), 9.51 (1H, s, br), 7.83-7.73 (3H, m), 7.53 (1H, d,J= 2.7 Hz), 7.36 (1H, d,J= 8.29 Hz), 7.16-6.97 (2H, m), 6.93-6.77 (2H, m).Yellow crystals; Yield 47%; mp 121-125 ° C; IR (KBr) 3540, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.01 (1H, s, br), 9.51 (1H, s, br), 7.83-7.73 (3H, m), 7.53 (1H, d, J = 2.7 Hz ), 7.36 (1H, d, J = 8.29 Hz), 7.16-6.97 (2H, m), 6.93-6.77 (2H, m).

(E)-1-(2,5-디히드록시페닐)-3-(4-디메틸아미노페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (4-dimethylaminophenyl) -2-propen-1-one (2 -21-21 ).).

노란색 결정; 수율 61%; m.p. 147-149 ℃; IR (KBr) 3350, 1670 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.35 (1H, s), 9.16 (1H, s), 7.82 (1H, d,J= 14.49 Hz), 7.72 (2H, d,J= 8.45 Hz), 7.53 (1H, d,J= 2.75 Hz), 7.00 (1H, dd,J= 2.75, 8.81 Hz), 6.86 (1H, dd,J= 15.00 Hz), 6.78 (2H, dd,J= 8.45 Hz), 6.69 (1H, dd,J= 8.81 Hz), 3.00 (6H, s).Yellow crystals; Yield 61%; mp 147-149 ° C; IR (KBr) 3350, 1670 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.35 (1H, s), 9.16 (1H, s), 7.82 (1H, d, J = 14.49 Hz), 7.72 (2H, d, J = 8.45 Hz) , 7.53 (1H, d, J = 2.75 Hz), 7.00 (1H, dd, J = 2.75, 8.81 Hz), 6.86 (1H, dd, J = 15.00 Hz), 6.78 (2H, dd, J = 8.45 Hz) , 6.69 (1H, doublet of doublets, J = 8.81 Hz), 3.00 (6H, s).

(E)-1-(2,5-디히드록시페닐)-3-(4-메틸티오페닐)-2-프로펜-1-온(E) -1- (2,5-dihydroxyphenyl) -3- (4-methylthiophenyl) -2-propen-1-one (2(2 -22-22 ).).

노란색 결정; 수율 58%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz ) 12.07 (1H, s), 9.21 (1H, s, br), 7.78 (1H, d,J= 15.12 Hz), 7.65 (2H, d,J= 8.84 Hz), 7.31 (2H, d,J= 8.84 Hz), 7.21 (1H, dd,J= 2.21, 8.37 Hz), 7.00 (1H, d,J= 15.12 Hz), 6.85 (2H, d,J= 2.21 Hz), 6.82 (2H, d,J= 8.37 Hz), 3.75 (3H, s).Yellow crystals; Yield 58%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.07 (1H, s), 9.21 (1H, s, br), 7.78 (1H, d, J = 15.12 Hz), 7.65 (2H, d, J = 8.84 Hz), 7.31 (2H, d, J = 8.84 Hz), 7.21 (1H, dd, J = 2.21, 8.37 Hz), 7.00 (1H, d, J = 15.12 Hz), 6.85 (2H, d, J = 2.21 Hz), 6.82 (2H, d, J = 8.37 Hz), 3.75 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(2,5-디메틸페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,5-dimethylphenyl) -2-propen-1-one (2 -23-23 ).).

노란색 결정; 수율 83%; IR (KBr) 3400, 1680 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.74 (1H, s), 9.11 (1H, s), 7.95 (1H, d,J= 15.47 Hz), 7.71 (1H, d,J= 15.45 Hz), 7.49 (1H, d,J= 2.75 Hz), 7.23-7.01 (2H, m), 7.00 (1H, d,J= 2.11 Hz), 6.83 (1H, d,J= 8.84 Hz), 2.47 (3H, s), 2.39 (3H, s).Yellow crystals; Yield 83%; IR (KBr) 3400, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.74 (1H, s), 9.11 (1H, s), 7.95 (1H, d, J = 15.47 Hz), 7.71 (1H, d, J = 15.45 Hz) , 7.49 (1H, d, J = 2.75 Hz), 7.23-7.01 (2H, m), 7.00 (1H, d, J = 2.11 Hz), 6.83 (1H, d, J = 8.84 Hz), 2.47 (3H, s), 2.39 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(2,3-디메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,3-dimethoxyphenyl) -2-propen-1-one (2 -24-24 ).).

노란색 결정; 수율 81%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.00 (1H, s), 10.87 (1H, s), 7.88 (1H, d,J= 15.78 Hz), 7.45-7.09 (3H, m), 7.00-6.67 (4H, m), 3.81 (3H, s), 3.79 (3H, s).Yellow crystals; Yield 81%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.00 (1H, s), 10.87 (1H, s), 7.88 (1H, d, J = 15.78 Hz), 7.45-7.09 (3H, m), 7.00- 6.67 (4H, m), 3.81 (3H, s), 3.79 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(2,4-디메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,4-dimethoxyphenyl) -2-propen-1-one (2 -25-25 ).).

노란색 결정; 수율 77%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.08 (1H, s), 10.35 (1H, s), 7.89 (1H, d,J= 15.31 Hz), 7.37-7.00 (4H, m), 6.92-6.61 (3H, m), 3.84 (3H, s), 3.80 (3H, s).Yellow crystals; Yield 77%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.08 (1H, s), 10.35 (1H, s), 7.89 (1H, d, J = 15.31 Hz), 7.37-7.00 (4H, m), 6.92- 6.61 (3H, m), 3.84 (3H, s), 3.80 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(2,5-디메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,5-dimethoxyphenyl) -2-propen-1-one (2 -26-26 ).).

노란색 결정; 수율 69%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.16 (1H, s), 9.97 (1H, s), 7.84 (1H, d,J= 14.39 Hz), 7.64-7.31 (3H, m), 7.18 (1H, d,J= 14.39 Hz), 7.02-6.75 (3H, m), 3.84 (3H, s), 3.79 (3H, s).Yellow crystals; Yield 69%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.16 (1H, s), 9.97 (1H, s), 7.84 (1H, d, J = 14.39 Hz), 7.64-7.31 (3H, m), 7.18 ( 1H, d, J = 14.39 Hz), 7.02-6.75 (3H, m), 3.84 (3H, s), 3.79 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(3,5-디메톡시페닐)-2-프로펜-1-온(E) -1- (2,5-dihydroxyphenyl) -3- (3,5-dimethoxyphenyl) -2-propen-1-one (2(2 -27-27 ).).

노란색 결정; 수율 66%; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.86 (1H, s), 9.20 (1H, s), 7.85-7.64 (3H, m), 7.52 (1H, d,J= 2.11 Hz), 7.30 (1H, d,J= 8.91 Hz), 7.00 (1H, d,J= 2.81 Hz), 6.84 (1H, dd,J= 2.81, 8.91 Hz), 3.79 (6H, s).Yellow crystals; Yield 66%; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.86 (1H, s), 9.20 (1H, s), 7.85-7.64 (3H, m), 7.52 (1H, d, J = 2.11 Hz), 7.30 ( 1H, d, J = 8.91 Hz), 7.00 (1H, d, J = 2.81 Hz), 6.84 (1H, dd, J = 2.81, 8.91 Hz), 3.79 (6H, s).

(E)-1-(2,5-디히드록시페닐)-3-(3,4-디메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (3,4-dimethoxyphenyl) -2-propen-1-one (2 -28-28 ).).

노란색 결정; 수율 50%; m.p. 131-132 ℃; IR (KBr) 3400, 1680 cm-1;1H-NMR(DMSO-d 6, 300 MHz) 7.45 (1H, d,J= 2.01 Hz) , 7.37 (1H, d,J= 2.31 Hz), 7.31 (1H, dd,J= 2.31, 8.01 Hz), 7.03 (1H, dd,J= 2.01, 8.00 Hz), 7.00 (1H, d,J= 8.00 Hz), 6.81 (1H, d,J= 8.01 Hz), 3.91 (3H, s), 3.88 (3H, s).Yellow crystals; Yield 50%; mp 131-132 ° C; IR (KBr) 3400, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.45 (1H, d, J = 2.01 Hz), 7.37 (1H, d, J = 2.31 Hz), 7.31 (1H, dd, J = 2.31, 8.01 Hz) , 7.03 (1H, dd, J = 2.01, 8.00 Hz), 7.00 (1H, d, J = 8.00 Hz), 6.81 (1H, d, J = 8.01 Hz), 3.91 (3H, s), 3.88 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(2,3,4-트리메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,3,4-trimethoxyphenyl) -2-propen-1-one (2 -29-29 ).).

노란색 결정; 수율 62%; IR (KBr) 3360, 1660 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.87 (1H, s), 9.41 (1H, s), 7.81 (1H, d,J= 14.49 Hz), 7.56 (1H, d,J= 14.92 Hz), 7.17 (1H, d,J= 2.21 Hz), 7.05-6.99 (2H, m), 6.78-6.52 (2H, m), 3.85 (3H, s), 3.83 (3H, s), 3.79 (3H, s).Yellow crystals; Yield 62%; IR (KBr) 3360, 1660 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.87 (1H, s), 9.41 (1H, s), 7.81 (1H, d, J = 14.49 Hz), 7.56 (1H, d, J = 14.92 Hz) , 7.17 (1H, d, J = 2.21 Hz), 7.05-6.99 (2H, m), 6.78-6.52 (2H, m), 3.85 (3H, s), 3.83 (3H, s), 3.79 (3H, s ).

(E)-1-(2,5-디히드록시페닐)-3-(2,4,5-트리메톡시페닐)-2-프로펜-1-온(E) -1- (2,5-dihydroxyphenyl) -3- (2,4,5-trimethoxyphenyl) -2-propen-1-one (2(2 -30-30 ).).

노란색 결정; 수율 76%; IR (KBr) 3330, 1650 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.03 (1H, s), 9.37 (1H, s), 7.88 (1H, d,J= 15.11 Hz), 7.34 (1H, d,J= 15.11 Hz), 7.15 (1H, d,J= 2.07 Hz), 7.00-6.85 (2H, m), 6.73-6.52 (2H, m), 3.86 (3H, s), 3.84 (3H, s), 3.81 (3H, s).Yellow crystals; Yield 76%; IR (KBr) 3330, 1650 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.03 (1H, s), 9.37 (1H, s), 7.88 (1H, d, J = 15.11 Hz), 7.34 (1H, d, J = 15.11 Hz) , 7.15 (1H, d, J = 2.07 Hz), 7.00-6.85 (2H, m), 6.73-6.52 (2H, m), 3.86 (3H, s), 3.84 (3H, s), 3.81 (3H, s ).

(E)-1-(2,5-디히드록시페닐)-3-(2,4,6-트리메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,4,6-trimethoxyphenyl) -2-propen-1-one (2 -31-31 ).).

노란색 결정; 수율 46%; IR (KBr) 3340, 1660 cm-1;1H-NMR (DMSO-d 6, 90MHz) 12.00 (1H, s), 9.12 (1H, s), 7.77 (1H, d,J= 15.39 Hz), 7.28 (1H, d,J= 2.12 Hz), 7.11-6.81 (2H, m), 6.76 (2H, s), 3.82 (3H, s), 3.81 (3H, s), 3.79 (3H, s).Yellow crystals; Yield 46%; IR (KBr) 3340, 1660 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.00 (1H, s), 9.12 (1H, s), 7.77 (1H, d, J = 15.39 Hz), 7.28 (1H, d, J = 2.12 Hz), 7.11-6.81 (2H, m), 6.76 (2H, s), 3.82 (3H, s), 3.81 (3H, s), 3.79 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(3,4,5-트리메톡시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (3,4,5-trimethoxyphenyl) -2-propen-1-one (2 -32-32 ).).

노란색 결정; 수율 65%; m.p. 188-191 ℃; IR (KBr) 3360, 1680 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.93 (1H, s), 9.23 (1H, s), 8.00-7.54 (3H, m), 7.33 (2H, s), 7.04 (1H, d,J= 2.75 Hz), 6.88 (1H, d,J= 8.84 Hz), 3.86 (6H, s), 3.81 (3H, s).Yellow crystals; Yield 65%; mp 188-191 ° C; IR (KBr) 3360, 1680 cm -1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.93 (1H, s), 9.23 (1H, s), 8.00-7.54 (3H, m), 7.33 (2H, s), 7.04 (1H, d, J = 2.75 Hz), 6.88 (1H, d, J = 8.84 Hz), 3.86 (6H, s), 3.81 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(2,3-디히드록시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,3-dihydroxyphenyl) -2-propen-1-one (2 -33-33 ).).

노란색 결정; 수율 55%; m.p. 145-148 ℃; IR (KBr) 3380, 1680 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.21 (1H, s), 9.32 (1H, s), 8.87 (2H, br), 7.89 (1H, d,J= 14.51 Hz), 7.32-7.05 (3H, m), 7.00-6.81 (3H, m), 6.56 (1H, d,J= 14.51 Hz).Yellow crystals; Yield 55%; mp 145-148 ° C; IR (KBr) 3380, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.21 (1H, s), 9.32 (1H, s), 8.87 (2H, br), 7.89 (1H, d, J = 14.51 Hz), 7.32-7.05 ( 3H, m), 7.00-6.81 (3H, m), 6.56 (1H, d, J = 14.51 Hz).

(E)-1-(2,5-디히드록시페닐)-3-(2,4-디히드록시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,4-dihydroxyphenyl) -2-propen-1-one (2 -34-34 ).).

노란색 결정; 수율 27%; m.p. 110-114℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.97 (1H, s), 9.08 (1H, s), 7.85 (1H, d,J= 15.91 Hz),7.34 (1H, d,J= 15.91 Hz), 7.17-6.84 (3H, m), 6.75-6.57 (3H, m).Yellow crystals; Yield 27%; mp 110-114 ° C .; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.97 (1H, s), 9.08 (1H, s), 7.85 (1H, d, J = 15.91 Hz), 7.34 (1H, d, J = 15.91 Hz) , 7.17-6.84 (3H, m), 6.75-6.57 (3H, m).

(E)-1-(2,5-디히드록시페닐)-3-(2,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one (2 -35-35 ).).

1-38와 갑다.Going with 1 -38.

(E)-1-(2,5-디히드록시페닐)-3-(3,4-디히드록시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (3,4-dihydroxyphenyl) -2-propen-1-one (2 -36-36 ).).

노란색 결정; 수율 52%; m.p. 143-146℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.99 (1H, s), 9.27 (1H, s), 8.85 (2H, br), 7.78 (1H, d,J= 15.49 Hz), 7.31-6.88 (4H, m), 6.78-6.51 (3H, m).Yellow crystals; Yield 52%; mp 143-146 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.99 (1H, s), 9.27 (1H, s), 8.85 (2H, br), 7.78 (1H, d, J = 15.49 Hz), 7.31-6.88 ( 4H, m), 6.78-6.51 (3H, m).

(E)-1-(2,5-디히드록시페닐)-3-(3,5-디히드록시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (3,5-dihydroxyphenyl) -2-propen-1-one (2 -37-37 ).).

노란색 결정; 수율 49%; m.p. 138-141℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.01 (1H, s), 9.41 (1H, s), 8.97 (2H, br), 7.99 (1H, d,J= 14.57 Hz), 7.27 (1H, d,J= 14.57 Hz), 7.05-6.84 (3H, m), 6.78 (2H, s), 6.51 (1H, s).Yellow crystals; Yield 49%; mp 138-141 ° C .; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.01 (1H, s), 9.41 (1H, s), 8.97 (2H, br), 7.99 (1H, d, J = 14.57 Hz), 7.27 (1H, d, J = 14.57 Hz), 7.05-6.84 (3H, m), 6.78 (2H, s), 6.51 (1H, s).

(E)-1-(2,5-디히드록시페닐)-3-[(2-히드록시-5-메톡시)페닐]-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3-[(2-hydroxy-5-methoxy) phenyl] -2-propen-1-one (2 -38-38 ).).

노란색 결정; 수율 78 %; m.p. 174-178 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.12 (1H, s), 9.34 (1H, s), 8.84 (1H, br), 7.98 (1H, d,J= 16.01 Hz), 7.42 (1H, d,J= 16.01 Hz), 7.12-6.75 (3H, m), 6.73-6.51 (3H, s), 3.78 (3H, s).Yellow crystals; Yield 78%; mp 174-178 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.12 (1H, s), 9.34 (1H, s), 8.84 (1H, br), 7.98 (1H, d, J = 16.01 Hz), 7.42 (1H, d, J = 16.01 Hz), 7.12-6.75 (3H, m), 6.73-6.51 (3H, s), 3.78 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-[(4-히드록시-3-메톡시)페닐]-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3-[(4-hydroxy-3-methoxy) phenyl] -2-propen-1-one (2 -39-39 ).).

노란색 결정; 수율 66%; m.p. 153-156 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.27 (1H, s), 9.18 (1H, s), 8.87 (1H, br), 8.01 (1H, d,J= 15.49 Hz), 7.34 (1H, d,J= 15.49 Hz), 7.21-6.84 (3H, m), 6.74-6.55 (3H, s), 3.79 (3H, s).Yellow crystals; Yield 66%; mp 153-156 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.27 (1H, s), 9.18 (1H, s), 8.87 (1H, br), 8.01 (1H, d, J = 15.49 Hz), 7.34 (1H, d, J = 15.49 Hz), 7.21-6.84 (3H, m), 6.74-6.55 (3H, s), 3.79 (3H, s).

(E)-1-(2,5-디히드록시페닐)-3-(3,4-메틸렌디옥시페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (3,4-methylenedioxyphenyl) -2-propen-1-one (2 -40-40 ).).

노란색 결정; 수율 85%; m.p. 115-118 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.02 (1H, s), 9.88 (1H, s), 7.85 (1H, d,J= 15.51 Hz), 7.56 (1H, s), 7.51 (1H, d,J= 2.24 Hz), 7.34 (1H, d,J= 15.51 Hz), 7.11 (1H, dd,J= 2.24, 8.33 Hz), 6.98 (1H, d,J= 8.12 Hz), 6.75 (1H, d,J= 8.33 Hz), 6.69 (1H, dd,J= 8.12 Hz), 5.91 (2H, s).Yellow crystals; Yield 85%; mp 115-118 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.02 (1H, s), 9.88 (1H, s), 7.85 (1H, d, J = 15.51 Hz), 7.56 (1H, s), 7.51 (1H, d, J = 2.24 Hz), 7.34 (1H, d, J = 15.51 Hz), 7.11 (1H, dd, J = 2.24, 8.33 Hz), 6.98 (1H, d, J = 8.12 Hz), 6.75 (1H, d, J = 8.33 Hz), 6.69 (1H, dd, J = 8.12 Hz), 5.91 (2H, s).

(E)-1-(2,5-디히드록시페닐)-3-(4-페닐페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (4-phenylphenyl) -2-propen-1-one (2 -41-41 ).).

노란색 결정; 수율 68%; m.p. 147-150 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR(DMSO-d 6, 90 MHz) 11.97 (1H, s), 10.01 (1H, s), 7.91 (1H, d,J= 15.24 Hz), 7.51-22 (10H, m), 7.13-6.84 (3H, m).Yellow crystals; Yield 68%; mp 147-150 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.97 (1H, s), 10.01 (1H, s), 7.91 (1H, d, J = 15.24 Hz), 7.51-22 (10H, m), 7.13- 6.84 (3 H, m).

(E)-1-(2,5-디히드록시페닐)-3-(4-메틸설포닐페닐)-2-프로펜-1-온 (2(E) -1- (2,5-dihydroxyphenyl) -3- (4-methylsulfonylphenyl) -2-propen-1-one (2 -42-42 ).).

황색 결정, 수율 56%; m.p. 174-176 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.53 (1H, s), 9.25 (1H, s), 8.18 (1H, d,J= 15.10 Hz), 8.09-8.02 (2H, m), 7.87-7.64 (3H, m), 7.48 (1H, d,J= 2.12 Hz), 7.03 (1H, dd,J= 2.12, 8.81 Hz), 6.91 (1H, d,J= 8.81 Hz), 3.26 (3H, s).Yellow crystals, yield 56%; mp 174-176 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.53 (1H, s), 9.25 (1H, s), 8.18 (1H, d, J = 15.10 Hz), 8.09-8.02 (2H, m), 7.87- 7.64 (3H, m), 7.48 (1H, d, J = 2.12 Hz), 7.03 (1H, dd, J = 2.12, 8.81 Hz), 6.91 (1H, d, J = 8.81 Hz), 3.26 (3H, s ).

실시예 3: 일반식(Ic1)의 2-브로모-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜Example 3: 2-bromo-1- (2,5-dihydroxyphenyl) -3-phenyl-2-propene of general formula (Ic1)

-1-온유도체의 제조(공통적 제조법)-1-Production of hot derivatives (common manufacturing method)

1-(2,5-디히드록시페닐)-3-(치환) 페닐-2-프로펜-1-온 (2mmol)을 사염화탄소Carbon tetrachloride 1- (2,5-dihydroxyphenyl) -3- (substituted) phenyl-2-propene-1-one (2 mmol)

(20ml)에 용해시키고 여기에 브롬 2mmol을 용해한 사염화탄소 (5ml) 용액을 45분에 걸쳐 적가한다. 반응액을 감압 하에서 증발 건조한다. 이 건조물을 에탄올 (10 ml)에 용해시키고 여기에 28% 암모니수 1.5 ml를 가하고 3시간 동안 교반하였다. 반응 후 반응물은 감압 하에 농축하고 이 농축물에 물 20 ml를 가한 다음 초산에칠 30ml씩으로 3회 추출하였다. 초산 에칠 추출물은 무수 망초로 탈수한 다음 건조하였다. 건조물은 물성에 따라 재결정화든지 실리카겔 칼럼 상에서 초산에칠-헥산으로 분획하여 정제하였다.(20 ml) and a carbon tetrachloride (5 ml) solution containing 2 mmol of bromine was added dropwise over 45 minutes. The reaction solution is evaporated to dryness under reduced pressure. This dry matter was dissolved in ethanol (10 ml) and 1.5 ml of 28% ammonia water was added thereto and stirred for 3 hours. After the reaction, the reaction mixture was concentrated under reduced pressure, and 20 ml of water was added to the concentrate, followed by extraction three times with 30 ml of ethyl acetate. Acetyl acetate extract was dehydrated with anhydrous forget-me-not and dried. The dried product was purified by recrystallization or fractionation with ethyl acetate-hexane on a silica gel column depending on physical properties.

실시예 3에 의하여 합성한 물질과 그들의 물성을 다음과 같았다.The materials synthesized according to Example 3 and their physical properties were as follows.

(Z)-2-브로모-3-(2-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (3-1).(Z) -2-bromo-3- (2-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (3-1).

적색결정, 수율 23%; m.p. 111-113 ℃; IR (KBr) 3340, 1660 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.33 (1H, s), 8.31-7.25 (3H, m), 7.19-7.07 (3H, m), 7.00-6.88 (2H, m).Red crystals, yield 23%; mp 111-113 ° C; IR (KBr) 3340, 1660 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.33 (1H, s), 8.31-7.25 (3H, m), 7.19-7.07 (3H, m), 7.00-6.88 (2H, m).

(Z)-2-브로모-3-(3-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (3-2).(Z) -2-bromo-3- (3-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (3-2).

적색 결정, 수율 31%; m.p. 121-123 ℃; IR (KBr) 3380, 1650 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 8.11 (1H, s), 7.35-7.27 (2H, m), 7.07-7.22 (3H, m), 6.85-6.97 (2H, m).Red crystals, yield 31%; mp 121-123 ° C; IR (KBr) 3380, 1650 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 8.11 (1H, s), 7.35-7.27 (2H, m), 7.07-7.22 (3H, m), 6.85-6.97 (2H, m).

(Z)-2-브로모-3-(4-클로로페닐)-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (3-3).(Z) -2-bromo-3- (4-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-propen-1-one (3-3).

적색 결정, 수율 31%; m.p. 109-111 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.21 (1H, H-, s), 7.75-7.71 (2H, H-2, H-6, m), 7.48-7.42 (3H, H-6, H-3, H-5, m), 7.05 (1H, H-4, dd,J= 7.88, 2.01 Hz), 6.84 (1H, H-3, d,J= 7.88 Hz).Red crystals, yield 31%; mp 109-111 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.21 (1H, H-, s), 7.75-7.71 (2H, H-2, H-6, m), 7.48-7.42 (3H, H-6, H-3, H-5, m), 7.05 (1H, H-4, dd, J = 7.88, 2.01 Hz), 6.84 (1H, H-3, d, J = 7.88 Hz).

실시예 4: 일반식(Ic2)의(Z)-3-(2-페닐)-2-시아노-1-(2,5-디벤질옥시페닐)-2-프로펜-1-온 유도체의 합성(공통적 제조법)Example 4 of (Z) -3- (2-phenyl) -2-cyano-1- (2,5-dibenzyloxyphenyl) -2-propen-1-one derivative of formula (Ic2) Synthesis (common recipe)

2-시아노-2,5-디벤질옥시아세토페논 (1.21 g, 3.3 mmol) 과 치환된 벤즈알데히드 (0.46 g, 3.3 mmol)의 혼합물을 에탄올(10 mL)에 용해시키고 여기에 트리에칠 아민(0.2 mL)을 가하고 3시간 실온에서 교반한다. 반응물에 물(10 mL)을 가하고 방치한 후 생성된 고형물을 여과하여 사용한다.A mixture of 2-cyano-2,5-dibenzyloxyacetophenone (1.21 g, 3.3 mmol) and substituted benzaldehyde (0.46 g, 3.3 mmol) was dissolved in ethanol (10 mL) and triethylamine ( 0.2 mL) is added and stirred at room temperature for 3 hours. Water (10 mL) is added to the reaction, and the resulting solid is filtered.

이 고형물을 아세토니트릴 (15ml)에 용해시키고 여기에 NaI (3mmol)을 가하고 30분간 교반한다. 이 반응액에 트리에칠실릴 클로라이드(0.5ml)를 가하고 실온에서 18시간 동안 교반한다. 반응이 끝나면 물10 ml를 가한 후 초산에칠로 추출한다. 초산에칠 용액은 무수망초로 탈수한 다음 증발 농축하였다. 농축물은 실리카겔 칼럼상에서 초산에칠-헥산으로 정제하였다.This solid is dissolved in acetonitrile (15 ml), to which NaI (3 mmol) is added and stirred for 30 minutes. Triethylsilyl chloride (0.5 ml) is added to the reaction solution, and the mixture is stirred at room temperature for 18 hours. After the reaction, 10 ml of water is added and extracted with ethyl acetate. The ethyl acetate solution was dehydrated with anhydrous forget-me-not and concentrated by evaporation. The concentrate was purified by ethyl acetate-hexanes on silica gel column.

실시예 4에 의하여 합성한 물질과 그들의 물성은 다음과 같았다.The materials synthesized according to Example 4 and their physical properties were as follows.

(Z)-3-(2-클로로페닐)-2-시아노-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (4-1).(Z) -3- (2-chlorophenyl) -2-cyano-1- (2,5-dihydroxyphenyl) -2-propen-1-one (4-1).

황색 결정, 수율 43%; m.p. 223-225 ℃; IR (KBr) 3350, 2240, 1680 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 8.07 (1H, s), 7.75-7.43 (4H, m), 7.00 (1H, d,J= 8.21 Hz), 7.00 (1H, dd,J= 8.21, 2.21 Hz), 6.85 (1H, d,J= 2.21 Hz).Yellow crystals, yield 43%; mp 223-225 ° C; IR (KBr) 3350, 2240, 1680 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 8.07 (1H, s), 7.75-7.43 (4H, m), 7.00 (1H, d, J = 8.21 Hz), 7.00 (1H, dd, J = 8.21 , 2.21 Hz), 6.85 (1H, d, J = 2.21 Hz).

(Z)-3-(3-클로로페닐)-2-시아노-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (4-2).(Z) -3- (3-chlorophenyl) -2-cyano-1- (2,5-dihydroxyphenyl) -2-propen-1-one (4-2).

황색 결정, 수율 31% ; m.p. 199-201 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR(DMSO-d 6, 90 MHz) 7.97 (1H, s), 7.41 (1H, s), 7.25-7.13 (2H, m), 7.08 (1H, s), 7.00-6.84 (2H, m).Yellow crystals, yield 31%; mp 199-201 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.97 (1H, s), 7.41 (1H, s), 7.25-7.13 (2H, m), 7.08 (1H, s), 7.00-6.84 (2H, m ).

(Z)-3-(4-클로로페닐)-2-시아노-1-(2,5-디히드록시페닐)-2-프로펜-1-온 (4-3).(Z) -3- (4-chlorophenyl) -2-cyano-1- (2,5-dihydroxyphenyl) -2-propen-1-one (4-3).

황색 결정, 수율 27% ; m.p. 157-159 ℃; IR (KBr) 3340, 1640 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.93 (1H, s), 7.39 (2H, d,J=7.38 Hz), 7.26 (2H, d,J= 7.26 Hz), 7.11 (1H, s), 6.97-6.81 (2H, m).Yellow crystals, yield 27%; mp 157-159 ° C; IR (KBr) 3340, 1640 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.93 (1H, s), 7.39 (2H, d, J = 7.38 Hz), 7.26 (2H, d, J = 7.26 Hz), 7.11 (1H, s) , 6.97-6.81 (2H, m).

실시예 5: 일반식(Ic3)의 1-(2,5-디히드록시페닐)-2-메틸-3-페닐-2-프로펜-1-온 유도체의 제조(공통적 제조법)Example 5: Preparation of 1- (2,5-dihydroxyphenyl) -2-methyl-3-phenyl-2-propen-1-one derivative of general formula (Ic3) (common method)

건조 에탄올(30 mL) 내의 2,5-디히드록시프로피오페논(0.49 g, 3 mmol), 치환된 벤즈알데히드 (0.44 g, 3 mmol), 피페리딘(10 mL), 및 아세트산(5 mL)의 용액을 환류하여 가열시켰다. 에탄올은 Soxhlet 장치의 사용에 의해 4-Ao 분자체르 통해 증류물을 통과시킴으로써 건조시켰다. 18시간 후, 용매를 제거시키고, 잔류물은 용리제로서 헥산 내의 25% EA를 사용하여 섬광 실리카겔 칼럼 상에서 크로마토그래피시켰다. 생성물을 에테르로부터 결정화시켰다.2,5-dihydroxypropiophenone (0.49 g, 3 mmol), substituted benzaldehyde (0.44 g, 3 mmol), piperidine (10 mL), and acetic acid (5 mL) in dry ethanol (30 mL) The solution of was heated to reflux. Ethanol was dried by passing distillate through a 4-Ao molecular sieve by use of a Soxhlet apparatus. After 18 hours, the solvent was removed and the residue was chromatographed on flash silica gel column using 25% EA in hexane as eluent. The product was crystallized from ether.

실시예 5에 의해 합성한 물질과 그 물성은 다음과 같았다.The material synthesized in Example 5 and its physical properties were as follows.

(1)(E)-3-(2-클로로페닐)-1-(2,5-디히드록시페닐)-2-메틸-2-프로펜-1-온 (5-1)(1) (E) -3- (2-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-methyl-2-propen-1-one (5-1)

수율 70%; m.p. 147-149 ℃; IR (KBr) 3360, 1670 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 7.56-7.38 (2H, m), 7.31-7.15 (2H, m), 7.11 (1H, s, br), 6.85-6.50 (3H, m), 2.25 (3H, br, s).Yield 70%; mp 147-149 ° C; IR (KBr) 3360, 1670 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 7.56-7.38 (2H, m), 7.31-7.15 (2H, m), 7.11 (1H, s, br), 6.85-6.50 (3H, m), 2.25 (3H, br, s).

(2)(E)-3-(3-클로로페닐)-1-(2,5-디히드록시페닐)-2-메틸-2-프로펜-1-온 (5-2).(2) (E) -3- (3-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-methyl-2-propen-1-one (5-2).

적색 결정; 수율 71%; m.p. 125-127 ℃; IR (KBr) 3400, 1660 cm-1;1H-NMR (DMSO-d 6, 90 0MHz) 7.67-7.45 (2H, m), 7.33-7.19 (2H, m), 7.18 (1H, s, br), 6.88-6.62 (2H, m), 6.45 (1H, d,J= 2.15 Hz), 2.31 (3H, br, s).Red crystals; Yield 71%; mp 125-127 ° C; IR (KBr) 3400, 1660 cm - 1; 1 H-NMR (DMSO- d 6 , 90 0 MHz) 7.67-7.45 (2H, m), 7.33-7.19 (2H, m), 7.18 (1H, s, br), 6.88-6.62 (2H, m), 6.45 (1H, d, J = 2.15 Hz), 2.31 (3H, br, s).

(E)-3-(4-클로로페닐)-1-(2,5-디히드록시페닐)-2-메틸-2-프로펜-1-온 (5-3).(E) -3- (4-chlorophenyl) -1- (2,5-dihydroxyphenyl) -2-methyl-2-propen-1-one (5-3).

수율 85%; m.p. 138-140 ℃; IR (KBr) 3420, 1650 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 7.73-7.67 (2H, m), 7.51-7.39 (3H, m), 7.11 (1H, dd,J= 7.98, 2.21 Hz), 7.09 (1H, s, br), 6.87 (1H, d,J= 7.98 Hz), 2.27 (2H, s, br).Yield 85%; mp 138-140 ° C; IR (KBr) 3420, 1650 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 7.73-7.67 (2H, m), 7.51-7.39 (3H, m), 7.11 (1H, dd, J = 7.98, 2.21 Hz), 7.09 (1H, s , br), 6.87 (1H, d, J = 7.98 Hz), 2.27 (2H, s, br).

실시예 6: 일반식(Id)의 1,4,5-트리페닐-2,4-펜탄디엔-1-온 유도체의 제조(공통적 제조법)Example 6: Preparation of 1,4,5-triphenyl-2,4-pentanedien-1-one derivative of general formula (Id) (Common Preparation)

(1) (E)-3-(R3-페닐)-2-(R4-페닐)아크릴산(중간체-1).(1) (E) -3- (R 3 -phenyl) -2- (R 4 -phenyl) acrylic acid (intermediate-1).

R4로 치환된 페닐 아세트산(30.0 g, 0.13 mol), R3로 치환된 벤즈알데히드(18.9 g, 0.13 mol), 및 트리에틸아민 (20 mL)을 무수초산(100 mL)에 가하여 용해시키고 140 ℃ 에서 12시간 가열하였다. 반응물은 감압 농축하였다. 생성물에 1N-NaOH 50 ml를 가하고 30분 가온한 다음 초산으로 산성화하였다. 이 용액은 메티렌클로라이드 100 ml씩으로 3번 추출하였다. 추출액은 무수망초를 가하여 탈수한 다음 증발 건조시켰다. 잔류물은 초산에칠-헥산 혼합액에서 재결정하여 E)-3-(R3-페닐)-2-(R4-페닐)아크릴산(중간체-1)을 얻었다. 백색결정, 수율; 16.5 g (36%):1H-NMR (DMSO-d 6, 300 MHz)Phenyl acetic acid (30.0 g, 0.13 mol) substituted with R 4 , benzaldehyde (18.9 g, 0.13 mol) substituted with R 3 , and triethylamine (20 mL) were added to acetic anhydride (100 mL) to dissolve and 140 ° C. Heated for 12 h. The reaction was concentrated under reduced pressure. 50 ml of 1N-NaOH was added to the product, warmed for 30 minutes, and then acidified with acetic acid. This solution was extracted three times with 100 ml of methylene chloride. The extract was dehydrated by adding anhydrous forage and then evaporated to dryness. The residue was recrystallized in an ethyl acetate-hexane mixture to obtain E) -3- (R 3 -phenyl) -2- (R 4 -phenyl) acrylic acid (intermediate-1). White crystals, yield; 16.5 g (36%): 1 H-NMR (DMSO- d 6 , 300 MHz)

(2) (E)-메틸 3-(R3-페닐)-2-(R4-페닐)아크릴레이트 (중간체-2).(2) (E) -methyl 3- (R 3 -phenyl) -2- (R 4 -phenyl) acrylate (intermediate-2).

상기 중간체-1(6.5 g, 18.2 mmol) 을 디메틸폼아마이드 (60 mL)에 용해시키고 여기에 K2CO3(6.5 g, 47.1 mmol) 및 메틸아이오다이드(1.35 mL, 21.8 mmol)를 가하고 실온에서 3시간 교반하였다. 반응물은 여과하고 여액을 증발건조하였다. 잔류물은 초산에칠 50 ml에 녹이고 물로 세척한 다음 무수망초로 탈수하고 증발 건조하여 (E)-메틸 3-(R3-페닐)-2-(R4-페닐)아크릴레이트 (중간체-2)를 얻었다.The intermediate-1 (6.5 g, 18.2 mmol) was dissolved in dimethylformamide (60 mL), to which K 2 CO 3 (6.5 g, 47.1 mmol) and methyl iodide (1.35 mL, 21.8 mmol) were added and room temperature Stirred for 3 hours. The reaction was filtered and the filtrate was evaporated to dryness. The residue was dissolved in 50 ml of ethyl acetate, washed with water, dehydrated with anhydrous forget-me-not and evaporated to dryness (E) -methyl 3- (R 3 -phenyl) -2- (R 4 -phenyl) acrylate (Intermediate-2). )

(3) (E)-3-(R3-페닐)-2-(R4-페닐)-프로프-2-엔-1-올 (중간체-3).(3) (E) -3- (R 3 -phenyl) -2- (R 4 -phenyl) -prop-2-en-1-ol (intermediate-3).

상기 중간체-2 (10.5 g, 29.3 mmol)를 테트라하이드로퓨란 (60 mL)에 용해시켜 0 ℃ 로 냉각시키고 여기에 1.0 M LiAlH4-THF (30 mL, 30 mmol )을 소량씩 가한다. .0 ℃에서 1시간 반응시킨 다음 식염수 50 ml에 가하고 메칠렌클로라이드(MC)로 추출하였다. MC추출물은 무수망초로 탈수한 다음 증발 건조하였다. 잔류물은 실리카겔 칼럼에서 초산에칠 및 헥산으로 정제하여 (E)-3-(R3-페닐)-2-(R4-페닐)-프로프-2-엔-1-올 (중간체-3)을 얻었다. 무색의 유상 물질l (6.0 g, 18.2 mmol, 62%):1H-NMR (DMSO-d 6, 300 MHz)Intermediate-2 (10.5 g, 29.3 mmol) is dissolved in tetrahydrofuran (60 mL), cooled to 0 ° C. and 1.0 M LiAlH 4 -THF (30 mL, 30 mmol) is added in small portions. The mixture was reacted at 0 ° C. for 1 hour, and then added to 50 ml of brine, and extracted with methylene chloride (MC). MC extract was dehydrated with anhydrous forget-me-not and evaporated to dryness. The residue was purified by ethyl acetate and hexane on a silica gel column to give (E) -3- (R 3 -phenyl) -2- (R 4 -phenyl) -prop-2-en-1-ol (intermediate-3). ) Colorless oily substance (6.0 g, 18.2 mmol, 62%): 1 H-NMR (DMSO- d 6 , 300 MHz)

(4) (E)-3-(R3-페닐)-2-(R4-페닐)프로페날(중간체-4).(4) (E) -3- (R 3 -phenyl) -2- (R 4 -phenyl) propenal (intermediate-4).

상기 중간체-3 (2.5 g, 7.6 mmol)을 MC (25 mL)에 용해시키고 여기에 MnO2(20 g)를 가하고 실온에서 2시간 교반하였다. 반응물은 여과한 다음 여액을 증발 건조하였다. 잔류물은 실리카겔 칼럼에서 초산에칠-헥산으로 정제하여 (E)-3-(R3-페닐)-2-(R4-페닐)프로페날(중간체-4)을 얻었다. 초산에칠-헥산에서 무색결정(1.71 g, 5.2 mmol, 68%), mp 109-110 ℃;1H-NMR (DMSO-d 6, 300 MHz)The intermediate-3 (2.5 g, 7.6 mmol) was dissolved in MC (25 mL), to which MnO 2 (20 g) was added and stirred at room temperature for 2 hours. The reaction was filtered and the filtrate was evaporated to dryness. The residue was purified by ethyl acetate-hexane on a silica gel column to give (E) -3- (R 3 -phenyl) -2- (R 4 -phenyl) propenal (intermediate-4). Colorless crystals (1.71 g, 5.2 mmol, 68%) in ethyl acetate-hexane, mp 109-110 ° C .; 1 H-NMR (DMSO- d 6 , 300 MHz)

(5) 1,4,5-트리페닐-2,4-펜탄디엔-1-온 유도체의 제조(5) Preparation of 1,4,5-triphenyl-2,4-pentanedien-1-one derivative

실시예 1에서 얻은 중간체인 2,5-비스(테트라히드로피란-2-일옥시)아세토페논(25 mmol), 상기 중간체-4(25 mmol) 및 수산화 바륨 옥타하이드레이트 (25 mmol)을 혼합하고 여기에 메탄올(100 mL)에 가하고 40℃에서 12시간 반응시킨다. 반응 후 감압 하에서 메탄올을 날려 보내고 남은 찌꺼기에 물을 가한 후 1N염산으로 중화한다. 중성용액은 메칠렌 클로라이드로 추출하고 합한 추출액은 건조용 망초로 탈수한 다음 증발 건조시킨다.2,5-bis (tetrahydropyran-2-yloxy) acetophenone (25 mmol), the intermediate obtained in Example 1, the intermediate-4 (25 mmol) and barium octahydrate (25 mmol) were mixed and To methanol (100 mL) and reacted at 40 ° C for 12 hours. After the reaction, methanol is blown out under reduced pressure, water is added to the remaining residue, and neutralized with 1N hydrochloric acid. The neutral solution is extracted with methylene chloride and the combined extracts are dehydrated with a dry forget-me-not and evaporated to dryness.

이 잔류 물질과p-톨루엔설폰산 (0.2 g, 1.05 mmol)을 메탄올(100 mL)에 용해시키고 실온에서 4시간 반응시켰다. 반응물질로부터 메탄올을 날려 보내고 남은 것에 물 100ml를 가한 후 5% NaHCO3로 중화하였다. 중화용액은 초산에칠로 추출하고 건조용 망초로 탈수시킨 후 증발 건조하였다. 남은 고형 물질을 실리카겔 칼럼상에서 헥산-초산에칠(4:1)로 크로마토그래피하여 정제하여 표제화합물을 얻었다.This residue and p -toluenesulfonic acid (0.2 g, 1.05 mmol) were dissolved in methanol (100 mL) and reacted at room temperature for 4 hours. Methanol was blown off from the reaction and 100 ml of water was added to the residue and neutralized with 5% NaHCO 3 . The neutralized solution was extracted with ethyl acetate, dehydrated with a dry forget-me-not and evaporated to dryness. The remaining solid material was purified by chromatography on silica gel column with hexane-ethyl acetate (4: 1) to afford the title compound.

실시예 6에 의하여 합성한 물질과 그들의 물성을 다음에 기술하였다.The materials synthesized according to Example 6 and their physical properties are described below.

all-트랜스-1-(2,5-디히드록시페닐)-5-(4-메톡시페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-1).all-trans-1- (2,5-dihydroxyphenyl) -5- (4-methoxyphenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1 -On (6-1).

수율 71%; IR (KBr) 3340, 1640 cm-1; 1H-NMR (DMSO-d 6, 300 MHz) 11.76 1H, s), 9.19 (1H, s), 7.81 (1H, d,J= 14.91 Hz), 7.24 (1H, s), 6.96 (2H, dd,J= 8.85, 2.12 Hz), 6.95-6.89 (3H, m), 6.83 (2H, dd,J= 8.86, 2.12 Hz), 6.64 (1H, d,J= 14.91 Hz), 6.49 (2H, s), 3.82 (3H, s), 3.81 (3H, s), 3.73 (6H, s).Yield 71%; IR (KBr) 3340, 1640 cm -1; 1 H-NMR (DMSO- d 6 , 300 MHz) 11.76 1H, s), 9.19 (1H, s), 7.81 (1H, d, J = 14.91 Hz), 7.24 (1H, s), 6.96 (2H, dd , J = 8.85, 2.12 Hz), 6.95-6.89 (3H, m), 6.83 (2H, dd, J = 8.86, 2.12 Hz), 6.64 (1H, d, J = 14.91 Hz), 6.49 (2H, s) , 3.82 (3H, s), 3.81 (3H, s), 3.73 (6H, s).

all-트랜스-1-(2,5-디히드록시페닐)-4-(4-메톡시페닐)-5-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-2).all-trans-1- (2,5-dihydroxyphenyl) -4- (4-methoxyphenyl) -5- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1 -On (6-2).

적색 결정; IR (KBr) 3360, 1660 cm-1;1H-NMR (DMSO-d 6, 300 MHz) 11.51 1H, s), 9.19 (1H, s), 7.82 (1H, d,J= 14.85 Hz), 7.22 (1H, s), 7.19 (2H, dd,J= 8.88, 2.15 Hz), 6.96 (1H, dd,J= 8.15, 2.04 Hz), 6.87 (1H, d,J= 2.04 Hz), 6.86 (1H, d,J= 8.15 Hz), 6.79 (2H, dd,J= 8.88, 2.15 Hz), 6.63 (1H, d,J= 14.85 Hz), 6.35 (2H, s), 3.82 (3H, s), 3.62 (3H, s), 3.49 (6H, s).Red crystals; IR (KBr) 3360, 1660 cm −1 ; 1 H-NMR (DMSO- d 6 , 300 MHz) 11.51 1H, s), 9.19 (1H, s), 7.82 (1H, d, J = 14.85 Hz), 7.22 (1H, s), 7.19 (2H, dd , J = 8.88, 2.15 Hz), 6.96 (1H, dd, J = 8.15, 2.04 Hz), 6.87 (1H, d, J = 2.04 Hz), 6.86 (1H, d, J = 8.15 Hz), 6.79 (2H , dd, J = 8.88, 2.15 Hz), 6.63 (1H, d, J = 14.85 Hz), 6.35 (2H, s), 3.82 (3H, s), 3.62 (3H, s), 3.49 (6H, s) .

all-트랜스-1-(2,5-디히드록시페닐)-4-(3,4-디메톡시페닐)-5-(4-메톡시페닐)-2,4-펜탄디엔-1-온 (6-3).all-trans-1- (2,5-dihydroxyphenyl) -4- (3,4-dimethoxyphenyl) -5- (4-methoxyphenyl) -2,4-pentanedien-1-one ( 6-3).

적색 결정; IR (KBr) 3350, 1660 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.68 (1H, s), 9.37 (1H, s), 7.81 (1H, d,J= 15.21 Hz), 7.35-7.21 (3H, m), 7.11-6.89 (4H, m), 6.84-6.66 (4H, m), 6.61 (1H, s), 3.84 (3H, s), 3.82 (3H, s), 3.79 (3H, s).Red crystals; IR (KBr) 3350, 1660 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.68 (1H, s), 9.37 (1H, s), 7.81 (1H, d, J = 15.21 Hz), 7.35-7.21 (3H, m), 7.11- 6.89 (4H, m), 6.84-6.66 (4H, m), 6.61 (1H, s), 3.84 (3H, s), 3.82 (3H, s), 3.79 (3H, s).

all-트랜스-1-(2,5-디히드록시페닐)-4-(4-메톡시페닐)-5-(4-메톡시페닐)-2,4-펜탄디엔-1-온 (6-4).all-trans-1- (2,5-dihydroxyphenyl) -4- (4-methoxyphenyl) -5- (4-methoxyphenyl) -2,4-pentanedien-1-one (6- 4).

적색결정;1H-NMR (DMSO-d 6, 90 MHz) 11.87 (1H, s), 9.21 (1H, s), 7.78 (1H, d,J= 15.49 Hz), 7.35-7.21 (5H, m), 7.14 (1H, s), 6.87-6.71 (4H, m), 6.57 (1H, s), 3.87 (3H, s), 3.81 (3H, s).Red crystals; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.87 (1H, s), 9.21 (1H, s), 7.78 (1H, d, J = 15.49 Hz), 7.35-7.21 (5H, m), 7.14 ( 1H, s), 6.87-6.71 (4H, m), 6.57 (1H, s), 3.87 (3H, s), 3.81 (3H, s).

all-트랜스-1-(2,5-디히드록시페닐)-5-(4-메톡시페닐)-4-페닐-2,4-펜탄디엔-1-온 (6-5).all-trans-1- (2,5-dihydroxyphenyl) -5- (4-methoxyphenyl) -4-phenyl-2,4-pentanedien-1-one (6-5).

적색 결정,1H-NMR (DMSO-d6, 90 MHz) 12.01 (1H, s), 9.07 (1H, s), 7.82 (1H, d,J= 15.78 Hz), 7.47-7.23 (7H, m), 7.12 (1H, d,J= 2.11 Hz), 6.89-6.73 (4H, m), 6.62 (1H, s), 3.83 (3H, s).Red crystal, 1 H-NMR (DMSO-d 6 , 90 MHz) 12.01 (1H, s), 9.07 (1H, s), 7.82 (1H, d, J = 15.78 Hz), 7.47-7.23 (7H, m) , 7.12 (1H, d, J = 2.11 Hz), 6.89-6.73 (4H, m), 6.62 (1H, s), 3.83 (3H, s).

all-트랜스-1-(2,5-디히드록시페닐)-5-페닐-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-6).all-trans-1- (2,5-dihydroxyphenyl) -5-phenyl-4- (3,4,5-trimethoxyphenyl) -2,4-pentanedien-1-one (6-6 ).

적색 결정;1H-NMR (DMSO-d 6, 90 MHz) 11.98 (1H, s), 9.31 (1H, s), 7.92 (1H, d,J= 14.45 Hz), 7.51-7.21 (6H, m), 7.07 (1H, s), 6.89-6.73 (2H, m), 6.62 (1H, s), 6.52 (2H, s), 3.83 (6H, s), 3.79 (3H, s).Red crystals; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.98 (1H, s), 9.31 (1H, s), 7.92 (1H, d, J = 14.45 Hz), 7.51-7.21 (6H, m), 7.07 ( 1H, s), 6.89-6.73 (2H, m), 6.62 (1H, s), 6.52 (2H, s), 3.83 (6H, s), 3.79 (3H, s).

all-트랜스-1-(2,5-디히드록시페닐)-4-페닐-5-페닐-2,4-펜탄디엔-1-온 (6-7).all-trans-1- (2,5-dihydroxyphenyl) -4-phenyl-5-phenyl-2,4-pentanedien-1-one (6-7).

적색 결정; IR (KBr) cm-1;1H-NMR (DMSO-d 6, 90 MHz) 11.72 (1H, s), 9.24 (1H, s), 7.81 (1H, d,J= 15.59 Hz), 7.47-7.19 (11H, m), 7.11 (1H, s), 6.88-6.75 (2H, m), 6.58 (1H, s).Red crystals; IR (KBr) cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 11.72 (1H, s), 9.24 (1H, s), 7.81 (1H, d, J = 15.59 Hz), 7.47-7.19 (11H, m), 7.11 ( 1 H, s), 6.88-6.75 (2 H, m), 6.58 (1 H, s).

all-트랜스-1-(2,5-디히드록시페닐)-5-(4-eth옥시페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-8).all-trans-1- (2,5-dihydroxyphenyl) -5- (4-ethoxyphenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1 -On (6-8).

적색 결정 ; IR (KBr) 3330, 1660 cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.07 (1H, s), 9.21 (1H, s), 7.91 (1H, d,J= 14.58 Hz), 7.56-7.21 (5H, m), 7.09 (1H, d, J = 1.89 Hz), 6.94-6.81 (2H, m), 6.67 (1H, s), 6.51 (2H, s), 3.99(2H, d,J= 7.73 Hz), 1.28 (3H, t,J= 7.75 Hz), 3.88 (6H, s), 3.80 (3H, s).Red crystals; IR (KBr) 3330, 1660 cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.07 (1H, s), 9.21 (1H, s), 7.91 (1H, d, J = 14.58 Hz), 7.56-7.21 (5H, m), 7.09 ( 1H, d, J = 1.89 Hz), 6.94-6.81 (2H, m), 6.67 (1H, s), 6.51 (2H, s), 3.99 (2H, d, J = 7.73 Hz), 1.28 (3H, t , J = 7.75 Hz), 3.88 (6H, s), 3.80 (3H, s).

all-트랜스-1-(2,5-디히드록시페닐)-5-(4-클로로페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-9).all-trans-1- (2,5-dihydroxyphenyl) -5- (4-chlorophenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanediene-1- On (6-9).

적색 결정 ; IR (KBr) cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.33 (1H, s), 9.21 (1H, s), 7.98 (1H, s,J= 15.51 Hz), 7.71-7.17 (6H, m), 7.05-6.61 (4H, m), 6.38 (2H, s), 3.88 (6H, s), 3.81 (3H, s).Red crystals; IR (KBr) cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.33 (1H, s), 9.21 (1H, s), 7.98 (1H, s, J = 15.51 Hz), 7.71-7.17 (6H, m), 7.05- 6.61 (4H, m), 6.38 (2H, s), 3.88 (6H, s), 3.81 (3H, s).

all-트랜스-1-(2,5-디히드록시페닐)-5-(4-메틸페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-10).all-trans-1- (2,5-dihydroxyphenyl) -5- (4-methylphenyl) -4- (3,4,5-trimethoxyphenyl) -2,4-pentanedien-1-one (6-10).

적색 결정; IR (KBr) cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.21 (1H, s), 9.33 (1H, s), 7.88 (1H, s,J= 14.49 Hz), 7.76-7.12 (5H, m), 7.07-6.68 (5H, m), 6.41 (2H, s), 3.84 (6H, s), 3.83 (3H, s), 2.43 (3H, s).Red crystals; IR (KBr) cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.21 (1H, s), 9.33 (1H, s), 7.88 (1H, s, J = 14.49 Hz), 7.76-7.12 (5H, m), 7.07- 6.68 (5H, m), 6.41 (2H, s), 3.84 (6H, s), 3.83 (3H, s), 2.43 (3H, s).

all-트랜스-1-(2,5-디히드록시페닐)-5-[(3-니트로-4-메톡시)페닐]-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-11).all-trans-1- (2,5-dihydroxyphenyl) -5-[(3-nitro-4-methoxy) phenyl] -4- (3,4,5-trimethoxyphenyl) -2, 4-pentanedien-1-one (6-11).

적색 결정 ; IR (KBr) cm-1;1H-NMR (CDCl3) 12.41 (1H, s), 9.31 (1H, s), 7.81 (1H, s,J= 15.89 Hz), 7.71-7.05 (4H, m), 7.00-6.62 (5H, m), 6.52 (2H, s), 3.86 (6H, s), 3.85 (3H, s), 3.79 (3H, s).Red crystals; IR (KBr) cm −1 ; 1 H-NMR (CDCl 3 ) 12.41 (1H, s), 9.31 (1H, s), 7.81 (1H, s, J = 15.89 Hz), 7.71-7.05 (4H, m), 7.00-6.62 (5H, m ), 6.52 (2H, s), 3.86 (6H, s), 3.85 (3H, s), 3.79 (3H, s).

all-트랜스-5-[(3-아미노-4-메톡시)페닐]-1-(2,5-디히드록시페닐)-4-(3,4,5-트리메톡시페닐)-2,4-펜탄디엔-1-온 (6-12).all-trans-5-[(3-amino-4-methoxy) phenyl] -1- (2,5-dihydroxyphenyl) -4- (3,4,5-trimethoxyphenyl) -2, 4-pentanedien-1-one (6-12).

적색 결정 , 수율 65%; IR (KBr) cm-1;1H-NMR (DMSO-d 6, 90 MHz) 12.38 (1H, s), 9.21 (1H, s), 7.80 (1H, s,J= 15.43 Hz), 7.74-7.12 (4H, m), 6.99-6.64 (5H, m), 6.49 (2H, s), 3.87 (6H, s), 3.84 (3H, s), 3.81 (3H, s).Red crystals, yield 65%; IR (KBr) cm −1 ; 1 H-NMR (DMSO- d 6 , 90 MHz) 12.38 (1H, s), 9.21 (1H, s), 7.80 (1H, s, J = 15.43 Hz), 7.74-7.12 (4H, m), 6.99- 6.64 (5H, m), 6.49 (2H, s), 3.87 (6H, s), 3.84 (3H, s), 3.81 (3H, s).

실시예 7: 암 세포(B16, HTC116, A431 및 HUVEC세포주)에 대한 세포독성 실험Example 7: Cytotoxicity Experiments on Cancer Cells (B16, HTC116, A431 and HUVEC Cell Lines)

(1) 세포와 배양액 준비(1) Cell and culture preparation

배양액은 멸균 주사용 증류수 1 L에 RPMI 1640 배지 1 포장단위, 중탄산나트륨 2 g, 페니실린 10만 단위, 스트렙토마이신 100 mg을 넣어 용해시킨 후, 0.1 N HCl로 pH를 조절 (pH 7.2 ~ 7.3)한 후 세균여과하여 제조하였으며, 사용 전에 56℃ 수조에서 30 분 동안 가열하여 불활성화시킨 태아 소 혈청(FBS) 100 mL를 넣어 4℃에서 보관하면서 사용하였다. 세포는 3 일에 한번씩 계대 (propagation)하여 유지하였으며, 세포를 부착면으로부터 분리하기 위하여 포스페이트 버퍼된 식염수 용액에 0.5% 트립신과 2% EDTA (에틸렌디아민테트라아세트산)를 녹인 용액을 사용하였다.The culture solution was dissolved in 1 L of sterile injectable distilled water in 1 package of RPMI 1640 medium, 2 g of sodium bicarbonate, 100,000 units of penicillin, and 100 mg of streptomycin, and then adjusted to pH with 0.1 N HCl (pH 7.2 to 7.3). After bacterial filtration, 100 mL of fetal bovine serum (FBS), inactivated by heating for 30 minutes in a 56 ° C. water bath, was used and stored at 4 ° C. before use. Cells were maintained every three days (propagation) and a solution of 0.5% trypsin and 2% EDTA (ethylenediaminetetraacetic acid) in phosphate buffered saline solution was used to separate the cells from the adherent surface.

(2) 세포 독성 실험(2) cytotoxicity experiment

암세포에 대한 독성실험은 Skehan 등(Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening.J. Natl. Cancer Inst., 82 (13), 1107 ~ 12 (1990))에 의해 개발된SRB (sulforhodamine-B)법을 사용하였다. 실험에 사용할 세포들을 0.5% 트립신-EDTA 용액으로 부착면으로부터 분리시키고 B16(생쥐 폐암 세포주), HCT116(인간 직장암 세포주), A431(피부암 세포주)세포는 5 × 104세포/mL의 농도의 세포현탁액이 되고, HUVEC(인간 배꼽 상피세포)은 5 × 104세포/mL이 되게 만든 다음 각 세포주 현탁액을 96 웰 평판의 각 웰에 180 L 씩 가하여 배양기 (37℃, 5% CO2)에서 24시간 배양하였다. 24시간 배양한 시점에서 시간 제로인 평판을 꺼내 아래의 방법으로 흡광도를 측정하였다. 즉, 시료를 가하는 시점(타임 제로)의 세포에 의한 흡광도(Tz)를 측정하였다. 시료는 디메틸설폭사이드 (DMSO)에 녹여 실험에 필요한 농도까지 실험용 배지 또는 멸균 3차 증류수를 이용하여 세포에 가해지는 최종 DMSO의 농도가 0.2% 이하가 되도록 단계별로 희석하였다. 96 웰 평판의 각 웰에 단계별 농도로 희석한 시료를 각각 20 L씩 넣어준 다음 37℃, 5% CO2배양기에서 B16, A431, HTC116은 48 시간, HUVEC은 72시간 배양하였다. 배양이 끝난 후 각 평판의 배지를 조심스럽게 제거하고 10% TCA (트리클로로아세트산)를 각 웰 당 50 L씩 가하여 4℃에서 1 시간동안 방치하여 세포들을 평판의 바닥면에 고정시킨다. 세포를 고정시킨 후 평판을 물로 5-6 회 세척하여 남아있는 TCA 용액을 완전히 제거하고 실온에서 남은 물기가 없도록 건조시켰다. 완전히 건조된 평판은 웰 당 50 L 의 1% 아세트산 용액에 SRB (0.4%)를 녹인 염색용액을 가하여 30 분간 세포를 염색하고 다시 1% 아세트산 용액으로 수회 세척하여 세포에 결합하지 않은 SRB를 모두 제거하였다. 이렇게 염색한 후 평판을 다시 실온에서 건조시켰다. 여기에 10 mM 트리스-염기 용액 100 L를 가해 마이크로평판 판독기로 520 nM에서 OD 값을 측정하였다. 암세포에 대한 ED50(50% 효과 용량) 값은 다음과 같이 계산하였다. 시료를 가하여 배양을 시작하는 시간에 수집하여 측정한 흡광도를 Tz로 하였다. 시료를 처리하지 않고 배양한 OD 값을 대조군 (C)으로 하고 시료를 처리하고 배양한 웰의 OD 값을 약물 처리된 실험값 (T)으로 하였다. Tz, C 및 T로 부터 다음의 수식에 의해 물질들의 세포독성을 측정하였다. 즉, 세포성장율 (%) = [(T - Tz) / (C - Tz)]× 100의 수식으로 계산한다. 이렇게 계산된 값들로부터 약물의 암세포 성장을 50% 억제하는 농도인 ED50값을 계산하여 각 물질들의 세포독성을 비교하였다.Toxicity tests for cancer cells include Skehan et al. (Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, JT, Bokesch, H., Kenney, S., Boyd, MR, New colorimetric cytotoxicity assay for anticancer-drug screening.Sulforhodamine-B (SRB) method developed by J. Natl. Cancer Inst. , 82 (13), 1107-12 (1990)) It was. The cells to be used for the experiment were separated from the adherent surface with 0.5% trypsin-EDTA solution, and B16 (mouse lung cancer cell line), HCT116 (human rectal cancer cell line) and A431 (skin cancer cell line) cells were suspended in a cell suspension at a concentration of 5 × 10 4 cells / mL. HUVEC (Human Belly Epithelial Cells) was made 5 × 10 4 cells / mL and each cell line suspension was added to each well of a 96 well plate by adding 180 L to each well in an incubator (37 ° C., 5% CO 2 ) for 24 hours. Incubated. At the time of incubation for 24 hours, the plate of time zero was taken out and the absorbance was measured by the following method. That is, the absorbance (Tz) by the cell at the time of adding a sample (time zero) was measured. Samples were dissolved in dimethylsulfoxide (DMSO) and diluted in stages so that the concentration of final DMSO added to the cells was 0.2% or less using experimental media or sterile tertiary distilled water to the concentration required for the experiment. Into each well of a 96 well plate, 20 L of the diluted sample was added to each well, followed by incubation of B16, A431, HTC116 for 48 hours and HUVEC for 72 hours in a 37 ° C., 5% CO 2 incubator. After incubation, the medium of each plate is carefully removed and 50% of 10% TCA (trichloroacetic acid) is added to each well and left at 4 ° C. for 1 hour to fix the cells on the bottom of the plate. After fixing the cells, the plates were washed 5-6 times with water to completely remove the remaining TCA solution and dried to dryness at room temperature. Completely dried plates were stained with 30 L of 1% acetic acid solution per well in SRB (0.4%) staining solution and stained for 30 minutes and washed several times with 1% acetic acid solution to remove all unbound SRB. It was. After this dyeing, the plates were again dried at room temperature. To this was added 100 L of 10 mM Tris-base solution and the OD value was measured at 520 nM with a microplate reader. ED 50 (50% effect dose) values for cancer cells were calculated as follows. The absorbance measured and collected at the time of starting a culture by adding a sample was made into Tz. The OD value cultured without the sample was treated as a control (C), and the OD value of the well treated and cultured as the sample was the drug treated experimental value (T). Cytotoxicity of the substances was determined from Tz, C and T by the following formula. In other words, the cell growth rate (%) = [(T-Tz) / (C-Tz)] x 100. From these values, the ED 50 value, which is a concentration that inhibits the cancer cell growth of the drug by 50%, was calculated to compare the cytotoxicity of each substance.

암 세포(B16, HTC116, A431 및 HUVEC 세포주)에 대한 세포독성실험 결과 평가Evaluation of cytotoxicity test results on cancer cells (B16, HTC116, A431 and HUVEC cell lines)

1. 일반식(Ia)의 3-(2,5-디히드록시페닐)-1-페닐-2-프로펜-1-온 유도체(1-1 내지 1-47 화합물)의 세포독성1. Cytotoxicity of 3- (2,5-dihydroxyphenyl) -1-phenyl-2-propen-1-one derivatives (1-1 to 1-47 compound) of general formula (Ia)

일반식(Ia)의 화합물의 B16, HCT116, A431, HUVE 세포에 대한 세포독성은 표 5에 나타내었다.The cytotoxicity of the compounds of formula (Ia) against B16, HCT116, A431, and HUVE cells is shown in Table 5.

표 5: 일반식(Ia)의 화합물의 세포독성 데이타(단위: IC50, ug/ml)Table 5: Cytotoxicity data of compounds of general formula (la) in IC 50 , ug / ml

(AP: average potency(평균 강도))(AP: average potency)

평균 강도(AP)로 평가하면 전반적으로 전자 끌개효과를 갖는 치환기를 갖는 화합물(1-2, 1-3, 1-4, 1-6, 1-7, 1-10, 1-11, 1-12, 1-13)이 비교적 강한 세포독성을 보이고 있다. 반면 전자 주개 효과를 갖는 치환기를 갖는 화합물(1-16, 1-17, 1-22에서 1-30, 1-34, 1-35, 1-37, 1-38)은 치환기의 숫자가 증가하면 세포독성이 약해지는 경향을 보인다. 페닐기의 파라 위치에 파리-디렉터 즉, 활성화 효과가 큰 OH, 알콕시기가 결합된 화합물의 경우 다른 치환 패턴에 비하여 세포독성이 약화된다(1-18, 1-19 대 1-20, 1-31, 1-32 대 1-33).When evaluated by the average intensity (AP), the compound having a substituent having an overall electron attracting effect (1-2, 1-3, 1-4, 1-6, 1-7, 1-10, 1-11, 1- 12, 1-13) show relatively strong cytotoxicity. On the other hand, a compound having a substituent having an electron donor effect (1-30, 1-34, 1-35, 1-37, 1-38 in 1-16, 1-17, 1-22) increases when the number of substituents increases. Cytotoxicity tends to be weakened. In the para-position of the phenyl group, a compound having a Paris-director, that is, an OH or alkoxy group having a high activation effect, has a weaker cytotoxicity than other substitution patterns (1-18, 1-19 vs. 1-20, 1-31, 1-32 vs 1-33).

화합물 1-3인 [3-(2,5-디히드록시페닐)-1-(2-클로로페닐)-2-프로펜-1-온]은 HUVEC에 대하여 특히 강한 세포독성을 보인다. 이 물질은 혈관 신생 억제제로서의 가능성을 보이고 있다.Compound 1-3, [3- (2,5-dihydroxyphenyl) -1- (2-chlorophenyl) -2-propen-1-one], exhibits particularly strong cytotoxicity against HUVECs. This material has shown potential as an angiogenesis inhibitor.

2. 일반식(Ib)의 1-(2,5-디히드록시페닐)-3-(치환) 페닐-2-프로펜-1-온 유도체의 세포독성2. Cytotoxicity of 1- (2,5-dihydroxyphenyl) -3- (substituted) phenyl-2-propen-1-one derivatives of general formula (lb)

일반식(Ib)의 화합물의 B16, HCT116, A431, HUVE 세포에 대한 세포독성은 표6에 나타내었다.The cytotoxicity of the compounds of formula (Ib) against B16, HCT116, A431, and HUVE cells is shown in Table 6.

표 6: 일반식(Ib)의 화합물의 세포독성 데이타(단위: IC50, ug/ml)Table 6: Cytotoxicity data of compounds of formula (Ib) in IC 50 , ug / ml

일반식(Ia)의 화합물의 경우에서와 마찬가지로 평균 강도(AP)로 기준으로 평가하여 보면 전자 끌개 기인 할로겐이 치환된 화합물(2-2, 2-3, 2-4 )은 좋은 세포독성을 보인다. 이 물질군에서도 파라-치환된 화합물(2-4)은 다른 위치에서 치환된 화합물보다 약한 세포독성을 보이고 있다. 두개의 기가 치환된 것들 중 전자 끌개 효과가 강한 기로 치환된 화합물(2-9, 2-10, 2-11, 2-12, 2-13)도 비교적 강한 세포독성을 보인다. 전자 끌개 효과를 보이는 옥시기들이 치환된 화합물(2-15, 2-16, 2-19)도 비교적 좋은 세포독성을 보이고 페닐을 활성화시키는 4-옥시기를 가진 화합물(2-17, 2-20)은 약한 작용을 보인다. 그러나 기들이 밀집되면 세포독성은 약화된다(2-24, 2-25, 2-28 등). 이 물질 중에서도 2-클로로페닐 구조를 포함한 1-(2,5-디히드록시페닐)-3- (2-클로로페닐) 페닐-2-프로펜-1-온 (2-3)은 구조적으로 물질 1-3에 해당하며 역시 HUVE에 대하여 특히 강한 세포독성을 보인다. 혈관 신생 억제제로서 개발을 고려할 필요가 있는 화합물이다.As in the case of the compound of general formula (Ia), the halogen-substituted compound (2-2, 2-3, 2-4), which is an electron withdrawing group, has good cytotoxicity when evaluated based on average intensity (AP). . In this group of compounds, para-substituted compounds (2-4) show weaker cytotoxicity than compounds substituted at other positions. Of the two substituted groups, the compound substituted with a strong electron attracting effect (2-9, 2-10, 2-11, 2-12, 2-13) also shows relatively strong cytotoxicity. Compounds with substituted oxy groups (2-15, 2-16, 2-19), which have an electron withdrawing effect, also have relatively good cytotoxicity and compounds with 4-oxy groups that activate phenyl (2-17, 2-20) Has a weak action. However, when the groups are concentrated, cytotoxicity is weakened (2-24, 2-25, 2-28, etc.). Among these substances, 1- (2,5-dihydroxyphenyl) -3- (2-chlorophenyl) phenyl-2-propen-1-one (2-3) containing a 2-chlorophenyl structure is structurally a substance. It corresponds to 1-3 and also shows particularly strong cytotoxicity against HUVE. It is a compound that needs to be considered for development as an angiogenesis inhibitor.

3. 일반식(Ic)의 2-치환-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온유도체의 세포독성3. Cytotoxicity of 2-Substituted-1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one derivative of Formula (Ic)

일반식(Ic1) 내지 일반식(Ic3)의 화합물의 B16, HCT116, A431, HUVE 세포에 대한 세포독성은 표 7에 나타내었다.Cytotoxicity of B16, HCT116, A431, HUVE cells of the compounds of Formulas (Ic1) to (Cc3) is shown in Table 7.

표 7: 일반식(Ic1) 내지 일반식(Ic3)의 화합물의 세포독성 데이타(단위: IC50, ug/ml)Table 7: Cytotoxicity data of compounds of formulas (Ic1) to (Ic3) in IC 50 , ug / ml

(1) 일반식(Ic1)의 2-브로모-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온 유도체의 세포독성(1) Cytotoxicity of 2-bromo-1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one derivative of general formula (Ic1)

표 7에 표시한 화합물 중 3-1, 3-2, 3-3에 해당된다. 구조 중 2번 탄소에 전자 끌개 효과가 있는 Br을 도입하였으나 일반식(Ib)의 1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온 유도체에 비하여 세포독성이 향상되지 않았다.It corresponds to 3-1, 3-2, 3-3 among the compounds shown in Table 7. Br, which has an electron withdrawing effect, was introduced to carbon number 2 in the structure, but compared to 1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one derivative of general formula (Ib) Toxicity did not improve.

(2) 일반식(Ic2)의 2-시아노-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온유도체의 세포 독성(2) Cytotoxicity of 2-cyano-1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one derivative of general formula (Ic2)

표 7에 표시된 화합물 중 화합물 4-1, 4-2, 4-3에 해당한다. 세 물질 모두 HUVEC(인간 배꼽 상피세포)과 B16(생쥐 폐암세포)에 대하여 비교적으로 강한 세포독성을 보였다.Corresponds to compound 4-1, 4-2, 4-3 among the compounds shown in Table 7. All three substances showed relatively strong cytotoxicity against HUVEC (human navel epithelial cells) and B16 (mouse lung cancer cells).

(3) 일반식(Ic3)의 1-(2,5-디히드록시페닐)-2-메틸-3-페닐-2-프로펜-1-온 유도체의 세포독성(3) Cytotoxicity of 1- (2,5-dihydroxyphenyl) -2-methyl-3-phenyl-2-propen-1-one derivative of general formula (Ic3)

표 7에 표시된 화합물 중 화합물 5-1, 5-2, 5-3에 해당한다. 일반식(Ib)의 1-(2,5-디히드록시페닐) -3-페닐-2-프로펜-1-온 유도체의 세포독성에 비하여 전반적으로 약화된 효과를 보였다.Corresponds to compound 5-1, 5-2, 5-3 among the compounds shown in Table 7. In general, compared to the cytotoxicity of the 1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one derivative of the general formula (Ib) showed a weakened effect.

4. 일반식(Id)의 all-트랜스-1,4,5-트리페닐-2,4-펜탄디온 유도체의 세포독성4. Cytotoxicity of all-trans-1,4,5-triphenyl-2,4-pentanedione derivatives of general formula (Id)

일반식(Id)의 화합물의 B16, HCT116, A431, HUVE 세포에 대한 세포독성은 표 8에 나타내었다.Cytotoxicity of B16, HCT116, A431, and HUVE cells of the compound of formula (Id) is shown in Table 8.

표 8: 일반식(Id)의 화합물의 세포독성 데이타(단위: IC50, ug/ml)Table 8: Cytotoxicity data of compounds of formula (Id) in IC 50 , ug / ml

표 8에 표시한 화합물 중 화합물 6-1, 6-2를 제외하고는 세포독성의 강화효과를 보이지 않고 있다. 화합물 6-1과 6-2는 두 페닐기 중 하나는 3,4,5-트리메톡시기를 갖고 있다. 이와 같은 구조 부분은 세포분열 독성(mitotoxicity)를 보이는 포도필로톡신계 물질에 포함되어 있는 파마코포어(pharmacophore)이다. 특히 화합물 6-1의 4-(트리메톡시페닐)-5-(4-메톡시페닐) 에탄 구조 부분은 세포분열 독성을 갖는 콤프레타스타틴(compretastatin) 유도체의 중의 하나이다.Except for compounds 6-1 and 6-2 among the compounds shown in Table 8, there is no enhancement effect of cytotoxicity. Compounds 6-1 and 6-2 have 3,4,5-trimethoxy group in one of the two phenyl groups. Such a structural part is a pharmacophore contained in the grape phytotoxin-based material showing mitotoxicity. In particular, the 4- (trimethoxyphenyl) -5- (4-methoxyphenyl) ethane structural moiety of compound 6-1 is one of the compressastatin derivatives having cytotoxicity.

나머지 물질들에서는 세포독성의 향상을 관찰 할 수 없었다.No improvement in cytotoxicity was observed in the remaining substances.

6. 화학적 민감도(chemosensitivity index)와 혈관 신생 억제물질의 선택6. Chemosensitivity index and selection of angiogenesis inhibitors

화학적 민감도(chemosensitivity index)는 인간 직장암 세포주인 HCT116에 대한 인간 배꼽 상피세포에 대한 세포독성의 비, 즉IC50(HCT116)/IC50(HUVEC)로 계산되는데, 이 수치가 높을 수록 혈관 신생 억제 작용이 두드러지는 것으로 판단된다. 상기 표 5 및 표 6의 화합물 중 그 수치가 2 이상인 것을 골라서 표 9에 나타내었다.The chemosensitivity index is calculated as the ratio of cytotoxicity to human navel epithelial cells to the human rectal cancer cell line HCT116, i.e.IC 50 (HCT116) / IC 50 (HUVEC). This seems to stand out. Table 9 and Table 6 show that the numerical value of 2 or more is shown in Table 9.

표 9: 화학적 민감도 데이타Table 9: Chemical Sensitivity Data

표 9에 나타낸 화합물 중 특히 화합물 1-3인 (E)-1-(2-클로로페닐)- 3-(2,5-디히드록시페닐)-2-프로펜-1-온과 2-3인 (E)-3-(2-클로로페닐)-1-(2,5-디히드록시 페닐)-2-프로펜-1-온의 화학적 민감도는 각각 5.39 및 61로서 다른 화합물에 비하여 현저히 높았다. 이들 구조 중 공통적인 부분은 2-클로로페닐기이며 2-프로펜-1-온 구조 상의 카보닐기에서 멀리 떨어진 화합물인 2-3이 화학적 민감도가 더욱 현저히 높았다. 표 5에 나타낸 화합물들은 항암제로서 좋은 후보 물질이다.(E) -1- (2-chlorophenyl) -3- (2,5-dihydroxyphenyl) -2-propen-1-one and 2-3 which are compounds 1-3 especially among the compounds shown in Table 9 The chemical sensitivity of phosphorus (E) -3- (2-chlorophenyl) -1- (2,5-dihydroxy phenyl) -2-propen-1-one was 5.39 and 61, respectively, which was significantly higher than other compounds. . A common part of these structures is 2-chlorophenyl group, and the compound 2-3, far from the carbonyl group on the 2-propen-1-one structure, was significantly more chemically sensitive. The compounds shown in Table 5 are good candidates as anticancer agents.

실시예 8: HUVE 세포에 대한 튜브형성 억제 실험Example 8: Inhibition of Tube Formation on HUVE Cells

화학적 민감도 수치가 61을 보였던 화합물 2-3인(E)-3-(2-클로로페닐)-1-(2,5-디히드록시 페닐)-2-프로펜-1-온 및 양성 대조구로서의 수라민(suramin)에 대해 HUVE 세포에 대한 튜브형성 억제실험을 하여 혈관 신생 억제 효과를 테스트하였다.(E) -3- (2-chlorophenyl) -1- (2,5-dihydroxy phenyl) -2-propen-1-one and a positive control as compound 2-3 with a chemical sensitivity value of 61 Suramin was tested for the inhibitory effect of angiogenesis on tuberculosis inhibition experiments on HUVE cells.

(1) HUVE 세포와 배양액 제조(1) Preparation of HUVE Cells and Cultures

HUVE 세포와 배양액 제조는 Yasumasa, I., Yukihide, I., Kazuhiro, T., Kiyotaka, O. and Yoichi, S., A quantitative assay using basement membrane extract to study tumor angiogenesisin vivo. Int. J. Cancer, 67, 148 52 (1996)에 따라서 다음과 같이 수행하였다.Preparation of HUVE cells and cultures is described in Yasumasa, I., Yukihide, I., Kazuhiro, T., Kiyotaka, O. and Yoichi, S., A quantitative assay using basement membrane extract to study tumor angiogenesis in vivo. Int. According to J. Cancer , 67, 148 52 (1996) as follows.

배양액은 멸균 주사용 증류수에 M199 배지 1 포장단위, 중탄산나트륨 2 g, 페니실린 10만 단위, 스트렙토마이신 100 mg을 넣어 용해시킨 후 0.1N HCl로 pH를 조절 (pH 7.2 ~ 7.3)하여 전체를 1 L가 되게 한 후 세균여과하여 제조하였으며, 사용 전에 56℃ 수조에서 30분간 가열하여 불활성화시킨 FBS 200 mL, bFGF 0.9 mg, 헤파린 21000 단위를 가하여 4℃에서 보관하면서 사용하였다. 세포는 일주일에 한번씩 계대하여 유지하였으며, 세포를 부착면으로부터 분리하기 위하여 포스페이트-버퍼된 식염수 용액에 0.5% 트립신과 2% EDTA를 녹인 용액을 사용하였다The culture solution was dissolved by dissolving 1 package unit of M199 medium, 2 g of sodium bicarbonate, 100,000 units of penicillin, and 100 mg of streptomycin in sterile injectable distilled water, and adjusting the pH with 0.1 N HCl (pH 7.2 to 7.3). After the preparation was made by bacterial filtration, 200 mL of FBS, 0.9 mg of bFGF, 21000 units of heparin, which were inactivated by heating in a 56 ° C. water bath for 30 minutes before use, were used while being stored at 4 ° C. Cells were kept passaged once a week and a solution of 0.5% trypsin and 2% EDTA in phosphate-buffered saline solution was used to separate the cells from the adherent surface.

(2)Matrigel 준비(2) Matrigel preparation

-20℃가 일정하게 유지되는 냉동고에서 보관되어진 매트리겔을 4℃에서 하룻밤 방치하여 천천히 녹인 후 동결 튜브에 1 mL씩 분주한 후 4℃에서 보관하였다.The matrigel stored in a freezer at -20 ° C was kept at room temperature overnight at 4 ° C to be slowly dissolved, and then dispensed in a 1 mL aliquot in a freezing tube and stored at 4 ° C.

(3) HUVE 세포배양을 위한 배지의 조제(3) Preparation of medium for HUVE cell culture

① 용액 A: M199 배지 1 포장단위, 페니실린 10만 단위, 스트렙토마이신100 mg, 중탄산나트륨 2.2 g을 증류수 1 L에 녹인 다음 pH 7.2 ~ 7.3으로 조절한 후 세균여과하였다.① Solution A: 1 package unit of M199 medium, 100,000 units of penicillin, 100 mg of streptomycin, 2.2 g of sodium bicarbonate were dissolved in 1 L of distilled water, and then adjusted to pH 7.2 ~ 7.3, followed by bacterial filtration.

② 용액 B: bFGF 10 g을 멸균한 증류수 100 L에 녹였다.② Solution B: 10 g of bFGF was dissolved in 100 L of sterilized distilled water.

③ 용액 C: 헤파린 100,000 단위(175 단위/mg)를 용액 A 5.7 mL에 녹였다.③ Solution C: 100,000 units (175 units / mg) of heparin were dissolved in 5.7 mL of Solution A.

④ 용액 A 240 mL에 용액 B 9 L, 용액 C 300 L, FBS 60 mL를 넣어 하루동안 오염 여부를 확인한 후 사용하였다.④ In 240 mL of Solution A, 9 L of Solution B, 300 L of Solution C, and 60 mL of FBS were added to check contamination for one day.

(4) 젤라틴 코팅(4) gelatin coating

시판되고 있는 젤라틴 2% 용액을 3 차 증류수를 사용하여 0.3%로 희석하여 멸균 후 사용하였다. 이것을 T75 배양 플라스크에 1.5 mL로 바닥을 코팅하여 클린 벤치 안의 평평한 곳에 2 시간 동안 방치한 후 냉장보관하며 사용하였다.A commercially available 2% gelatin solution was diluted to 0.3% with tertiary distilled water and used after sterilization. This was coated with a bottom of 1.5 mL in a T75 culture flask and left on a flat place in a clean bench for 2 hours.

(5) 시료처리(5) sample processing

위에서 제조한 매트리겔을 96 웰 평판에 1 웰당 50 L씩 거품이 생기지 않게 평판 바닥에 균일하게 도포한 후 평판을 37℃에서 30 분 동안 방치하였다. 96 웰 평판의 1 웰 당 2 × 104세포/180 mL의 HUVE 세포용액를 넣은 후 곧 바로 DMSO에 녹인 시료용액을 가하였다. 이때 최종 농도는 50 mg/mL이 되도록 조정하였으며 양성대조군으로는 TNP-470 (50 ng/mL)를 20 mL 가하였다.The Matrigel prepared above was uniformly applied to the bottom of the plate without foaming 50 L per well on a 96 well plate, and the plate was left at 37 ° C. for 30 minutes. 2 x 10 4 cells / 180 mL of HUVE cell solution per well of a 96 well plate was immediately added to the sample solution dissolved in DMSO. The final concentration was adjusted to 50 mg / mL and 20 mL of TNP-470 (50 ng / mL) was added as a positive control.

(6) 튜브형성 억제도 평가(6) evaluation of tube formation inhibition

각 웰을 100배로 확대한 후 5개의 영역을 무작위로 선정, 사진 촬영하여 인화한 후 각 인화지에 나타난 혈관의 전체길이를 아도브 포토삽TM소프트웨어로 측정하여 평균값을 계산한 후 음성대조군과 시료처리군과의 전체 길이의 백분율로 활성도를 나타내었다. 실험 결과를 표 10에 나타내었다.After expanding each well fold 100 randomly selected five regions, the picture recorded by printing and then after measuring the full length of the blood vessel shown in each photo to Adobe Photo shovel TM software calculates the average negative control group and the sample group treated Activity is expressed as a percentage of the total length of the family. The experimental results are shown in Table 10.

표 10: 화합물 2-3인 (E)-3-(2-클로로페닐)-1-(2,5-디히드록시 페닐)-2-프로펜-1-온의 HUVE 세포에 대한 튜브형성 억제실험 데이타Table 10: Inhibition of tube formation of HUVE cells of (E) -3- (2-chlorophenyl) -1- (2,5-dihydroxy phenyl) -2-propen-1-one as compound 2-3 Experimental data

화합물 2-3의 HCT116에 대한 IC50값은 1.81 ug/ml 인데 이 실험에서는 이 농도 보다 훨씬 낮은 즉 세포독성을 나타내지 않는 농도인 0.3 ug/ml를 최고 농도로 하여 HUVEC의 튜브 형성(혈관 신생)에 대한 억제 효과를 관찰하였다. 표 10에서 나타낸 바와 같이 화합물 2-3은 0.1ug/ml에서도 강한 튜브 형성 억제 작용을 보인다. 비교 물질로 사용하였던 수라민보다 현저하게 강한 억제 효과를 보임을 알 수 있다.The IC 50 value for HCT116 of compound 2-3 is 1.81 ug / ml, in this experiment a tube formation of HUVEC (angiogenesis) with a concentration of 0.3 ug / ml, which is much lower than this concentration, which is not cytotoxic. The inhibitory effect on was observed. As shown in Table 10, the compound 2-3 shows a strong tube formation inhibitory effect even at 0.1ug / ml. It can be seen that it shows a significantly stronger inhibitory effect than the suramin used as a comparative material.

실시예 9: LL/2 세포를 이용한 동물실험Example 9: Animal Experiments with LL / 2 Cells

혈관 신생 억제 효과가 우수한 것으로 판명된 화합물 2-3을 사용하여 LL/2 세포를 이용한 동물실험에 의해 항암 효과를 실험하였다. 화합물 2-3의 항암성이 세포독성보다 혈관 신생 억제에 기인함을 알기 위하여 비교 물질로써 화합물 2-4를 선택하였다. 이 물질은 세포독성은 화합물 2-3과 유사하나 화학적 민감도가 1이어서 혈관 신생 억제와 세포독성을 구별할 수 없다.Anti-cancer effects were tested by animal experiments using LL / 2 cells using Compound 2-3, which was found to be excellent in inhibiting angiogenesis. Compound 2-4 was selected as a comparative to understand that the anticancer properties of compound 2-3 were due to inhibition of angiogenesis rather than cytotoxicity. This substance has cytotoxicity similar to that of compound 2-3, but has a chemical sensitivity of 1, making it impossible to distinguish angiogenesis from cytotoxicity.

(1) LL/2세포와 배양액 제조(1) Preparation of LL / 2 Cells and Culture Solution

배양액은 멸균 주사용 증류수에 L-글루타민이 포함된 RPMI 1640 배지 1 포장단위, 56℃ 수조에서 30분간 가열하여 불활성화시킨 태아 소 혈청(FBS) 100 mL, 중탄산나트륨 2 g, 페니실린 10만 단위, 스트렙토마이신 100 mg을 넣어 용해시킨 후 0.1N HCl으로 pH를 조절하여 전체를 1 L가 되게 한 후 세균 여과하여 제조하였으며, 4℃에서 보관하면서 사용하였다. 세포를 3일에 한 번씩 계대하여 유지하였으며, 세포를 부착면으로부터 분리하기 위하여 포스페이트 버퍼된 식염수 용액에 0.5% 트립신과 2% EDTA를 녹인 용액을 사용하였다.The culture medium was packaged in RPMI 1640 medium 1 containing L-glutamine in sterile distilled water, 100 mL of fetal bovine serum (FBS) inactivated by heating in a 56 ° C water bath for 30 minutes, 2 g of sodium bicarbonate, 100,000 units of penicillin, After dissolving 100 mg of streptomycin and adjusting the pH with 0.1N HCl to make the whole to 1 L was prepared by bacterial filtration, it was used while storing at 4 ℃. Cells were kept passaged once every 3 days and a solution of 0.5% trypsin and 2% EDTA in phosphate buffered saline solution was used to separate the cells from the adherent surface.

(2)LL/2세포를 이용한 동물실험(2) Animal experiment using LL / 2 cell

LL/2세포를 이용한 동물실험은 Teruhiro, U., Jiro, S., Yoshikazu, S., Kumio, A. and Yuji, Y. ; Antitumor activity of a novel podophyllotoxin derivative (TOP53) against lung cancer and lung matastatic cancer,Cancer Res., 56, 2809 14 (1996)에 따라서 다음과 같이 수행하였다.Animal experiments using LL / 2 cells include Teruhiro, U., Jiro, S., Yoshikazu, S., Kumio, A. and Yuji, Y .; Antitumor activity of a novel podophyllotoxin derivative (TOP53) against lung cancer and lung matastatic cancer, Cancer Res ., 56, 2809 14 (1996) was performed as follows.

시험관내에서 배양한 LL/2세포를 멸균된 냉 생리식염수를 사용하여 충분히 세척한 후 세포를 혈구계 (haemacytometer)로 세어 5 × 106세포/mL의 농도로 세포 부유액을 만들고 이 부유액을 0.2 mL 씩 BDF1 마우스의 겨드랑이에 피하로 이식하였다. 이식 24 시간 후에 각군을 5 마리로 분류하였다. 시료는 주사하기 바로 직전에 5%의 디메틸설폭사이드, 20%의 크레모포어(cremophore)를 함유한 생리식염수에 용해시켜 제조하여, 실험동물의 복강 내에 0.2 mL씩 주사하였다. 음성대조군에는 5%의 디메틸설폭사이드, 20%의 크레모포어를 함유한 생리식염수만을 시료 투여량과 같은 용량으로 투여하였으며 양성 대조군으로는 에토포사이드 (36 mg/kg/일)를 암세포 이식 후 1, 5, 9 일째에 주사하였으며 주사일정은 시료에 따라 다르나 여기에서는 시료 50mg/kg/day의 투여량으로 암세포 이식 후 24 시간이 지난 후에 시작하여 3, 5, 7, 9, 11 일에 투여하다가 16, 17, 18 일 투여하여 전체 9 회 투여하였다.After LL / 2 cells cultured in vitro are sufficiently washed with sterile cold saline solution, the cells are counted with a haemacytometer to form a cell suspension at a concentration of 5 × 10 6 cells / mL, and the suspension is 0.2 mL. Tissues were implanted subcutaneously in the armpits of BDF1 mice. Twenty four hours after transplantation, each group was divided into five animals. Samples were prepared by dissolving in physiological saline containing 5% dimethyl sulfoxide and 20% cremophore immediately before injection, and injected 0.2 mL into the abdominal cavity of the experimental animal. In the negative control group, only physiological saline containing 5% dimethyl sulfoxide and 20% cremophore was administered at the same dose as the sample dose. As a positive control, etoposide (36 mg / kg / day) was added after cancer cell transplantation. The injection schedule was based on the sample, but the injection schedule was 50 mg / kg / day, starting at 24 hours after cancer cell transplantation and starting at 3, 5, 7, 9, or 11 days. 16, 17, 18 days of administration was administered a total of nine times.

마우스에 대한 각각의 시료의 독성을 측정하기 위해 2 일에 1 회 몸무게를 측정하였으며, 항암 효과는 약물투여 11 일 ∼ 19 일에 대조군과 약물처리군의 암괴의 부피를 측정 후 다음 식에 따라 계산하였다.To determine the toxicity of each sample to mice, weight was measured once every 2 days, and the anticancer effect was calculated according to the following formula after measuring the volume of the mass of the control and drug treatment groups from 11 to 19 days of drug administration. It was.

암의 부피 (mm3) = 길이 (mm) × 폭2(mm2) / 2Arm volume (mm 3 ) = length (mm) × width 2 (mm 2 ) / 2

암성장저지율 (%)=(C - T) × 100 / CCancer growth inhibition rate (%)=(C-T) × 100 / C

상기 식에서, C : 대조군의 평균 암부피 (mm3), T : 시료투약군의 평균 암부피 (mm3)를 나타낸다.In the above formula, C: mean cancer volume of the control group (mm 3 ), T: mean cancer volume of the sample administration group (mm 3 ).

(3) 동물실험 결과의 평가(3) Evaluation of animal test results

LL/2 세포를 이용한 동물실험의 결과를 표 11에 나타내었다.Table 11 shows the results of animal experiments using LL / 2 cells.

표 11: 화합물 2-3인 (E)-3-(2-클로로페닐)-1-(2,5-디히드록시 페닐)-2-프로펜-1-온의 항암 활성 데이타Table 11: Anticancer activity data of (E) -3- (2-chlorophenyl) -1- (2,5-dihydroxy phenyl) -2-propen-1-one as compound 2-3

(세포독성 단위: IC50, ug/ml)(Cytotoxic unit: IC 50 , ug / ml)

표 11 나타낸 바와 같이 화합물 2-3은 투여 후 11일에 저해율=72.6%로 비교 물질인 에토포사이드(15일째, 양성 대조구)의 73.6%와 실제로 같은 수준의 항암 효과를 보였다.As shown in Table 11, compound 2-3 showed an anticancer effect on the 11th day after administration with 73.6% of inhibition rate of 73.6% of the etoposide (day 15, positive control) as a comparative substance.

이와는 대조적으로 화합물 2-4는 구조적으로는 3번 탄소에 결합된 기가 3-클로로페닐인 것이 물질 2-3과 다를 뿐이지만 약한 항암 작용을 보였다.In contrast, Compound 2-4 showed a weak anti-cancer activity, although structurally different from substance 2-3 in that the group bonded to carbon 3 is 3-chlorophenyl.

상기에서 입증된 바와 같이, 본발명에 따른 일반식(I)의 화합물은 우수한 항암 효과를 갖는다.As demonstrated above, the compounds of formula (I) according to the invention have excellent anticancer effects.

Claims (5)

아래 일반식(I)의 1,4-디히드록시벤젠 유도체 및 약제학적으로 허용가능한 그의 염:1,4-dihydroxybenzene derivative of the general formula (I) below and pharmaceutically acceptable salts thereof: (I)(I) 상기 식에서In the above formula Y는 -CH=CH-CO-, -CO-CH=CH-, 또는 -CO-CR2=CH- 이고, X는 페닐 또는 1-5개의 치환기 R1으로 치환된 페닐이거나; Y는 -CO-CH=CH-이고 X는이며;Y is —CH═CH—CO—, —CO—CH═CH—, or —CO—CR 2 ═CH—, and X is phenyl or phenyl substituted with 1-5 substituents R 1 ; Y is -CO-CH = CH- and X is Is; R1은 수소, 할로겐, 히드록시, 불소에 의해 치환되거나 치환되지 않은 알킬, 알콕시, 알킬티오, 니트로, 아미노, 디메틸아미노, 알킬설포닐, 페닐 또는 알킬렌디옥시, 또는 이들의 조합이고; R2는 시아노, 할로겐 또는 알킬, 또는 이들의 조합이며; R3는 수소, 할로겐, 알콕시, 알킬, 아미노 또는 니트로, 또는 이들의 조합이고; R4는 수소 또는 알콕시, 또는 이들의 조합이며,R 1 is alkyl, alkoxy, alkylthio, nitro, amino, dimethylamino, alkylsulfonyl, phenyl or alkylenedioxy, or a combination thereof, substituted or unsubstituted by hydrogen, halogen, hydroxy, fluorine; R 2 is cyano, halogen or alkyl, or a combination thereof; R 3 is hydrogen, halogen, alkoxy, alkyl, amino or nitro, or a combination thereof; R 4 is hydrogen or alkoxy, or a combination thereof, 단, Y가 -CH=CH-CO- 일 때 X는 페닐이 아니고, 페닐의 4-번 위치에 치환되는 R1은 수소가 아니거나 페닐의 2, 3, 5 또는 6번 위치에 치환되는 R1은 알킬설포닐, 페닐 또는 알킬렌디옥시이다.Provided that when Y is -CH = CH-CO-, X is not phenyl, and R 1 substituted at the 4-position of phenyl is not hydrogen or R substituted at the 2, 3, 5 or 6 position of phenyl; 1 is alkylsulfonyl, phenyl or alkylenedioxy. 제 1항에 있어서, 일반식(I)의 화합물이A compound according to claim 1 wherein (E)-3-(2,5-디히드록시페닐)-1-(4-티오메틸페닐)-2-프로펜-1-온,( E ) -3- (2,5-dihydroxyphenyl) -1- (4-thiomethylphenyl) -2-propen-1-one, (E)-3-(2,5-디히드록시페닐)-1-(2,4-디메톡시페닐)-2-프로펜-1-온,( E ) -3- (2,5-dihydroxyphenyl) -1- (2,4-dimethoxyphenyl) -2-propen-1-one, (E)-3-(2,5-디히드록시페닐)-1-(2,3,4-트리메톡시페닐)-2-프로펜-1-온,( E ) -3- (2,5-dihydroxyphenyl) -1- (2,3,4-trimethoxyphenyl) -2-propen-1-one, (E)-3-(2,5-디히드록시페닐)-1-(2,4,6-트리메톡시페닐)-2-프로펜-1-온,( E ) -3- (2,5-dihydroxyphenyl) -1- (2,4,6-trimethoxyphenyl) -2-propen-1-one, (E)-3-(2,5-디히드록시페닐)-1-(3,4,5-트리메톡시페닐)-2-프로펜-1-온,( E ) -3- (2,5-dihydroxyphenyl) -1- (3,4,5-trimethoxyphenyl) -2-propen-1-one, (E)-3-(2,5-디히드록시페닐)-1-(3,4-디히드록시페닐)-2-프로펜-1-온,( E ) -3- (2,5-dihydroxyphenyl) -1- (3,4-dihydroxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(2-클로로페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (2-chlorophenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(2,4-디메톡시페닐)-2-프로펜-1-온,(E) -1- (2,5-dihydroxyphenyl) -3- (2,4-dimethoxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(3,5-디메톡시페닐)-2-프로펜-1-온,(E) -1- (2,5-dihydroxyphenyl) -3- (3,5-dimethoxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(3,4-디메톡시페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4-dimethoxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(2,3,4-트리메톡시페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (2,3,4-trimethoxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(3,4,5-트리메톡시페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4,5-trimethoxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(2,3-디히드록시페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (2,3-dihydroxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(3,4-디히드록시페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4-dihydroxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(3,5-디히드록시페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (3,5-dihydroxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(3,4-메틸렌디옥시페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (3,4-methylenedioxyphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(4-페닐페닐)-2-프로펜-1-온,( E ) -1- (2,5-dihydroxyphenyl) -3- (4-phenylphenyl) -2-propen-1-one, (E)-1-(2,5-디히드록시페닐)-3-(4-메틸설포닐페닐)-2-프로펜-1-온인 화합물.( E ) -1- (2,5-dihydroxyphenyl) -3- (4-methylsulfonylphenyl) -2-propen-1-one. 제 1항에 있어서, 일반식(I)의 화합물이 (E)-1-(2,5-디히드록시페닐)-3-(2-클로로페닐)-2-프로펜-1-온인 화합물.A compound according to claim 1, wherein the compound of general formula (I) is ( E ) -1- (2,5-dihydroxyphenyl) -3- (2-chlorophenyl) -2-propen-1-one. (1) 2,5-디히드록시벤즈알데히드를 3,4-디히드로-2H-피란과 반응시켜 일반식(II)의 화합물을 얻고 이를 R1(R1은 제 1항에서 정의된 바와 같음)으로 치환된 아세토페논과 염기 존재 하에서 축합시켜 일반식(III)의 화합물을 얻고, 산촉매 존재하에서 테트라히드로피란기를 제거하여 일반식(Ia)의 3-(2,5-디히드록시페닐)-1-페닐-2-프로펜-1-온을 제조하거나,(1) reacting 2,5-dihydroxybenzaldehyde with 3,4-dihydro-2H-pyran to give a compound of formula II, which is R 1 (R 1 is as defined in claim 1); Condensed with acetophenone substituted with a base to obtain a compound of formula (III), and tetrahydropyran group is removed in the presence of an acid catalyst to give 3- (2,5-dihydroxyphenyl) -1 of formula (Ia) -Phenyl-2-propen-1-one, or (2) 2,5-디히드록시아세토페논을 3,4-디히드로-2H-피란과 반응시켜 일반식(II)의 화합물을 얻고 이를 R1(R1은 제 1항에서 정의한 바와 같음)으로 치환된 벤즈알데히드와 염기 존재하에서 축합시켜 일반식(IV)의 화합물을 얻고 산촉매 존재 하에서 3,4-디히드로-2H-피란기를 제거하여 일반식(Ib)의 1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온을 제조하거나,(2) reacting 2,5-dihydroxyacetophenone with 3,4-dihydro-2H-pyran to obtain a compound of formula (II), which is R 1 (R 1 is as defined in claim 1); Condensed with benzaldehyde substituted in the presence of a base to obtain a compound of formula (IV) and 3,4-dihydro-2H-pyran group in the presence of an acid catalyst to remove 1- (2,5-dialdehyde of formula (Ib) Oxyphenyl) -3-phenyl-2-propen-1-one, or (3) 일반식(Ib)의 화합물을 브롬화시켜 2,3-디브로모 화합물을 얻고, 이를 알칼리로 처리하여 일반식(Ic1)의 2-브로모-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온을 제조하거나,(3) bromination of the compound of formula (Ib) to give a 2,3-dibromo compound, which is treated with alkali to give 2-bromo-1- (2,5-dihydroxy of formula (Ic1) Phenyl) -3-phenyl-2-propen-1-one, or (4) 2',5'-디벤질옥시페닐-2-시아노아세토페논과 R1(R1은 제 1항에서 정의된 바와 같음)으로 치환된 벤즈알데히드를 Knoevenagel 축합반응시켜 일반식(V)의 2-시아노-1-2',5'-디벤질옥시페닐-3-페닐-2-프로펜-1-온을 얻고 이를 탈벤질화제를 사용하여 탈벤질화시켜 일반식(Ic2)의 2-시아노-1-(2,5-디히드록시페닐)-3-페닐-2-프로펜-1-온을 제조하거나,(4) Knoevenagel condensation reaction of benzaldehyde substituted with 2 ', 5'-dibenzyloxyphenyl-2-cyanoacetophenone and R 1 (R 1 is as defined in claim 1) to general formula (V). 2-cyano-1-2 ', 5'-dibenzyloxyphenyl-3-phenyl-2-propen-1-one was obtained and debenzylated using a debenzylating agent to yield a compound of formula (Ic2). 2-cyano-1- (2,5-dihydroxyphenyl) -3-phenyl-2-propen-1-one, or (5) 2',5'-디히드록시프로피오페논과 R1(R1은 제 1항에서 정의된 바와 같음)으로 치환된 벤즈알데히드를 축합시켜 2-메틸-3-페닐-1-(2,5-디테트라히드로푸라닐옥시)-2-프로펜-1-온을 얻고 이를 산존재 하에서 반응시켜 일반식(Ic3)의 1-(2,5-디히드록시페닐)-2-메틸-3-페닐-2-프로펜-1-온을 제조하거나,(5) condensation of 2 ', 5'-dihydroxypropiophenone with benzaldehyde substituted with R 1 (R 1 is as defined in claim 1) to form 2-methyl-3-phenyl-1- (2, 5-Ditetrahydrofuranyloxy) -2-propen-1-one was obtained and reacted in the presence of acid to yield 1- (2,5-dihydroxyphenyl) -2-methyl-3 of formula (Ic3). -Phenyl-2-propen-1-one, or (6) 일반식(VI)의 페닐아세트산을 일반식(VII)의 벤즈알데히드와 축합시켜 일반식(VIII)의 2,3-디아릴프로펜산을 얻고 이를 메틸 에스터화시켜 일반식(IX)의 화합물을 얻고 이를 수소화시켜 일반식(X)의 알콜을 얻고 이를 산화시켜 일반식(XI)의 알데히드를 얻고 이 알데히드를 아세토페논과 축합하여 일반식(Id)의 1,4,5-트리페닐-2,4-펜탄디엔-1-온 유도체를 합성하는 것을 포함하는 일반식(I)의 화합물을 제조방법.(6) Condensation of phenylacetic acid of general formula (VI) with benzaldehyde of general formula (VII) to give 2,3-diarylpropenic acid of general formula (VIII), which is methyl esterified to give a compound of general formula (IX) And hydrogenated to obtain an alcohol of general formula (X), which is oxidized to give an aldehyde of general formula (XI), which is condensed with acetophenone to yield 1,4,5-triphenyl-2 of general formula (Id). A method for producing a compound of formula (I), comprising synthesizing a, 4-pentanedien-1-one derivative. (I)(I) (Ia)(Ia) (Ib)(Ib) (Ic)(Ic) (Id)(Id) (II)(II) (III)(III) (IV)(IV) (V)(V) (VI)(VI) (VII)(VII) (VIII)(VIII) (XI)(XI) 약제학적으로 허용되는 담체와 함께 일반식(I)의 1,4-디히드록시벤젠 유도체를 유효성분으로 함유함을 특징으로 하는 항암제 조성물.An anticancer composition comprising a 1,4-dihydroxybenzene derivative of formula (I) as an active ingredient together with a pharmaceutically acceptable carrier.
KR10-2001-0074621A 2001-11-28 2001-11-28 1,3-dihydroxybenzene derivatives, a process for the preparation thereof, and a composition as a anticancer agent comprising them KR100466168B1 (en)

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WO1999000114A2 (en) * 1997-06-26 1999-01-07 Statens Serum Institut Biologically active 1,3-bis-aromatic-prop-2-en-1-ones, 1,3-bis-aromatic-propan-1-ones, and 1,3-bis-aromatic-prop-2-yn-1-ones

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WO1999000114A2 (en) * 1997-06-26 1999-01-07 Statens Serum Institut Biologically active 1,3-bis-aromatic-prop-2-en-1-ones, 1,3-bis-aromatic-propan-1-ones, and 1,3-bis-aromatic-prop-2-yn-1-ones

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