KR20220156464A

KR20220156464A - Novel compound and composition for inhibiting biofilm formation or virulence of pathogenic bacteria comprising the same as active ingredient

Info

Publication number: KR20220156464A
Application number: KR1020220060568A
Authority: KR
Inventors: 이준희; 황현지; 문형룡; 최희정; 홍소정
Original assignee: 부산대학교 산학협력단
Priority date: 2021-05-18
Filing date: 2022-05-18
Publication date: 2022-11-25
Also published as: KR20220156463A

Abstract

The present invention relates to a composition and a method for inhibiting the biofilm formation or virulence of pathogenic microorganisms, wherein the composition can inhibit the formation of biofilms while simultaneously inhibiting the generation and pathogenicity of virulence factors in bacteria, does not inhibit the growth of bacteria, such that resistance to bacteria does not occur, and can exhibit effects at an extremely low concentration and thus has sufficient stability. The composition can therefore be helpful in the development of a method or an agent for treating infectious diseases caused by pathogenic microorganisms.

Description

신규 화합물 및 이를 유효성분으로 함유하는 병원성 미생물의 생물막 형성 또는 병독성 억제용 조성물{Novel compound and composition for inhibiting biofilm formation or virulence of pathogenic bacteria comprising the same as active ingredient}Novel compound and composition for inhibiting biofilm formation or virulence of pathogenic microorganisms containing the same as an active ingredient {Novel compound and composition for inhibiting biofilm formation or virulence of pathogenic bacteria comprising the same as active ingredient}

본 발명은 신규 화합물, 이를 유효성분으로 함유하는 병원성 미생물의 생물막 형성 또는 병독성 억제용 조성물 및 억제방법을 제공한다.The present invention provides a novel compound, a composition for inhibiting biofilm formation or virulence of pathogenic microorganisms containing them as an active ingredient, and a method for inhibiting them.

세균이 감염된 부분에는, 폴리머 (polymer) 기질로 감싸인 세균의 집락인 점액질이 존재할 때가 있다. 이 세균에 의해 형성된 점액질의 세균 복합체를 생물막 (biofilm) 또는 균막이라고 부른다. 생물막은 다당류와 폴리펩타이드로 이루어진 폴리머 기질 (polymeric matrix) 외막에 둘러싸인 미생물들의 3차원적 복합체 구조물로써, 고형 (solid)의 생물학적 혹은 비생물학적 표면 (biological or non-biological surface) 모두에 형성되는 세균 집락이다. 생물막 내부에서 세균은 서로 의사소통을 하고, 외부세계에 대하여 방어를 한다. 이를 통하여 생물막은 항생제를 포함한 여러 환경 스트레스 (environmental stress) 아래에서도 세균의 생존을 가능하게 만든다.In the area infected with bacteria, mucilage, which is a colony of bacteria wrapped in a polymer matrix, is sometimes present. The mucilaginous bacterial complex formed by these bacteria is called a biofilm or biofilm. A biofilm is a three-dimensional complex structure of microorganisms surrounded by an outer membrane of a polymeric matrix composed of polysaccharides and polypeptides, and is a bacterial colony formed on both biological and non-biological surfaces. to be. Inside the biofilm, bacteria communicate with each other and defend against the outside world. Through this, the biofilm enables the survival of bacteria under various environmental stresses including antibiotics.

이런 생물막은 일반 자연환경 외에 세균감염성 질환과 관련하여서도 자주 발견된다. 사람의 장기에 형성되기도 하고 치아의 플라크 형태로 나타나기도 하며, 산업용 장비나 의료용 이식 기구에 생길 수도 있다. 이런 탓에 생물막은 치주 질환 (periodontal disease)이나 낭포성 섬유증 (cystic fibrosis)에 동반하는 폐렴, 중이 (middle ear)에 생기는 이통 (earache) 등을 연구하는 학자들의 관심 대상이 되어 왔다. 박테리아 군의 최대 80 %가 이 같은 생물막 형성을 통해 병원균을 퍼트리고 있는 것으로 추산했다.These biofilms are frequently found in relation to bacterial infectious diseases in addition to the general natural environment. It can form on human organs, appear in the form of plaque on teeth, and can also occur on industrial equipment or medical implants. For this reason, biofilms have been of interest to scholars who study periodontal disease, pneumonia accompanying cystic fibrosis, and earache in the middle ear. It was estimated that up to 80% of bacterial populations spread pathogens through such biofilm formation.

이러한 이유들로 인하여 생물막이 형성되면 감염증 치료에 널리 사용되던 항생제의 작용이 어렵게 되어 결과적으로 항생제에 의한 치료 효과가 약화되며, 만성적인 세균 감염 상태에 돌입하게 된다. 이 경우 상기에 기술했듯이 세균들의 항생제에 대한 감수성이 낮아져 항생제를 사용해도 거의 효과가 없으며 이를 극복하기 위해 단순하게 항생제를 과다처방하면 세균의 항생제 내성만을 키우게 된다. 즉, 생물막이 형성된 세균 감염증은 단순히 항생제로만 치료하는 것은 더 이상 효과적 치료가 되지 못함을 의미한다. 특히, 생물막을 형성하고 있는 세균에 의한 감염은 여러 가지 항생제에 대해 내성을 갖는 다제내성 (multi-drug resistance) 균에 의한 경우가 많아 더욱 문제가 심각해진다.For these reasons, when a biofilm is formed, the action of antibiotics widely used in the treatment of infections becomes difficult, and as a result, the treatment effect of antibiotics is weakened, and a chronic bacterial infection state is entered. In this case, as described above, the susceptibility of bacteria to antibiotics is lowered, and antibiotics are almost ineffective. In other words, it means that simply treating bacterial infections with biofilms with antibiotics is no longer an effective treatment. In particular, infections caused by bacteria forming biofilms are often caused by multi-drug resistance bacteria that are resistant to various antibiotics, making the problem more serious.

따라서, 상기 문제를 해결하기 위하여, 생물막 또는 생물막에 존재하는 외막을 파괴할 수 있는 치료제의 개발이 필요한 실정이다.Therefore, in order to solve the above problem, it is necessary to develop a biofilm or a therapeutic agent capable of destroying the outer membrane present in the biofilm.

1. 대한민국 공개특허 10-2016-0025445호.1. Republic of Korea Patent Publication No. 10-2016-0025445.

본 발명의 목적은 신규 화합물 및 이의 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용도 및 억제방법을 제공하는 데에 있다.An object of the present invention is to provide new compounds and their use and methods for inhibiting biofilm formation or virulence of pathogenic microorganisms.

본 발명의 또 다른 목적은 신규 화합물을 포함하는 병원성 미생물에 의한 감염성 질환 예방 또는 치료용 약학 조성물을 제공하는 데에 있다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating infectious diseases caused by pathogenic microorganisms containing a novel compound.

본 발명의 또 다른 목적은 신규 화합물을 포함하는 병원성 미생물에 의한 감염성 질환 예방 또는 개선용 건강기능식품 조성물 또는 화장료 조성물을 제공하는 데에 있다.Another object of the present invention is to provide a health functional food composition or cosmetic composition for preventing or improving infectious diseases caused by pathogenic microorganisms containing novel compounds.

상기 목적을 달성하기 위하여, 본 발명은 하기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 제공한다.In order to achieve the above object, the present invention provides a compound selected from a compound characterized by being represented by the following formula (I), a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof.

[화학식 I][Formula I]

이때, 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소 또는 황이고; 상기 R⁵가 수소 또는 (C1~C4)알킬이고; 1) 상기 R⁴가 수소이고, i) 상기 R¹ 내지 R³ 중 어느 하나는 (C1~C4)알킬, 나이트로 또는 페녹시이고, 나머지는 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬 또는 (C1~C4)알콕시, 또는 ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있거나, 2) 상기 R⁴가 (C1~C4)알킬 또는 (C1~C4)알콕시페닐이고, i) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시, 또는 ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있다.At this time, the

is a single bond or a double bond; X is oxygen or sulfur; wherein R ⁵ is hydrogen or (C1~C4)alkyl; 1) R ⁴ is hydrogen, i) any one of R ¹ to R ³ is (C1-C4) alkyl, nitro or phenoxy, the others may be the same or different, and hydrogen, hydroxy, halogen , (C1~C4)alkyl or (C1~C4)alkoxy, or ii) wherein R ¹ is hydrogen, and R ² and R ³ may be connected to each other to form a dioxol or benzene ring, or 2) Wherein R ⁴ is (C1~C4)alkyl or (C1~C4)alkoxyphenyl, i) wherein R ¹ to R ³ may be the same or different, respectively, hydrogen, hydroxy, halogen, (C1~C4)alkyl, (C1~C4) alkoxy, nitro, benzyloxy or phenoxy that is unsubstituted or substituted with halogen, or ii) wherein R ¹ is hydrogen, and R ² and R ³ are connected to form a dioxol or benzene ring can form

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물을 제공한다.In addition, the present invention relates to the formation of a biofilm or virulence of pathogenic microorganisms, including a compound selected from a compound characterized in that represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof. An inhibitory composition is provided.

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention is for preventing or treating infectious diseases caused by pathogenic microorganisms, including a compound selected from a compound characterized by the formula (I), a stereoisomer thereof, a racemate thereof, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition is provided.

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention is for preventing or improving infectious diseases caused by pathogenic microorganisms, including a compound selected from a compound characterized by the formula (I), a stereoisomer thereof, a racemate thereof, or a pharmaceutically acceptable salt thereof. It provides a health functional food composition.

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 개선용 화장료 조성물을 제공한다.In addition, the present invention is for preventing or improving infectious diseases caused by pathogenic microorganisms, including a compound selected from a compound characterized by the formula (I), a stereoisomer thereof, a racemate thereof, or a pharmaceutically acceptable salt thereof. A cosmetic composition is provided.

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제방법을 제공한다.In addition, the present invention relates to the formation of a biofilm or virulence of pathogenic microorganisms, including a compound selected from a compound characterized in that represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof. Provides suppression methods.

본 발명은 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물 및 억제방법에 관한 것으로, 상기 조성물은 세균에서 병독인자의 생성과 병원성을 억제하거나, 생물막 형성도 억제할 수 있고, 특히, 세균의 성장을 저해하지 않기 때문에 선택압이 작용하지 않기에 내성이 발생하지 않으며, 극히 낮은 농도에서도 효과를 나타낼 수 있다. The present invention relates to a composition and method for inhibiting biofilm formation or virulence of pathogenic microorganisms. Because it does not inhibit growth, it does not cause selection pressure, so tolerance does not occur, and it can show effects even at extremely low concentrations.

도 1은 본 발명에 따른 화합물의 합성 모식도를 나타낸다.
도 2는 본 발명에 따른 화합물의 LasR의 활성을 나타낸다.
도 3은 본 발명에 따른 화합물의 프로테아제 활성 감소를 나타낸다.
도 4는 본 발명에 따른 화합물의 독성을 확인한 결과를 나타낸다.
도 5는 본 발명에 따른 화합물의 생물막 형성 억제효과를 나타낸다.
도 6은 본 발명에 따른 화합물이 낮은 농도에서도 효과가 있는지 여부를 확인한 것을 나타낸다.
도 7은 본 발명에 따른 화합물이 낮은 농도에서도 생물막 형성 억제 효과를 확인한 것을 나타낸다.
도 8은 본 발명에 따른 화합물이 세균의 성장을 저해여부를 확인한 것을 나타낸다.1 shows a schematic diagram of the synthesis of the compound according to the present invention.
Figure 2 shows the LasR activity of the compounds according to the present invention.
Figure 3 shows the reduced protease activity of the compounds according to the present invention.
Figure 4 shows the results of confirming the toxicity of the compound according to the present invention.
Figure 5 shows the biofilm formation inhibitory effect of the compound according to the present invention.
Figure 6 shows whether or not the compound according to the present invention is effective even at low concentrations.
Figure 7 shows that the compound according to the present invention confirmed the biofilm formation inhibitory effect even at low concentrations.
8 shows whether or not the compound according to the present invention inhibits the growth of bacteria.

이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.

본 발명자들은 신규 화합물을 개발하여, 병원성 미생물에 의한 감염성 질환에 대한 치료 또는 예방 효과가 있는 새로운 용도를 확인하여 본 발명을 완성하였다.The inventors of the present invention completed the present invention by developing a novel compound and confirming a new use having a therapeutic or preventive effect on infectious diseases caused by pathogenic microorganisms.

본 발명은 하기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 제공한다.The present invention provides a compound selected from compounds characterized by the following formula (I), stereoisomers thereof, racemates thereof, and pharmaceutically acceptable salts thereof.

[화학식 I][Formula I]

이때, 상기

상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고, 상기 X는 산소 또는 황이고; 상기 R⁴는 수소이고; 상기 R⁵가 수소이고; i) 상기 R¹ 내지 R³ 중 어느 하나는 (C1~C4)알킬, 나이트로 또는 페녹시이고, 나머지는 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬 또는 (C1~C4)알콕시, 또는 ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있다.In Formula I above

is a single bond or a double bond, and X is oxygen or sulfur; wherein R ⁴ is hydrogen; wherein R ⁵ is hydrogen; i) wherein any one of R ¹ to R ³ is (C1~C4)alkyl, nitro or phenoxy, the others may be the same or different, and hydrogen, hydroxy, halogen, (C1~C4)alkyl or ( C1~C4) alkoxy, or ii) wherein R ¹ is hydrogen, and R ² and R ³ are connected to each other to form a dioxol or benzene ring.

상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고, 상기 X는 산소 또는 황이고; 상기 R⁴는 (C1~C2)알킬 또는 (C1~C2)알콕시페닐이고; 상기 R⁵가 수소 또는 메틸이고; i) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있다.In Formula I above

is a single bond or a double bond, and X is oxygen or sulfur; wherein R ⁴ is (C1~C2)alkyl or (C1~C2)alkoxyphenyl; wherein R ⁵ is hydrogen or methyl; i) The R ¹ to R ³ may be the same or different, respectively, and are hydrogen, hydroxy, halogen, (C1~C4)alkyl, (C1~C4)alkoxy, nitro, benzyloxy optionally substituted with halogen, or phenoxy, or ii) wherein R ¹ is hydrogen, and R ² and R ³ are connected to each other to form a dioxol or benzene ring.

상기 화합물은 하기 화합물 Az 내지 화합물 Hk로 이루어진 군에서 선택될 수 있다.The compound may be selected from the group consisting of Compound Az to Compound Hk.

(화합물 Az) 5-(나프탈렌-1-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Az) 5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine -4,6( 1H , 5H )-dione];

(화합물 AB) 5-(4-하이드록시-3,5-디아이소프로필벤질리덴)-2-티옥소하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-diisopropylbenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound AB) 5-(4-hydroxy-3,5-diisopropylbenzylidene)-2-thioxohydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy -3,5-diisopropylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Bq) 5-(4-플루오로벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Fluorobenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Bq) 5-(4-fluorobenzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Fluorobenzylidene)pyrimidine-2,4,6 ( 1H , 3H , 5H )-trione];

(화합물 Bu) 5-(4-((4-플루오로벤질)옥시)벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Bu) 5-(4-((4-fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-( (4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Bx) 5-(벤조[d][1,3]디옥솔-5-일메틸렌)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Bx) 5-(benzo[ d ][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione [5-(Benzo [ d ][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6( 1H , 3H ,5H) -trione ];

(화합물 BA) 5-(나프탈렌-2-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound BA) 5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6( 1H,3H,5H)-trione];

(화합물 Cn) 5-(3,5-디-tert-부틸-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,5-Di-tert-butyl-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cn) 5-(3,5-di- tert -butyl-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3 ,5- Ditert -butyl-4-hydroxybenzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];

(화합물 Cq) 5-(4-플루오로벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cq) 5-(4-fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Cr) 5-(2-나이트로벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cr) 5-(2-nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Cv) 5-(4-((4-클로로벤질)옥시)벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-((4-Chlorobenzyl)oxy)benzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cv) 5-(4-((4-chlorobenzyl)oxy)benzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(( 4-Chlorobenzyl)oxy)benzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];

(화합물 Cw) 5-(3-페녹시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cw) 5-(3-phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Cx) 5-(벤조[d][1,3]디옥솔-5-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione [5-( Benzo[ d ][1,3]dioxol-5-ylmethyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];

(화합물 Cz) 5-(나프탈렌-1-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione]; (Compound Cz) 5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine -4,6( 1H , 5H )-dione];

(화합물 CB) 5-(4-하이드록시-3,5-디아이소프로필벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound CB) 5-(4-hydroxy-3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy -3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Dq) 5-(4-플루오로벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Fluorobenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Dq) 5-(4-fluorobenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Fluorobenzyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Du) 5-(4-((4-플루오로벤질)옥시)벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Du) 5-(4-((4-fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-(( 4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Dx) 5-(벤조[d][1,3]디옥솔-5-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Dx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Benzo [ d ][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6( 1H , 3H ,5H) -trione ];

(화합물 Dy) 5-((2-하이드록시나프탈렌-1-일)메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-((2-Hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Dy) 5-((2-hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione [5-((2- Hydroxynaphthalen- 1-yl)methyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 DA) 5-(나프탈렌-2-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound DA) 5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4 ,6( 1H , 3H ,5H) -trione ];

(화합물 Ef-1) (E)-5-(3-하이드록시-4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ef-1) ( E )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H)-trione [ (E ) -5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione] ;

(화합물 Ef-2) (Z)-5-(3-하이드록시-4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ef-2) ( Z )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H)-trione [( Z )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H ) -trione ] ;

(화합물 Ep-1) (E)-5-(4-하이드록시-3,5-디메틸벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; (Compound Ep-1) ( E )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H )-trione [( E )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];

(화합물 Ep-2) (Z)-5-(4-하이드록시-3,5-디메틸벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; (Compound Ep-2) ( Z )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H )-trione [( Z )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];

(화합물 Ex-1) (E)-5-(벤조[d][1,3]디옥솔-5-일메틸렌)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ex-1) ( E )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3H ,5H)-trione [ (E ) -5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Ex-2) (Z)-5-(벤조[d][1,3]디옥솔-5-일메틸렌)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ex-2) ( Z )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3H ,5H) -trione [( Z )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Fa) 5-(4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fa) 5-(4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4- Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fb) 5-(3,4-디하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fb) 5-(3,4-dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Fc) 5-(2,4-디하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fc) 5-(2,4-dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (2,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fd) 5-(4-하이드록시-3-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fd) 5-(4-hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(4-Hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fe) 5-(3-에톡시;-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fe) 5-(3-ethoxy;-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3-Ethoxy-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Ff) 5-(3-하이드록시-4-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ff) 5-(3-hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(3-Hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fg) 5-(4-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fg) 5-(4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4- Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fh) 5-(3,4-디메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fh) 5-(3,4-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-( 3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fi) 5-(2,4-디메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fi) 5-(2,4-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-( 2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fj) 1-(4-메톡시페닐)-5-(3,4,5-트리메톡시벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fj) 1-(4-methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fk) 5-(4-하이드록시-3,5-디메톡시벤질)-1-(4메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fk) 5-(4-hydroxy-3,5-dimethoxybenzyl)-1-(4methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fl) 5-(3,5-디브로모-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,5-Dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fl) 5-(3,5-dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )- trione [5-(3,5-Dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fm) 5-(3-브로모-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fm) 5-(3-bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(3-Bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fp) 5-(4-하이드록시-3,5-디메틸벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fp) 5-(4-hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Fx) 5-(벤조[d][1,3]디옥솔-5-일메틸)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Fx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )- trione];

(화합물 Ga) 5-(4-하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ga) 5-(4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxybenzylidene) -1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Gb) 5-(3,4-디하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Gb) 5-(3,4-dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 ,4-Dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Gd) 5-(4-하이드록시-3-메톡시벤지리딘)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Gd) 5-(4-hydroxy-3-methoxybenziridine)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (4-Hydroxy-3-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Ge) 5-(3-에톡시-4-하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ge) 5-(3-ethoxy-4-hydroxybenzyridene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3-Ethoxy-4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Gf) 5-(3-하이드록시-4-메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Gf) 5-(3-hydroxy-4-methoxybenzyridene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3-Hydroxy-4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Gg) 5-(4-메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione]; (Compound Gg) 5-(4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzylidene) -1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Gk) 5-(4-하이드록시-3,5-디메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Gk) 5-(4-hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Ha) 5-(4-하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Ha) 5-(4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxybenzyl)-1 ,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Hb) 5-(3,4-디하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Hb) 5-(3,4-dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4 -Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Hd) 5-(4-하이드록시-3-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Hd) 5-(4-hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4 -Hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 He) 5-(3-에톡시-4-하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound He) 5-(3-ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 -Ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Hf) 5-(3-하이드록시-4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Hf) 5-(3-hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 -Hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Hg) 5-(4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione]; 및(Compound Hg) 5-(4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzyl)-1 ,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione]; and

(화합물 Hk) 5-(4-하이드록시y-3,5-디메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione].(Compound Hk) 5-(4-hydroxyy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5 -(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione].

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물을 제공하는데, 상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소 또는 황이고; 1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고; 상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며, 상기 R⁵가 수소 또는 (C1~C4)알킬일 수 있다.In addition, the present invention relates to the formation of a biofilm or virulence of pathogenic microorganisms, including a compound selected from a compound characterized in that represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof. Provided is an inhibitory composition, wherein in Formula I above

is a single bond or a double bond; X is oxygen or sulfur; 1) The R ¹ to R ³ may be the same or different, respectively, and are hydrogen, hydroxy, halogen, (C1~C4)alkyl, (C1~C4)alkoxy, nitro, benzyloxy which is optionally substituted with halogen, or phenoxy, or 2) wherein R ¹ is hydrogen, and R ² and R ³ are connected to form a dioxol or benzene ring; R ⁴ is hydrogen, (C1~C4)alkyl, or (C1~C4)alkoxyphenyl, and R ⁵ may be hydrogen or (C1~C4)alkyl.

상기 화학식 I에 있어서, 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소 또는 황이고; 1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 브롬, 플루오르, 메틸, 아이소프로필 (iso-Pr), 털트-부틸 (tert-Bu), 메톡시, 에톡시, 나이트로, 플로오르 또는 염소로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고; 상기 R⁴는 수소인 화합물이며, 상기 R⁵가 수소일 수 있으며, 바람직하게, 상기 화합물은 하기 화합물 Aa 내지 화합물 BA로 이루어진 군에서 선택될 수 있다.In the above formula I,

is a single bond or a double bond; X is oxygen or sulfur; 1) The R ¹ to R ³ may be the same or different, respectively, and are selected from hydrogen, hydroxy, bromine, fluorine, methyl, isopropyl (iso-Pr), tert-butyl (tert-Bu), methoxy, ethoxy, benzyloxy or phenoxy, optionally substituted with nitro, fluorine or chlorine, or 2) wherein R ¹ is hydrogen, and R ² and R ³ are connected to each other to form a dioxol or benzene ring. there is; R ⁴ is a hydrogen compound, wherein R ⁵ may be hydrogen, and preferably, the compound may be selected from the group consisting of compounds Aa to BA.

(화합물 Aa) 5-(4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Aa) 5-(4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(4-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6 (1H,5H)-dione];

(화합물 Ab) 5-(3,4-디하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H, 5H)-디온 [5-(3, 4-Dihydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ab) 5-(3,4-dihydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3,4-Dihydroxybenzylidene)-2- thioxodihydropyrimidine-4, 6(1H, 5H)-dione];

(화합물 Ac) 5-(2,4-디하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H, 5H)-디온 [5-(2,4-Dihydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione];(Compound Ac) 5-(2,4-dihydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione [5-(2,4-Dihydroxybenzylidene)-2- thioxodihydropyrimidine-4,6(1H, 5H)-dione];

(화합물 Ad) 5-(4-하이드록시-3-메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3-methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione];(Compound Ad) 5-(4-hydroxy-3-methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(4-Hydroxy-3-methoxybenzylidene )-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione];

(화합물 Ae) 5-(3-에톡시-4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Ethoxy-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ae) 5-(3-ethoxy-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3-Ethoxy-4-hydroxybenzylidene )-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];

(화합물 Af) 5-(3-하이드록시-4-메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온[5-(3-Hydroxy-4-methoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Af) 5-(3-hydroxy-4-methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione[5-(3-Hydroxy-4-methoxybenzylidene )-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];

(화합물 Ag) 5-(4-메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ag) 5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4,6 (1H, 5H)-dione];

(화합물 Ah) 5-(3, 4-디메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ah) 5-(3,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine -4, 6(1H, 5H)-dione];

(화합물 Ai) 5-(2, 4-디메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2, 4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ai) 5-(2,4-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(2,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine -4, 6(1H, 5H)-dione];

(화합물 Aj) 2-티옥소-5-(3, 4, 5-트리메톡시벤질리덴)디하이드로피리미딘-4, 6(1H, 5H)-디온 [2-Thioxo-5-(3, 4, 5-trimethoxybenzylidene)dihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Aj) 2-thioxo-5-(3,4,5-trimethoxybenzylidene)dihydropyrimidine-4,6(1H,5H)-dione [2-Thioxo-5-(3,4 , 5-trimethoxybenzylidene)dihydropyrimidine-4,6(1H,5H)-dione];

(화합물 Ak) 5-(4-하이드록시-3, 5-디메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온[5-(4-Hydroxy-3, 5-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ak) 5-(4-hydroxy-3,5-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione[5-(4-Hydroxy-3 , 5-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];

(화합물 Am) 5-(3-브로모-4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Bromo-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Am) 5-(3-Bromo-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3-Bromo-4-hydroxybenzylidene )-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];

(화합물 An) 5-(3, 5-디-tert-부틸-4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound An) 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];

(화합물 Ao) 5-(2-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ao) 5-(2-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(2-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6 (1H, 5H)-dione];

(화합물 Ap) 5-(4-하이드록시-3, 5-디메틸벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Ap) 5-(4-hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy- 3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Aq) 5-(4-플루오로벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H,5H)-디온 [5-(4-Fluorobenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Aq) 5-(4-fluorobenzylidene)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione [5-(4-Fluorobenzylidene)-2-thioxodihydropyrimidine-4 ,6( 1H , 5H )-dione];

(화합물 Ar) 5-(2-니트로벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H,5H)-디온 [5-(2-Nitrobenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Ar) 5-(2-nitrobenzylidene)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione [5-(2-Nitrobenzylidene)-2-thioxodihydropyrimidine-4 ,6( 1H , 5H )-dione];

(화합물 As) 5-(4-(벤질옥시)벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-(Benzyloxy)benzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound As) 5-(4-(benzyloxy)benzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(Benzyloxy)benzylidene)- 2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];

(화합물 Av) 5-(4-(4-클로로벤질옥시)벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-(4-Chlorobenzyloxy)benzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Av) 5-(4-(4-chlorobenzyloxy)benzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(4-) Chlorobenzyloxy)benzylidene)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];

(화합물 Aw) 5-(3-페녹시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3-Phenoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Aw) 5-(3-phenoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Phenoxybenzylidene)-2-thioxodihydropyrimidine-4 ,6( 1H , 5H )-dione];

(화합물 Ax) 5-(벤조[d][1,3]디옥솔-5-일메틸렌)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(Benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ax) 5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione [5-( Benzo[ d ][1,3]dioxol-5-ylmethylene)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];

(화합물 Ba) 5-(4-하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ba) 5- (4-hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (4-Hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H)-trione];

(화합물 Bb) 5-(3,4-디하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3,4-Dihydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bb) 5-(3,4-dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(3,4-Dihydroxybenzylidene)pyrimidine-2,4 , 6(1H, 3H, 5H)-trione];

(화합물 Bc) 5-(2,4-디하이드록시벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Bc) 5-(2,4-dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(2,4-Dihydroxybenzylidene)pyrimidine-2,4 ,6(1H,3H,5H)-trione];

(화합물 Bd) 5-(4-하이드록시-3-메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bd) 5-(4-hydroxy-3-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione [5-(4-Hydroxy-3-methoxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];

(화합물 Be) 5-(3-에톡시-4-하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Be) 5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione [5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];

(화합물 Bf) 5-(3-하이드록시-4-메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Hydroxy-4-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bf) 5-(3-hydroxy-4-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione [5-(3-Hydroxy-4-methoxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];

(화합물 Bg) 5-(4-메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bg) 5-(4-Methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(4-Methoxybenzylidene)pyrimidine-2,4,6(1H, 3H, 5H)-trione];

(화합물 Bh) 5-(3, 4-디메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4-Dimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bh) 5-(3,4-dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(3,4-Dimethoxybenzylidene)pyrimidine-2,4, 6(1H, 3H, 5H)-trione];

(화합물 Bi) 5-(2, 4-디메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H) -트리온 [5-(2, 4-Dimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bi) 5- (2, 4-dimethoxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (2, 4-Dimethoxybenzylidene) pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];

(화합물 Bj) 5-(3, 4, 5-트리메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4, 5-Trimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bj) 5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(3,4,5-Trimethoxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];

(화합물 Bk) 5-(4-하이드록시-3, 5-디메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3, 5-dimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bk) 5-(4-hydroxy-3,5-dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(4-Hydroxy-3,5 -dimethoxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H)-trione];

(화합물 Bl) 5-(3, 5-디브로모-4-하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 5-Dibromo-4-hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Bl) 5- (3, 5-dibromo-4-hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (3, 5-Dibromo- 4-hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H)-trione];

(화합물 Bs) 5-(4-(벤질옥시)벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Bs) 5-(4-(benzyloxy)benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-(Benzyloxy)benzylidene)pyrimidine- 2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Bt) 5-(3-(벤질옥시)벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Bt) 5-(3-(benzyloxy)benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3-(Benzyloxy)benzylidene)pyrimidine- 2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 By) 5-((2-하이드록시나프탈렌-1-일)메틸렌)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온[5-((2-Hydroxynaphthalen-1-yl)methylene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound By) 5-((2-hydroxynaphthalen-1-yl)methylene)pyrimidine-2,4,6( 1H , 3H ,5H)-trione[5-((2- Hydroxynaphthalen- 1-yl) methylene) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];

(화합물 Ca) 5-(4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ca) 5-(4-hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione [5-(4-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Cb) 5-(3, 4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Cb) 5-(3,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];

(화합물 Cc) 5-(2, 4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2, 4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Cc) 5-(2,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];

(화합물 Cd) 5-(4-하이드록시-3-메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Cd) 5-(4-hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy-3- methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione];

(화합물 Ce) 5-(3-에톡시-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ce) 5-(3-ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Ethoxy-4- hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione];

(화합물 Cf) 5-(3-하이드록시-4-메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Hydroxy-4-methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Cf) 5-(3-hydroxy-4-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Hydroxy-4- methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione];

(화합물 Cg) 5-(4-메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Cg) 5-(4-methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Ch) 5-(3, 4-디메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ch) 5-(3,4-dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4-Dimethoxybenzyl)-2- thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];

(화합물 Ci) 5-(2, 4-디메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2, 4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ci) 5-(2,4-dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2,4-Dimethoxybenzyl)-2- thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];

(화합물 Cj) 5-(3, 4, 5-트리메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4, 5-Trimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Cj) 5-(3,4,5-trimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4,5- Trimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione];

(화합물 Ck) 5-(4-하이드록시-3, 5-디메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3, 5-dimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Ck) 5-(4-hydroxy-3,5-dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy- 3, 5-dimethoxybenzyl) -2-thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];

(화합물 Cl) 5-(3,5-디브로모-4-하이드록시)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,5-Dibromo-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione]; (Compound Cl) 5-(3,5-dibromo-4-hydroxy)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,5- Dibromo-4-hydroxybenzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];

(화합물 Cm) 5-(3-브로모-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Bromo-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Cm) 5-(3-bromo-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Bromo-4- hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione];

(화합물 Co) 5-(2-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H, 5H)-디온 [5-(2-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];(Compound Co) 5-(2-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H , 5 H )-dione [5-(2-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Cp) 5-(4-하이드록시-3,5-디메틸벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-dimethylbenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cp) 5-(4-hydroxy-3,5-dimethylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy-3 ,5-dimethylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Cs) 5-(4-(벤질옥시)벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-(Benzyloxy)benzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cs) 5-(4-(benzyloxy)benzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(Benzyloxy)benzyl)-2 -thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Cw) 5-(3-페녹시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cw) 5-(3-phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Cz) 5-(나프탈렌-1-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cz) 5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine -4,6( 1H , 5H )-dione];

(화합물 Da) 5-(4-하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Da) 5- (4-hydroxybenzyl) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (4-Hydroxybenzyl) pyrimidine-2, 4, 6 (1 H , 3H , 5H )-trione];

(화합물 Db) 5-(3, 4-디하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4-Dihydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Db) 5-(3,4-dihydroxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4-Dihydroxybenzyl)pyrimidine-2 , 4, 6 (1 H , 3 H , 5 H )-trione];

(화합물 Dc) 5-(2, 4-디하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(2, 4-Dihydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione]; (Compound Dc) 5- (2, 4-dihydroxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione [5- (2, 4-Dihydroxybenzyl) pyrimidine-2 , 4, 6 (1 H , 3 H , 5 H )-trione];

(화합물 Dd) 5-(4-하이드록시-3-메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Dd) 5-(4-hydroxy-3-methoxybenzyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione [5-(4-Hydroxy-3-methoxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];

(화합물 De) 5-(3-에톡시-4-하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound De) 5-(3-ethoxy-4-hydroxybenzyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [5-(3-Ethoxy-4-hydroxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];

(화합물 Df) 5-(3-하이드록시-4-메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Df) 5-(3-hydroxy-4-methoxybenzyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione [5-(3-Hydroxy-4-methoxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];

(화합물 Dg) 5-(4-메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Methoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Dg) 5-(4-Methoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzyl)pyrimidine-2,4,6( 1 H , 3 H , 5 H )-trione];

(화합물 Dh) 5-(3, 4-디메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4-Dimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Dh) 5- (3, 4-dimethoxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione [5- (3, 4-Dimethoxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H )-trione];

(화합물 Di) 5-(2, 4-디메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(2, 4-Dimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Di) 5-(2,4-dimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(2,4-Dimethoxybenzyl)pyrimidine-2, 4, 6 (1 H , 3 H , 5 H )-trione];

(화합물 Dj) 5-(3, 4, 5-트리메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4, 5-Trimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Dj) 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4,5-Trimethoxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];

(화합물 Dk) 5-(4-하이드록시-3, 5-디메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3, 5-dimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Dk) 5-(4-hydroxy-3,5-dimethoxybenzyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [5-(4-Hydroxy-3 , 5-dimethoxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];

(화합물 Dl) 5-(3, 5-디브로모-4-하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 5-Dibromo-4-hydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Dl) 5-(3,5-dibromo-4-hydroxybenzyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [5-(3,5- Dibromo-4-hydroxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];

(화합물 Dt) 5-(3-(벤질옥시)벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-(Benzyloxy)benzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Dt) 5-(3-(benzyloxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3-(Benzyloxy)benzyl)pyrimidine-2 ,4,6( 1H , 3H , 5H )-trione];

(화합물 Dy) 5-((2-하이드록시나프탈렌-1-일)메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-((2-Hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; 및(Compound Dy) 5-((2-hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione [5-((2- Hydroxynaphthalen- 1-yl)methyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione]; and

(화합물 DA) 5-(나프탈렌-2-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione].(Compound DA) 5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4 ,6( 1H , 3H ,5H) -trione ].

상기 화학식 I에 있어서, 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소이고; 1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 브롬, 플루오르, 메틸, 아이소프로필 (iso-Pr), 털트-부틸 (tert-Bu), 메톡시, 에톡시, 나이트로, 플로오르 또는 염소로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고; 상기 R⁴는 메톡시페닐인 화합물이며, 상기 R⁵가 수소일 수 있으며, 바람직하게, 상기 화합물은 하기 화합물 Ea-1 내지 화합물 Fx로 이루어진 군에서 선택될 수 있다.In the above formula I,

is a single bond or a double bond; wherein X is oxygen; 1) The R ¹ to R ³ may be the same or different, respectively, and are selected from hydrogen, hydroxy, bromine, fluorine, methyl, isopropyl (iso-Pr), tert-butyl (tert-Bu), methoxy, ethoxy, benzyloxy or phenoxy, optionally substituted with nitro, fluorine or chlorine, or 2) wherein R ¹ is hydrogen, and R ² and R ³ are connected to each other to form a dioxol or benzene ring. there is; R ⁴ is a methoxyphenyl compound, R ⁵ may be hydrogen, and preferably, the compound may be selected from the group consisting of compound Ea-1 to compound Fx.

(화합물 Ea-1) (E)-5-(4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ea-1) ( E )-5-(4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( E )-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];

(화합물 Ea-2) (Z)-5-(4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ea-2) ( Z )-5-(4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( Z )-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];

(화합물 Eb-1) (E)-5-(3, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Eb-1) ( E )-5-(3,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( E )-5-(3,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Eb-2) (Z)-5-(3, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Eb-2) ( Z )-5-(3,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( Z )-5-(3,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Ec-1) (E)-5-(2, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(2, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ec-1) ( E )-5-(2,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( E )-5-(2,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Ec-2) (Z)-5-(2, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(2, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ec-2) ( Z )-5-(2,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( Z )-5-(2,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Ed-1) (E)-5-(4-하이드록시-3-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ed-1) ( E )-5-(4-hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [ (E ) -5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;

(화합물 Ed-2) (Z)-5-(4-하이드록시-3-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ed-2) ( Z )-5-(4-hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H )-trione [( Z )-5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;

(화합물 Ee-1) (E)-5-(3-에톡시-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ee-1) ( E )-5-(3-ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [(E ) -5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;

(화합물 Ee-2) (Z)-5-(3-에톡시-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ee-2) ( Z )-5-(3-ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H )-trione [( Z )-5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;

(화합물 Eg-1) (E)-5-(4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione]; (Compound Eg-1) ( E )-5-(4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( E )-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];

(화합물 Eg-2) (Z)-5-(4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione]; (Compound Eg-2) ( Z )-5-(4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( Z )-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];

(화합물 Eh-1) (E)-5-(3, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Eh-1) ( E )-5-(3,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)- trione [( E )-5-(3,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione];

(화합물 Eh-2) (Z)-5-(3, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Eh-2) ( Z )-5-(3,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)- trione [( Z )-5-(3,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione];

(화합물 Ei-1) (E)-5-(2, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(2, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ei-1) ( E )-5-(2,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H ) -trione [( E )-5-(2,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];

(화합물 Ei-2) (Z)-5-(2, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(2, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ei-2) ( Z )-5-(2,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H ) -trione [( Z )-5-(2,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];

(화합물 Ej-1) (E)-1-(4-메톡시페닐)-5-(3, 4, 5-트리메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-1-(4-Methoxyphenyl)-5-(3, 4, 5-trimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ej-1) ( E )-1-(4-methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1 H , 3 H , 5H) -trione [(E ) -1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione] ;

(화합물 Ej-2) (Z)-1-(4-메톡시페닐)-5-(3, 4, 5-트리메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-1-(4-Methoxyphenyl)-5-(3, 4, 5-trimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ej-2) ( Z )-1-(4-methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [( Z )-1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6( 1H , 3H , 5H ) -trione ] ;

(화합물 Ek-1) (E)-5-(4-하이드록시-3, 5-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Hydroxy-3, 5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ek-1) ( E )-5-(4-hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H ,3 H , 5H )-trione [( E )-5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 Ek-2) (Z)-5-(4-하이드록시-3, 5-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Hydroxy-3, 5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Ek-2) ( Z )-5-(4-hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H ,3 H , 5H )-trione [( Z )-5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];

(화합물 El-1) (E)-5-(3, 5-디브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3, 5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound El-1) ( E )-5-(3,5-dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3 H ,5 H )-trione [( E )-5-(3,5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 El-2) (Z)-5-(3, 5-디브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3, 5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound El-2) ( Z )-5-(3,5-dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3 H ,5 H )-trione [( Z )-5-(3,5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Em-1) (E)-5-(3-브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Em-1) ( E )-5-(3-bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [ (E ) -5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;

(화합물 Em-2) (Z)-5-(3-브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];(Compound Em-2) ( Z )-5-(3-bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H )-trione [( Z )-5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;

(화합물 Fp) 5-(4-하이드록시-3,5-디메틸벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; 및(Compound Fp) 5-(4-hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione]; and

(화합물 Fx) 5-(벤조[d][1,3]디옥솔-5-일메틸)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione].(Compound Fx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )- trione].

상기 화학식 I에 있어서, 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소이고; 1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 브롬, 플루오르, 메틸, 아이소프로필 (iso-Pr), 털트-부틸 (tert-Bu), 메톡시, 에톡시, 나이트로, 플로오르 또는 염소로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고; 상기 R⁴는 메틸인 화합물이며, 상기 R⁵가 메틸일 수 있으며, 바람직하게, 상기 화합물은 하기 화합물 Ga 내지 화합물 Hk로 이루어진 군에서 선택될 수 있다.In the above formula I,

is a single bond or a double bond; wherein X is oxygen; 1) The R ¹ to R ³ may be the same or different, respectively, and are selected from hydrogen, hydroxy, bromine, fluorine, methyl, isopropyl (iso-Pr), tert-butyl (tert-Bu), methoxy, ethoxy, benzyloxy or phenoxy, optionally substituted with nitro, fluorine or chlorine, or 2) wherein R ¹ is hydrogen, and R ² and R ³ are connected to each other to form a dioxol or benzene ring. there is; The R ⁴ is a methyl compound, the R ⁵ may be methyl, and preferably, the compound may be selected from the group consisting of compound Ga to compound Hk.

(화합물 Gg) 5-(4-메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Gg) 5-(4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzylidene) -1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

상기 화합물은 하기 화합물 Ap 내지 화합물 Hk로 이루어진 군에서 선택될 수 있다.The compound may be selected from the group consisting of compound Ap to compound Hk.

(화합물 Ap) 5-(4-하이드록시-3,5-디메틸벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Ap) 5-(4-hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy- 3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Cb) 5-(3,4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cb) 5-(3,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Cc) 5-(2,4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(2,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cc) 5-(2,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Cd) 5-(4-하이드록시-3-메톡시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cd) 5-(4-hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy-3- methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Ce) 5-(3-에톡시-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3-Ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Ce) 5-(3-ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Ethoxy-4- hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];

(화합물 Cg) 5-(4-메톡시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];(Compound Cg) 5-(4-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];

(화합물 Db) 5-(3,4-디하이드록시벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Db) 5-(3,4-dihydroxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4-Dihydroxybenzyl)pyrimidine-2 ,4,6( 1H , 3H , 5H )-trione];

(화합물 Dj) 5-(3,4,5-트리메톡시벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];(Compound Dj) 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4,5-Trimethoxybenzyl) ) pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];

(화합물 Du) 5-(4-((4-플루오로벤질)옥시)벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; 및(Compound Du) 5-(4-((4-fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-(( 4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione]; and

(화합물 Hk) 5-(4-하이드록시-3,5-디메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione].(Compound Hk) 5-(4-hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione].

상기 화합물은 병원성 미생물의 세포사멸 없이 생물막 또는 균막 형성을 억제할 수 있다.The compound can inhibit biofilm or biofilm formation without cell death of pathogenic microorganisms.

상기 화합물은 조성물 내에 30 내지 3,500,000 pg/L의 농도로 첨가될 수 있고, 바람직하게 상기 농도는 31.033 내지 3,103,300 pg/L일 수 있다.The compound may be added in a concentration of 30 to 3,500,000 pg/L in the composition, preferably the concentration may be 31.033 to 3,103,300 pg/L.

상기 병원성 미생물은 녹농균 (Pseudomonas aeruginosa), 대장균 (Escherichia coli), 살모넬라균 (Salmonella enterica) 및 고초균 (Bacillus subtilis)으로 이루어진 군에서 하나 이상 선택될 수 있으나, 이에 한정되는 것은 아니다.The pathogenic microorganism is Pseudomonas aeruginosa ( Pseudomonas aeruginosa ), Escherichia coli ( Escherichia coli ), Salmonella ( Salmonella enterica ), and Bacillus subtilis ( Bacillus subtilis ), but one or more may be selected from the group consisting of, but is not limited thereto.

상기 병원성 미생물에 의한 감염성 질환은 피부염, 육아종, 구내염, 질염, 귀두염, 요도염, 장염, 수막염, 심내막염, 패혈증 및 손발톱염으로 이루어진 군으로부터 선택될 수 있으나, 이에 한정되는 것은 아니다.Infectious diseases caused by the pathogenic microorganisms may be selected from the group consisting of dermatitis, granuloma, stomatitis, vaginitis, balanitis, urethritis, enteritis, meningitis, endocarditis, sepsis, and nailitis, but are not limited thereto.

본 발명의 다른 구체예에서, 약학 조성물은 약학 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제, 붕해제, 감미제, 피복제, 팽창제, 윤활제, 활택제, 향미제, 항산화제, 완충액, 정균제, 희석제, 분산제, 계면활성제, 결합제 및 윤활제로 이루어진 군에서 선택되는 하나 이상의 첨가제를 추가로 포함할 수 있다.In another embodiment of the present invention, the pharmaceutical composition is a suitable carrier, excipient, disintegrant, sweetener, coating agent, swelling agent, lubricant, lubricant, flavoring agent, antioxidant, buffer, bacteriostatic agent, One or more additives selected from the group consisting of diluents, dispersants, surfactants, binders and lubricants may be further included.

구체적으로 담체, 부형제 및 희석제는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 사용할 수 있으며, 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제할 수 있다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용할 수 있다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 있으며 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제 등이 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기재로는 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Specifically, carriers, excipients and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil may be used, and solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules. These solid preparations may be prepared by mixing at least one or more excipients, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, solutions for oral use, emulsions, syrups, and the like, and various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included in addition to commonly used simple diluents such as water and liquid paraffin. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions. As a base material of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.

본 발명의 일실시예에 따르면, 상기 약학 조성물은 정맥내, 동맥내, 복강내, 근육내, 동맥내, 복강내, 흉골내, 경피, 비측내, 흡입, 국소, 직장, 경구, 안구내 또는 피내 경로를 통해 통상적인 방식으로 대상체로 투여할 수 있다.According to one embodiment of the present invention, the pharmaceutical composition is intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, intranasal, inhalational, topical, rectal, oral, intraocular or It can be administered to a subject in a conventional manner via the intradermal route.

본 발명에 따른 유효성분의 투여량은 대상체의 상태 및 체중, 질환의 종류 및 정도, 약물 형태, 투여경로 및 기간에 따라 달라질 수 있으며 당업자에 의해 적절하게 선택될 수 있고, 1일 투여량이 0.01 mg/kg 내지 200 mg/kg, 바람직하게는 0.1 mg/kg 내지 200 mg/kg, 보다 바람직하게는 0.1 mg/kg 내지 100 mg/kg 일 수 있다. 투여는 하루에 한번 투여할 수도 있고 수회로 나누어 투여할 수도 있으며, 이에 의해 본 발명의 범위가 제한되는 것은 아니다.The dosage of the active ingredient according to the present invention may vary depending on the condition and weight of the subject, the type and severity of the disease, the drug type, the route and duration of administration, and may be appropriately selected by a person skilled in the art, and the daily dosage is 0.01 mg. /kg to 200 mg/kg, preferably 0.1 mg/kg to 200 mg/kg, and more preferably 0.1 mg/kg to 100 mg/kg. Administration may be administered once a day or divided into several times, and the scope of the present invention is not limited thereby.

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 개선용 건강기능식품 조성물을 제공하는데, 상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소 또는 황이고; 1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고; 상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며, 상기 R⁵가 수소 또는 (C1~C4)알킬일 수 있다.In addition, the present invention is for preventing or improving infectious diseases caused by pathogenic microorganisms, including a compound selected from a compound characterized by the formula (I), a stereoisomer thereof, a racemate thereof, or a pharmaceutically acceptable salt thereof. Provides a health functional food composition, in the above formula (I)

상기 건강기능식품은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다.The health functional food includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, It may contain organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, and the like.

그밖에 천연 과일 주스, 합성 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 또한, 건강기능식품 조성물은 육류, 소세지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알코올 및 비타민 복합제 중 어느 하나의 형태일 수 있다.In addition, it may contain fruit flesh for the production of natural fruit juice, synthetic fruit juice and vegetable beverages. These components may be used independently or in combination. In addition, the health functional food composition is any one form of meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcohol and vitamin complex can be

또한, 상기 건강기능식품은 식품첨가물을 추가로 포함할 수 있으며, "식품첨가물"로서의 적합 여부는 다른 규정이 없는 한 식품의약품안전청에 승인된 식품첨가물공전의 총칙 및 일반 시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.In addition, the health functional food may additionally contain food additives, and the suitability as a "food additive" is determined according to the general rules of the Food Additive Code and general test methods approved by the Korea Food and Drug Administration unless otherwise specified. It is judged according to the relevant standards and standards.

상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀룰로오스, 고랭색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류 첨가 알칼리제, 보존료제제, 타르색소 제제 등의 혼합 제제류 등을 들 수 있다.Examples of items listed in the “Food Additives Codex” include, for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as dark pigment, licorice extract, crystalline cellulose, goreng pigment, guar gum, L -Mixed preparations such as sodium glutamate preparations, noodle-added alkali preparations, preservative preparations, tar color preparations, and the like.

이때, 건강기능식품을 제조하는 과정에서 식품에 첨가되는 유효성분은 필요에 따라 그 함량을 적절히 가감할 수 있으며, 바람직하게는 식품 100 중량부에 1 중량부 내지 90 중량부 포함되도록 첨가될 수 있다.At this time, the content of the active ingredient added to the food in the process of manufacturing the health functional food may be appropriately increased or decreased as necessary, and preferably may be added so that 1 part by weight to 90 parts by weight is included in 100 parts by weight of the food. .

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 개선용 화장료 조성물을 제공하는데, 상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소 또는 황이고; 1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고; 상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며, 상기 R⁵가 수소 또는 (C1~C4)알킬일 수 있다.In addition, the present invention is for preventing or improving infectious diseases caused by pathogenic microorganisms, including a compound selected from a compound characterized by the formula (I), a stereoisomer thereof, a racemate thereof, or a pharmaceutically acceptable salt thereof. Provides a cosmetic composition, wherein in the formula (I)

본 발명의 화장료 조성물은 그 제형에 있어서 특별히 한정되는 바가 없으며, 예를 들면, 유연화장수, 수렴화장수, 영양화장수, 영양크림, 마사지크림, 에센스, 아이크림, 아이에센스, 클렌징크림, 클렌징폼, 클렌징워터, 팩, 파우더, 바디로션, 바디크림, 바디오일 및 바디에센스 등의 화장품으로 제형화가 될 수 있고 피부에 바르는 형태 또는 마이크로 니들 등을 이용하여, 피부 내부로 흡수되는 형태로 적용될 수도 있다.The cosmetic composition of the present invention is not particularly limited in its formulation, for example, softening lotion, astringent lotion, nutrient lotion, nutrient cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing It can be formulated into cosmetics such as water, pack, powder, body lotion, body cream, body oil, and body essence, and can be applied in a form applied to the skin or absorbed into the skin using a microneedle.

본 발명의 화장료 조성물에서, 약제학상 또는 화장품 공전상 허용되는 담체로는 그의 제형에 따라 다르나, 바셀린, 유동 파라핀, 겔화 탄화수소(별명: 플라스티베이스)등의 탄화수소류; 중쇄지방산 트리글리세라이드, 돈지, 하드 팻트, 카카오지 등의 동식물성 오일; 세탄올, 스테아릴알코올, 스테아린산, 팔미틴산이소프로필 등의 고급지방산 알코올 및 지방산 및 그의 에스테르류; 마크로골(폴리에틸렌글리콜), 1,3-부틸렌글리콜, 글리세롤, 젤라틴, 백당, 당알코올 등의 수용성 기제; 글리세린 지방산에스테르, 스테아린산폴리옥실, 폴리옥시에틸렌경화 피마자유 등의 유화제; 아크릴산에스테르, 알긴산나트륨 등의 점착제; 액화석유가스, 이산화탄소 등의 분사제; 파라옥시벤조산에스테르류 등의 방부제 등을 들 수 있으며, 본 발명의 외용제는 이들을 사용하여 통상의 방법에 따라 제조할 수 있다. 또한, 이들 이외에도 안정제, 향료, 착색제, pH 조정제, 희석제, 계면활성제, 보존제, 항산화제 등을 필요에 따라 배합할 수도 있다. 본 발명의 외용제의 사용은 통상의 방법에 의해 국소창상부에 도포 될 수 있다.In the cosmetic composition of the present invention, pharmaceutically or cosmetically acceptable carriers vary depending on the formulation, but include hydrocarbons such as petroleum jelly, liquid paraffin, and gelled hydrocarbons (alias: plastibase); animal and vegetable oils such as medium-chain fatty acid triglycerides, lard, hard fat, and cacao butter; higher fatty alcohols and fatty acids and their esters, such as cetanol, stearyl alcohol, stearic acid and isopropyl palmitate; water-soluble bases such as macrogol (polyethylene glycol), 1,3-butylene glycol, glycerol, gelatin, white sugar, and sugar alcohol; emulsifiers such as glycerin fatty acid ester, polyoxyl stearate, and polyoxyethylene hydrogenated castor oil; adhesives such as acrylic esters and sodium alginate; propellants such as liquefied petroleum gas and carbon dioxide; preservatives such as paraoxybenzoic acid esters, and the like, and the external preparation of the present invention can be prepared according to a conventional method using these. In addition to these, stabilizers, fragrances, colorants, pH adjusters, diluents, surfactants, preservatives, antioxidants and the like may be blended as necessary. The external preparation of the present invention can be applied to a local wound by a conventional method.

또한, 본 발명은 상기 화학식 I로 표시되는 것을 특징으로 하는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제방법을 제공하는데, 상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소 또는 황이고; 1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고; 상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며, 상기 R⁵가 수소 또는 (C1~C4)알킬일 수 있다.In addition, the present invention relates to the formation of a biofilm or virulence of pathogenic microorganisms, including a compound selected from a compound characterized in that represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof. Provides a method of inhibiting, wherein in the above formula (I)

이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 다만 하기의 실시예 등은 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예 등에 한정되는 것은 아니다. 본 발명의 실시예 등은 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples and the like will be described in detail to aid understanding of the present invention. However, the following examples are merely illustrative of the content of the present invention, and the scope of the present invention is not limited to the following examples. Examples of the present invention and the like are provided to more completely explain the present invention to those skilled in the art.

<실험예 1> 박테리아 균주, 배양 조건 및 플라스미드<Experimental Example 1> Bacterial strains, culture conditions and plasmids

사용된 박테리아 균주와 플라스미드는 표 1에 나열되어 있다. 녹농균 (P. aeruginosa) 야생형 (wild-type) 균주인 PAO1은 하기 대부분의 실험예에 사용되었다. 대장균 (E. coli) 이중 플라스미드 리포터 시스템 (dual plasmid reporter system)의 경우 대장균 (E. coli) DH5α 균주를 사용하였다. 이 박테리아 균주의 배양에는 Luria-Bertani 배지 (LB; 10 g/L tryptone, 5 g/L yeast extract 및 5 g/L NaCl)가 사용되었으며, 37 ℃, 170 rpm에서 호기적으로 배양하였다. 성장은 600 nm (OD₆₀₀)에서 광학 밀도 (optical density, OD)로 측정되었다. 고체 배지는 한천 (agar)을 1.5 % (wt/vol)로 첨가하여 제조하였다. 단백질 발현 유도는 L-아라비노스 (L-arabinose; 0.4 %)가 사용되었다. 항생제는 다음 농도로 사용되었다: 카르베니실린 (carbenicillin), 150 μg/ml; 엠피실린 (ampicillin), 100 μg/ml; 젠타마이신 (gentamicin), 10 μg/ml.The bacterial strains and plasmids used are listed in Table 1. Pseudomonas aeruginosa ( P. aeruginosa ) wild-type (wild-type) strain PAO1 was used in most of the following experimental examples. E. coli ( E. coli ) For the dual plasmid reporter system (dual plasmid reporter system), E. coli ( E. coli ) DH5α strain was used. For the culture of this bacterial strain, Luria-Bertani medium (LB; 10 g/L tryptone, 5 g/L yeast extract and 5 g/L NaCl) was used and cultured aerobically at 37 °C and 170 rpm. Growth was measured as optical density (OD) at 600 nm (OD ₆₀₀ ). A solid medium was prepared by adding 1.5% (wt/vol) of agar. L-arabinose (0.4%) was used to induce protein expression. Antibiotics were used at the following concentrations: carbenicillin, 150 μg/ml; ampicillin, 100 μg/ml; gentamicin, 10 μg/ml.

<실험예 2> 억제제 스크리닝용 화학물질<Experimental Example 2> Chemicals for inhibitor screening

녹농균 (P. aeruginosa)에 대한 항독성 활성을 스크리닝하기 위해 인하우스 (in-house) 합성 화학 라이브러리가 사용되었다. 이 라이브러리에는 20개의 하이드록삼산 (hydroxamic acid) 및 카르복실산 (carboxylic acid) 유도체, 13개의 비스-아릴 (bis-aryl) 유도체, 23개의 벤조티아졸/벤조이미다졸 (benzothiazoles/benzimidazoles), 13개의 아조/디아조 (azo/diazo) 화합물, 8개의 비고전적인 뉴클레오사이드 (nonclassical nucleosides), 2개의 플라보노이드 (flavonoids), 30개의 벤질리딘 (benzylidene) 유도체 및 17개의 기타 유도체가 포함되어 있었다. 이들 화합물을 DMSO (dimethyl sulfoxide)에 용해시키고 지시된 농도로 배지에 희석하였다.An in-house synthetic chemical library was used to screen for antitoxic activity against P. aeruginosa . The library contains 20 hydroxamic acid and carboxylic acid derivatives, 13 bis-aryl derivatives, 23 benzothiazoles/benzimidazoles, 13 2 azo/diazo compounds, 8 nonclassical nucleosides, 2 flavonoids, 30 benzylidene derivatives and 17 other derivatives. These compounds were dissolved in dimethyl sulfoxide (DMSO) and diluted in the medium at the indicated concentrations.

<실험예 3> QS (quorum sensing) 억제 활성 측정<Experimental Example 3> QS (quorum sensing) inhibition activity measurement

QS 조절자의 활성은 조절자 특이적 프로모터-lacZ 융합 플라스미드, pSC11 (LasR 활성의 경우 lasI _p-lacZ), pJL101 (QscR 활성의 경우 PA1897 _p-lacZ), pJL501 (RhlR 활성의 경우 rhlA _p-lacZ) 및 pJL301 (PqsR 활성에 대한 pqsA _p-lacZ)을 사용하여 측정되었다. 대장균 (E. coli) 시스템 분석에서 이중 플라스미드 기반 LacZ 생물 검정 (dual plasmid-based LacZ bioassay)은 하기 실시예 1의 화합물들 (이하, MHY라함)의 QS 억제 활성을 측정하는데 사용되었다. 2개의 호환 가능한 플라스미드, pSC11 및 pJN105L 또는 pJL101 및 pJN105Q를 대장균 (E. coli) DH5α로 공동 형질전환하여 리포터 균주를 만들었다. pJN105L 및 pJN105Q는 각각 LasR 및 QscR 발현 플라스미드이고, pSC11 및 pJL101은 각각 lasI _p-lacZ 및 PA1897 _p-lacZ 융합 플라스미드이며, pSC11 및 pJN105L을 포함하는 대장균 (E. coli) 리포터 균주는 LasR 활성을 반영하고, pJL101 및 pJN105Q를 포함하는 균주는 QscR 활성을 반영했다. 따라서, 3OC12-HSL에 반응하여 LasR 및 QscR의 활성을 측정하는데 사용할 수 있었다. 형질전환체 대장균 (E. coli)는 젠타마이신 (gentamicin) 및 엠피실린 (ampicillin)을 함유하는 LB 액체 배지에서 37 ℃에서 진탕하면서 OD₆₀₀가 0.3이 될 때까지 배양되었다. 그 후, 아라비노스 (arabinose; 0.4 %), 3OC12-HSL (LasR 활성화의 경우 50 nM 및 QscR 활성화의 경우 100 nM) 및 MHY를 표시된 농도로 배양액에 첨가하였다. 추가적인 90분 배양 후, 베타갈락토시다아제 (β-galactosidase) 활성을 아래에 기술된 바와 같이 측정하였다. 녹농균에서의 측정은 리포터 플라스미드가 PAO1으로 형질전환 되었다. 각 리포터 균주의 오버나잇시킨 (overnight) 배양액을 카르베니실린 (carbenicillin)을 함유하는 새 LB 액체 배지에 OD₆₀₀가 0.02가 되도록 접종하고 MHY와 함께 7시간 동안 배양 후, β-galactosidase 활성을 아래에 기재된 바와 같이 측정하였다. MHY의 용매인 DMSO (dimethyl sulfoxide)를 MHY와 동일한 방법으로 희석하여 대조군으로 첨가하였다.The activity of QS regulators was determined by the regulator-specific promoter- lacZ fusion plasmids, pSC11 (lasI _p - lacZ for LasR activity), pJL101 ( PA1897 _p - lacZ for QscR activity), pJL501 ( rhlA _p - lacZ for RhlR activity). and pJL301 ( pqsA _p - lacZ for PqsR activity). In the E. coli system assay, a dual plasmid-based LacZ bioassay was used to measure the QS inhibitory activity of the compounds of Example 1 (hereinafter referred to as MHY). A reporter strain was created by co-transformation of two compatible plasmids, pSC11 and pJN105L or pJL101 and pJN105Q, into E. coli DH5α. pJN105L and pJN105Q are LasR and QscR expression plasmids, pSC11 and pJL101 are lasI _p - lacZ and PA1897 _p - lacZ fusion plasmids, respectively, E. coli reporter strains including pSC11 and pJN105L reflect LasR activity, , strains containing pJL101 and pJN105Q reflected QscR activity. Therefore, it could be used to measure the activities of LasR and QscR in response to 3OC12-HSL. The transformant E. coli was cultured in LB liquid medium containing gentamicin and ampicillin while shaking at 37° C. until an OD ₆₀₀ of 0.3. Then, arabinose (0.4%), 3OC12-HSL (50 nM for LasR activation and 100 nM for QscR activation) and MHY were added to the cultures at the indicated concentrations. After an additional 90 min incubation, β-galactosidase activity was measured as described below. For measurement in Pseudomonas aeruginosa, the reporter plasmid was transformed into PAO1. The overnight culture of each reporter strain was inoculated into a new LB liquid medium containing carbenicillin to an OD ₆₀₀ of 0.02, and after incubation with MHY for 7 hours, β-galactosidase activity was measured as follows. Measured as described. DMSO (dimethyl sulfoxide), a solvent of MHY, was diluted in the same way as MHY and added as a control.

<실험예 4> 베타갈락토시다아제 (β-galactosidase) 활성 분석<Experimental Example 4> Beta galactosidase (β-galactosidase) activity assay

베타갈락토시다아제 (β-galactosidase) 활성은 Galacto-Light Plus kit (Applied Biosystems, USA)를 사용하여 측정되었다. 배양액의 앨리쿼트 (aliquot)를 OD₆₀₀에서 측정하고 10 %의 클로로포름과 혼합하였다. 격한 볼텍싱 (Vigorous vortexing)을 하여 실온에서 15분 배양 후, 10 μl의 상등액을 새로운 튜브에 옮기고 기질 (substrate) 용액을 첨가하였다. 암실 상태의 상온에서 1시간 배양한 후 발광 (light emission) 용액 (Accelerator II) 150 μl를 첨가하고 multiwell plate reader (Tristar LB941; Berthold)를 사용하여 즉시 발광도 (luminescence)를 측정하였다. 최종 베타갈락토시다아제 (β-galactosidase) 활성은 발광도를 OD₆₀₀값으로 나눠주어 (luminescence/OD₆₀₀)얻었고, 억제제를 처리하지 않은 샘플에 대한 상대값으로 제시되었다.Beta-galactosidase activity was measured using Galacto-Light Plus kit (Applied Biosystems, USA). An aliquot of the culture was measured at OD ₆₀₀ and mixed with 10% chloroform. After 15 minutes of incubation at room temperature by vigorous vortexing, 10 μl of the supernatant was transferred to a new tube and a substrate solution was added. After incubation at room temperature in the dark for 1 hour, 150 μl of a light emission solution (Accelerator II) was added, and luminescence was immediately measured using a multiwell plate reader (Tristar LB941; Berthold). The final β-galactosidase activity was obtained by dividing the luminescence intensity by the OD ₆₀₀ value (luminescence/OD ₆₀₀ ) and is presented as a relative value to the sample not treated with inhibitor.

<실험예 5> 총 프로테아제 활성 측정<Experimental Example 5> Measurement of total protease activity

녹농균 (P. aeruginosa) 세포를 LB 액체 배지에서 오버나잇 (overnight) 배양시킨 배양액을 MHY를 함유하는 5 ml의 새 LB 액체 배지에 1:100 희석하고, 37 ℃에서 OD₆₀₀가 최대 2.0이 될 때까지 진탕하면서 배양하였다. 4 ℃에서 원심분리하여 세포를 제거하고, 배양 상등액 (이하, CS라함)을 취하여 0.2 μm 필터 (GVS Abluo 주사기 필터)를 통해 여과하였다. 총 프로테아제 활성을 측정하기 위해 5 μl의 CS를 skim milk agar plates (0.5 % skim milk, 0.5 % peptone, 0.1 % glucose 및 1.5 % agar) 위에 있는 디스크 (discs)에 떨어뜨리고 37 ℃에서 오버나잇 (overnight) 배양하였다. 총 프로테아제 활성은 투명 구역 (clear zones)의 직경으로 측정하였다. DMSO는 MHY와 동일한 방식으로 희석하여 대조군으로 사용하였다.Pseudomonas aeruginosa ( P. aeruginosa ) Cells were cultured overnight in LB liquid medium (overnight) diluted 1:100 in 5 ml of new LB liquid medium containing MHY, and at 37 ° C. OD ₆₀₀ when it reaches a maximum of 2.0 Incubated while shaking until Cells were removed by centrifugation at 4° C., and the culture supernatant (hereinafter referred to as CS) was taken and filtered through a 0.2 μm filter (GVS Abluo syringe filter). To measure total protease activity, 5 μl of CS was dropped onto discs on skim milk agar plates (0.5% skim milk, 0.5% peptone, 0.1% glucose and 1.5% agar) and overnight at 37 °C. ) cultured. Total protease activity was measured as the diameter of clear zones. DMSO was diluted in the same way as MHY and used as a control.

<실험예 6> 갈색거저리 (<Experimental Example 6> Brown mealworm ( Tenebrio molitorTenebrio molitor )를 사용한 병독성 분석) Virulence analysis using

상기 실험예 5에 의해 제조된 CS를 10 kDa cutoff Centricon (Vivaspin; Satorious)을 사용하여 10배 농축하고, 그 중 5 μl를 미세주사기를 사용하여 갈색거저리 (Tenebrio molitor) 유충에 주입하였다. 대조군으로 동일한 부피의 곤충 염류 (insect saline; IS) (IS; 130 mM NaCl, 5 mM KCl 및 1 mM CaCl₂)를 주입하였다. 유충을 25 ℃의 페트리 접시에서 2일 동안 배양하고, 생존한 유충을 계수하여 생존율을 계산하였다.The CS prepared in Experimental Example 5 was concentrated 10-fold using a 10 kDa cutoff Centricon (Vivaspin; Satorious), and 5 μl of it was injected into a brown mealworm ( Tenebrio ) using a microinjector. molitor ) larvae were injected. As a control, an equal volume of insect saline (IS) (IS; 130 mM NaCl, 5 mM KCl and 1 mM CaCl ₂ ) was injected. The larvae were cultured in a Petri dish at 25° C. for 2 days, and the survival rate was calculated by counting the surviving larvae.

<실험예 7> 생물막 형성 측정<Experimental Example 7> Measurement of biofilm formation

생물막 형성은 정적 생물막 분석을 사용하여 정량화 되었다. 세포의 오버나잇 (overnight) 배양액을 96-웰 폴리스티렌 플레이트 상의 새로운 배지에 2 % 접종하였다. 배지는 M63 최소 배지 [M63 salt (KH₂PO₄3g/L,K₂HPO₄7g/L,(NH₄)₂SO₄2g/L),1mMMgSO₄]로 두 가지 다른 탄소원, 0.5 % 카사미노산 (casamino acid; 이하, CAA라함) + 0.2 % 구연산염 (citrate; M63-cit+CAA), 또는 0.2 % 글리세롤 (glycerol; M63-gly) 중 하나를 포함했다. MHY를 각각의 농도로 배지에 첨가하고, 세포를 37 ℃에서 24시간 동안 진탕하지 않고 배양시켰다. OD₆₀₀로 세포 성장을 측정한 후, 플레이트를 물로 세척하여 부유생물 (planktonic) 세포를 제거하고 10분 동안 건조시켰다. 크리스탈 바이올렛 (0.1 % wt/vol) 180 μl를 각 웰에 첨가하고 10분 동안 배양하여 웰 표면에 부착된 생물막을 염색하였다. 짧은 세척 후, 생물막을 염색한 크리스탈 바이올렛을 200 μl의 30 % 아세트산에 용해시켰다. 생물막 형성은 600 nm에서의 흡광도 (A₆₀₀)에서 측정된 염색 수준으로부터 정량화 되었으며, 이는 세포 성장 (OD₆₀₀)에 의해 정규화 되었다. 억제제를 처리하지 않은 샘플 (100 %에 해당)에 대한 상대값으로 제시되었다.Biofilm formation was quantified using a static biofilm assay. Overnight cultures of cells were seeded at 2% in fresh medium on 96-well polystyrene plates. The medium was M63 minimal medium [M63 salt (KH ₂ PO ₄ 3 g/L, K ₂ HPO ₄ 7 g/L, (NH ₄ ) ₂ SO ₄ 2 g/L), 1mMMgSO ₄ ] containing two different carbon sources, 0.5% casamino acids. (casamino acid; hereinafter referred to as CAA) + 0.2% citrate (citrate; M63-cit+CAA) or 0.2% glycerol (M63-gly). MHY was added to the medium at each concentration and the cells were cultured at 37° C. for 24 hours without shaking. After measuring cell growth by OD ₆₀₀ , the plate was washed with water to remove planktonic cells and dried for 10 minutes. 180 μl of crystal violet (0.1% wt/vol) was added to each well and incubated for 10 minutes to stain the biofilm attached to the well surface. After a brief wash, crystal violet stained biofilm was dissolved in 200 μl of 30% acetic acid. Biofilm formation was quantified from staining levels measured in absorbance at 600 nm (A ₆₀₀ ), which was normalized by cell growth (OD ₆₀₀ ). Relative values to samples not treated with inhibitor (corresponding to 100%) are presented.

<실험예 8> 세포내 c-di-GMP 측정<Experimental Example 8> Intracellular c-di-GMP measurement

세포내 c-di-GMP 수준은 cdrA _p-lacZ 리포터를 사용하여 측정되었다. pSKcdrA를 포함하는 녹농균 (P. aeruginosa) 균주 오버나잇 (overnight) 배양액을 MHY를 함유하는 새 LB 액체 배지로 1 % 희석하고 7시간 동안 배양한 다음, 세포 내 c-di-GMP 수준을 반영하는 베타갈락토시다제 (β-galactosidase) 활성을 측정하였다. 비교를 위해 동일한 조건에서 5 μM 나이트로프루사이드나트륨 (sodium nitroprusside) (SNP; Bio Basic, Inc., Canada)를 첨가하였다. 억제제를 처리하지 않은 샘플 (100 %에 해당)에 대한 상대값으로 제시되었다.Intracellular c-di-GMP levels were measured using the cdrA _p - lacZ reporter. Pseudomonas aeruginosa ( P. aeruginosa ) strain overnight culture medium containing pSKcdrA was diluted 1% with fresh LB liquid medium containing MHY and incubated for 7 hours, then beta Galactosidase (β-galactosidase) activity was measured. For comparison, 5 μM sodium nitroprusside (SNP; Bio Basic, Inc., Canada) was added under the same conditions. Relative values to samples not treated with inhibitor (corresponding to 100%) are presented.

<실험예 9> 통계분석<Experimental Example 9> Statistical analysis

Student’s t test (등분산을 가정하는 2개 표본)는 Microsoft Office Excel을 사용하여 차이의 유의성을 결정하는 데 사용되었다. p < 0.05는 유의미한 것으로 간주되었다. 모든 실험은 3중으로 수행되었으며 독립적으로 최소 2회 반복되었다.Student's t test (two samples assuming equal variances) was used to determine the significance of differences using Microsoft Office Excel. p < 0.05 was considered significant. All experiments were performed in triplicate and independently repeated at least two times.

<실시예 1> 화합물 합성<Example 1> Compound synthesis

(1) 1-(4-메톡시페닐)우레아 [1-(4-Methoxyphenyl)urea; 화합물 1] 합성(1) 1-(4-methoxyphenyl)urea [1-(4-Methoxyphenyl)urea; compound 1] synthesis

p-아니시딘 (anisidine; 10.0 g, 81.20 mmol)을 초산 (30 mL)과 물 (30 mL)에 녹이고 시안산 나트륨 (sodium cyanate; 10.56 g, 162.44 mmol)를 물 80 mL에 녹인 수용액을 천천히 부가하였다. 실온에서 15분간 교반한 후, 3시간 동안 방치하였다. 상기 혼합물에 물 100 mL 부가하고 0 ℃에서 5분간 방치한 후 여과하여 얻은 여과고체를 실리카 겔 컬럼 크로마토그래피 (메틸렌 클로라이드:메탄올 = 10:1)로 정제하였다. 상기 정제 후 얻은 고체에 헥산:메틸렌 클로라이드 (5:1) 용매를 200 mL 부가한 후, 여과하여 화합물 1 (10.1 g)을 75 % 수율로 얻었다.An aqueous solution of p-anisidine (10.0 g, 81.20 mmol) dissolved in acetic acid (30 mL) and water (30 mL) and sodium cyanate (10.56 g, 162.44 mmol) dissolved in 80 mL of water was slowly added. did After stirring at room temperature for 15 minutes, it was allowed to stand for 3 hours. 100 mL of water was added to the mixture, left at 0° C. for 5 minutes, filtered, and the solid obtained was purified by silica gel column chromatography (methylene chloride:methanol = 10:1). 200 mL of a hexane:methylene chloride (5:1) solvent was added to the solid obtained after the purification, and then filtered to obtain Compound 1 (10.1 g) in a yield of 75%.

¹H NMR (500MHz, DMSO-d ₆)δ 8.28 (s, 1H), 7.26 (d, 2H, J=9.0Hz), 6.78 (d, 2H, J=9.0Hz), 5.69 (s, 2H), 3.67 (s, 3H).1H NMR (500MHz, DMSO ^- _d6 ) δ 8.28 (s, 1H), 7.26 ( d , 2H, J=9.0Hz), 6.78 (d, 2H, J=9.0Hz), 5.69 (s, 2H), 3.67 (s, 3H).

(2) 1-(4-(2) 1-(4- 메톡시페닐methoxyphenyl )피리미딘-2, 4, 6(1)Pyrimidine-2, 4, 6 (1 HH , 3, 3 HH , 5, 5 HH )-트리온[1-(4-Methoxyphenyl)pyrimidine-2,4,6(1)-trione [1- (4-Methoxyphenyl) pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 2] 합성)-trione; compound 2] synthesis

상기 화합물 1 (8.6 g, 51.75 mmol)과 말론산다이에틸 (diethyl malonate; 17.29 mL, 113.88 mmol)을 에탄올 50 mL에 녹이고 1 N NaOEt 용액 (82 mL, 82 mmol)을 가한 후 2일간 환류 교반하였다. 그 후, 진한 염산 (11.5 mL)과 물 (54 mL)를 부가하여 냉각한 후, 여과하고 얻은 고체를 실리카 겔 컬럼 크로마토그래피 (메틸렌 클로라이드:메탄올 = 5:1)로 정제하여 얻은 고체를 소량의 메틸렌 클로라이드로 세척하면서 여과하여 상기의 화합물 2 (8.49 g)를 70 % 수율로 얻었다.The above compound 1 (8.6 g, 51.75 mmol) and diethyl malonate (diethyl malonate; 17.29 mL, 113.88 mmol) were dissolved in 50 mL of ethanol, and 1 N NaOEt solution (82 mL, 82 mmol) was added thereto, followed by reflux stirring for 2 days. Thereafter, concentrated hydrochloric acid (11.5 mL) and water (54 mL) were added, cooled, filtered, and the obtained solid was purified by silica gel column chromatography (methylene chloride:methanol = 5:1), and a small amount of the obtained solid was obtained. The compound 2 (8.49 g) was obtained in 70% yield by filtering while washing with methylene chloride.

¹H NMR (400MHz, DMSO-d ₆)δ 11.41 (s, 1H), 7.10 (d, 2H, J=8.8Hz), 6.96 (d, 2H, J=8.8Hz), 3.75 (s, 3H), 3.68 (s, 2H); ¹³CNMR(100MHz,DMSO-d ₆)δ 167.6, 167.3, 159.6, 152.4, 130.6, 128.1, 114.7, 56.0, 41.0.1H NMR (400MHz, DMSO ^- _d6 ) δ 11.41 (s, 1H), 7.10 ( d , 2H, J=8.8Hz), 6.96 (d, 2H, J=8.8Hz), 3.75 (s, 3H), 3.68 (s, 2H); ¹³ CNMR (100 MHz, DMSO- d ₆ ) δ 167.6, 167.3, 159.6, 152.4, 130.6, 128.1, 114.7, 56.0, 41.0.

(3) 그룹 A 화합물 합성(3) Synthesis of Group A Compounds

에탄올 (4~8 mL) 및 물 (4~8 mL)용매에서 다양한 알데히드 (1.52~1.97 mmol) 및 티오바르비투르산 (thiobarbituric acid) (0.9~1.1 당량(eq.))의 현탁액을 실온 또는 80 ℃로 가열하였다. 상기 가열반응 동안 침전물이 형성되었으며, 에탄올을 감압 휘발 후 침전물을 여과하거나, 에탄올을 감압 휘발 없이 바로 침전물을 여과하였다. 반응 후, 남아있는 알데히드 유도체 및 티오바르비투르산의 물리적 특성을 고려하여, 여과 고체를 에탄올 및/또는 메틸렌 클로라이드 및 물로 세정하여 그룹 A 화합물을 얻었다.Suspensions of various aldehydes (1.52-1.97 mmol) and thiobarbituric acid (0.9-1.1 eq.) in ethanol (4-8 mL) and water (4-8 mL) solvents were prepared at room temperature or 80 °C. Heated to °C. A precipitate was formed during the heating reaction, and the precipitate was filtered after evaporating ethanol under reduced pressure, or the precipitate was directly filtered without evaporating ethanol under reduced pressure. After the reaction, considering the physical properties of the remaining aldehyde derivative and thiobarbituric acid, the filtered solid was washed with ethanol and/or methylene chloride and water to obtain a Group A compound.

1) 5-(4-1) 5-(4- 하이드록시벤질리덴hydroxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-)- 디온Dion [5-(4-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 화합물 Aa (MHY1342)] [5-(4-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; compound Aa (MHY1342)]

수율: 82%; 녹는점 291.7-293.5℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.30 (s, 1H), 12.20 (s, 1H), 10.93 (s, 1H), 8.34 (d, 2H, J=8.8Hz), 8.19(s, 1H), 6.86(d, 2H, J=8.8Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 178.8, 164.4, 163.1, 160.7, 157.2, 139.5, 124.6, 116.4, 114.9; LRMS(ESI-) m/z 247(M-H)^-.Yield: 82%; melting point 291.7-293.5°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.30 (s, 1H), 12.20 (s, 1H), 10.93 (s, 1H), 8.34 (d, 2H, J=8.8Hz), 8.19(s, 1H) , 6.86 (d, 2H, J=8.8 Hz); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.8, 164.4, 163.1, 160.7, 157.2, 139.5, 124.6, 116.4, 114.9; LRMS (ESI-) m/z 247 (MH) ^- .

2) 5-(3,4-2) 5-(3,4- 디하이드록시벤질리덴dihydroxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-디온 [5-(3,4-)-dione [5-(3,4- DihydroxybenzylideneDihydroxybenzylidene )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-dione; 화합물 Ab]) -dione; compound Ab]

수율: 99%; 녹는점 >300℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.28 (s, 1H), 12.19 (s, 1H), 10.55 (brs, 1H), 9.56 (brs, 1H), 8.25 (s, 1H), 8.10 (s, 1H), 7.63 (d, 1H, J=8.4Hz), 6.83(d, 1H, J=8.4Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 178.8, 163.2, 160.7, 157.7, 153.9, 145.7, 132.9, 125.2, 122.1, 116.2, 114.3; LRMS(ESI-) m/z 263(M-H)^-.Yield: 99%; melting point >300°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.28 (s, 1H), 12.19 (s, 1H), 10.55 (brs, 1H), 9.56 (brs, 1H), 8.25 (s, 1H), 8.10 (s, 1H), 7.63 (d, 1H, J=8.4Hz), 6.83 (d, 1H, J=8.4Hz); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.8, 163.2, 160.7, 157.7, 153.9, 145.7, 132.9, 125.2, 122.1, 116.2, 114.3; LRMS (ESI-) m/z 263 (MH) ^- .

3) 5-(2,4-3) 5-(2,4- 디하이드록시벤질리덴dihydroxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-디온 [5-(2,4-)-dione [5-(2,4- DihydroxybenzylideneDihydroxybenzylidene )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-dione; 화합물 Ac (MHY1343)] ) -dione; compound Ac (MHY1343)]

수율: 83%; 녹는점 >300℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.16 (s, 1H), 12.06 (s, 1H), 11.00 (s, 1H), 10.89 (brs, 1H), 8.77 (d, 1H, J=8.8Hz), 8.76(s, 1H), 6.37(d, 1H, J=1.6Hz), 6.31(dd, 1H, J=2.0, 9.2Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 178.6, 167.3, 164.8, 163.6, 161.0, 151.2, 137.3, 113.5, 111.9, 109.1, 102.1; LRMS(ESI-) m/z263(M-H)^-.Yield: 83%; melting point >300°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.16 (s, 1H), 12.06 (s, 1H), 11.00 (s, 1H), 10.89 (brs, 1H), 8.77 (d, 1H, J=8.8Hz) , 8.76 (s, 1H), 6.37 (d, 1H, J = 1.6 Hz), 6.31 (dd, 1H, J = 2.0, 9.2 Hz); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.6, 167.3, 164.8, 163.6, 161.0, 151.2, 137.3, 113.5, 111.9, 109.1, 102.1; LRMS (ESI-) m/z263 (MH) ^- .

4) 5-(4-4) 5-(4- 하이드록시hydroxy -3--3- 메톡시벤질리덴methoxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4, 6(1H,5H)-디온 [5-(4--4,6(1H,5H)-dione [5-(4- HydroxyHydroxy -3--3- methoxybenzylidenemethoxybenzylidene )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1H,5H)-dione; 화합물 Ad]-4,6(1H,5H)-dione; compound Ad]

수율: 99%; 녹는점 260.9-263.6℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.31 (s, 1H), 12.20 (s, 1H), 10.70 (s, 1H), 8.46 (s, 1H), 8.20 (s, 1H), 7.83 (d, 1H, J=8.8Hz), 6.88(d, 1H, J=8.4Hz), 3.80(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 178.7, 163.1, 160.9, 157.6, 154.5, 147.7, 133.9, 125.1, 118.9, 116.2, 114.7, 56.2; LRMS(ESI-) m/z 277(M-H)^-.Yield: 99%; melting point 260.9-263.6°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.31 (s, 1H), 12.20 (s, 1H), 10.70 (s, 1H), 8.46 (s, 1H), 8.20 (s, 1H), 7.83 (d, 1H, J = 8.8 Hz), 6.88 (d, 1H, J = 8.4 Hz), 3.80 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.7, 163.1, 160.9, 157.6, 154.5, 147.7, 133.9, 125.1, 118.9, 116.2, 114.7, 56.2; LRMS (ESI-) m/z 277 (MH) ^- .

5) 5-(3-5) 5-(3- 에톡시ethoxy -4--4- 하이드록시벤질리덴hydroxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4, 6(1H,5H)-디온 [5-(3--4,6(1H,5H)-dione [5-(3- EthoxyEthoxy -4--4- hydroxybenzylidenehydroxybenzylidene )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1H,5H)-dione; 화합물 Ae]-4,6(1H,5H)-dione; compound Ae]

수율: 88%; 녹는점 285.0-287.3℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.30 (s, 1H), 12.19 (s, 1H), 10.65 (brs, 1H), 8.47 (d, 1H, J=2.0Hz), 8.19(s, 1H), 7.78(dd, 1H, J=2.0, 8.4Hz), 6.89(d, 1H, J=8.4Hz), 4.05(q, 2H, J=7.2Hz), 1.33(t, 3H, J=7.2Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 178.7, 163.1, 160.9, 157.7, 154.8, 146.9, 134.0, 125.1, 119.8, 116.2, 114.6, 64.5, 15.2; LRMS(ESI-) m/z 291(M-H)^-.Yield: 88%; Melting point 285.0-287.3°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.30 (s, 1H), 12.19 (s, 1H), 10.65 (brs, 1H), 8.47 (d, 1H, J=2.0Hz), 8.19(s, 1H) , 7.78(dd, 1H, J=2.0, 8.4Hz), 6.89(d, 1H, J=8.4Hz), 4.05(q, 2H, J=7.2Hz), 1.33(t, 3H, J=7.2Hz) ; ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.7, 163.1, 160.9, 157.7, 154.8, 146.9, 134.0, 125.1, 119.8, 116.2, 114.6, 64.5, 15.2; LRMS (ESI-) m/z 291 (MH) ^- .

6) 5-(3-6) 5-(3- 하이드록시hydroxy -4--4- 메톡시벤질리덴methoxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1H,5H)-디온 [5-(3--4,6(1H,5H)-dione [5-(3- HydroxyHydroxy -4--4- methoxybenzylidenemethoxybenzylidene )-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 화합물 Af])-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; compound Af]

수율: 84%; 녹는점 278.9-280.5℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.32 (s, 1H), 12.23 (s, 1H), 9.58 (brs, 1H), 8.16 (d, 1H, J=2.0Hz), 8.13(s, 1H), 7.73(dd, 1H, J=2.0Hz, 8.4Hz), 7.04(d, 1H, J=8.8Hz), 3.86(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 178.9, 163.0, 160.6, 157.3, 154.2, 146.6, 131.8, 126.2, 121.2, 115.7, 112.1, 56.6; LRMS(ESI-) m/z 277(M-H)^-.Yield: 84%; melting point 278.9-280.5°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.32 (s, 1H), 12.23 (s, 1H), 9.58 (brs, 1H), 8.16 (d, 1H, J=2.0Hz), 8.13(s, 1H) , 7.73 (dd, 1H, J = 2.0 Hz, 8.4 Hz), 7.04 (d, 1H, J = 8.8 Hz), 3.86 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.9, 163.0, 160.6, 157.3, 154.2, 146.6, 131.8, 126.2, 121.2, 115.7, 112.1, 56.6; LRMS (ESI-) m/z 277 (MH) ^- .

7) 5-(4-7) 5-(4- 메톡시벤질리덴methoxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-)- 디온Dion [5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 화합물 Ag] [5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; compound Ag]

수율: 71%; 녹는점 >300℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.34 (s, 1H), 12.25 (s, 1H), 8.38 (d, 2H, J=8.8Hz), 8.23(s, 1H), 7.04(d, 2H, J=9.2Hz), 3.85(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 179.0, 164.7, 162.9, 160.6, 156.6, 138.6, 126.0, 116.3, 114.8, 56.5; LRMS(ESI-) m/z 261(M-H)^-.Yield: 71%; melting point >300°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.34 (s, 1H), 12.25 (s, 1H), 8.38 (d, 2H, J=8.8Hz), 8.23 (s, 1H), 7.04 (d, 2H, J = 9.2 Hz), 3.85 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 179.0, 164.7, 162.9, 160.6, 156.6, 138.6, 126.0, 116.3, 114.8, 56.5; LRMS (ESI-) m/z 261 (MH) ^- .

8) 5-(3,4-8) 5-(3,4- 디메톡시벤질리덴dimethoxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-)- 디온Dion [5-(3,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 화합물 Ah] [5-(3,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; compound Ah]

수율: 92%; 녹는점 269.9-271.7℃; ¹HNMR(500MHz,DMSO-d₆)δ 12.37 (s, 1H), 12.26 (s, 1H), 8.41 (s, 1H), 8.26 (s, 1H), 7.95 (d, 1H, J=8.5Hz), 7.12(d, 1H, J=8.5Hz), 3.88(s, 3H), 3.80(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 178.8, 163.0, 160.8, 157.2, 154.9, 148.5, 133.0, 126.1, 117.6, 116.0, 111.9, 56.6, 56.1; LRMS(ESI-) m/z 291(M-H)^-.Yield: 92%; melting point 269.9-271.7°C; ¹ HNMR (500 MHz, DMSO-d ₆ )δ 12.37 (s, 1H), 12.26 (s, 1H), 8.41 (s, 1H), 8.26 (s, 1H), 7.95 (d, 1H, J=8.5Hz) , 7.12 (d, 1H, J = 8.5 Hz), 3.88 (s, 3H), 3.80 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.8, 163.0, 160.8, 157.2, 154.9, 148.5, 133.0, 126.1, 117.6, 116.0, 111.9, 56.6, 56.1; LRMS (ESI-) m/z 291 (MH) ^- .

9) 5-(2,4-9) 5-(2,4- 디메톡시벤질리덴dimethoxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1H, 5H)--4,6(1H, 5H)- 디온Dion [5-(2,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 화합물 Ai] [5-(2,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; compound Ai]

수율: 98%; 녹는점 294.1-295.4℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.27 (s, 1H), 12.16 (s, 1H), 8.62 (s, 1H), 8.61 (d, 1H, J=8.4Hz), 6.61(s, 1H), 6.60(d, 1H, J=8.0Hz), 3.89(s, 3H), 3.86(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 178.9, 167.3, 163.6, 163.1, 160.6, 150.5, 136.5, 115.1, 115.1, 106.9, 98.1, 57.1, 56.7; LRMS(ESI-) m/z 291(M-H)^-.Yield: 98%; melting point 294.1-295.4°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.27 (s, 1H), 12.16 (s, 1H), 8.62 (s, 1H), 8.61 (d, 1H, J=8.4Hz), 6.61 (s, 1H) , 6.60 (d, 1H, J = 8.0 Hz), 3.89 (s, 3H), 3.86 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 178.9, 167.3, 163.6, 163.1, 160.6, 150.5, 136.5, 115.1, 115.1, 106.9, 98.1, 57.1, 56.7; LRMS (ESI-) m/z 291 (MH) ^- .

10) 2-10) 2- 티옥소Thioxo -5-(3,4,5--5-(3,4,5- 트리메톡시벤질리덴trimethoxybenzylidene )) 디하이드로피리미딘Dihydropyrimidine -4,6(1H, 5H)-디온 [2--4,6(1H, 5H)-dione [2- ThioxoThioxo -5-(3,4,5--5-(3,4,5- trimethoxybenzylidenetrimethoxybenzylidene )) dihydropyrimidinedihydropyrimidine -4,6(1H,5H)-dione; 화합물 Aj]-4,6(1H,5H)-dione; compound Aj]

수율: 66%; 녹는점 258.9-260.7℃; ¹HNMR(400MHz,DMSO-d₆)δ 12.41 (s, 1H), 12.30 (s, 1H), 8.24 (s, 1H), 7.85 (s, 2H), 3.79 (s, 6H), 3.77 (s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 179.0, 162.7, 160.6, 156.8, 152.6, 143.2, 128.3, 118.0, 113.6, 61.0, 56.7; LRMS(ESI-) m/z 321(M-H)^-.Yield: 66%; melting point 258.9-260.7°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 12.41 (s, 1H), 12.30 (s, 1H), 8.24 (s, 1H), 7.85 (s, 2H), 3.79 (s, 6H), 3.77 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 179.0, 162.7, 160.6, 156.8, 152.6, 143.2, 128.3, 118.0, 113.6, 61.0, 56.7; LRMS (ESI-) m/z 321 (MH) ^- .

11) 5-(4-11) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메톡시벤질리덴dimethoxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1H,5H)-디온 [5-(4--4,6(1H,5H)-dione [5-(4- HydroxyHydroxy -3, 5--3, 5- dimethoxybenzylidenedimethoxybenzylidene )-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 화합물 Ak (MHY1344)])-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; compound Ak (MHY1344)]

수율: 98%; 녹는점 >300℃; ¹HNMR(500MHz,DMSO-d₆)δ 12.33 (s, 1H), 12.23 (s, 1H), 10.17 (brs, 1H), 8.27 (s, 1H), 8.05 (s, 2H), 3.83 (s, 6H); ¹³CNMR(100MHz,DMSO-d₆)δ 178.7, 163.2, 160.9, 158.0, 147.9, 144.0, 123.7, 115.0, 114.9, 56.7; LRMS(ESI-) m/z 307(M-H)^-.Yield: 98%; melting point >300°C; ¹ HNMR (500 MHz, DMSO-d ₆ )δ 12.33 (s, 1H), 12.23 (s, 1H), 10.17 (brs, 1H), 8.27 (s, 1H), 8.05 (s, 2H), 3.83 (s, 6H); ¹³ CNMR (100 MHz, DMSO-d ₆ ) δ 178.7, 163.2, 160.9, 158.0, 147.9, 144.0, 123.7, 115.0, 114.9, 56.7; LRMS (ESI-) m/z 307 (MH) ^- .

12) 5-(3-12) 5-(3- 브로모Bromo -4--4- 하이드록시벤질리덴hydroxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1H,5H)-디온 [5-(3--4,6(1H,5H)-dione [5-(3- BromoBromo -4--4- hydroxybenzylidenehydroxybenzylidene )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1H,5H)-dione; 화합물 Am]-4,6(1H,5H)-dione; compound Am]

수율: 76%; ¹H NMR (400MHz, DMSO-d ₆)d 12.35 (s, 1H), 12.26 (s, 1H), 11.75 (brs, 1H), 8.87 (d, 1H, J=2.0Hz), 8.13 (s, 1H), 8.07 (dd, 1H, J=2.0, 8.4Hz), 7.00 (d, 1H, J=8.4Hz); ¹³CNMR(100MHz,DMSO-d ₆)d 178.9, 162.7, 160.7, 160.1, 155.3, 140.3, 138.5, 125.9, 116.5, 116.5, 110.2.Yield: 76%; ¹ H NMR (400 MHz, DMSO- d ₆ ) d 12.35 (s, 1H), 12.26 (s, 1H), 11.75 (brs, 1H), 8.87 (d, 1H, J =2.0Hz), 8.13 (s, 1H) ), 8.07 (dd, 1H, J =2.0, 8.4 Hz), 7.00 (d, 1H, J =8.4 Hz); ¹³ CNMR(100MHz,DMSO- d ₆ ) d 178.9, 162.7, 160.7, 160.1, 155.3, 140.3, 138.5, 125.9, 116.5, 116.5, 110.2.

13) 5-(3, 5-디-털트-부틸-4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,5-13) 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3,5- didi -- terttert -butyl-4--butyl-4- hydroxybenzylidenehydroxybenzylidene )-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione; 화합물 An (MHY5173)])-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione; compound An (MHY5173)]

수율: 57%; ¹H NMR (400MHz, DMSO-d ₆ ) δ 12.26 (s, 2H), 8.33 (s, 2H), 8.24 (s, 1H), 1.38 (s, 18H); LRMS(ESI-) m/z 359(M-H)^-;LRMS(ESI+)m/z361(M+H)⁺.Yield: 57%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.26 (s, 2H), 8.33 (s, 2H), 8.24 (s, 1H), 1.38 (s, 18H); LRMS(ESI-) m/z 359(MH) ^- ;LRMS(ESI+)m/z361(M+H) ⁺ .

14) 5-(2-14) 5-(2- 하이드록시벤질리덴hydroxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1H,5H1H,5H )-)- 디온Dion [5-(2-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 화합물 Ao] [5-(2-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; compound Ao]

수율: 66%; 녹는점 250.6-251.4℃; ¹HNMR(400MHz,DMSO-d₆)δ 11.40 (s, 1H), 9.75 (s, 1H), 9.60 (s, 1H), 9.00 (s, 1H), 8.01 (dd, 1H, J=2.0, 8.0Hz), 7.79(td, 1H, J=2.0, 8.0Hz), 7.52(d, 1H, J=8.4Hz), 7.44(td, 1H, J=0.8, 7.6Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 181.2, 161.7, 161.1, 154.9, 150.7, 136.1, 131.5, 126.2, 119.0, 118.1, 117.1; LRMS(ESI) m/z 247(M-H)^-.Yield: 66%; melting point 250.6-251.4°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 11.40 (s, 1H), 9.75 (s, 1H), 9.60 (s, 1H), 9.00 (s, 1H), 8.01 (dd, 1H, J=2.0, 8.0 Hz), 7.79 (td, 1H, J = 2.0, 8.0 Hz), 7.52 (d, 1H, J = 8.4 Hz), 7.44 (td, 1H, J = 0.8, 7.6 Hz); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 181.2, 161.7, 161.1, 154.9, 150.7, 136.1, 131.5, 126.2, 119.0, 118.1, 117.1; LRMS (ESI) m/z 247 (MH) ^- .

15) 5-(4-15) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메틸벤질리덴Dimethylbenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(4-)-dione [5-(4- HydroxyHydroxy -3,5--3,5- dimethylbenzylidenedimethylbenzylidene )-2-thioxodihydropyrimidine-4,6(1)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Ap (MHY5174)]) -dione; compound Ap (MHY5174)]

수율: 80%; ¹H NMR (500MHz, DMSO-d ₆ ) δ 12.29 (s, 1H), 12.18 (s, 1H), 9.85 (s, 1H), 8.15 (s, 2H), 2.19 (s, 6H).Yield: 80%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.29 (s, 1H), 12.18 (s, 1H), 9.85 (s, 1H), 8.15 (s, 2H), 2.19 (s, 6H).

16) 5-(4-16) 5-(4- 플루오로벤질리덴fluorobenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(4-Fluorobenzylidene)-2-thioxodihydropyrimidine-4,6(1 [5-(4-Fluorobenzylidene)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Aq]) -dione; compound Aq]

수율: 76%; ¹H NMR (400MHz, DMSO-d ₆ ) δ 12.46 (s, 1H), 12.36 (s, 1H), 8.28 - 8.24 (m, 3H), 7.31 (t, 2H, J=8.8Hz).Yield: 76%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.46 (s, 1H), 12.36 (s, 1H), 8.28 - 8.24 (m, 3H), 7.31 (t, 2H, J=8.8Hz).

17) 5-(2-17) 5-(2- 니트로벤질리덴nitrobenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(2-Nitrobenzylidene)-2-thioxodihydropyrimidine-4,6(1 [5-(2-Nitrobenzylidene)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Ar] ) -dione; compound Ar]

수율: 71%; ¹H NMR (400MHz, DMSO-d ₆ ) δ 12.52 (s, 1H), 12.30 (s, 1H), 8.59 (s, 1H), 8.21 (d, 1H, J = 8.4 Hz), 7.76 (t, 1H, J=7.6Hz), 7.66 (t, 1 H, J=7.6Hz), 7.58 (d, 1H, J=7.6Hz); ¹³CNMR(100MHz,DMSO-d ₆ ) δ 179.7, 161.3, 159.8, 154.0, 146.9, 134.4, 132.2, 131.1, 131.0, 124.7, 121.3.Yield: 71%; 1H NMR (400MHz, DMSO ^- _d6 ) δ 12.52 ( s , 1H), 12.30 (s, 1H), 8.59 (s, 1H), 8.21 (d, 1H, J = 8.4 Hz), 7.76 (t, 1H) , J=7.6 Hz), 7.66 (t, 1 H, J=7.6 Hz), 7.58 (d, 1 H, J=7.6 Hz); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 179.7, 161.3, 159.8, 154.0, 146.9, 134.4, 132.2, 131.1, 131.0, 124.7, 121.3.

18) 5-(4-(18) 5-(4-( 벤질옥시benzyloxy )) 벤질리덴benzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(4-(Benzyloxy)benzylidene)-2-thioxodihydropyrimidine-4,6(1 [5-(4-(Benzyloxy)benzylidene)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 As]) -dione; compound As]

수율: 52%; ¹H NMR (500MHz, DMSO-d ₆ ) δ 12.36 (s, 1H), 12.27 (s, 1H), 8.39 (d, 2H, J=8.5 Hz), 8.25 (s, 1H), 7.46 (d, 2H, J=8.0Hz), 7.39 (t, 2H, J=7.5Hz), 7.33 (t, 1H, J=7.5Hz), 7.14 (d, 2H, J=8.5Hz), 5.24 (s, 2H); ¹³CNMR(100MHz,DMSO-d ₆ ) δ 179.0, 163.7, 162.9, 160.6, 156.6, 138.6, 136.9, 129.2, 128.8, 128.6, 126.1, 116.4, 115.5, 70.4.Yield: 52%; 1H NMR (500MHz, DMSO ^- _d6 ) δ 12.36 (s, 1H), 12.27 (s, 1H), 8.39 ( d , 2H, J=8.5 Hz), 8.25 (s, 1H), 7.46 (d, 2H) , J=8.0 Hz), 7.39 (t, 2H, J=7.5 Hz), 7.33 (t, 1H, J=7.5 Hz), 7.14 (d, 2H, J=8.5 Hz), 5.24 (s, 2H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 179.0, 163.7, 162.9, 160.6, 156.6, 138.6, 136.9, 129.2, 128.8, 128.6, 126.1, 116.4, 115.5, 70.4.

19) 5-(4-(4-19) 5-(4-(4-) 클로로벤질옥시chlorobenzyloxy )) 벤질리덴benzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(4-(4-)-dione [5-(4-(4- ChlorobenzyloxyChlorobenzyloxy )) benzylidenebenzylidene )-2-thioxodihydropyrimidine-4,6(1)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Av]) -dione; compound Av]

수율: 74%; ¹H NMR (500MHz, DMSO-d ₆ ) δ 12.36 (s, 1H), 12.27 (s, 1H), 8.39 (d, 2H, J=9.5Hz), 8.24 (s, 1H), 7.49 (d, 2H, J=8.5 Hz), 7.45 (d, 2H, J=8.5 Hz), 7.13 (d, 2H, J=9.5Hz), 5.24 (s, 2H).Yield: 74%; 1H NMR (500MHz, DMSO ^- d6) δ 12.36 (s, 1H), 12.27 (s, 1H), 8.39 ( d , 2H, J= _9.5Hz ), 8.24 (s, 1H), 7.49 (d, 2H) , J=8.5 Hz), 7.45 (d, 2H, J=8.5 Hz), 7.13 (d, 2H, J=9.5 Hz), 5.24 (s, 2H).

20) 5-(3-20) 5-(3- 페녹시벤질리덴Phenoxybenzylidene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(3-Phenoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1 [5-(3-Phenoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Aw]) -dione; compound Aw]

수율: 39%; ¹H NMR (400 MHz, DMSO-d ₆) δ 12.42 (s, 1H), 12.29 (s, 1H), 8.21 (s, 1H), 7.90 (s, 1H), 7.73 (d, 1H, J = 8.0 Hz), 7.46 (t, 1H, J = 8.0 Hz), 7.36 (t, 2H, J = 7.6 Hz), 7.17 (dd, 1H, J = 8.4, 2.0 Hz), 7.12 (t, 1H, J = 7.6 Hz), 7.01 (d, 2H, J = 8.0 Hz); ¹³CNMR(100MHz,DMSO-d ₆) δ 179.3, 162.2, 160.1, 157.1, 156.6, 155.0, 135.1, 130.8, 130.4, 129.6, 124.3, 123.5, 123.2, 120.6, 119.2.Yield: 39%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.42 (s, 1H), 12.29 (s, 1H), 8.21 (s, 1H), 7.90 (s, 1H), 7.73 (d, 1H, J = 8.0 Hz), 7.46 (t, 1H, J = 8.0 Hz), 7.36 (t, 2H, J = 7.6 Hz), 7.17 (dd, 1H, J = 8.4, 2.0 Hz), 7.12 (t, 1H, J = 7.6 Hz), 7.01 (d, 2H, J = 8.0 Hz); ¹³ CNMR (100 MHz, DMSO-d6) δ 179.3 , 162.2, _160.1 , 157.1, 156.6, 155.0, 135.1, 130.8, 130.4, 129.6, 124.3, 123.5, 123.2, 120.6, 119.2.

21) 5-(21) 5-( 벤조[benzo[ dd ][1,3]디옥솔][1,3]dioxol -5--5- 일메틸렌ilmethylene )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4, 6(1-4, 6(1 HH ,5,5 HH )-디온 [5-()-dione [5-( Benzo[Benzo[ dd ][1,3]dioxol][1,3]dioxol -5--5- ylmethyleneylmethylene )-2-thioxodihydropyrimidine-4,6(1)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Ax]) -dione; compound Ax]

수율: 54%; ¹H NMR (500MHz, DMSO-d ₆ ) δ 12.38 (s, 1H), 12.29 (s, 1H), 8.27 (d, 1H, J=2.0Hz), 8.20 (s, 1H), 7.78 (dd, 1H, J=8.5, 1.5Hz), 7.07 (d, 1H, J=8.0Hz), 6.18 (s, 2H); ¹³CNMR(100MHz,DMSO-d ₆ ) δ 178.9, 162.8, 160.6, 156.6, 153.1, 148.1, 135.1, 127.6, 116.6, 113.2, 109.1, 103.2.Yield: 54%; 1H NMR (500MHz, DMSO ^- d6) δ 12.38 (s, 1H), 12.29 (s, 1H), 8.27 ( d , 1H, J= _2.0Hz ), 8.20 (s, 1H), 7.78 (dd, 1H) , J=8.5, 1.5Hz), 7.07 (d, 1H, J=8.0Hz), 6.18 (s, 2H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 178.9, 162.8, 160.6, 156.6, 153.1, 148.1, 135.1, 127.6, 116.6, 113.2, 109.1, 103.2.

22) 5-(나프탈렌-1-22) 5-(naphthalene-1- 일메틸ilmethyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Az]) -dione; compound Az]

수율: 64%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.51 (s, 1H, NH), 12.26 (s, 1H, NH),8.81 (s, 1H), 8.04 (d, 1H, J = 8.5 Hz), 7.99 (d, 1H, J = 9.0 Hz), 7.89 - 7.87 (m, 2H), 7.60 - 7.53 (m, 3H).Yield: 64%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.51 (s, 1H, NH), 12.26 (s, 1H, NH), 8.81 (s, 1H), 8.04 (d, 1H, J = 8.5 Hz), 7.99 (d, 1H, J = 9.0 Hz), 7.89 - 7.87 (m, 2H), 7.60 - 7.53 (m, 3H).

23) 5-(4-23) 5-(4- 하이드록시hydroxy -3,5--3,5- 디아이소프로필벤질리덴Diisopropylbenzylidene )-2-)-2- 티옥소하이드로피리미딘Thioxohydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(4-)-dione [5-(4- HydroxyHydroxy -3,5--3,5- diisopropylbenzylidenediisopropylbenzylidene )-2-thioxodihydropyrimidine-4,6(1)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 AB (MHY5178)]) -dione; compound AB (MHY5178)]

수율: 87%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.29 (brs, 1H, NH), 12.18 (brs, 1H, NH), 9.70 (s, 1H, OH), 8.28 (s, 2H), 8.26 (s, 1H), 3.30 (hept, 2H, J = 7.0 Hz), 1.17 (d, 12H, J = 7.0 Hz).Yield: 87%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.29 (brs, 1H, NH), 12.18 (brs, 1H, NH), 9.70 (s, 1H, OH), 8.28 (s, 2H), 8.26 (s , 1H), 3.30 (hept, 2H, J = 7.0 Hz), 1.17 (d, 12H, J = 7.0 Hz).

(4) 그룹 B 화합물 합성(4) Synthesis of Group B Compounds

에탄올 (4 mL) 및 물 (4 mL)용매에서 다양한 알데히드 (aldehyde) (1.44 ~ 2.60 mmol) 및 바르비투르산 (barbituric acid) (0.7 ~ 1.2 당량(eq.))의 현탁액을 80 ℃로 가열하고 형성된 침전물을 여과하였다. 남아있는 알데히드와 바르비투르산의 물리적인 특성을 고려하여, 여과 고체를 에탄올 (ethanol) 및/또는 메틸렌 클로라이드 (methylene chloride) 및 물로 세정하여 그룹 B 화합물을 얻었다. Suspensions of various aldehydes (1.44 ~ 2.60 mmol) and barbituric acid (0.7 ~ 1.2 eq.) in ethanol (4 mL) and water (4 mL) solvents were heated to 80 °C. The precipitate formed was filtered off. Considering the physical properties of the remaining aldehyde and barbituric acid, the filtered solid was washed with ethanol and/or methylene chloride and water to obtain a Group B compound.

1) 5-(4-1) 5-(4- 하이드록시벤질리덴hydroxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(4-Hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Ba])-trione [5-(4-Hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Ba]

수율: 81%; 녹는점 >300 ℃; ¹HNMR(400MHz,DMSO-d₆)δ 11.23 (s, 1H), 11.10 (s, 1H), 10.79 (s, 1H), 8.29 (d, 2H, J=8.8Hz), 8.17(s, 1H), 6.84(d, 2H, J=8.8Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 164.8, 163.7, 163.0, 156.1, 150.9, 139.0, 124.4, 116.2, 114.9; LRMS(ESI-) m/z 231(M-H)^-.Yield: 81%; melting point >300 °C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 11.23 (s, 1H), 11.10 (s, 1H), 10.79 (s, 1H), 8.29 (d, 2H, J=8.8Hz), 8.17(s, 1H) , 6.84 (d, 2H, J=8.8 Hz); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.8, 163.7, 163.0, 156.1, 150.9, 139.0, 124.4, 116.2, 114.9; LRMS (ESI-) m/z 231 (MH) ^- .

2) 5-(3,4-2) 5-(3,4- 디하이드록시벤질리덴dihydroxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(3,4-Dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Bb])-trione [5-(3,4-Dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Bb]

수율: 71%; 녹는점 >300℃; ¹HNMR(500MHz,DMSO-d₆)δ 11.14 (brs, 2H), 9.76 (brs, 1H), 9.55 (brs, 1H), 8.18 (s, 1H), 8.10 (s, 1H), 7.61 (d, 1H, J=8.0Hz), 6.83(d, 1H, J=7.5Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 164.9, 162.9, 156.7, 153.0, 150.9, 145.5, 132.0, 124.9, 122.0, 116.0, 114.3; LRMS(ESI-) m/z 247(M-H)^-.Yield: 71%; melting point >300°C; ¹ HNMR (500 MHz, DMSO-d ₆ )δ 11.14 (brs, 2H), 9.76 (brs, 1H), 9.55 (brs, 1H), 8.18 (s, 1H), 8.10 (s, 1H), 7.61 (d, 1H, J = 8.0 Hz), 6.83 (d, 1H, J = 7.5 Hz); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.9, 162.9, 156.7, 153.0, 150.9, 145.5, 132.0, 124.9, 122.0, 116.0, 114.3; LRMS (ESI-) m/z 247 (MH) ^- .

3) 5-(2,4-3) 5-(2,4- 디하이드록시벤질리덴dihydroxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(2,4-Dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Bc])-trione [5-(2,4-Dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Bc]

수율: 69%; 녹는점 >300℃; ¹HNMR(500MHz,D₂O+NaOH)δ 8.07 (s, 1H), 7.26 (d, 1H, J=8.5Hz), 6.44(dd, 1H, J=2.0, 9.0Hz), 6.24(s, 1H); ¹³CNMR(100MHz,DMSO-d₆)δ 168.5, 166.7, 162.2, 157.2, 156.8, 145.7, 134.0, 116.5, 113.1, 109.8, 103.3; LRMS(ESI-) m/z 247(M-H)^-.Yield: 69%; melting point >300°C; 1HNMR (500MHz,D ² O ₊ NaOH)δ 8.07 (s, 1H), 7.26 (d, 1H, J=8.5Hz), 6.44 (dd, 1H, J=2.0, 9.0Hz), 6.24(s, 1H) ); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 168.5, 166.7, 162.2, 157.2, 156.8, 145.7, 134.0, 116.5, 113.1, 109.8, 103.3; LRMS (ESI-) m/z 247 (MH) ^- .

4) 5-(4-4) 5-(4- 하이드록시hydroxy -3--3- 메톡시벤질리덴methoxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(4-Hydroxy-3-methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Bd])-trione [5-(4-Hydroxy-3-methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Bd]

수율: 87%; 녹는점 288.6-290.7℃; ¹HNMR(400MHz,DMSO-d₆)δ 11.23 (s, 1H), 11.11 (s, 1H), 10.54 (s, 1H), 8.44 (d, 1H, J=2.0Hz), 8.18(s, 1H), 7.77(dd, 1H, J=2.0, 8.4Hz), 6.86(d, 1H, J=8.4Hz), 3.79 (s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 164.8, 163.2, 156.6, 153.7, 150.9, 147.6, 133.2, 124.9, 118.6, 116.0, 114.6, 56.2; LRMS(ESI-) m/z 261(M-H)^-.Yield: 87%; Melting point 288.6-290.7°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 11.23 (s, 1H), 11.11 (s, 1H), 10.54 (s, 1H), 8.44 (d, 1H, J=2.0Hz), 8.18(s, 1H) , 7.77 (dd, 1H, J = 2.0, 8.4 Hz), 6.86 (d, 1H, J = 8.4 Hz), 3.79 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.8, 163.2, 156.6, 153.7, 150.9, 147.6, 133.2, 124.9, 118.6, 116.0, 114.6, 56.2; LRMS (ESI-) m/z 261 (MH) ^- .

5) 5-(3-5) 5-(3- 에톡시ethoxy -4--4- 하이드록시벤질리덴hydroxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Be])-trione [5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Be]

수율: 67%; 녹는점, 244.7-246.1℃; ¹HNMR(500MHz,DMSO-d₆)δ 11.24 (s, 1H), 11.11 (s, 1H), 10.46 (s, 1H), 8.48 (s, 1H), 8.20 (s, 1H), 7.74 (d, 1H, J=8.5Hz), 6.90(d, 1H, J=8.5Hz), 4.08(q, 2H, J=7.0Hz), 1.36(t, 3H, J=7.0Hz); ¹³CNMR(100MHz,DMSO-d₆)δ 164.8, 163.1, 156.6, 154.0, 150.8, 146.8, 133.2, 124.9, 119.7, 116.1, 114.6, 64.5, 15.2; LRMS(ESI-) m/z 275(M-H)^-.Yield: 67%; Melting point, 244.7-246.1 °C; ¹ HNMR (500 MHz, DMSO-d ₆ )δ 11.24 (s, 1H), 11.11 (s, 1H), 10.46 (s, 1H), 8.48 (s, 1H), 8.20 (s, 1H), 7.74 (d, 1H, J=8.5 Hz), 6.90 (d, 1H, J=8.5 Hz), 4.08 (q, 2H, J=7.0 Hz), 1.36 (t, 3H, J=7.0 Hz); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.8, 163.1, 156.6, 154.0, 150.8, 146.8, 133.2, 124.9, 119.7, 116.1, 114.6, 64.5, 15.2; LRMS (ESI-) m/z 275 (MH) ^- .

6) 5-(3-6) 5-(3- 하이드록시hydroxy -4--4- 메톡시벤질리덴methoxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(3-Hydroxy-4-methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione](화합물 Bf))-trione [5-(3-Hydroxy-4-methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione] (compound Bf)

수율: 91%; 녹는점 279.3-281.4℃; ¹HNMR(500MHz,DMSO-d₆)δ 11.26 (s, 1H), 11.13 (s, 1H), 9.42 (s, 1H), 8.14 (s, 1H), 8.10 (s, 1H), 7.70 (d, 1H, J=8.5Hz), 7.03(d, 1H, J=9.0Hz), 3.87(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 164.7, 162.8, 156.2, 153.6, 150.9, 146.4, 131.0, 126.1, 121.1, 115.7, 112.0, 56.4; LRMS(ESI-) m/z 261(M-H)^-.Yield: 91%; melting point 279.3-281.4°C; ¹ HNMR (500 MHz, DMSO-d ₆ )δ 11.26 (s, 1H), 11.13 (s, 1H), 9.42 (s, 1H), 8.14 (s, 1H), 8.10 (s, 1H), 7.70 (d, 1H, J = 8.5 Hz), 7.03 (d, 1H, J = 9.0 Hz), 3.87 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ ) δ 164.7, 162.8, 156.2, 153.6, 150.9, 146.4, 131.0, 126.1, 121.1, 115.7, 112.0, 56.4; LRMS (ESI-) m/z 261 (MH) ^- .

7) 5-(4-7) 5-(4- 메톡시벤질리덴methoxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(4-Methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Bg])-trione [5-(4-Methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Bg]

수율: 80%; 녹는점, 292.4-294.3 ℃; ¹HNMR(400MHz,DMSO-d₆)δ 11.27 (s, 1H), 11.14 (s, 1H), 8.33 (d, 2H, J=9.2Hz), 8.21(s, 1H), 7.02(d, 2H, J=8.8Hz), 3.83(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 164.6, 164.1, 162.8, 155.6, 150.9, 138.1, 125.8, 116.2, 114.6, 56.4; LRMS(ESI-) m/z 245(M-H)^-.Yield: 80%; melting point, 292.4-294.3 °C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 11.27 (s, 1H), 11.14 (s, 1H), 8.33 (d, 2H, J=9.2Hz), 8.21 (s, 1H), 7.02 (d, 2H, J = 8.8 Hz), 3.83 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.6, 164.1, 162.8, 155.6, 150.9, 138.1, 125.8, 116.2, 114.6, 56.4; LRMS (ESI-) m/z 245 (MH) ^- .

8) 5-(3,4-8) 5-(3,4- 디메톡시벤질리덴dimethoxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(3,4-Dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Bh (MHY1333)] )-trione [5-(3,4-Dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Bh (MHY1333)]

수율: 83%; 녹는점 300℃; ¹HNMR(400MHz,DMSO-d₆)δ 11.27 (s, 1H), 11.15 (s, 1H), 8.37 (d, 1H, J=2.0Hz), 8.21(s, 1H), 7.86(dd, 1H, J=2.0, 8.4Hz), 7.07(d, 1H, J=8.4Hz), 3.84(s, 3H), 3.77(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 164.7, 163.0, 156.1, 154.3, 150.9, 148.5, 132.4, 125.9, 117.4, 115.9, 111.8, 56.5, 56.1; LRMS(ESI-) m/z 275(M-H)^-.Yield: 83%; melting point 300°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 11.27 (s, 1H), 11.15 (s, 1H), 8.37 (d, 1H, J=2.0Hz), 8.21 (s, 1H), 7.86 (dd, 1H, J = 2.0, 8.4 Hz), 7.07 (d, 1H, J = 8.4 Hz), 3.84 (s, 3H), 3.77 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.7, 163.0, 156.1, 154.3, 150.9, 148.5, 132.4, 125.9, 117.4, 115.9, 111.8, 56.5, 56.1; LRMS (ESI-) m/z 275 (MH) ^- .

9) 5-(2,4-9) 5-(2,4- 디메톡시벤질리덴dimethoxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(2,4-Dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Bi])-trione [5-(2,4-Dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Bi]

수율: 83%; 녹는점, 291.1-291.7 ℃; ¹HNMR(500MHz,DMSO-d₆)δ 11.21 (s, 1H), 11.06 (s, 1H), 8.61 (s, 1H), 8.53 (d, 1H, J=8.5Hz), 6.63(d, 1H, J=2.0Hz), 6.61(dd, 1H, J=2.0, 9.0Hz), 3.90(s, 3H), 3.87(s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 166.5, 164.8, 163.1, 162.8, 150.9, 149.7, 136.1, 115.3, 114.9, 106.5, 98.1, 56.9, 56.5; LRMS(ESI-) m/z 275(M-H)^-.Yield: 83%; melting point, 291.1-291.7 °C; ¹ HNMR (500 MHz, DMSO-d ₆ )δ 11.21 (s, 1H), 11.06 (s, 1H), 8.61 (s, 1H), 8.53 (d, 1H, J=8.5Hz), 6.63 (d, 1H, J = 2.0 Hz), 6.61 (dd, 1H, J = 2.0, 9.0 Hz), 3.90 (s, 3H), 3.87 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ ) δ 166.5, 164.8, 163.1, 162.8, 150.9, 149.7, 136.1, 115.3, 114.9, 106.5, 98.1, 56.9, 56.5; LRMS (ESI-) m/z 275 (MH) ^- .

10) 5-(3,4,5-10) 5-(3,4,5- 트리메톡시벤질리덴trimethoxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(3,4,5-Trimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Bj])-trione [5-(3,4,5-Trimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione; compound Bj]

수율: 84%; 녹는점 274.8-275.4℃; ¹HNMR(400MHz,DMSO-d₆)δ 11.33 (s, 1H), 11.20 (s, 1H), 8.22 (s, 1H), 7.80 (s, 2H), 3.78 (s, 6H), 3.75 (s, 3H); ¹³CNMR(100MHz,DMSO-d₆)δ 164.4, 162.8, 155.9, 152.6, 150.8, 142.6, 128.2, 117.9, 113.3, 61.0, 56.7; LRMS(ESI-) m/z 305(M-H)^-.Yield: 84%; Melting point 274.8-275.4°C; ¹ HNMR (400 MHz, DMSO-d ₆ )δ 11.33 (s, 1H), 11.20 (s, 1H), 8.22 (s, 1H), 7.80 (s, 2H), 3.78 (s, 6H), 3.75 (s, 3H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.4, 162.8, 155.9, 152.6, 150.8, 142.6, 128.2, 117.9, 113.3, 61.0, 56.7; LRMS (ESI-) m/z 305 (MH) ^- .

11) 5-(4-11) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메톡시벤질리덴dimethoxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3,5--3,5- dimethoxybenzylidenedimethoxybenzylidene )pyrimidine-2,4,6()pyrimidine-2,4,6( 1H,3H,5H1H,3H,5H )-)- trionetrione ; 화합물 Bk (MHY1334)]; Compound Bk (MHY1334)]

수율: 99%; 녹는점 >300℃; ¹HNMR(500MHz,DMSO-d₆)δ 11.25 (s, 1H), 11.12 (s, 1H), 9.97 (brs, 1H), 8.24 (s, 1H), 8.00 (s, 2H), 3.82 (s, 6H); ¹³CNMR(100MHz,DMSO-d₆)δ 164.8, 163.2, 157.0, 150.9, 147.8, 143.1, 123.5, 114.9, 114.6, 56.7; LRMS(ESI-) m/z 291(M-H)^-.Yield: 99%; melting point >300°C; ¹ HNMR (500 MHz, DMSO-d ₆ )δ 11.25 (s, 1H), 11.12 (s, 1H), 9.97 (brs, 1H), 8.24 (s, 1H), 8.00 (s, 2H), 3.82 (s, 6H); ¹³ CNMR (100 MHz, DMSO-d ₆ )δ 164.8, 163.2, 157.0, 150.9, 147.8, 143.1, 123.5, 114.9, 114.6, 56.7; LRMS (ESI-) m/z 291 (MH) ^- .

12) 5-(3,5-12) 5-(3,5- 디브로모dibromo -4--4- 하이드록시벤질리덴hydroxybenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(3,5-)-trion [5-(3,5- DibromoDibromo -4--4- hydroxybenzylidenehydroxybenzylidene )pyrimidine-2,4,6()pyrimidine-2,4,6( 1H,3H,5H1H,3H,5H )-)- trionetrione ; 화합물 Bl]; compound Bl]

수율: 78%; ¹H NMR (500MHz, DMSO-d ₆)δ 11.33 (s, 1H), 11.22 (s, 1H), 8.54 (s, 2H), 8.10 (s, 1H); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.0, 162.7, 155.5, 152.4, 150.8, 139.0, 127.1, 118.2, 111.4.Yield: 78%; ¹ H NMR (500 MHz, DMSO- d ₆ )δ 11.33 (s, 1H), 11.22 (s, 1H), 8.54 (s, 2H), 8.10 (s, 1H); ¹³ CNMR(100MHz,DMSO _- d6 )δ 164.0, 162.7, 155.5, 152.4, 150.8, 139.0, 127.1, 118.2, 111.4.

13) 5-(4-13) 5-(4- 플루오로벤질리덴fluorobenzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Fluorobenzylidene)pyrimidine-2,4,6(1)-trione [5-(4-Fluorobenzylidene)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Bq])-trione; compound Bq]

수율: 79%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.37 (s, 1H, NH), 11.23 (s, 1H, NH), 8.25 (s, 1H), 8.21 (dd, 2H, J = 8.5, 6.0 Hz), 7.30 (t, 2H, J = 9.0 Hz). Yield: 79%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 11.37 ( s , 1H, NH), 11.23 (s, 1H, NH), 8.25 (s, 1H), 8.21 (dd, 2H, J = 8.5, 6.0 Hz ), 7.30 (t, 2H, J = 9.0 Hz).

14) 5-(4-(14) 5-(4-( 벤질옥시benzyloxy )) 벤질리덴benzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1)-trione [5-(4-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 )-trione; compound BsBs (MHY1420)] (MHY1420)]

수율: 95%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.29 (s, 1H, NH), 11.16 (s, 1H, NH), 8.35 (d, 2H, J = 9.0 Hz), 8.24 (s, 1H), 7.47 (d, 2H, J = 7.5 Hz), 7.40 (t, 2H, J = 7.5 Hz), 7.34 (t, 1H, J = 7.5 Hz), 7.13 (d, 2H, J = 9.0 Hz), 5.23 (s, 2H). Yield: 95%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 11.29 ( s , 1H, NH), 11.16 (s, 1H, NH), 8.35 (d, 2H, J = 9.0 Hz), 8.24 (s, 1H), 7.47 (d, 2H, J = 7.5 Hz), 7.40 (t, 2H, J = 7.5 Hz), 7.34 (t, 1H, J = 7.5 Hz), 7.13 (d, 2H, J = 9.0 Hz), 5.23 ( s, 2H).

15) 5-(3-(15) 5-(3-( 벤질옥시benzyloxy )) 벤질리덴benzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1)-trione [5-(3-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Bt])-trione; compound Bt]

수율: 83%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.38 (s, 1H, NH), 11.23 (s, 1H, NH), 8.23 (s, 1H), 7.89 (s, 1H), 7.61 (d, 1H, J = 7.0 Hz), 7.45 (d, 2H, J = 7.5 Hz), 7.40 - 7.36 (m, 3H), 7.32 (t, 1H, J = 7.5 Hz), 7.18 (d, 1H, J = 8.0 Hz), 5.12 (s, 2H).Yield: 83%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.38 (s, 1H, NH), 11.23 (s, 1H, NH), 8.23 (s, 1H), 7.89 (s, 1H), 7.61 (d, 1H) , J = 7.0 Hz), 7.45 (d, 2H, J = 7.5 Hz), 7.40 - 7.36 (m, 3H), 7.32 (t, 1H, J = 7.5 Hz), 7.18 (d, 1H, J = 8.0 Hz) ), 5.12 (s, 2H).

16) 5-(4-((4-16) 5-(4-((4- 플루오로벤질fluorobenzyl )) 옥시oxy )) 벤질리덴benzylidene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1)-trione [5-(4-((4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Bu])-trione; compound Bu]

수율: 85%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.28 (s, 1H, NH), 11.16 (s, 1H, NH), 8.34 (d, 2H, J = 7.0 Hz), 8.23 (s, 1H), 7.51 (t, 2H, J = 6.5 Hz), 7.22 (t, 2H, J = 8.5 Hz), 7.12 (d, 2H, J = 7.0 Hz), 5.20 (s, 2H).Yield: 85%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 11.28 ( s , 1H, NH), 11.16 (s, 1H, NH), 8.34 (d, 2H, J = 7.0 Hz), 8.23 (s, 1H), 7.51 (t, 2H, J = 6.5 Hz), 7.22 (t, 2H, J = 8.5 Hz), 7.12 (d, 2H, J = 7.0 Hz), 5.20 (s, 2H).

17) 5-(17) 5-( 벤조[benzo[ dd ][1,3]디옥솔][1,3]dioxol -5--5- 일메틸렌ilmethylene )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(Benzo[)-trion [5-(Benzo[ dd ][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6(1][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Bx])-trione; compound Bx]

수율: 80%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.29 (s, 1H, NH), 11.17 (s, 1H, NH), 8.23 (d, 1H, J = 2.0 Hz), 8.18 (s, 1H) 7.72 (dd, 1H, J = 8.5, 2.0 Hz), 7.05 (d, 1H, J = 8.5 Hz), 6.16 (s, 2H).Yield: 80%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 11.29 ( s , 1H, NH), 11.17 (s, 1H, NH), 8.23 (d, 1H, J = 2.0 Hz), 8.18 (s, 1H) 7.72 (dd, 1H, J = 8.5, 2.0 Hz), 7.05 (d, 1H, J = 8.5 Hz), 6.16 (s, 2H).

18) 5-((2-18) 5-((2- 하이드록시나프탈렌Hydroxynaphthalene -1-일)메틸렌)피리미딘-2,4,6(-1-yl) methylene) pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-((2-)-trion [5-((2- HydroxynaphthalenHydroxynaphthalene -1--One- ylyl )) methylenemethylene )pyrimidine-2,4,6()pyrimidine-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-)- trionetrione ; 화합물 By]; Compound By]

수율: 68%; ¹H NMR (400MHz, DMSO-d ₆ ) δ 12.08 (s, 1H), 11.23 (s, 1H), 11.19 (s, 1H), 11.06 (s, 1H), 8.53 (d, 1H, J=8.4Hz), 8.01 (d, 1H, J=8.4Hz), 7.97 (d, 1H, J=9.2Hz), 7.70 (t, 1H, J=7.2Hz), 7.56 (t, 1H, J=7.2Hz), 7.29 (d, 1H, J=9.2Hz).Yield: 68%; 1H NMR (400MHz, DMSO ^- _d6 ) δ 12.08 ( s , 1H), 11.23 (s, 1H), 11.19 (s, 1H), 11.06 (s, 1H), 8.53 (d, 1H, J=8.4Hz ), 8.01 (d, 1H, J=8.4Hz), 7.97 (d, 1H, J=9.2Hz), 7.70 (t, 1H, J=7.2Hz), 7.56 (t, 1H, J=7.2Hz), 7.29 (d, 1H, J=9.2 Hz).

19) 5-(나프탈렌-2-19) 5-(naphthalene-2- 일메틸ilmethyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 BA])-trione [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione; compound BA]

수율: 76%; ¹H NMR (500MHz, DMSO-d ₆ ) δ 11.40 (s, 1H), 11.25 (s, 1H), 8.63 (s, 1H), 8.43 (s, 1H), 8.17 (d, 1H, J = 8.5 Hz), 7.98 (d, 1H, J = 8.0 Hz), 7.94 (d, 1H, J = 8.0 Hz), 7.92 (d, 1H, J = 8.5 Hz), 7.63 (t, 1H, J = 7.5 Hz), 7.57 (t, 1H, J = 7.5 Hz). Yield: 76%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.40 (s, 1H), 11.25 (s, 1H), 8.63 (s, 1H), 8.43 (s, 1H), 8.17 (d, 1H, J = 8.5 Hz ), 7.98 (d, 1H, J = 8.0 Hz), 7.94 (d, 1H, J = 8.0 Hz), 7.92 (d, 1H, J = 8.5 Hz), 7.63 (t, 1H, J = 7.5 Hz), 7.57 (t, 1H, J = 7.5 Hz).

(5) 그룹 C 화합물 합성(5) Synthesis of Group C Compounds

상기 그룹 A 화합물 각각(30 mg)을 에탄올 (5 mL)에 현탁시키고 0 ℃ 현탁 용액에 소듐 보로하이드라이드 (NaBH₄, 3당량)를 천천히 부가하고, 그 혼합용액을 실온에서 10분 내지 2시간 동안 교반하였다. 그 후, 용매를 감압 하에서 휘발시키고 물을 부가한 후 1 N 염산 (HCl)을 첨가하여 pH를 7로 맞췄다. 물을 감압 하에서 증발시킨 후, 에테르/물 (10 ~ 20 : 1) 또는 에탄올/물 (10:1)을 부가하고 생성된 고체를 여과하고 에테르/물 (10 ~ 20 : 1) 또는 에탄올/물 (10:1)로 세척하여 그룹 C에 해당하는 각각의 화합물을 고체로 얻었다.Each of the Group A compounds (30 mg) was suspended in ethanol (5 mL), sodium borohydride (NaBH ₄ , 3 equivalents) was slowly added to the suspension solution at 0 ° C, and the mixed solution was allowed to stand at room temperature for 10 minutes to 2 hours. while stirring. Thereafter, the solvent was volatilized under reduced pressure, water was added, and the pH was adjusted to 7 by adding 1 N hydrochloric acid (HCl). After evaporating water under reduced pressure, ether/water (10-20:1) or ethanol/water (10:1) was added and the resulting solid was filtered and ether/water (10-20:1) or ethanol/water (10:1) to obtain each compound corresponding to Group C as a solid.

1) 5-(4-1) 5-(4- 하이드록시벤질hydroxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(4-Hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(4-Hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Ca (MHY1385)]) -dione; compound Ca (MHY1385)]

수율: 73%; ¹H NMR (500MHz, DMSO-d ₆)δ 11.71 (brs, 2H), 9.03 (brs, 1H), 6.94 (d, 2H, J=7.5Hz), 6.59 (d, 2H, J=8.5Hz), 3.44 (s, 1H), 3.43 (s, 2H); ¹³CNMR(100MHz,DMSO-d ₆)δ 173.3, 161.6, 155.8, 131.9, 129.6, 115.4, 94.8, 26.9.Yield: 73%; 1H NMR (500MHz, DMSO ^- _d6 ) δ 11.71 (brs, 2H), 9.03 (brs, 1H), 6.94 ( d , 2H, J =7.5Hz), 6.59 (d, 2H, J =8.5Hz), 3.44 (s, 1H), 3.43 (s, 2H); ¹³ CNMR (100 MHz, DMSO- d ₆ ) δ 173.3, 161.6, 155.8, 131.9, 129.6, 115.4, 94.8, 26.9.

2) 5-(3,4-2) 5-(3,4- 디하이드록시벤질dihydroxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(3,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(3,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Cb (MHY5135)]) -dione; compound Cb (MHY5135)]

수율: 87%; ¹H NMR (400MHz, D₂O)δ 6.60 (dd, 1H, J=2.4,8.0Hz), 6.60 (d, 1H, J=2.4Hz), 6.49 (d, 1H, J=8.4Hz), 3.29 (s, 2H); ¹³CNMR(100MHz,D₂O)d 171.6, 165.1, 143.8, 141.8, 134.5, 120.1, 116.2, 115.8, 95.0, 26.9; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.07 (s, 2H, 2×NH), 8.70 (brs, 2H, 2×OH), 6.56 (d, 1H, J = 8.0 Hz, 5-H), 6.52 (s, 1H, 2-H), 6.39 (d, 1H, J = 8.0 Hz, 6-H), 3.40 (s, 2H, CH₂).Yield: 87%; 1H NMR _{(400MHz, D 2} ^O ) δ 6.60 (dd, 1H, J =2.4,8.0Hz), 6.60 (d, 1H, J =2.4Hz), 6.49 (d, 1H, J =8.4Hz), 3.29 (s, 2H); ¹³ CNMR(100MHz,D ₂ O) d 171.6, 165.1, 143.8, 141.8, 134.5, 120.1, 116.2, 115.8, 95.0, 26.9; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.07 (s, 2H, 2×NH), 8.70 (brs, 2H, 2×OH), 6.56 (d, 1H, J = 8.0 Hz, 5-H) , 6.52 (s, 1H, 2-H), 6.39 (d, 1H, J = 8.0 Hz, 6-H), 3.40 (s, 2H, CH ₂ ).

3) 5-(2,4-3) 5-(2,4- 디하이드록시벤질dihydroxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(2,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(2,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Cc (MHY5134)]) -dione; compound Cc (MHY5134)]

수율: 88%; ¹H NMR (500MHz, D₂O)δ 6.98 (d, 1H, J=9.0Hz), 6.30-6.28 (m, 2H), 3.34 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 171.7, 165.2, 155.1, 154.8, 131.0, 120.4, 107.8, 103.8, 95.0, 22.4.Yield: 88%; ¹ H NMR (500 MHz, D ₂ O) δ 6.98 (d, 1H, J =9.0 Hz), 6.30-6.28 (m, 2H), 3.34 (s, 2H); ¹³ CNMR(100MHz, D ₂ O) δ 171.7, 165.2, 155.1, 154.8, 131.0, 120.4, 107.8, 103.8, 95.0, 22.4.

4) 5-(4-4) 5-(4- 하이드록시hydroxy -3-메톡시벤질)-2--3-methoxybenzyl)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-디온 [5-(4-)-dione [5-(4- HydroxyHydroxy -3--3- methoxybenzylmethoxybenzyl )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-dione; 화합물 Cd (MHY5136)]) -dione; Compound Cd (MHY5136)]

수율: 87%; ¹H NMR (500MHz, D₂O)δ 6.76 (s, 1H), 6.66 (dd, 1H, J=8.0Hz), 6.59 (d, 1H, J=8.0Hz), 3.68 (s, 3H), 3.38 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 171.7, 165.2, 147.3, 142.7, 134.4, 120.5, 115.5, 112.4, 94.9, 56.0, 27.2.Yield: 87%; ¹ H NMR (500 MHz, D ₂ O) δ 6.76 (s, 1H), 6.66 (dd, 1H, J =8.0Hz), 6.59 (d, 1H, J =8.0Hz), 3.68 (s, 3H), 3.38 (s, 2H); ¹³ CNMR(100MHz, D ₂ O) δ 171.7, 165.2, 147.3, 142.7, 134.4, 120.5, 115.5, 112.4, 94.9, 56.0, 27.2.

5) 5-(3-5) 5-(3- 에톡시ethoxy -4--4- 하이드록시벤질hydroxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-디온 [5-(3-)-dione [5-(3- EthoxyEthoxy -4--4- hydroxybenzylhydroxybenzyl )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-dione; 화합물 Ce (MHY5137)]) -dione; compound Ce (MHY5137)]

수율: 94%; ¹H NMR (500MHz, D₂O)δ 6.77 (s, 1H), 6.68 (d, 1H, J=8.0Hz), 6.62 (d, 1H, J=8.0Hz), 3.95 (q, 2H, J=7.0Hz), 3.41 (s, 2H), 1.23 (t, 3H, J=7.0Hz); ¹³CNMR(100MHz,D₂O)δ 169.5, 163.1, 144.1, 140.9, 132.2, 118.5, 113.4, 111.7, 92.8, 63.1, 25.0, 12.0.Yield: 94%; 1H NMR _{(500MHz, D 2} ^O ) δ 6.77 (s, 1H), 6.68 (d, 1H, J =8.0Hz), 6.62 (d, 1H, J =8.0Hz), 3.95 (q, 2H, J = 7.0 Hz), 3.41 (s, 2H), 1.23 (t, 3H, J =7.0 Hz); ¹³ CNMR(100MHz, D ₂ O) δ 169.5, 163.1, 144.1, 140.9, 132.2, 118.5, 113.4, 111.7, 92.8, 63.1, 25.0, 12.0.

6) 5-(3-6) 5-(3- 하이드록시hydroxy -4-메톡시벤질)-2--4-methoxybenzyl)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-디온 [5-(3-)-dione [5-(3- HydroxyHydroxy -4--4- methoxybenzylmethoxybenzyl )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-dione; 화합물 Cf (MHY5138)]) -dione; compound Cf (MHY5138)]

수율: 97%; ¹H NMR (500MHz, D₂O)δ 6.78 (d, 1H, J=8.0Hz), 6.67 (s, 1H), 6.65 (d, 1H, J=8.0Hz), 3.68 (s, 3H), 3.37 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 169.5, 163.1, 143.4, 142.6, 133.0, 117.8, 113.1, 110.8, 92.7, 54.2, 24.8.Yield: 97%; ¹ H NMR (500 MHz, D ₂ O) δ 6.78 (d, 1H, J =8.0Hz), 6.67 (s, 1H), 6.65 (d, 1H, J =8.0Hz), 3.68 (s, 3H), 3.37 (s, 2H); ¹³ CNMR(100MHz, D ₂ O) δ 169.5, 163.1, 143.4, 142.6, 133.0, 117.8, 113.1, 110.8, 92.7, 54.2, 24.8.

7) 5-(4-메톡시벤질)-2-7) 5-(4-methoxybenzyl)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione ; 화합물 Cg (MHY5140)])-dione; compound Cg (MHY5140)]

수율: 78%; ¹H NMR (400MHz, D₂O)δ 7.02 (brs, 2H), 6.71 (brs, 2H), 3.61 (s, 3H), 3.38 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 171.6, 165.2, 157.0, 134.3, 129.1, 114.0, 95.0, 55.6, 26.9.Yield: 78%; ¹ H NMR (400 MHz, D ₂ O) δ 7.02 (brs, 2H), 6.71 (brs, 2H), 3.61 (s, 3H), 3.38 (s, 2H); ¹³ CNMR(100MHz, D ₂ O) δ 171.6, 165.2, 157.0, 134.3, 129.1, 114.0, 95.0, 55.6, 26.9.

8) 5-(3,4-8) 5-(3,4- 디메톡시벤질dimethoxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(3,4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(3,4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 ) -dione; compound ChCh (MHY5141)] (MHY5141)]

수율: 64%; ¹H NMR (500 MHz, DMSO-d ₆) δ 10.38 (s, 2H, 2×NH), 6.84 (d, 1H, J = 1.0 Hz, 2-H), 6.69 (d, 1H, J = 8.5 Hz, 5-H), 6.66 (dd, 1H, J = 8.5, 1.0 Hz, 6-H), 3.62 (s, 6H, 2×OCH₃),3.30 (s, 2H, benzylic H₂); ¹³CNMR(100MHz,DMSO-d ₆)δ 172.6, 163.7, 148.8, 147.0, 137.4, 120.6, 113.3, 112.3, 90.8, 56.3, 56.0, 28.6.Yield: 64%; 1H NMR (500 MHz, DMSO ^- d6) δ 10.38 (s, 2H, ₂ ×NH), 6.84 ( d , 1H, J = 1.0 Hz, 2-H), 6.69 (d, 1H, J = 8.5 Hz , 5-H), 6.66 (dd, 1H, J = 8.5, 1.0 Hz, 6-H), 3.62 (s, 6H, 2×OCH ₃ ), 3.30 (s, 2H, benzylic H ₂ ); ¹³ CNMR (100 MHz, DMSO _- d6) δ 172.6 , 163.7, 148.8, 147.0, 137.4, 120.6, 113.3, 112.3, 90.8, 56.3, 56.0, 28.6.

9) 5-(2,4-9) 5-(2,4- 디메톡시벤질dimethoxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(2,4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(2,4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 ) -dione; compound CiCi (MHY1386)] (MHY1386)]

수율: 87%; ¹H NMR (400MHz, DMSO-d ₆)δ 10.55 (s, 2H), 6.71 (d, 1H, J=8.0Hz), 6.38 (s, 1H), 6.27 (d, 1H, J=8.0Hz), 3.71 (s, 3H), 3.64 (s, 3H), 3.38 (s, 1H), 3.22 (s, 2H); ¹³CNMR(100MHz,DMSO-d ₆)δ 172.7, 164.0, 158.7, 158.4, 128.6, 123.2, 104.3, 98.2, 88.0, 55.8, 55.7, 22.1.Yield: 87%; 1H NMR (400MHz, DMSO ^- _d6 ) δ 10.55 (s, 2H), 6.71 ( d , 1H, J =8.0Hz), 6.38 (s, 1H), 6.27 (d, 1H, J =8.0Hz), 3.71 (s, 3H), 3.64 (s, 3H), 3.38 (s, 1H), 3.22 (s, 2H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 172.7, 164.0, 158.7, 158.4, 128.6, 123.2, 104.3, 98.2, 88.0, 55.8, 55.7, 22.1.

10) 5-(3,4,5-10) 5-(3,4,5- 트리메톡시벤질trimethoxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(3,4,5-Trimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(3,4,5-Trimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Cj (MHY5142)]) -dione; compound Cj (MHY5142)]

수율: 100%; ¹H NMR (500MHz, D₂O)δ 6.46 (s, 2H), 3.67 (s, 6H), 3.56 (s, 3H), 3.41 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 169.7, 163.0, 150.1, 136.6, 132.6, 103.2, 92.2, 58.9, 53.9, 25.9.Yield: 100%; ¹ H NMR (500 MHz, D ₂ O) δ 6.46 (s, 2H), 3.67 (s, 6H), 3.56 (s, 3H), 3.41 (s, 2H); ¹³ CNMR(100MHz, D ₂ O) δ 169.7, 163.0, 150.1, 136.6, 132.6, 103.2, 92.2, 58.9, 53.9, 25.9.

11) 5-(4-11) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메톡시벤질dimethoxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(4-)-dione [5-(4- HydroxyHydroxy -3,5--3,5- dimethoxybenzyldimethoxybenzyl )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1-4,6(1 HH , 5, 5 HH )-dione; 화합물 Ck (MHY1387)]) -dione; compound Ck (MHY1387)]

수율: 99%; ¹H NMR (400MHz, D₂O)δ 6.44 (s, 2H), 3.66 (s, 6H), 3.37 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 171.8, 165.2, 147.7, 133.8, 131.8, 105.4, 94.7, 56.4, 27.7.Yield: 99%; ¹ H NMR (400 MHz, D ₂ O) δ 6.44 (s, 2H), 3.66 (s, 6H), 3.37 (s, 2H); ¹³ CNMR(100MHz, D ₂ O) δ 171.8, 165.2, 147.7, 133.8, 131.8, 105.4, 94.7, 56.4, 27.7.

12) 5-(3,5-12) 5-(3,5- 디브로모dibromo -4--4- 하이드록시hydroxy )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(3,5-)-dione [5-(3,5- DibromoDibromo -4--4- hydroxybenzylhydroxybenzyl )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-dione; 화합물 Cl (MHY5176)]) -dione; compound Cl (MHY5176)]

수율: 82%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.03 (s, 2H, 2×NH), 9.64 (brs, 1H, OH), 7.29 (s, 2H, 2-H, 6-H), 3.46 (s, 2H, CH₂);¹H NMR (500MHz, CD₃OD)δ 7.32 (s, 2H), 3.54 (s, 2H); ¹³CNMR(100MHz,CD₃OD)δ 173.9, 162.2, 149.1, 134.7, 131.7, 110.8, 93.9, 25.8.Yield: 82%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.03 (s, 2H, 2×NH), 9.64 (brs, 1H, OH), 7.29 (s, 2H, 2-H, 6-H), 3.46 ( s, 2H, CH ₂ ); ¹ H NMR (500 MHz, CD ₃ OD) δ 7.32 (s, 2H), 3.54 (s, 2H); ¹³ CNMR(100MHz, CD ₃ OD) δ 173.9, 162.2, 149.1, 134.7, 131.7, 110.8, 93.9, 25.8.

13) 5-(3-13) 5-(3- 브로모Bromo -4--4- 하이드록시벤질hydroxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(3-)-dione [5-(3- BromoBromo -4--4- hydroxybenzylhydroxybenzyl )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-dione; 화합물 Cm (MHY5143)]) -dione; compound Cm (MHY5143)]

수율: 59%; ¹H NMR (500MHz, CD₃OD)δ 7.32 (d, 1H, J=1.5Hz), 7.04 (dd, 1H, J=8.5, 2.0Hz), 6.6.74 (d, 1H, J= 8.5Hz), 3.50 (s, 2H); ¹H NMR (500 MHz, DMSO-d ₆) δ 12.07 (s, 2H, 2×NH), 9.95 (s, 1H, OH), 7.22 (s, 1H, 2-H), 6.95 (d, 1H, J = 8.0 Hz, 6-H), 6.80 (d, 1H, J = 8.0 Hz, 5-H), 3.45 (s, 2H, benzylic H₂);¹³C NMR (100MHz, CD₃OD)δ 173.0, 164.6, 151.5, 135.3, 132.2, 128.3, 115.6, 109.0, 93.2, 26.7.Yield: 59%; ¹ H NMR (500 MHz, CD ₃ OD) δ 7.32 (d, 1H, J=1.5 Hz), 7.04 (dd, 1H, J=8.5, 2.0 Hz), 6.6.74 (d, 1H, J= 8.5 Hz) , 3.50 (s, 2H); ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.07 (s, 2H, 2×NH), 9.95 (s, 1H, OH), 7.22 (s, 1H, 2-H), 6.95 (d, 1H, J = 8.0 Hz, 6-H), 6.80 (d, 1H, J = 8.0 Hz, 5-H), 3.45 (s, 2H, benzylic H ₂ ); ¹³ C NMR (100 MHz, CD ₃ OD) δ 173.0, 164.6, 151.5, 135.3, 132.2, 128.3, 115.6, 109.0, 93.2, 26.7.

14) 5-(3,5-디-털트-부틸-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(114) 5-(3,5-di-tert-butyl-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-디온 [5-(3,5-)-dione [5-(3,5- DiDi -- terttert -butyl-4--butyl-4- hydroxybenzylhydroxybenzyl )-2-thioxodihydropyrimidine-4,6(1)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione (화합물 Cn (MHY5145)))-dione (compound Cn (MHY5145))

수율: 84%; ¹H NMR (500 MHz, CDCl₃) δ 8.84 (s, 2H, 2×NH), 6.91 (s, 2H, 2-H, 6-H), 3.68 (t, 1H, J = 5.0 Hz, methine H), 3.43 (d, 2H, J = 5.0 Hz, benzylic H₂),1.39(s,18H,2×t-Bu).Yield: 84%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.84 (s, 2H, 2×NH), 6.91 (s, 2H, 2-H, 6-H), 3.68 (t, 1H, J = 5.0 Hz, methine H ), 3.43 (d, 2H, J = 5.0 Hz, benzylic H ₂ ), 1.39 (s, 18H, 2 × t -Bu).

15) 5-(2-15) 5-(2- 하이드록시벤질hydroxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(2-Hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(2-Hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Co (MHY5139)]) -dione; Compound Co (MHY5139)]

수율: 63%; ¹H NMR (400MHz, D₂O)δ 7.06 (d, 1H, J=7.6Hz), 6.97 (td, 1H, J=1.2, 7.2Hz), 6.72 (t, 1H, J=6.8Hz), 6.70 (d, 1H, J=7.2Hz), 3.36 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 171.8, 165.2, 153.7, 130.2, 128.2, 127.9, 121.0, 116.5, 94.5, 23.0.Yield: 63%; 1H NMR (400MHz, D ² O) δ 7.06 ( _d , 1H, J =7.6Hz), 6.97 (td, 1H, J =1.2, 7.2Hz), 6.72 (t, 1H, J =6.8Hz), 6.70 (d, 1H, J =7.2Hz), 3.36 (s, 2H); ¹³ CNMR (100 MHz, D ₂ O) δ 171.8, 165.2, 153.7, 130.2, 128.2, 127.9, 121.0, 116.5, 94.5, 23.0.

16) 5-(4-16) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메틸벤질dimethylbenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(4-)-dione [5-(4- HydroxyHydroxy -3,5--3,5- dimethylbenzyldimethylbenzyl )-2-)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-dione; 화합물 Cp (MHY5169)]) -dione; compound Cp (MHY5169)]

수율: 81%; ¹H NMR(500MHz, DMSO-d ₆) δ 11.14 (s, 2H), 11.10 (s, 2H), 8.14 (s, 1H), 8.06 (s, 1H), 6.59 (s, 2H), 6.55 (s, 2H), 6.28 (s, 1H), 3.70 (t, 1H, J = 5.0 Hz), 3.07 (d, 2H, J = 5.0 Hz), 2.93 (s, 2H), 2.05 (s, 12H).Yield: 81%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.14 (s, 2H), 11.10 (s, 2H), 8.14 (s, 1H), 8.06 (s, 1H), 6.59 (s, 2H), 6.55 (s , 2H), 6.28 (s, 1H), 3.70 (t, 1H, J = 5.0 Hz), 3.07 (d, 2H, J = 5.0 Hz), 2.93 (s, 2H), 2.05 (s, 12H).

17) 5-(4-17) 5-(4- 플루오로벤질fluorobenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion ; [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1; [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 ) -dione; compound CqCq (MHY5150)] (MHY5150)]

수율: 72%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.87 (s, 2H, 2×NH), 7.19 (brt, 2H, J = 8.0 Hz, 2-H, 6-H), 7.01 (t, 2H, J = 8.0 Hz, 3-H, 5-H), 3.53 (s, 2H, CH₂).Yield: 72%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.87 (s, 2H, 2×NH), 7.19 (brt, 2H, J = 8.0 Hz, 2-H, 6-H), 7.01 (t, 2H, J = 8.0 Hz, 3-H, 5-H), 3.53 (s, 2H, CH ₂ ).

18) 5-(2-18) 5-(2- 나이트로벤질nitrobenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion ; [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1; [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 ) -dione; compound CrCr (MHY5146)] (MHY5146)]

수율: 70%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.17 (s, 2H, 2×NH), 7.91 (d, 1H, J = 7.5 Hz, 3-H), 7.57 (t, 1H, J = 7.5 Hz, 5-H), 7.42 (t, 1H, J = 7.5 Hz, 4-H), 7.20 (d, 1H, J = 7.5 Hz, 6-H), 3.82 (s, 2H, benzylic H₂).Yield: 70%; 1H NMR (500 MHz, DMSO- d6 ) δ 12.17 (s, 2H, ² ×NH), 7.91 ( d , 1H, J = 7.5 Hz, ₃ -H), 7.57 (t, 1H, J = 7.5 Hz , 5-H), 7.42 (t, 1H, J = 7.5 Hz, 4-H), 7.20 (d, 1H, J = 7.5 Hz, 6-H), 3.82 (s, 2H, benzylic H ₂ ).

19) 5-(4-(19) 5-(4-( 벤질옥시benzyloxy )) 벤질benzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(4-(Benzyloxy)benzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(4-(Benzyloxy)benzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Cs (MHY5168))) -dione; Compound Cs (MHY5168))

수율: 74%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.07 (s, 2H, 2×NH), 7.40 (d, 2H, J = 7.0 Hz, 2′-H, 6′-H), 7.35 (t, 2H, J = 7.0 Hz, 3′-H, 5′-H), 7.29 (t, 1H, J = 7.0 Hz, 4′-H), 7.05 (d, 2H, J = 8.5 Hz, 2-H, 6-H), 6.86 (d, 2H, J = 8.5 Hz, 3-H, 5-H), 5.02 (s, 2H, OCH₂),3.50(s,2H,CH₂).Yield: 74%; 1H NMR (500 MHz, DMSO ^- d6) δ 12.07 (s, 2H, ₂ ×NH), 7.40 ( d , 2H, J = 7.0 Hz, 2′-H, 6′-H), 7.35 (t, 2H, J = 7.0 Hz, 3′-H, 5′-H), 7.29 (t, 1H, J = 7.0 Hz, 4′-H), 7.05 (d, 2H, J = 8.5 Hz, 2-H, 6-H), 6.86 (d, 2H, J = 8.5 Hz, 3-H, 5-H), 5.02 (s, 2H, OCH ₂ ), 3.50 (s, 2H, CH ₂ ).

20) 5-(4-((4-20) 5-(4-((4- 클로로벤질chlorobenzyl )) 옥시oxy )) 벤질benzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(4-((4-)-dione [5-(4-((4- ChlorobenzylChlorobenzyl )oxy)benzyl)-2-)oxy)benzyl)-2- thioxodihydropyrimidinethioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-dione; 화합물 Cv (MHY5151)]) -dione; Compound Cv (MHY5151)]

수율: 81%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.91 (s, 2H, 2×NH), 7.44 (d, 2H, J = 8.0 Hz, 3′-H, 5′-H), 7.42 (d, 2H, J = 8.0 Hz, 2′-H, 6′-H), 7.08 (d, 2H, J = 8.0 Hz, 2-H, 6-H), 6.85 (d, 2H, J = 8.0 Hz, 3-H, 5-H), 5.03 (s, 2H, OCH₂),3.49(s,2H,CH₂).Yield: 81%; 1H NMR (500 MHz, DMSO ^- d6) δ 11.91 (s, 2H, ₂ ×NH), 7.44 ( d , 2H, J = 8.0 Hz, 3′-H, 5′-H), 7.42 (d, 2H, J = 8.0 Hz, 2′-H, 6′-H), 7.08 (d, 2H, J = 8.0 Hz, 2-H, 6-H), 6.85 (d, 2H, J = 8.0 Hz, 3 -H, 5-H), 5.03 (s, 2H, OCH ₂ ), 3.49 (s, 2H, CH ₂ ).

21) 5-(3-21) 5-(3- 페녹시벤질phenoxybenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 ) -dione; compound CwCw (MHY5171)] (MHY5171)]

수율: 68%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.01 (s, 2H, 2×NH), 6.36 (t, 2H, J = 7.0 Hz, 3′-H, 5′-H), 7.22 (t, 1H, J = 8.0 Hz, 5-H), 7.11 (t, 1H, J = 7.0 Hz, 4′-H), 6.96 (d, 2H, J = 7.0 Hz, 2′-H, 6′-H), 6.93 (d, 1H, J = 8.0 Hz, 6-H), 6.84 (s, 1H, 2-H), 6.74 (d, 1H, J = 8.0 Hz, 4-H), 3.56 (s, 2H, CH₂).Yield: 68%; 1H NMR (500 MHz, DMSO- d6 ) δ 12.01 ( s , 2H, ² ×NH), _6.36 (t, 2H, J = 7.0 Hz, 3′-H, 5′-H), 7.22 (t, 1H, J = 8.0 Hz, 5-H), 7.11 (t, 1H, J = 7.0 Hz, 4′-H), 6.96 (d, 2H, J = 7.0 Hz, 2′-H, 6′-H) , 6.93 (d, 1H, J = 8.0 Hz, 6-H), 6.84 (s, 1H, 2-H), 6.74 (d, 1H, J = 8.0 Hz, 4-H), 3.56 (s, 2H, CH ₂ ).

22) 5-(22) 5-( 벤조[benzo[ dd ][1,3]디옥솔][1,3]dioxol -5--5- 일메틸ilmethyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-()-dione [5-( Benzo[Benzo[ dd ][1,3]dioxol][1,3]dioxol -5--5- ylmethylylmethyl )-2-thioxodihydropyrimidine-4,6(1)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 Cx (MHY5147)]) -dione; compound Cx (MHY5147)]

수율: 87%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.07 (s, 2H, 2×NH), 6.75 (d, 1H, J = 8.0 Hz, 7-H), 7.71 (s, 1H, 4-H), 6.61 (d, 1H, J = 8.0 Hz, 6-H), 5.91 (s, 2H, 2-H₂),3.48(s,2H,benzylic H₂).Yield: 87%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.07 (s, 2H, 2×NH), 6.75 (d, 1H, J = 8.0 Hz, 7-H), 7.71 (s, 1H, 4-H) , 6.61 (d, 1H, J = 8.0 Hz, 6-H), 5.91 (s, 2H, 2-H ₂ ), 3.48 (s, 2H, benzylic H ₂ ).

23) 5-(나프탈렌-1-23) 5-(naphthalene-1- 일메틸ilmethyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(-4,6( 1One HH ,5,5 HH )-)- 디온Dion [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; (화합물 Cz (MHY5148)]) -dione; (Compound Cz (MHY5148)]

수율: 70%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.16 (s, 2H, 2×NH), 8.19 (d, 1H, J = 8.5 Hz), 7.91 (d, 1H, J = 8.0 Hz), 7.74 (d, 1H, J = 8.0 Hz), 7.56 (t, 1H, J = 8.0 Hz), 7.53 (t, 1H, J = 8.0 Hz, 6-H), 7.37 (t, 1H, J = 8.0 Hz, 3-H), 7.08 (d, 1H, J = 8.0 Hz, 2-H), 4.03 (s, 2H, CH₂).Yield: 70%; 1H NMR (500 MHz, DMSO ^- d6) δ 12.16 (s, 2H, ₂ ×NH), 8.19 ( d , 1H, J = 8.5 Hz), 7.91 (d, 1H, J = 8.0 Hz), 7.74 ( d, 1H, J = 8.0 Hz), 7.56 (t, 1H, J = 8.0 Hz), 7.53 (t, 1H, J = 8.0 Hz, 6-H), 7.37 (t, 1H, J = 8.0 Hz, 3 -H), 7.08 (d, 1H, J = 8.0 Hz, 2-H), 4.03 (s, 2H, CH ₂ ).

24) 5-(4-24) 5-(4- 하이드록시hydroxy -3,5--3,5- 디아이소프로필벤질diisopropylbenzyl )-2-)-2- 티옥소디하이드로피리미딘Thioxodihydropyrimidine -4,6(1-4,6(1 HH ,5,5 HH )-디온 [5-(4-)-dione [5-(4- HydroxyHydroxy -3,5--3,5- diisopropylbenzyldiisopropylbenzyl )-2-thioxodihydropyrimidine-4,6(1)-2-thioxodihydropyrimidine-4,6(1 HH ,5,5 HH )-dione; 화합물 CB (MHY5167)]) -dione; compound CB (MHY5167)]

수율: 82%; ¹H NMR (500 MHz, DMSO-d ₆) δ 10.28 (s, 2H, 2×NH), 7.47 (s, 1H, OH), 6.79 (s, 2H), 3.26 (s, 2H), 3.19 (hept, 2H, J = 7.0 Hz), 1.07 (d, 12H, J = 7.0 Hz).Yield: 82%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 10.28 (s, 2H, 2×NH), 7.47 (s, 1H, OH), 6.79 (s, 2H), 3.26 (s, 2H), 3.19 (hept , 2H, J = 7.0 Hz), 1.07 (d, 12H, J = 7.0 Hz).

(6) 그룹 D 화합물 합성(6) Synthesis of Group D Compounds

5-(벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 (30 mg)을 에탄올 (5 mL)에 현탁시키고, 0 ℃ 현탁 용액에 소듐 보로하이드라이드 (NaBH₄, 3당량)를 천천히 부가시킨 혼합용액을 실온에서 0.5 내지 4 시간 동안 교반하였다. 5-(benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione (30 mg) was suspended in ethanol (5 mL), and sodium borohydride was added to the 0 °C suspension solution. (NaBH ₄ , 3 equivalents) was added slowly and stirred at room temperature for 0.5 to 4 hours.

상기 혼합용액의 용매를 감압 하에서 휘발시키고 물을 부가한 후, 1 N 염산(HCl)을 이용하여 pH를 7로 맞췄다. 그 후, 물을 감압 하에서 휘발시키고 에테르/물 (5 ~ 10 : 1) 또는 에탄올/물 (5:1)을 부가하고 생성된 고체를 여과하고 에테르/물 (5 ~ 10 : 1) 또는 에탄올/물 (5:1)로 세척하여 그룹 D 화합물에 해당하는 각각의 화합물을 고체로 얻었다.After volatilizing the solvent of the mixed solution under reduced pressure and adding water, the pH was adjusted to 7 using 1 N hydrochloric acid (HCl). Then, the water was volatilized under reduced pressure, ether/water (5-10:1) or ethanol/water (5:1) was added, and the resulting solid was filtered and ether/water (5-10:1) or ethanol/ Washing with water (5:1) gave each compound corresponding to group D compound as a solid.

1) 5-(4-1) 5-(4- 하이드록시벤질hydroxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1H,3H,5H1H,3H,5H )-트리온 [5-(4-Hydroxybenzyl)pyrimidine-2,4,6(1)-trione [5-(4-Hydroxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Da (MHY1377)])-trione; compound Da (MHY1377)]

수율: 52%; ¹H NMR (500MHz, DMSO-d ₆)δ 11.10 (s, 2H), 9.25 (s, 1H), 6.84 (d, 2H, J=8.0Hz), 6.61 (d, 2H, J=7.5Hz), 3.73 (t, 1H, J=4.5Hz), 3.13 (d, 2H, J=4.5Hz); ¹³C NMR(100MHz,DMSO-d ₆)δ 170.8, 156.8, 151.2, 130.6, 127.6, 115.7, 50.3, 33.9; LRMS(ESI) m/z 233 (M-H)^-.Yield: 52%; 1H NMR (500MHz, DMSO ^- _d6 ) δ 11.10 (s, 2H), 9.25 (s, 1H), 6.84 ( d , 2H, J =8.0Hz), 6.61 (d, 2H, J =7.5Hz), 3.73 (t, 1H, J =4.5 Hz), 3.13 (d, 2H, J =4.5 Hz); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 170.8, 156.8, 151.2, 130.6, 127.6, 115.7, 50.3, 33.9; LRMS(ESI) m/z 233 (MH) ^- .

2) 5-(3, 4-2) 5-(3, 4- 디하이드록시벤질dihydroxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,4-Dihydroxybenzyl)pyrimidine-2,4,6(1)-trione [5-(3,4-Dihydroxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Db (MHY5154)])-trione; compound Db (MHY5154)]

수율: 56%; ¹H NMR (400MHz, D₂O)δ 6.64 (brd, 1H, J=8.0Hz), 6.61 (s, 1H), 6.52 (d, 1H, J=8.0Hz), 3.29 (s, 2H); ¹³C NMR(100MHz,D₂O)δ 166.7, 153.3, 143.9, 141.7, 135.3, 120.0, 116.3, 115.7, 89.5, 26.9; LRMS(ESI) m/z 249 (M-H)^-.Yield: 56%; ¹ H NMR (400 MHz, D ₂ O) δ 6.64 (brd, 1H, J =8.0Hz), 6.61 (s, 1H), 6.52 (d, 1H, J =8.0Hz), 3.29 (s, 2H); ¹³ C NMR (100 MHz, D ₂ O) δ 166.7, 153.3, 143.9, 141.7, 135.3, 120.0, 116.3, 115.7, 89.5, 26.9; LRMS(ESI) m/z 249 (MH) ^- .

3) 5-(2,4-3) 5-(2,4- 디하이드록시벤질dihydroxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(2,4-Dihydroxybenzyl)pyrimidine-2,4,6(1)-trione [5-(2,4-Dihydroxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dc (MHY5153)])-trione; compound Dc (MHY5153)]

수율: 83%; ¹H NMR (400MHz, DMSO-d ₆)δ 11.64 (s, 1H), 10.94 (s, 2H), 9.69 (s, 1H), 7.02 (d, 1H, J=7.6Hz), 6.53 (d, 1H, J=7.6Hz), 6.36 (s, 1H), 3.41 (s, 1H), 3.32 (s, 2H); ¹³C NMR(100MHz,DMSO-d ₆)δ 164.8, 157.7, 154.4, 150.3, 131.1, 113.4, 110.3, 103.3, 84.8, 20.4; LRMS(ESI) m/z 249 (M-H)^-.Yield: 83%; 1H NMR (400MHz, DMSO ^- _d6 ) δ 11.64 ( s , 1H), 10.94 (s, 2H), 9.69 (s, 1H), 7.02 (d, 1H, J =7.6Hz), 6.53 (d, 1H) , J =7.6 Hz), 6.36 (s, 1H), 3.41 (s, 1H), 3.32 (s, 2H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.8, 157.7, 154.4, 150.3, 131.1, 113.4, 110.3, 103.3, 84.8, 20.4; LRMS(ESI) m/z 249 (MH) ^- .

4) 5-(4-4) 5-(4- 하이드록시hydroxy -3-메톡시벤질)피리미딘-2,4,6(-3-methoxybenzyl) pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Hydroxy-3-methoxybenzyl)pyrimidine-2,4,6(1)-trione [5-(4-Hydroxy-3-methoxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 )-trione; compound DdDd (MHY5180)] (MHY5180)]

수율: 73%; ¹H NMR (500MHz, D₂O)δ 6.79 (s, 1H), 6.69 (d, 1H, J=8.0Hz), 6.62 (d, 1H, J=8.0Hz), 3.71 (s, 3H), 3.40 (s, 2H); ¹H NMR (500 MHz, DMSO-d ₆) δ 11.14 (s, 2H, 2×NH), 8.87 (s, 1H, OH), 6.77 (d, 1H, J = 8.0 Hz, 5-H), 6.52 (d, 1H, J = 1.5 Hz, 2-H), 6.44 (dd, 1H, J = 8.0, 1.5 Hz, 6-H), 3.78 (t, 1H, J = 4.0 Hz, CH), 3.70 (s, 3H, OCH₃),3.12(d,2H,J = 4.0 Hz, CH₂);¹³C NMR (100MHz, D₂O)δ 166.7, 153.4, 147.3, 142.6, 135.1, 120.4, 115.5, 112.3, 89.5, 56.0, 27.2; LRMS(ESI) m/z 263 (M-H)^-.Yield: 73%; ¹ H NMR (500 MHz, D ₂ O) δ 6.79 (s, 1H), 6.69 (d, 1H, J =8.0Hz), 6.62 (d, 1H, J =8.0Hz), 3.71 (s, 3H), 3.40 (s, 2H); ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.14 (s, 2H, 2×NH), 8.87 (s, 1H, OH), 6.77 (d, 1H, J = 8.0 Hz, 5-H), 6.52 (d, 1H, J = 1.5 Hz, 2-H), 6.44 (dd, 1H, J = 8.0, 1.5 Hz, 6-H), 3.78 (t, 1H, J = 4.0 Hz, CH), 3.70 (s , 3H, OCH ₃ ),3.12(d,2H, J = 4.0 Hz, CH ₂ ); ¹³ C NMR (100 MHz, D ₂ O) δ 166.7, 153.4, 147.3, 142.6, 135.1, 120.4, 115.5, 112.3, 89.5, 56.0, 27.2; LRMS(ESI) m/z 263 (MH) ^- .

5) 5-(3-5) 5-(3- 에톡시ethoxy -4--4- 하이드록시벤질hydroxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)pyrimidine-2,4,6(1)-trione [5-(3-Ethoxy-4-hydroxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 De (MHY5155)])-trione; Compound De (MHY5155)]

수율: 35%; ¹H NMR (400MHz, D₂O)δ 6.73 (d, 1H, J=2.0Hz), 6.65 (d, 1H, J=8.0Hz), 6.58 (dd, 1H, J=2.0, 7.6Hz), 3.93 (q, 2H, J=6.8Hz), 3.33 (s, 2H), 1.19 (t, 3H, J=6.8Hz); ¹³CNMR(100MHz,D₂O)δ 166.7, 153.3, 146.2, 142.9, 135.1, 120.6, 115.5, 113.8, 89.5, 65.3, 27.1, 14.1; LRMS(ESI) m/z 277 (M-H)^-.Yield: 35%; ¹ H NMR (400 MHz, D ₂ O) δ 6.73 (d, 1H, J =2.0 Hz), 6.65 (d, 1H, J =8.0 Hz), 6.58 (dd, 1H, J =2.0, 7.6 Hz), 3.93 (q, 2H, J =6.8 Hz), 3.33 (s, 2H), 1.19 (t, 3H, J =6.8 Hz); ¹³ CNMR(100MHz, D ₂ O) δ 166.7, 153.3, 146.2, 142.9, 135.1, 120.6, 115.5, 113.8, 89.5, 65.3, 27.1, 14.1; LRMS(ESI) m/z 277 (MH) ^- .

6) 5-(3-6) 5-(3- 하이드록시hydroxy -4-메톡시벤질)피리미딘-2,4,6(-4-methoxybenzyl) pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-Hydroxy-4-methoxybenzyl)pyrimidine-2,4,6(1)-trione [5-(3-Hydroxy-4-methoxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 )-trione; compound DfDf (MHY5177)] (MHY5177)]

수율: 23%; ¹H NMR (400MHz, DMSO-d ₆)δ 11.11 (s, 2H), 8.85 (s, 1H), 6.73 (d, 1H, J=7.6Hz), 6.48 (s, 1H), 6.40 (d, 1H, J=7.2Hz), 3.74 (brs, 1H), 3.66 (s, 3H), 3.08 (brs, 2H); ¹³CNMR(100MHz,DMSO-d ₆)δ 170.7, 151.3, 147.1, 146.8, 130.1, 120.2, 117.0, 112.7, 56.2, 50.1, 33.7; LRMS(ESI) m/z 263 (M-H)^-.Yield: 23%; 1H NMR (400MHz, DMSO ^- _d6 ) δ 11.11 (s, 2H), 8.85 (s, 1H), 6.73 ( d , 1H, J =7.6Hz), 6.48 (s, 1H), 6.40 (d, 1H) , J =7.2 Hz), 3.74 (brs, 1H), 3.66 (s, 3H), 3.08 (brs, 2H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 170.7, 151.3, 147.1, 146.8, 130.1, 120.2, 117.0, 112.7, 56.2, 50.1, 33.7; LRMS(ESI) m/z 263 (MH) ^- .

7) 5-(4-메톡시벤질)피리미딘-2,4,6(7) 5-(4-methoxybenzyl)pyrimidine-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Methoxybenzyl)pyrimidine-2,4,6(1)-trione [5-(4-Methoxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dg (MHY5156)])-trione; compound Dg (MHY5156)]

수율: 68%; ¹H NMR (500MHz, DMSO-d ₆)δ 11.14 (s, 2H), 6.98 (d, 2H, J=8.0Hz), 6.80 (d, 2H, J=8.5Hz), 3.80 (t, 1H, J=3.5Hz), 3.69 (s, 3H), 3.19 (d, 2H, J = 3.5 Hz); ¹³C NMR(100MHz,DMSO-d ₆)δ 170.7, 158.7, 151.2, 130.7, 129.6, 114.4, 55.6, 50.2, 33.5; LRMS(ESI) m/z 247 (M-H)^-.Yield: 68%; 1H NMR (500MHz, DMSO ^- d6) δ 11.14 (s, 2H), 6.98 ( d , 2H, J =8.0Hz), _6.80 (d, 2H, J =8.5Hz), 3.80 (t, 1H, J =3.5 Hz), 3.69 (s, 3H), 3.19 (d, 2H, J = 3.5 Hz); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 170.7, 158.7, 151.2, 130.7, 129.6, 114.4, 55.6, 50.2, 33.5; LRMS(ESI) m/z 247 (MH) ^- .

8) 5-(3,4-8) 5-(3,4- 디메톡시벤질dimethoxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,4-Dimethoxybenzyl)pyrimidine-2,4,6(1)-trione [5-(3,4-Dimethoxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dh (MHY1378)])-trione; compound Dh (MHY1378)]

수율: 40%; ¹H NMR (500MHz, D₂O)δ 6.80 (s, 1H), 6.79 (d, 1H, J=8.0Hz), 6.70 (d, 1H, J=8.0Hz), 3.69 (s, 3H), 3.67 (s, 3H), 3.40 (s, 2H); ¹³C NMR(100MHz,D₂O)δ 166.7, 153.3, 148.0, 146.1, 135.7, 120.1, 112.1, 111.8, 89.4, 55.9, 55.7, 27.2; LRMS(ESI) m/z 277 (M-H)^-.Yield: 40%; ¹ H NMR (500 MHz, D ₂ O) δ 6.80 (s, 1H), 6.79 (d, 1H, J =8.0Hz), 6.70 (d, 1H, J =8.0Hz), 3.69 (s, 3H), 3.67 (s, 3H), 3.40 (s, 2H); ¹³ C NMR (100 MHz, D ₂ O) δ 166.7, 153.3, 148.0, 146.1, 135.7, 120.1, 112.1, 111.8, 89.4, 55.9, 55.7, 27.2; LRMS(ESI) m/z 277 (MH) ^- .

9) 5-(2,4-9) 5-(2,4- 디메톡시벤질dimethoxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(2,4-Dimethoxybenzyl)pyrimidine-2,4,6(1)-trione [5-(2,4-Dimethoxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Di (MHY5157)])-trione; Compound Di (MHY5157)]

수율: 88%; ¹H NMR (500MHz, DMSO-d ₆)δ 9.27 (s, 2H), 6.77 (d, 1H, J=8.0Hz), 6.40 (s, 1H), 6.29 (d, 1H, J=8.0Hz), 3.73 (s, 3H), 3.66 (s, 3H), 3.37 (s, 1H), 3.22 (s, 2H); ¹³CNMR(100MHz,DMSO-d ₆)δ 165.6, 158.5, 158.4, 153.0, 128.9, 124.3, 104.3, 98.1, 82.6, 55.7, 55.7, 22.2; LRMS(ESI) m/z 277 (M-H)^-.Yield: 88%; 1H NMR (500MHz, DMSO ^- _d6 ) δ 9.27 (s, 2H), 6.77 ( d , 1H, J =8.0Hz), 6.40 (s, 1H), 6.29 (d, 1H, J =8.0Hz), 3.73 (s, 3H), 3.66 (s, 3H), 3.37 (s, 1H), 3.22 (s, 2H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 165.6, 158.5, 158.4, 153.0, 128.9, 124.3, 104.3, 98.1, 82.6, 55.7, 55.7, 22.2; LRMS(ESI) m/z 277 (MH) ^- .

10) 5-(3,4,5-10) 5-(3,4,5- 트리메톡시벤질trimethoxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4,6(1)-trione [5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dj (MHY5172)] )-trione; Compound Dj (MHY5172)]

수율: 99%; ¹H NMR (400MHz, D₂O)δ 6.45 (s, 2H), 3.65 (s, 6H), 3.56 (s, 3H), 3.37 (s, 2H); ¹³CNMR(100MHz,D₂O)δ 166.7, 153.3, 152.3, 139.5, 134.6, 105.3, 89.0, 61.1, 56.1, 28.1; LRMS(ESI) m/z 307 (M-H)^-.Yield: 99%; ¹ H NMR (400 MHz, D ₂ O) δ 6.45 (s, 2H), 3.65 (s, 6H), 3.56 (s, 3H), 3.37 (s, 2H); ¹³ CNMR(100MHz, D ₂ O) δ 166.7, 153.3, 152.3, 139.5, 134.6, 105.3, 89.0, 61.1, 56.1, 28.1; LRMS(ESI) m/z 307 (MH) ^- .

11) 5-(4-11) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메톡시벤질dimethoxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)pyrimidine-2,4,6(1)-trione [5-(4-Hydroxy-3,5-dimethoxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dk (MHY1379)])-trione; compound Dk (MHY1379)]

수율: 90%; ¹H NMR (500MHz, DMSO-d ₆)δ 11.18 (brs, 1H), 9.31 (brs, 2H), 6.44 (brs, 2H), 3.65 (s, 6H), 3.61 (s, 1H), 3.27 (s, 2H); ¹³CNMR(100MHz,DMSO-d ₆)δ 165.5, 152.4, 148.1, 135.5, 133.9, 106.7, 86.0, 56.5, 29.2; LRMS(ESI) m/z 293 (M-H)^-.Yield: 90%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.18 (brs, 1H), 9.31 (brs, 2H), 6.44 (brs, 2H), 3.65 (s, 6H), 3.61 (s, 1H), 3.27 (s , 2H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 165.5, 152.4, 148.1, 135.5, 133.9, 106.7, 86.0, 56.5, 29.2; LRMS(ESI) m/z 293 (MH) ^- .

12) 5-(3,5-12) 5-(3,5- 디브로모dibromo -4--4- 하이드록시벤질hydroxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,5-Dibromo-4-hydroxybenzyl)pyrimidine-2,4,6(1)-trione [5-(3,5-Dibromo-4-hydroxybenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dl (MHY5144)])-trione; Compound Dl (MHY5144)]

수율: 98%; ¹H NMR (500MHz, CD₃OD)δ 7.35 (s, 2H), 3.48 (s, 2H); ¹³CNMR(100MHz,CD₃OD)δ 171.7, 150.8, 149.8, 137.9, 131.7, 110.8, 87.7, 26.8.Yield: 98%; ¹ H NMR (500 MHz, CD ₃ OD) δ 7.35 (s, 2H), 3.48 (s, 2H); ¹³ CNMR (100 MHz, CD ₃ OD) δ 171.7, 150.8, 149.8, 137.9, 131.7, 110.8, 87.7, 26.8.

13) 5-(4-13) 5-(4- 플루오로벤질fluorobenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Fluorobenzyl)pyrimidine-2,4,6(1)-trione [5-(4-Fluorobenzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dq (MHY5185)])-trione; Compound Dq (MHY5185)]

수율: 64%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.19 (s, 2H, 2×NH), 7.17 - 7.05 (m, 4H), 3.91 (t, 1H, J = 5.0 Hz, methine H), 3.24 (d, 2H, J = 5.0 Hz, benzylic H₂).Yield: 64%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.19 (s, 2H, 2×NH), 7.17 - 7.05 (m, 4H), 3.91 (t, 1H, J = 5.0 Hz, methine H), 3.24 ( d, 2H, J = 5.0 Hz, benzylic H ₂ ).

14) 5-(3-(14) 5-(3-( 벤질옥시benzyloxy )) 벤질benzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-(Benzyloxy)benzyl)pyrimidine-2,4,6(1)-trione [5-(3-(Benzyloxy)benzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dt (MHY5181)])-trione; compound Dt (MHY5181)]

수율: 73%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.19 (s, 2H, 2×NH), 7.43 (d, 2H, J = 7.5 Hz), 7.39 (t, 2H, J = 7.5 Hz), 7.33 (t, 1H, J = 7.5 Hz), 7.17 (t, 1H, J = 7.5 Hz), 6.86 (d, 1H, J = 7.5 Hz), 6.75 (s, 1H), 6.67 (d, 1H, J = 7.0 Hz), 5.03 (s, 2H, OCH₂), 3.91(t,1H, J=5.0Hz, methine H), 3.23(d, 2H, J=5.0Hz, benzylic H₂).Yield: 73%; 1H NMR (500 MHz, DMSO ^- d6) δ 11.19 (s, 2H, ₂ ×NH), 7.43 ( d , 2H, J = 7.5 Hz), 7.39 (t, 2H, J = 7.5 Hz), 7.33 ( t, 1H, J = 7.5 Hz), 7.17 (t, 1H, J = 7.5 Hz), 6.86 (d, 1H, J = 7.5 Hz), 6.75 (s, 1H), 6.67 (d, 1H, J = 7.0 Hz), 5.03 (s, 2H, OCH ₂ ), 3.91 (t, 1H, J=5.0 Hz, methine H), 3.23 (d, 2H, J=5.0 Hz, benzylic H ₂ ).

15) 5-(4-((4-15) 5-(4-((4- 플루오로벤질fluorobenzyl )) 옥시oxy )) 벤질benzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1)-trione [5-(4-((4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Du (MHY5152)])-trione; Compound Du (MHY5152)]

수율: 73%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.14 (s, 2H, 2×NH), 7.46 (dd, 2H, J = 8.5, 6.0 Hz), 7.18 (t, 2H, J = 9.0 Hz), 6.98 (d, 2H, J = 8.5 Hz), 6.88 (d, 2H, J = 8.5 Hz), 5.00 (s, 2H), 3.81 (t, 1H, J = 5.0 Hz, methine H), 3.18 (d, 2H, J = 5.0 Hz, benzylic H₂).Yield: 73%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.14 (s, 2H, 2×NH), 7.46 (dd, 2H, J = 8.5, 6.0 Hz), 7.18 (t, 2H, J = 9.0 Hz), 6.98 (d, 2H, J = 8.5 Hz), 6.88 (d, 2H, J = 8.5 Hz), 5.00 (s, 2H), 3.81 (t, 1H, J = 5.0 Hz, methine H), 3.18 (d, 2H, J = 5.0 Hz, benzylic H ₂ ).

16) 5-(16) 5-( 벤조[benzo[ dd ][1,3]디옥솔][1,3]dioxol -5--5- 일메틸ilmethyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(Benzo[)-trion [5-(Benzo[ dd ][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 )-trione; compound DxDx (MHY5182)] (MHY5182)]

수율: 60%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.18 (s, 2H, 2×NH), 6.79 (d, 1H, J = 8.5 Hz), 6.60 (s, 1H), 6.54 (d, 1H, J = 8.5 Hz), 5.96 (s, 2H), 3.83 (t, 1H, J = 5.0 Hz, methine H), 3.17 (d, 2H, J = 5.0 Hz, benzylic H₂).Yield: 60%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.18 (s, 2H, 2×NH), 6.79 (d, 1H, J = 8.5 Hz), 6.60 (s, 1H), 6.54 (d, 1H, J = 8.5 Hz), 5.96 (s, 2H), 3.83 (t, 1H, J = 5.0 Hz, methine H), 3.17 (d, 2H, J = 5.0 Hz, benzylic H ₂ ).

17) 5-((2-17) 5-((2- 하이드록시나프탈렌Hydroxynaphthalene -1-일)-1 day) 메틸methyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-((2-Hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6(1)-trione [5-((2-Hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Dy (MHY5183))-trione; Compound Dy (MHY5183)

수율: 33%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.86 (s, 1H), 11.10 (s, 1H), 7.97 (d, 1H, J = 7.5 Hz), 7.94 - 7.87 (m, 2H), 7.66 (t, 1H, J = 7.5 Hz), 7.55 (t, 1H, J = 7.5 Hz), 7.26 (d, 1H, J = 7.5 Hz), 3.78 (s, 2H, CH₂).Yield: 33%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 11.86 (s, 1H), 11.10 (s, 1H), 7.97 ( d , 1H, J = 7.5 Hz), 7.94 - 7.87 (m, 2H), 7.66 ( t, 1H, J = 7.5 Hz), 7.55 (t, 1H, J = 7.5 Hz), 7.26 (d, 1H, J = 7.5 Hz), 3.78 (s, 2H, CH ₂ ).

18) 5-(나프탈렌-2-18) 5-(naphthalene-2- 일메틸ilmethyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4,6(1)-trione [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 DA ()-trione; Compound DA ( MHY5184MHY5184 = MHY5149)] =MHY5149)]

수율: 83%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.17 (s, 2H, 2×NH), 7.86 (d, 1H, J = 7.5 Hz), 7.83 - 7.80 (m, 2H), 7.61 (s, 1H), 7.50 - 7.43 (m, 2H), 7.27 (d, 1H, J = 8.0 Hz), 4.00 (t, 1H, J = 5.0 Hz, methine H), 3.43 (d, 2H, J = 5.0 Hz, benzylic H₂).Yield: 83%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.17 (s, 2H, 2×NH), 7.86 (d, 1H, J = 7.5 Hz), 7.83 - 7.80 (m, 2H), 7.61 (s, 1H ), 7.50 - 7.43 (m, 2H), 7.27 (d, 1H, J = 8.0 Hz), 4.00 (t, 1H, J = 5.0 Hz, methine H), 3.43 (d, 2H, J = 5.0 Hz, benzylic H ₂ ).

(7) 그룹 E 화합물 합성(7) Synthesis of Group E Compounds

상기 화합물 2 (100 mg, 0.43 mmol)와 벤즈알데하이드 (benzaldehyde; 1.0 당량)를 포함하는 에탄올/물 (1 mL/1 mL) 혼합용액을 30분 내지 2일간 환류 교반하였다. 상기 혼합용액을 식힌 후 물을 가하고 생성된 고체를 여과하고 물과 적당한 유기용매로 세척하면서 정제하였다. 경우에 따라서는 여과 후에 얻어진 고체를 실리카 겔 컬럼 크로마토그래피를 하여 더욱 정제하여 그룹 E에 해당하는 각각의 화합물을 얻었다.A mixed solution of ethanol/water (1 mL/1 mL) containing Compound 2 (100 mg, 0.43 mmol) and benzaldehyde (benzaldehyde; 1.0 equivalent) was stirred under reflux for 30 minutes to 2 days. After cooling the mixed solution, water was added, and the resulting solid was filtered and purified while washing with water and an appropriate organic solvent. In some cases, the solid obtained after filtration was further purified by silica gel column chromatography to obtain each compound corresponding to Group E.

1) (One) ( E/ZE/Z )-5-(4-)-5-(4- 하이드록시벤질리덴hydroxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH , 5, 5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(4-)-5-(4- HydroxybenzylideneHydroxybenzylidenes )-1-(4-)-1-(4- methoxyphenylmethoxyphenyl )pyrimidine-2,4,6(1)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ea])-trione; compound Ea]

수율: 77%; E/Z = 1.1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.53 (s, 1H), 11.42 (s, 1H), 10.81 (s, 1H), 10.79 (s, 1H), 8.31 (d, 2H, J=7.5Hz), 8.29 (s, 1H), 8.26 (d, 2H, J=8.0Hz), 8.22 (s, 1H), 7.20 (m, 4H), 6.98 (d, 4H, J=7.5Hz), 6.88 (d, 2H, J=8.0Hz), 6.83 (d, 2H, J=8.0Hz), 3.78 (s, 6H); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.6, 163.8, 163.7 (ⅹ2), 162.6, 162.1, 159.5 (ⅹ2), 156.9, 156.5, 151.1 (ⅹ2), 139.0, 138.9, 130.8, 130.7, 128.9, 128.6, 124.6, 124.4, 116.2 (ⅹ2), 115.3, 115.2, 114.6 (ⅹ2), 56.0 (ⅹ2).Yield: 77%; E/Z = 1.1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.53 (s, 1H), 11.42 (s, 1H), 10.81 (s, 1H), 10.79 (s, 1H), 8.31 (d, 2H, J=7.5Hz), 8.29 (s, 1H), 8.26 (d , 2H, J=8.0Hz), 8.22 (s, 1H), 7.20 (m, 4H), 6.98 (d, 4H, J=7.5Hz), 6.88 (d, 2H, J=8.0Hz), 6.83 (d , 2H, J=8.0 Hz), 3.78 (s, 6H); ¹³ CNMR (100 MHz, DMSO- d ₆ ) δ 164.6, 163.8, 163.7 (x2), 162.6, 162.1, 159.5 (x2), 156.9, 156.5, 151.1 (x2), 139.0, 138.9, 128.9, 130.8, 130.8, 130.8 124.6, 124.4, 116.2 (x2), 115.3, 115.2, 114.6 (x2), 56.0 (x2).

2) (2) ( E/ZE/Z )-5-(3,4-)-5-(3,4- 디하이드록시벤질리덴dihydroxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(3,4-)-5-(3,4- DihydroxybenzylideneDihydroxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Eb])-trione; compound Eb]

수율: 79%; E/Z = 1.2:1 혼합물; ¹HNMR(400MHz,DMSO-d ₆)δ 11.48 (s, 1H), 11.37 (s, 1H), 10.39 (s, 1H), 10.34 (s, 1H), 9.49 (s, 1H), 9.47 (s, 1H), 8.21 (d, 1H, J=2.0Hz), 8.17 (s, 1H), 8.17 (d, 1H, J=2.0Hz), 8.11 (s, 1H), 7.59 (dd, 1H, J=8.4, 2.0Hz), 7.52 (dd, 1H, J=8.4, 2.0Hz), 7.19 (d, 2H, J=8.8Hz), 7.17 (d, 2H, J=8.8Hz), 6.96 (d, 2H, J=8.8Hz), 6.95 (d, 2H, J=8.8Hz), 6.82 (d, 1H, J=8.0Hz), 6.79 (d, 1H, J=8.4Hz), 3.76 (s, 6H); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.7, 163.9, 162.6, 162.1, 159.6, 159.5, 157.4, 157.0, 153.2, 153.1, 151.1 (ⅹ2), 145.6, 145.5, 132.6, 131.9, 130.9, 130.7, 128.9, 128.7, 125.0, 124.9, 121.9, 121.6, 116.1 (ⅹ2), 114.8, 114.6 (ⅹ2), 114.5, 56.0 (ⅹ2).Yield: 79%; E/Z = 1.2:1 mixture; ¹ HNMR (400 MHz, DMSO- d ₆ ) δ 11.48 (s, 1H), 11.37 (s, 1H), 10.39 (s, 1H), 10.34 (s, 1H), 9.49 (s, 1H), 9.47 (s, 1H), 8.21 (d, 1H, J=2.0Hz), 8.17 (s, 1H), 8.17 (d, 1H, J=2.0Hz), 8.11 (s, 1H), 7.59 (dd, 1H, J=8.4 , 2.0Hz), 7.52 (dd, 1H, J=8.4, 2.0Hz), 7.19 (d, 2H, J=8.8Hz), 7.17 (d, 2H, J=8.8Hz), 6.96 (d, 2H, J =8.8Hz), 6.95 (d, 2H, J=8.8Hz), 6.82 (d, 1H, J=8.0Hz), 6.79 (d, 1H, J=8.4Hz), 3.76 (s, 6H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 164.7, 163.9, 162.6, 162.1, 159.6, 159.5, 157.4, 157.0, 153.2, 153.1, 151.1 (ⅹ2), 145.6, 145.5, 132.6, 131.9, 130.9, 130.7, 128.9, 128.7, 125.0, 124.9, 121.9, 121.6 (x2), 114.8, 114.6 (x2), 114.5, 56.0 (x2).

3) (3) ( E/ZE/Z )-5-(2,4-)-5-(2,4- 디하이드록시벤질리덴dihydroxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(2,4-)-5-(2,4- DihydroxybenzylideneDihydroxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ec] )-trione; compound Ec]

수율: 36%; E/Z = 6:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.68 (s, 1H)*, 10.38 (s, 1H)*, 8.93 (s, 1H)*, 8.89 (s, 1H), 7.96 (d, 1H, J=9.0Hz), 7.88 (d, 1H, J=8.5Hz)*, 7.45 (d, 2H, J=8.5Hz)*, 7.13 (d, 2H, J=9.0Hz), 7.02 - 6.98 (m, 4H), 6.93 - 6.90 (m, 3H)*, 6.83 (d, 1H, J=2.0Hz)*, 3.78 (s, 3H), 3.72 (s, 3H)* (표시* 는 Z 형태 화합물의 데이터임).Yield: 36%; E/Z = 6:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.68 (s, 1H)*, 10.38 (s, 1H)*, 8.93 (s, 1H)*, 8.89 (s, 1H), 7.96 (d, 1H, J= 9.0Hz), 7.88 (d, 1H, J=8.5Hz)*, 7.45 (d, 2H, J=8.5Hz)*, 7.13 (d, 2H, J=9.0Hz), 7.02 - 6.98 (m, 4H) , 6.93 - 6.90 (m, 3H)*, 6.83 (d, 1H, J=2.0Hz)*, 3.78 (s, 3H), 3.72 (s, 3H)* (marking * is data for Z form compound).

4) (4) ( E/ZE/Z )-5-(4-)-5-(4- 하이드록시hydroxy -3--3- 메톡시벤질리덴methoxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 H,H, 33 H,H, 55 HH )-트리온 [()-trion [( E/ZE/Z )-5-(4-)-5-(4- HydroxyHydroxy -3--3- methoxybenzylidenemethoxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ed])-trione; compound Ed]

수율: 69%; E/Z = 1:1 혼합물; ¹HNMR(400MHz,DMSO-d ₆)δ 11.53 (s, 1H), 11.42 (s, 1H), 10.55 (brs, 2H), 8.44 (d, 1H, J=2.0Hz), 8.29 (s, 1H), 8.21 (brs, 2H), 7.85 (dd, 1H, J=8.4, 2.0Hz), 7.76 (dd, 1H, J=8.4, 2.0Hz), 7.19 (d, 2H, J= 8.4Hz), 7.17 (d, 2H, J=8.4Hz), 6.96 (d, 4H, J=8.4Hz), 6.88 (d, 1H, J=8.4Hz), 6.84 (d, 1H, J=8.4Hz), 3.80 (s, 3H), 3.76 (s, 6H), 3.72 (s, 3H); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.7, 163.9, 162.7, 162.3, 159.5 (ⅹ2), 157.3, 156.8, 153.8 (ⅹ2), 151.1, 151.0, 147.6 (ⅹ2), 133.2, 132.9, 130.9, 130.7, 128.9, 128.6, 124.9, 124.8, 119.2, 118.5, 116.0 (ⅹ2), 115.0 (ⅹ2), 114.6 (ⅹ2), 56.3, 56.2, 56.0 (ⅹ2). Yield: 69%; E/Z = 1:1 mixture; ¹ HNMR (400 MHz, DMSO- d ₆ ) δ 11.53 (s, 1H), 11.42 (s, 1H), 10.55 (brs, 2H), 8.44 (d, 1H, J=2.0Hz), 8.29 (s, 1H) ( d, 2H, J=8.4Hz), 6.96 (d, 4H, J=8.4Hz), 6.88 (d, 1H, J=8.4Hz), 6.84 (d, 1H, J=8.4Hz), 3.80 (s, 3H), 3.76 (s, 6H), 3.72 (s, 3H); ¹³ CNMR (100 MHz, DMSO- d ₆ ) δ 164.7, 163.9, 162.7, 162.3, 159.5 (x2), 157.3, 156.8, 153.8 (x2), 151.1, 151.0, 147.6 (x2), 133.2, 133.2, 132.9, 132.9 128.9, 128.6, 124.9, 124.8, 119.2, 118.5, 116.0 (x2), 115.0 (x2), 114.6 (x2), 56.3, 56.2, 56.0 (x2).

5) (5) ( E/ZE/Z )-5-(3-)-5-(3- 에톡시ethoxy -4--4- 하이드록시벤질리덴hydroxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(3-)-5-(3- EthoxyEthoxy -4--4- hydroxybenzylidenehydroxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ee])-trione; compound Ee]

수율: 81%; E/Z = 1.1:1 혼합물; ¹HNMR(400MHz,DMSO-d ₆)δ 11.51 (s, 1H), 11.40 (s, 1H), 10.47 (brs, 2H), 8.45 (s, 1H, 8.27 (s, 1H), 8.19 (s, 2H), 7.81 (d, 1H, J=7.6Hz), 7.71 (d, 1H, J=8.0Hz), 7.20 - 7.14 (m, 4H), 6.96 (d, 4H, J=8.4Hz), 6.92 - 6.84 (m, 2H), 4.06 (q, 2H, J=6.8Hz), 3.97 (q, 2H, J=6.8Hz), 3.76 (s, 6H), 1.34 (t, 3H, J=6.8Hz), 1.27 (t, 3H, J=6.8Hz); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.7, 163.8, 162.7, 162.3, 159.5 (ⅹ2), 157.3, 156.9, 154.0 (ⅹ2), 151.1, 151.0, 146.8 (ⅹ2), 133.2, 132.9, 130.9, 130.7, 128.9, 128.6, 124.9 (ⅹ2), 120.3, 119.5, 116.1 (ⅹ2), 115.0 (ⅹ2), 114.6 (ⅹ2), 64.6, 64.5, 56.0 (ⅹ2), 15.2 (ⅹ2).Yield: 81%; E/Z = 1.1:1 mixture; ¹ HNMR (400 MHz, DMSO- d ₆ ) δ 11.51 (s, 1H), 11.40 (s, 1H), 10.47 (brs, 2H), 8.45 (s, 1H, 8.27 (s, 1H), 8.19 (s, 2H), 7.81 (d, 1H, J=7.6 Hz), 7.71 (d, 1H, J=8.0Hz), 7.20 - 7.14 (m, 4H), 6.96 (d, 4H, J=8.4Hz), 6.92 - 6.84 (m, 2H), 4.06 (q, 2H) , J=6.8Hz), 3.97 (q, 2H, J=6.8Hz), 3.76 (s, 6H), 1.34 (t, 3H, J=6.8Hz), 1.27 (t, 3H, J=6.8Hz); ¹³ CNMR (100 MHz, DMSO- d ₆ ) δ 164.7, 163.8, 162.7, 162.3, 159.5 (x2), 157.3, 156.9, 154.0 (x2), 151.1, 151.0, 146.8 (x2), 133.2, 133.2, 132.9, 132.9 128.9, 128.6, 124.9 (x2), 120.3, 119.5, 116.1 (x2), 115.0 (x2), 114.6 (x2), 64.6, 64.5, 56.0 (x2), 15.2 (x2).

6) (6) ( EE // ZZ )-5-(3-)-5-(3- 하이드록시hydroxy -4--4- 메톡시벤질리덴methoxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( EE // ZZ )-5-(3-)-5-(3- hydroxyhydroxy -4--4- methoxybenzylidenemethoxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ef])-trione; compound Ef]

수율: 77%; E/Z = 1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.57 (s, 1H), 11.46 (s, 1H), 9.46 (s, 2H), 8.23 (s, 1H), 8.17 - 8.15 (m, 2H), 8.11 (d, 1H, J = 2.0 Hz), 7.71 (dd, 1H, J = 9.0, 2.0 Hz), 7.62 (dd, 1H, J = 8.5, 2.0 Hz), 7.21 (d, 2H, J = 9.0 Hz), 7.20 (d, 2H, J = 9.0 Hz), 7.06 (d, 1H, J = 9.0 Hz), 7.02 (d, 1H, J = 9.0 Hz), 6.99 (d, 2H, J = 9.0 Hz), 6.98 (d, 2H, J = 9.0 Hz), 3.87 (s, 3H), 3.84 (s, 3H), 3.78 (s, 6H). Yield: 77%; E/Z = 1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.57 (s, 1H), 11.46 (s, 1H), 9.46 (s, 2H), 8.23 (s, 1H), 8.17 - 8.15 (m, 2H), 8.11 ( d, 1H, J = 2.0 Hz), 7.71 (dd, 1H, J = 9.0, 2.0 Hz), 7.62 (dd, 1H, J = 8.5, 2.0 Hz), 7.21 (d, 2H, J = 9.0 Hz), 7.20 (d, 2H, J = 9.0 Hz), 7.06 (d, 1H, J = 9.0 Hz), 7.02 (d, 1H, J = 9.0 Hz), 6.99 (d, 2H, J = 9.0 Hz), 6.98 ( d, 2H, J = 9.0 Hz), 3.87 (s, 3H), 3.84 (s, 3H), 3.78 (s, 6H).

7) (7) ( E/ZE/Z )-5-(4-)-5-(4- 메톡시벤질리덴methoxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(4-)-5-(4- MethoxybenzylideneMethoxybenzylidenes )-1-(4-)-1-(4- methoxyphenylmethoxyphenyl )pyrimidine-2,4,6(1)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Eg])-trione; compound Eg]

수율: 56%; E/Z = 1.1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.58 (s, 1H), 11.47 (s, 1H), 8.35 (d, 2H, J=8.5Hz), 8.32 (s, 1H), 8.29 (d, 2H, J=8.5Hz), 8.26 (s, 1H), 7.20 (d, 2H, J=8.5Hz), 7.20 (d, 2H, J=8.5Hz), 7.06 (d, 2H, J=8.5Hz), 7.01 (d, 2H, J=8.5Hz), 6.98 (d, 2H, J=8.0Hz), 6.98 (d, 2H, J=8.5Hz), 3.87 (s, 3H), 3.83 (s, 3H), 3.78 (s, 6H); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.5, 164.1 (ⅹ2), 163.6, 162.5, 162.1, 159.5, 156.3, 155.9, 151.1, 151.0, 138.1 (ⅹ2), 130.8, 130.7, 128.8, 128.5, 125.9, 125.8, 116.7, 116.6, 114.6 (ⅹ4), 56.4, 56.3, 56.0 (ⅹ2).Yield: 56%; E/Z = 1.1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.58 (s, 1H), 11.47 (s, 1H), 8.35 (d, 2H, J=8.5Hz), 8.32 (s, 1H), 8.29 (d, 2H, J=8.5Hz), 8.26 (s, 1H) ), 7.20 (d, 2H, J=8.5Hz), 7.20 (d, 2H, J=8.5Hz), 7.06 (d, 2H, J=8.5Hz), 7.01 (d, 2H, J=8.5Hz), 6.98 (d, 2H, J=8.0 Hz), 6.98 (d, 2H, J=8.5 Hz), 3.87 (s, 3H), 3.83 (s, 3H), 3.78 (s, 6H); ¹³ CNMR (100MHz, DMSO- D ₆ ) δ 164.5, 164.1 (ⅹ2), 163.6, 162.5, 162.1, 159.5, 156.3, 155.9, 151.1, 151.0, 138.1 (ⅹ2), 130.8, 130.7, 128.8, 128.5, 125.9, 125.8, 125.8 , 116.7, 116.6, 114.6 (x4), 56.4, 56.3, 56.0 (x2).

8) (8) ( E/ZE/Z )-5-(3,4-)-5-(3,4- 디메톡시벤질리덴dimethoxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3H,5,3H,5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(3,4-)-5-(3,4- DimethoxybenzylideneDimethoxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3H,5,3H,5 HH )-trione; 화합물 Eh])-trione; compound Eh]

수율: 81%; E/Z = 1.1:1 혼합물; ¹HNMR(400MHz,DMSO-d ₆)δ 11.57 (s, 1H), 11.46 (s, 1H), 8.36 (s, 1H), 8.31 (s, 1H), 8.24 (s, 1H), 8.16 (s, 1H), 7.90 (d, 1H, J=8.4Hz), 7.85 (d, 1H, J=8.8Hz), 7.19 (d, 2H, J=8.0Hz), 7.18 (d, 2H, J=8.0Hz), 7.08 (d, 1H, J=8.0Hz), 7.05 (d, 1H, J=8.8Hz), 6.96 (d, 4H, J=8.4Hz), 3.85 (s, 3H), 3.82 (s, 3H), 3.78 (s, 3H), 3.76 (s, 6H), 3.70 (s, 3H); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.5, 163.7, 162.6, 162.2, 159.5 (ⅹ2), 156.8, 156.4, 154.4 (ⅹ2), 151.1, 151.0, 148.5 (ⅹ2), 132.3, 132.1, 130.8, 130.7, 128.8, 128.6, 126.0, 125.9, 117.8, 117.4, 116.5, 116.4, 114.7, 114.6, 111.8 (ⅹ2), 56.5 (ⅹ2), 56.2, 56.1, 56.0 (ⅹ2).Yield: 81%; E/Z = 1.1:1 mixture; ¹ HNMR (400 MHz, DMSO- d ₆ ) δ 11.57 (s, 1H), 11.46 (s, 1H), 8.36 (s, 1H), 8.31 (s, 1H), 8.24 (s, 1H), 8.16 (s, 1H), 7.90 (d, 1H, J= 8.4Hz), 7.85 (d, 1H, J=8.8Hz), 7.19 (d, 2H, J=8.0Hz), 7.18 (d, 2H, J=8.0Hz), 7.08 (d, 1H, J=8.0Hz) ), 7.05 (d, 1H, J=8.8Hz), 6.96 (d, 4H, J=8.4Hz), 3.85 (s, 3H), 3.82 (s, 3H), 3.78 (s, 3H), 3.76 (s , 6H), 3.70 (s, 3H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 164.5, 163.7, 162.6, 162.2, 159.5 (ⅹ2), 156.8, 156.4, 154.4 (ⅹ2), 151.1, 151.0, 148.5 (ⅹ2), 132.3, 132.1, 130.8, 130.7, 128.8, 128.6, 126.0, 125.9, 117.8, 117.8, 117.8, 117.8 , 116.5, 116.4, 114.7, 114.6, 111.8 (x2), 56.5 (x2), 56.2, 56.1, 56.0 (x2).

9) (9) ( E/ZE/Z )-5-(2,4-)-5-(2,4- 디메톡시벤질리덴dimethoxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(2,4-)-5-(2,4- DimethoxybenzylideneDimethoxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ei])-trione; compound Ei]

수율: 18%; E/Z = 1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.51 (s, 1H), 11.37 (s, 1H), 8.68 (s, 1H), 8.63 (s, 1H), 8.53 (d, 1H, J=9.5Hz), 8.39 (d, 1H, J=9.5Hz), 7.19 (d, 4H, J=8.0Hz), 6.98 (d, 2H, J=7.5Hz), 6.97 (d, 2H, J= 8.0Hz), 6.64 - 6.63 (m, 3H), 8.55 (d, 1H, J= 7.5Hz), 3.91 (s, 3H), 3.89 (s, 3H), 3.88 (s, 3H), 3.84 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H); ¹³CNMR(100MHz,DMSO-d ₆)δ 166.5 (ⅹ2), 164.6, 163.8, 163.1 (ⅹ2), 162.4, 161.9, 159.5 (ⅹ2), 151.2, 151.1, 150.6, 150.1, 136.1, 136.0, 130.8, 130.7, 128.8, 128.6, 115.7 (ⅹ2), 115.1, 114.9, 114.6 (ⅹ2), 106.6 (ⅹ2), 98.1, 98.0, 57.0, 56.9, 56.5 (ⅹ2), 56.0 (ⅹ2). Yield: 18%; E/Z = 1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.51 (s, 1H), 11.37 (s, 1H), 8.68 (s, 1H), 8.63 (s, 1H), 8.53 (d, 1H, J=9.5Hz), 8.39 (d, 1H, J=9.5Hz) ), 7.19 (d, 4H, J=8.0Hz), 6.98 (d, 2H, J=7.5Hz), 6.97 (d, 2H, J= 8.0Hz), 6.64 - 6.63 (m, 3H), 8.55 (d , 1H, J= 7.5Hz), 3.91 (s, 3H), 3.89 (s, 3H), 3.88 (s, 3H), 3.84 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H) ; ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 166.5 (x2), 164.6, 163.8, 163.1 (x2), 162.4, 161.9, 159.5 (x2), 151.2, 151.1, 150.6, 150.1, 136.0.8, 136.0.1, 136.0.1, 136.0.8 128.8, 128.6, 115.7 (x2), 115.1, 114.9, 114.6 (x2), 106.6 (x2), 98.1, 98.0, 57.0, 56.9, 56.5 (x2), 56.0 (x2).

10) (10) ( E/ZE/Z )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )-5-(3, 4, 5-)-5-(3, 4, 5- 트리메톡시벤질리덴trimethoxybenzylidene )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( E/ZE/Z )-1-(4-)-1-(4- MethoxyphenylMethoxyphenyl )-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ej])-trione; compound Ej]

수율: 84%; E/Z = 1.2:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.65 (s, 1H), 11.53 (s, 1H), 8.34 (s, 1H), 8.27 (s, 1H), 7.79 (s, 2H), 7.71 (s, 2H), 7.21 (d, 2H, J=8.5Hz), 7.20 (d, 2H, J=8.5Hz), 6.99 (d, 2H, J=8.5Hz), 6.98 (d, 2H, J=8.5Hz), 3.81 (s, 6H), 3.78 (s, 6H), 3.78 (s, 3H), 3.75 (s, 9H). Yield: 84%; E/Z = 1.2:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.65 (s, 1H), 11.53 (s, 1H), 8.34 (s, 1H), 8.27 (s, 1H), 7.79 (s, 2H), 7.71 (s, 2H), 7.21 (d, 2H, J=8.5Hz), 7.20 (d, 2H, J=8.5Hz), 6.99 (d, 2H, J=8.5Hz), 6.98 (d, 2H, J=8.5Hz) , 3.81 (s, 6H), 3.78 (s, 6H), 3.78 (s, 3H), 3.75 (s, 9H).

11) (11) ( E/ZE/Z )-5-(4-하이드록시-3,5-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1)-5-(4-hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-트리온[()-trion [( E/ZE/Z )-5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ek (MHY5175)])-trione; compound Ek (MHY5175)]

수율: 82%; E/Z = 1.1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.55 (s, 1H), 11.44 (s, 1H), 10.00 (brs, 2H), 8.34 (s, 1H), 8.26 (s, 1H), 7.97 (s, 2H), 7.92 (s, 2H), 7.22 (d, 2H, J=8.0Hz), 7.20 (d, 2H, J=9.0Hz), 6.99 (d, 4H, J=8.5Hz), 3.82 (s, 6H), 3.78 (s, 6H), 3.76 (s, 6H); ¹³CNMR(100MHz,DMSO-d ₆)δ 164.7, 163.9, 162.7, 162.4, 159.5 (ⅹ2), 157.6, 157.3, 151.2, 151.0, 147.8 (ⅹ2), 143.3, 143.2, 130.9, 130.7, 128.9, 128.7, 123.6, 123.5, 115.5, 115.3, 114.7 (ⅹ2), 114.6, 114.5, 56.8, 56.7, 56.0 (ⅹ2).Yield: 82%; E/Z = 1.1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.55 (s, 1H), 11.44 (s, 1H), 10.00 (brs, 2H), 8.34 (s, 1H), 8.26 (s, 1H), 7.97 (s, 2H), 7.92 (s, 2H), 7.22 (d, 2H, J=8.0Hz), 7.20 (d, 2H, J=9.0Hz), 6.99 (d, 4H, J=8.5Hz), 3.82 (s, 6H), 3.78 (s, 6H), 3.76 (s, 6H); ¹³ CNMR(100MHz,DMSO- d ₆ ) δ 164.7, 163.9, 162.7, 162.4, 159.5 (ⅹ2), 157.6, 157.3, 151.0, 147.8 (ⅹ2), 143.3, 143.2, 130.9, 130.7, 128.9, 128.7, 123.6, 123.5, 115.5, 115.3, 114.3 , 114.6, 114.5, 56.8, 56.7, 56.0 (x2).

12) (12) ( E/ZE/Z )-5-(3,5-디브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1)-5-(3,5-dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-트리온[()-trion [( E/ZE/Z )-5-(3,5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-5-(3,5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 El])-trione; compound El]

수율: 86%; E/Z = 1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆ ) δ 11.63 (s, 1H), 11.53 (s, 1H), 8.57 (s, 2H), 8.52 (s, 2H), 8.20 (s, 1H), 8.14 (s, 1H), 7.20 (d, 2H, J=8.0Hz), 7.18 (d, 2H, J=8.0Hz), 6.99 (d, 4H, J=8.5Hz), 3.78 (s, 6H); ¹³CNMR(100MHz,DMSO-d ₆ ) δ 163.9, 163.1, 162.4, 162.0, 159.6 (ⅹ2), 155.6 (ⅹ2), 153.1, 152.8, 151.0 (ⅹ2), 139.1, 139.0, 130.7, 130.6, 128.6, 128.3, 127.3, 127.2, 118.7, 118.5, 114.7 (ⅹ2), 111.5 (ⅹ2), 56.0 (ⅹ2). Yield: 86%; E/Z = 1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.63 (s, 1H), 11.53 (s, 1H), 8.57 (s, 2H), 8.52 (s, 2H), 8.20 (s, 1H), 8.14 (s, 1H), 7.20 (d, 2H, J=8.0Hz), 7.18 (d, 2H, J=8.0Hz), 6.99 (d, 4H, J=8.5Hz), 3.78 (s, 6H); ¹³ CNMR (100 MHz, DMSO- d ₆ ) δ 163.9, 163.1, 162.4, 162.0, 159.6 (x2), 155.6 (x2), 153.1, 152.8, 151.0 (x2), 139.1, 139.0, 3, 120.6, 130.7, 130.7 127.3, 127.2, 118.7, 118.5, 114.7 (x2), 111.5 (x2), 56.0 (x2).

13) (13) ( E/ZE/Z )-5-(3-)-5-(3- 브로모bromo -4--4- 하이드록시벤질리덴hydroxybenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( E/ZE/Z )-5-(3-)-5-(3- BromoBromo -4--4- hydroxybenzylidenehydroxybenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Em])-trione; compound Em]

수율: 82%; E/Z = 1.1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆ ) δ 11.60 (s, 1H), 11.49 (s, 1H), 8.84 (s, 1H), 8.76 (s, 1H), 8.24 (s, 1H), 8.17 (s, 1H), 8.06 (d, 1H, J=8.0Hz), 8.04 (d, 1H, J=8.0Hz), 7.20 (d, 2H, J=8.5Hz), 7.19 (d, 2H, J=8.5Hz), 7.03 (d, 1H, J= 8.0Hz), 7.00 (d, 1H, J=8.0Hz), 6.99 - 6.96 (m, 4H), 3.78 (s, 6H).Yield: 82%; E/Z = 1.1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.60 (s, 1H), 11.49 (s, 1H), 8.84 (s, 1H), 8.76 (s, 1H), 8.24 (s, 1H), 8.17 (s, 1H), 8.06 (d, 1H, J=8.0Hz), 8.04 (d, 1H, J=8.0Hz), 7.20 (d, 2H, J=8.5Hz), 7.19 (d, 2H, J=8.5Hz) , 7.03 (d, 1H, J = 8.0 Hz), 7.00 (d, 1H, J = 8.0 Hz), 6.99 - 6.96 (m, 4H), 3.78 (s, 6H).

14) (14) ( E/ZE/Z )-5-(4-)-5-(4- 하이드록시hydroxy -3,5--3,5- 디메틸벤질리덴Dimethylbenzylidene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1H,3H,5H)-트리온 [()Pyrimidine-2,4,6(1H,3H,5H)-trione [( E/ZE/Z )-5-(4-)-5-(4- hydroxyhydroxy -3,5--3,5- dimethylbenzylidenedimethylbenzylidene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione; 화합물 Ep))-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione; Compound Ep)

수율: 79%; E/Z = 1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.51 (s, 1H), 11.38 (s, 1H), 9.68 (s, 2H), 8.24 (s, 1H), 8.16 (s, 1H), 8.11 (s, 2H), 8.07 (s, 2H), 7.22 - 7.18 (m, 4H), 6.98 (d, 4H, J = 8.0 Hz), 3.78 (s, 3H, OCH₃),3.78(s,3H,OCH₃),2.20(s,6H),2.16(s,6H).Yield: 79%; E/Z = 1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.51 (s, 1H), 11.38 (s, 1H), 9.68 (s, 2H), 8.24 (s, 1H), 8.16 (s, 1H), 8.11 (s, 2H), 8.07 (s, 2H), 7.22 - 7.18 (m, 4H), 6.98 (d, 4H, J = 8.0 Hz), 3.78 (s, 3H, OCH ₃ ),3.78(s, 3H, OCH ₃ ) ,2.20(s,6H),2.16(s,6H).

15) (15) ( EE // ZZ )-5-()-5-( 벤조[benzo[ dd ][1,3]디옥솔][1,3]dioxol -5--5- 일메틸렌ilmethylene )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [()-trion [( EE // ZZ )-5-()-5-( benzo[benzo[ dd ][1,3]dioxol][1,3]dioxol -5--5- ylmethyleneylmethylene )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ex])-trione; Compound Ex]

수율: 76%; E/Z = 1:1 혼합물; ¹HNMR(500MHz,DMSO-d ₆)δ 11.60 (s, 1H), 11.50 (s, 1H), 8.28 (s, 1H), 8.25 (s, 1H), 8.22 (s, 1H), 8.08 (s, 1H), 7.72 (d, 2H, J = 7.5 Hz), 7.21 (d, 2H, J = 8.5 Hz), 7.19 (d, 2H, J = 8.5 Hz), 7.07 (d, 1H, J = 8.0 Hz), 7.04 (d, 1H, J = 7.5 Hz), 6.98 (d, 4H, J = 8.5 Hz), 6.17 (s, 2H), 6.13 (s, 2H), 3.78 (s, 6H).Yield: 76%; E/Z = 1:1 mixture; ¹ HNMR (500 MHz, DMSO- d ₆ ) δ 11.60 (s, 1H), 11.50 (s, 1H), 8.28 (s, 1H), 8.25 (s, 1H), 8.22 (s, 1H), 8.08 (s, 1H), 7.72 (d, 2H, J = 7.5 Hz), 7.21 (d, 2H, J = 8.5 Hz), 7.19 (d, 2H, J = 8.5 Hz), 7.07 (d, 1H, J = 8.0 Hz) , 7.04 (d, 1H, J = 7.5 Hz), 6.98 (d, 4H, J = 8.5 Hz), 6.17 (s, 2H), 6.13 (s, 2H), 3.78 (s, 6H).

(8) 그룹 F 화합물 합성(8) Synthesis of Group F Compounds

상기 그룹 E 화합물 각각 (100 mg)에 에탄올 (5-7mL)을 가하고 0 ℃에서 소듐 보로하이드라이드 (NaBH₄,3-5당량)를 천천히 부가시킨 혼합용액을 실온에서 1 내지 3 시간 동안 교반하였다. 용매를 감압증발시키고 얻어진 잔사에 소량의 물을 가하고 염산을 가하여 액성을 pH 3 - 4로 맞춘 후, 여과하고 여과케이크 (filter cake)를 물로 씻어주어 그룹 F 화합물을 얻었다. 경우에 따라서는 여과 후에 얻어진 고체를 실리카 겔 컬럼 크로마토그래피를 하여 더욱 정제하여 그룹 F에 해당하는 각각의 화합물을 얻었다.Ethanol (5-7mL) was added to each of the Group E compounds (100 mg), and sodium borohydride (NaBH ₄ , 3-5 equivalents) was slowly added at 0 ° C. The mixed solution was stirred at room temperature for 1 to 3 hours. . The solvent was evaporated under reduced pressure, a small amount of water was added to the resulting residue, and hydrochloric acid was added to adjust the pH of the solution to 3-4, followed by filtration, and the filter cake was washed with water to obtain a group F compound. In some cases, the solid obtained after filtration was further purified by silica gel column chromatography to obtain each compound corresponding to Group F.

1) 5-(4-1) 5-(4- 하이드록시벤질hydroxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-trione [5-(4-Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fa (MHY5162)])-trione; compound Fa (MHY5162)]

수율: 57%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.45 (s, 1H, NH), 9.35 (s, 1H, OH), 6.95 (d, 2H, J = 9.0 Hz), 6.91 - 6.83 (m, 4H), 6.68 (d, 2H, J = 9.0 Hz), 3.87 (t, 1H J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃),3.19(d,2H,J=5.0Hz,benzylicH₂).Yield: 57%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.45 (s, 1H, NH), 9.35 (s, 1H, OH), 6.95 (d, 2H, J = 9.0 Hz), 6.91 - 6.83 (m, 4H ), 6.68 (d, 2H, J = 9.0 Hz), 3.87 (t, 1H J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.19(d, 2H, J=5.0Hz, benzylicH ₂ ).

2) 5-(3,4-2) 5-(3,4- 디하이드록시벤질dihydroxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,4-)-trion [5-(3,4- DihydroxybenzylDihydroxybenzyl )-1-(4-)-1-(4- methoxyphenylmethoxyphenyl )pyrimidine-2,4,6()pyrimidine-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fb])-trione; compound Fb]

수율: 59%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.41 (s, 1H, NH), 9.00 (brs, 1H, OH), 8.88 (brs, 1H, OH), 6.95 (d, 2H, J = 8.5 Hz), 6.94 - 6.88 (brm, 2H), 6.64 (d, 1H, J = 8.5 Hz), 6.49 (d, 1H, J = 1.5 Hz), 6.33 (dd, 1H, J = 8.5, 1.5 Hz), 3.84 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃),3.13(d,2H,J=5.0Hz,benzylicH₂).Yield: 59%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.41 (s, 1H, NH), 9.00 (brs, 1H, OH), 8.88 (brs, 1H, OH), 6.95 (d, 2H, J = 8.5 Hz ), 6.94 - 6.88 (brm, 2H), 6.64 (d, 1H, J = 8.5 Hz), 6.49 (d, 1H, J = 1.5 Hz), 6.33 (dd, 1H, J = 8.5, 1.5 Hz), 3.84 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.13 (d, 2H, J = 5.0 Hz, benzylicH ₂ ).

3) 5-(2,4-3) 5-(2,4- 디하이드록시벤질dihydroxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(2,4-)-trion [5-(2,4- DihydroxybenzylDihydroxybenzyl )-1-(4-)-1-(4- methoxyphenylmethoxyphenyl )pyrimidine-2,4,6()pyrimidine-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fc (MHY5164)))-trione; Compound Fc (MHY5164))

수율: 42%; ¹H NMR (500 MHz, DMSO-d ₆) δ 12.07 (s, 1H, NH), 9.75 (brs, 1H, OH), 7.12 (d, 2H, J = 9.0 Hz), 7.11 (d, 1H, J = 8.5 Hz), 6.97 (d, 2H, J = 9.0 Hz), 6.60 (dd, 1H, J = 8.5, 2.0 Hz), 6.46 (d, 1H, J = 2.0 Hz), 3.77 (s, 3H, OCH₃),3.42(s,2H,benzylicH₂).Yield: 42%; 1H NMR (500 MHz, DMSO ^- d6) δ _12.07 ( s , 1H, NH), 9.75 (brs, 1H, OH), 7.12 (d, 2H, J = 9.0 Hz), 7.11 (d, 1H, J = 8.5 Hz), 6.97 (d, 2H, J = 9.0 Hz), 6.60 (dd, 1H, J = 8.5, 2.0 Hz), 6.46 (d, 1H, J = 2.0 Hz), 3.77 (s, 3H, OCH ₃ ),3.42(s,2H,benzylicH ₂ ).

4) 5-(4-4) 5-(4- 하이드록시hydroxy -3-메톡시벤질)-1-(4--3-methoxybenzyl)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3--3- methoxybenzylmethoxybenzyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fd (MHY5161)])-trione; compound Fd (MHY5161)]

수율: 82%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.50 (s, 1H, NH), 8.92 (s, 1H, OH), 6.95 (d, 2H, J = 8.5 Hz), 6.89 - 6.78 (brm, 2H), 6.70 (d, 1H, J = 8.0 Hz), 6.61 (s, 1H), 6.48 (d, 1H, J = 8.0 Hz), 3.89 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃),3.68(s,3H,OCH₃),3.21(d,2H,J=5.0Hz,benzylicH₂).Yield: 82%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.50 (s, 1H, NH), 8.92 (s, 1H, OH), 6.95 (d, 2H, J = 8.5 Hz), 6.89 - 6.78 (brm, 2H ), 6.70 (d, 1H, J = 8.0 Hz), 6.61 (s, 1H), 6.48 (d, 1H, J = 8.0 Hz), 3.89 (t, 1H, J = 5.0 Hz, methine H), 3.76 ( s, 3H, OCH ₃ ), 3.68(s, 3H, OCH ₃ ), 3.21(d, 2H, J=5.0 Hz, benzylicH ₂ ).

5) 5-(3-5) 5-(3- 에톡시ethoxy ;-4-;-4- 하이드록시벤질hydroxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-)-trion [5-(3- EthoxyEthoxy -4--4- hydroxybenzylhydroxybenzyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fe (MHY5195)])-trione; Compound Fe (MHY5195)]

수율: 66%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.47 (s, 1H, NH), 8.83 (s, 1H, OH), 6.95 (d, 2H, J = 9.0 Hz), 6.89 - 6.79 (brm, 2H), 6.71 (d, 1H, J = 7.5 Hz), 6.60 (d, 1H, J = 2.0 Hz), 6.48 (dd, 1H, J = 7.5, 2.0 Hz), 3.95 - 3.89 (m, 2H, OCH ₂ CH₃), 3.88(t,1H ,J=5.0Hz, methine H),3.76(s, 3H, OCH₃),3.21(dd,1H, J=14.0, 5.0Hz, benzylic H_a), 3.17(dd, 1H, J=14.0, 5.5Hz, benzylic H_b), 1.30(t, 3H, J=7.0Hz, OCH₂CH ₃ ).Yield: 66%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.47 (s, 1H, NH), 8.83 (s, 1H, OH), 6.95 (d, 2H, J = 9.0 Hz), 6.89 - 6.79 (brm, 2H ), 6.71 (d, 1H, J = 7.5 Hz), 6.60 (d, 1H, J = 2.0 Hz), 6.48 (dd, 1H, J = 7.5, 2.0 Hz), 3.95 - 3.89 (m, 2H , OCH ₂ CH ₃ ), 3.88(t, 1H , J=5.0Hz, methine H), 3.76(s, 3H, OCH ₃ ), 3.21(dd, 1H, J=14.0, 5.0Hz, benzylic H _a ), 3.17( dd, 1H, J=14.0, 5.5 Hz, benzylic H _b ), 1.30 (t, 3H, J=7.0 Hz, OCH ₂ CH ₃ ).

6) 5-(3-6) 5-(3- 하이드록시hydroxy -4-메톡시벤질)-1-(4--4-methoxybenzyl)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-)-trion [5-(3- HydroxyHydroxy -4--4- methoxybenzylmethoxybenzyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ff (MHY5200)])-trione; Compound Ff (MHY5200)]

수율: 59%;¹H NMR (500 MHz, DMSO-d ₆) δ 11.45 (s, 1H, NH), 8.97 (s, 1H, OH), 6.80 - 6.90 (brm, 4H), 6.84 (d, 1H, J = 8.5 Hz), 6.55 (d, 1H, J = 1.5 Hz), 6.48 (dd, 1H, J = 8.5, 1.5 Hz), 3.91 (t, 1H, 5.0 Hz, methine H), 3.78 (s, 3H, OCH₃), 3.74(s, 3H, OCH₃), 3.18(d, 2H, J=5.0Hz, benzylic H₂).Yield: 59%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.45 (s, 1H, NH), 8.97 (s, 1H, OH), 6.80 - 6.90 (brm, 4H), 6.84 (d, 1H, J = 8.5 Hz ), 6.55 (d, 1H, J = 1.5 Hz), 6.48 (dd, 1H, J = 8.5, 1.5 Hz), 3.91 (t, 1H, 5.0 Hz, methine H), 3.78 (s, 3H, OCH ₃ ) , 3.74 (s, 3H, OCH ₃ ), 3.18 (d, 2H, J=5.0 Hz, benzylic H ₂ ).

7) 5-(4-메톡시벤질)-1-(4-7) 5-(4-methoxybenzyl)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-trione [5-(4-Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fg (MHY5163)])-trione; compound Fg (MHY5163)]

수율: 41%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.46 (s, 1H, NH), 7.01 (d, 2H, J = 9.0 Hz), 6.96 (d, 2H, J = 8.5 Hz), 6.91 (brd, 2H), 6.87 (d, 2H, J = 8.5 Hz), 3.94 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃), 3.72(s, 3H, OCH₃), 3.25(d, 2H, J=5.0Hz, benzylic H₂).Yield: 41%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 11.46 (s, 1H, NH), 7.01 ( d , 2H, J = 9.0 Hz), 6.96 (d, 2H, J = 8.5 Hz), 6.91 (brd, 2H), 6.87 (d, 2H, J = 8.5 Hz), 3.94 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.72 (s, 3H, OCH ₃ ), 3.25(d, 2H, J=5.0 Hz, benzylic H ₂ ).

8) 5-(3,4-8) 5-(3,4- 디메톡시벤질dimethoxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-trione [5-(3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fh (MHY5166)])-trione; compound Fh (MHY5166)]

수율: 64%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.50 (s, 1H, NH), 6.96 (d, 2H, J = 9.0 Hz), 6.89 - 6.80 (brm, 3H), 6.66 (s, 1H), 6.61 (d, 1H, J = 8.0 Hz), 3.95 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃), 3.72(s, 3H, OCH₃),3.68(s, 3H, OCH₃),3.28-3.21(m, 2H, benzylic H₂).Yield: 64%; 1H NMR (500 MHz, DMSO ^- d6) δ 11.50 (s, 1H, NH), 6.96 ( d , 2H, J = 9.0 Hz), 6.89 - _6.80 (brm, 3H), 6.66 (s, 1H), 6.61 (d, 1H, J = 8.0 Hz), 3.95 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.72(s, 3H, OCH ₃ ), 3.68(s , 3H, OCH ₃ ),3.28-3.21 (m, 2H, benzylic H ₂ ).

9) 5-(2,4-9) 5-(2,4- 디메톡시벤질dimethoxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-trione [5-(2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; (화합물 Fi (MHY5165)])-trione; (Compound Fi (MHY5165)]

수율: 62%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.36 (s, 1H, NH), 6.95 - 6.87 (m, 5H), 6.51 (s, 1H), 6.43 (d, 1H, J = 8.0 Hz), 3.82 (t, 1H, J = 6.0 Hz, methine H), 3.75 (s, 3H, OCH₃), 3.73(s, 3H, OCH₃), 3.70(s, 3H, OCH₃), 3.23(dd, 1H, J=14.0, 6.0Hz, benzylic H_a), 3.19(dd, 1H, J=14.0, 6.5Hz, benzylic H_b).Yield: 62%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.36 (s, 1H, NH), 6.95 - 6.87 (m, 5H), 6.51 (s, 1H), 6.43 (d, 1H, J = 8.0 Hz), 3.82 (t, 1H, J = 6.0 Hz, methine H), 3.75 (s, 3H, OCH ₃ ), 3.73 (s, 3H, OCH ₃ ), 3.70 (s, 3H, OCH ₃ ), 3.23 (dd, 1H , J=14.0, 6.0 Hz, benzylic H _a ), 3.19 (dd, 1H, J=14.0, 6.5 Hz, benzylic H _b ).

10) 1-(4-10) 1-(4- 메톡시페닐methoxyphenyl )-5-(3,4,5-)-5-(3,4,5- 트리메톡시벤질trimethoxybenzyl )피리미딘-2,4,6() Pyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [1-(4-)-trion [1-(4- MethoxyphenylMethoxyphenyl )-5-(3,4,5-)-5-(3,4,5- trimethoxybenzyltrimethoxybenzyl )pyrimidine-2,4,6(1)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fj (MHY5160)])-trione; Compound Fj (MHY5160)]

수율: 50%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.55 (s, 1H, NH), 6.95 (d, 2H, J = 8.5 Hz), 6.90 - 6.78 (brm, 2H), 6.39 (s, 2H), 4.00 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃), 3.70(s, 6H, 2×OCH₃), 3.62(s, 3H, OCH₃), 3.27(dd, 1H, J=14.0, 5.0Hz, benzylic H_a), 3.22(dd, 1H, J=14.0, 5.0Hz, benzylic H_b)Yield: 50%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.55 (s, 1H, NH), 6.95 (d, 2H, J = 8.5 Hz), 6.90 - 6.78 (brm, 2H), 6.39 (s, 2H), 4.00 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.70 (s, 6H, 2×OCH ₃ ), 3.62 (s, 3H, OCH ₃ ), 3.27 (dd , 1H, J=14.0, 5.0 Hz, benzylic H _a ), 3.22(dd, 1H, J=14.0, 5.0 Hz, benzylic H _b )

11) 5-(4-11) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메톡시벤질dimethoxybenzyl )-1-()-One-( 4메톡시페닐4 methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3,5--3,5- dimethoxybenzyldimethoxybenzyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fk (MHY5197)])-trione; compound Fk (MHY5197)]

수율: 78%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.51 (s, 1H, NH), 8.29 (brs, 1H, OH), 6.94 (d, 2H, J = 9.0 Hz), 6.86 - 6.75 (brm, 2H), 6.32 (s, 2H), 3.90 (t, 1H, J = 5.0 Hz, methine H), 3.75 (s, 3H, OCH₃), 3.68(s, 6H, 2×OCH₃), 3.23(dd, 1H, J=14.0, 4.5Hz, benzylic H_a), 3.18(dd, 1H, J=14.0, 5.0Hz, benzylic H_b).Yield: 78%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.51 (s, 1H, NH), 8.29 (brs, 1H, OH), 6.94 (d, 2H, J = 9.0 Hz), 6.86 - 6.75 (brm, 2H ), 6.32 (s, 2H), 3.90 (t, 1H, J = 5.0 Hz, methine H), 3.75 (s, 3H, OCH ₃ ), 3.68 (s, 6H, 2×OCH ₃ ), 3.23 (dd, 1H, J=14.0, 4.5 Hz, benzylic H _a ), 3.18 (dd, 1H, J=14.0, 5.0 Hz, benzylic H _b ).

12) 5-(3,5-12) 5-(3,5- 디브로모dibromo -4--4- 하이드록시벤질hydroxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,5-)-trion [5-(3,5- DibromoDibromo -4--4- hydroxybenzylhydroxybenzyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fl (MHY5198)])-trione; compound Fl (MHY5198)]

수율: 72%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.54 (s, 1H, NH), 9.87 (s, 1H, OH), 7.28 (s, 2H), 7.00 - 6.94 (m, 4H), 4.06 (t, 1H, J = 5.0 Hz, methine H), 3.77 (s, 3H, OCH₃), 3.23(dd, 1H, J=14.0, 5.0Hz, benzylic H_a), 3.18(dd, 1H, J=14.0, 5.0Hz, benzylic H_b).Yield: 72%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.54 (s, 1H, NH), 9.87 (s, 1H, OH), 7.28 (s, 2H), 7.00 - 6.94 (m, 4H), 4.06 (t , 1H, J = 5.0 Hz, methine H), 3.77 (s, 3H, OCH ₃ ), 3.23 (dd, 1H, J=14.0, 5.0Hz, benzylic H _a ), 3.18 (dd, 1H, J=14.0, 5.0 Hz, benzylic _Hb ).

13) 5-(3-13) 5-(3- 브로모bromo -4--4- 하이드록시벤질hydroxybenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-)-trion [5-(3- BromoBromo -4--4- hydroxybenzylhydroxybenzyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fm (MHY5194)])-trione; compound Fm (MHY5194)]

수율: 36%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.48 (s, 1H, NH), 10.17 (s, 1H, OH), 7.18 (d, 1H, J = 1.5 Hz), 6.97 - 6.92 (m, 4H), 6.90 (dd, 1H, J = 8.5, 1.5 Hz), 6.86 (d, 1H, J = 8.5 Hz), 3.94 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃), 3.18(d, 2H, J=5.0Hz, benzylic H₂).Yield: 36%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.48 (s, 1H, NH), 10.17 (s, 1H, OH), 7.18 (d, 1H, J = 1.5 Hz), 6.97 - 6.92 (m, 4H ), 6.90 (dd, 1H, J = 8.5, 1.5 Hz), 6.86 (d, 1H, J = 8.5 Hz), 3.94 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.18(d, 2H, J=5.0 Hz, benzylic H ₂ ).

14) 5-(4-14) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메틸벤질dimethylbenzyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3,5--3,5- dimethylbenzyldimethylbenzyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fp (MHY5199)])-trione; compound Fp (MHY5199)]

수율: 33%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.43 (s, 1H, NH), 8.17 (s, 1H, OH), 6.96 (d, 2H, J = 9.0 Hz), 6.89 - 6.78 (brm, 2H), 6.62 (s, 2H), 3.83 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH₃), 3.14(d, 2H, J=5.0Hz, benzylic H₂), 2.11(s, 6H, 2×CH₃).Yield: 33%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.43 (s, 1H, NH), 8.17 (s, 1H, OH), 6.96 (d, 2H, J = 9.0 Hz), 6.89 - 6.78 (brm, 2H ), 6.62 (s, 2H), 3.83 (t, 1H, J = 5.0 Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.14 (d, 2H, J=5.0Hz, benzylic H ₂ ), 2.11(s, 6H, 2×CH ₃ ).

15) 5-(15) 5-( 벤조[benzo[ dd ][1,3]디옥솔][1,3]dioxol -5--5- 일메틸ilmethyl )-1-(4-)-1-(4- 메톡시페닐methoxyphenyl )피리미딘-2,4,6(1) Pyrimidine-2,4,6 (1 HH ,3,3 HH ,5,5 HH )-트리온 [5-()-trion [5-( Benzo[Benzo[ dd ][1,3]dioxol][1,3]dioxol -5--5- ylmethylylmethyl )-1-(4-methoxyphenyl)pyrimidine-2,4,6(1)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Fx (MHY5196)])-trione; compound Fx (MHY5196)]

수율: 65%; ¹H NMR (500 MHz, DMSO-d ₆) δ 11.49 (s, 1H, NH), 6.97 (d, 2H, J = 8.0 Hz), 6.96 - 6.80 (brm, 2H), 6.85 (d, 1H, J = 7.5 Hz), 6.63 (s, 1H), 6.57 (d, 1H, J = 7.5 Hz), 5.98 (s, 2H, CH₂), 3.96(t, 1H, J=5.0Hz, methine H),3.76(s, 3H, OCH₃), 3.23(d, 2H, J=5.0Hz, benzylic H₂).Yield: 65%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.49 (s, 1H, NH), 6.97 (d, 2H, J = 8.0 Hz), 6.96 - 6.80 (brm, 2H), 6.85 (d, 1H, J = 7.5 Hz), 6.63 (s, 1H), 6.57 (d, 1H, J = 7.5 Hz), 5.98 (s, 2H, CH ₂ ), 3.96 (t, 1H, J=5.0Hz, methine H), 3.76 (s, 3H, OCH ₃ ), 3.23(d, 2H, J=5.0 Hz, benzylic H ₂ ).

(9) 그룹 G 화합물 합성(9) Synthesis of Group G Compounds

화합물 1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 (13-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione; 100 mg)과 다양한 벤즈알테히드 (benzaldehyde, 1 당량)를 에탄올 (1.5 mL)과 물 (1.5 mL) 혼합 용액에서 6 - 8일간 80 ℃로 가열 교반한 후, 냉각하고 여과하고 찬물로 세척하여 그룹 G 화합물을 고체로 얻었다. 경우에 따라서는 여과 후에 얻어진 고체를 실리카 겔 컬럼 크로마토그래피를 하여 더욱 정제하여 그룹 G에 해당하는 각각의 화합물을 얻었다.Compound 1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione (13-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione; 100 mg) and various benzaldehydes (benzaldehyde, 1 equivalent) were stirred in a mixture of ethanol (1.5 mL) and water (1.5 mL) at 80 ° C for 6 - 8 days, cooled, filtered, and washed with cold water. Compound G was obtained as a solid. In some cases, the solid obtained after filtration was further purified by silica gel column chromatography to obtain each compound corresponding to Group G.

1) 5-(4-1) 5-(4- 하이드록시벤지리덴Hydroxybenzylidene )-1,3-디메틸피리미딘-2,4,6() -1,3-dimethylpyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1)-trione [5-(4-Hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ga))-trione; compound Ga)

수율: 98%; ¹H NMR (500 MHz, DMSO-d ₆) δ 10.82 (s, 1H, OH), 8.31 (d, 2H, J = 9.0 Hz), 8.28 (s, 1H, vinylic H), 6.89 (d, 2H, J = 9.0 Hz), 3.22 (s, 3H, NCH₃), 3.21(s, 3H, NCH₃).Yield: 98%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 10.82 (s, 1H, OH), 8.31 (d, 2H, J = 9.0 Hz), 8.28 (s, 1H, vinylic H), 6.89 (d, 2H, J = 9.0 Hz), 3.22 (s, 3H, NCH ₃ ), 3.21 (s, 3H, NCH ₃ ).

2) 5-(3,4-2) 5-(3,4- 디하이드록시벤지리덴dihydroxybenzyridene )-1,3-디메틸피리미딘-2,4,6() -1,3-dimethylpyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,4-)-trion [5-(3,4- DihydroxybenzylideneDihydroxybenzylidene )-1,3-)-1,3- dimethylpyrimidinedimethylpyrimidine -2,4,6(-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-trione; 화합물 Gb])-trione; compound Gb]

수율: 70%; ¹H NMR (500 MHz, DMSO-d ₆) δ 10.82 (s, 1H, OH), 9.47 (s, 1H, OH), 8.18 - 8.17 (m, 2H), 7.61 (dd, 1H, J = 8.0, 1.5 Hz), 6.85 (d, 1H, J = 8.0 Hz), 3.20 (s, 3H, NCH₃), 3.19(s, 3H, NCH₃). Yield: 70%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 10.82 (s, 1H, OH), 9.47 (s, 1H, OH), 8.18 - 8.17 (m, 2H), 7.61 (dd, 1H, J = 8.0, 1.5 Hz), 6.85 (d, 1H, J = 8.0 Hz), 3.20 (s, 3H, NCH ₃ ), 3.19 (s, 3H, NCH ₃ ).

3) 5-(4-3) 5-(4- 하이드록시hydroxy -3--3- 메톡시벤지리딘methoxybenziridine )-1,3-디메틸피리미딘-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3--3- methoxybenzylidenemethoxybenzylidene )-1,3-dimethylpyrimidine-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Gd (MHY5187)])-trione; compound Gd (MHY5187)]

수율: 72%; ¹H NMR (500 MHz, DMSO-d ₆) δ 10.55 (s, 1H, OH), 8.35 (s, 1H), 8.29 (s, 1H), 7.84 (d, 1H, J = 8.0 Hz), 6.90 (d, 1H, J = 8.0 Hz), 3.83 (s, 3H, OCH₃), 3.22(s, 6H, 2×NCH₃).Yield: 72%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 10.55 (s, 1H, OH), 8.35 (s, 1H), 8.29 (s, 1H), 7.84 (d, 1H, J = 8.0 Hz), 6.90 ( d, 1H, J = 8.0 Hz), 3.83 (s, 3H, OCH ₃ ), 3.22 (s, 6H, 2×NCH ₃ ).

4) 5-(3-4) 5-(3- 에톡시ethoxy -4--4- 하이드록시벤지리덴Hydroxybenzylidene )-1,3-디메틸피리미딘-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-)-trion [5-(3- EthoxyEthoxy -4--4- hydroxybenzylidenehydroxybenzylidene )-1,3-dimethylpyrimidine-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ge])-trione; compound Ge]

수율: 87%; ¹H NMR (500 MHz, DMSO-d ₆) δ 10.47 (s, 1H, OH), 8.34 (d, 1H, J = 1.5 Hz), 8.25 (s, 1H, vinylic H), 7.78 (dd, 1H, J = 8.0, 1.5 Hz), 6.90 (d, 1H, J = 8.0 Hz), 4.08 (q, 2H, J = 7.0 Hz), 3.20 (s, 3H, NCH₃), 3.20(s, 3H, NCH₃), 1.36(t, 3H, J=7.0Hz).Yield: 87%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 10.47 (s, 1H, OH), 8.34 (d, 1H, J = 1.5 Hz), 8.25 (s, 1H, vinylic H), 7.78 (dd, 1H, J = 8.0, 1.5 Hz), 6.90 (d, 1H, J = 8.0 Hz), 4.08 (q, 2H, J = 7.0 Hz), 3.20 (s, 3H, NCH ₃ ), 3.20 (s, 3H, NCH ₃ ), 1.36 (t, 3H, J=7.0 Hz).

5) 5-(3-5) 5-(3- 하이드록시hydroxy -4--4- 메톡시벤지리덴methoxybenzyridene )-1,3-디메틸피리미딘-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-)-trion [5-(3- HydroxyHydroxy -4--4- methoxybenzylidenemethoxybenzylidene )-1,3-dimethylpyrimidine-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Gf])-trione; compound Gf]

수율: 91%; ¹H NMR (500 MHz, DMSO-d ₆) δ 9.41 (s, 1H, OH), 8.21 (s, 1H, vinylic H), 8.08 (d, 1H, J = 2.0 Hz), 7.69 (dd, 1H, J = 8.5, 2.0 Hz), 7.05 (d, 1H, J = 8.5 Hz), 3.87 (s, 3H, OCH₃), 3.21(s, 3H, NCH₃), 3.20(s, 3H, NCH₃).Yield: 91%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 9.41 (s, 1H, OH), 8.21 (s, 1H, vinylic H), 8.08 (d, 1H, J = 2.0 Hz), 7.69 (dd, 1H, J = 8.5, 2.0 Hz), 7.05 (d, 1H, J = 8.5 Hz), 3.87 (s, 3H, OCH ₃ ), 3.21 (s, 3H, NCH ₃ ), 3.20 (s, 3H, NCH ₃ ).

6) 5-(4-6) 5-(4- 메톡시벤지리덴methoxybenzyridene )-1,3-디메틸피리미딘-2,4,6() -1,3-dimethylpyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1)-trione [5-(4-Methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Gg])-trione; compound Gg]

수율: 85%; ¹H NMR (500 MHz, DMSO-d ₆) δ 8.31 (d, 2H, J = 9.0 Hz), 8.29 (s, 1H, vinylic H), 7.05 (d, 2H, J = 9.0 Hz), 3.86 (s, 3H, OCH₃), 3.20(s, 3H, NCH₃), 3.19(s, 3H, NCH₃).Yield: 85%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 8.31 (d, 2H, J = 9.0 Hz), 8.29 (s, 1H, vinylic H), 7.05 (d, 2H, J = 9.0 Hz), 3.86 (s , 3H, OCH ₃ ), 3.20 (s, 3H, NCH ₃ ), 3.19 (s, 3H, NCH ₃ ).

7) 5-(4-7) 5-(4- 하이드록시hydroxy -3,5--3,5- 디메톡시벤지리덴dimethoxybenzyridene )-1,3-디메틸피리미딘-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3,5--3,5- dimethoxybenzylidenedimethoxybenzylidene )-1,3-dimethylpyrimidine-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Gk (MHY5186)])-trione; Compound Gk (MHY5186)]

수율: 98%; ¹H NMR (500 MHz, DMSO-d ₆) δ 9.99 (s, 1H, OH), 8.31 (s, 1H, vinylic H), 7.96 (s, 2H), 3.83 (s, 6H, 2×OCH₃), 3.22(s, 6H, 2×NCH₃).Yield: 98%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 9.99 (s, 1H, OH), 8.31 (s, 1H, vinylic H), 7.96 (s, 2H), 3.83 (s, 6H, 2×OCH ₃ ) , 3.22(s, 6H, 2×NCH ₃ ).

(10) 그룹 H 화합물 합성(10) Synthesis of Group H Compounds

상기 그룹 G 화합물 각각 (50 mg)에 에탄올 (5mL)을 가하고 0 ℃에서 소듐 보로하이드라이드 (NaBH₄, 3.5당량)를 천천히 부가시킨 혼합용액을 실온에서 1 내지 3 시간 동안 교반하였다. 용매를 감압증발시키고 얻어진 잔사에 소량의 물을 가하고 염산을 가하여 액성을 pH 1로 맞춘 후, 여과하고 필터케이크 (filter cake)를 물로 씻어주어 그룹 H 화합물을 얻었다. 경우에 따라서는 여과 후에 얻어진 고체를 실리카 겔 컬럼 크로마토그래피를 하여 더욱 정제하여 각각의 화합물을 얻었다.Ethanol (5mL) was added to each of the Group G compounds (50 mg), and sodium borohydride (NaBH ₄ , 3.5 equivalents) was slowly added at 0 °C. The mixed solution was stirred at room temperature for 1 to 3 hours. The solvent was evaporated under reduced pressure, a small amount of water was added to the resulting residue, and hydrochloric acid was added to adjust the pH of the solution to 1, followed by filtration, and the filter cake was washed with water to obtain a group H compound. In some cases, the solid obtained after filtration was further purified by silica gel column chromatography to obtain each compound.

1) 5-(4-1) 5-(4- 하이드록시벤질hydroxybenzyl )-1,3-디메틸피리미딘-2,4,6() -1,3-dimethylpyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1)-trione [5-(4-Hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Ha (MHY5189)])-trione; compound Ha (MHY5189)]

수율: 70%; ¹H NMR (500 MHz, DMSO-d ₆) δ 9.27 (s, 1H, OH), 6.76 (d, 2H, J = 8.0 Hz), 6.59 (d, 2H, J = 8.0 Hz), 3.86 (t, 1H, J = 5.0 Hz, methine H), 3.14 (d, 2H, J = 5.0 Hz, benzylic H₂), 2.98(s, 6H, 2×NCH₃).Yield: 70%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 9.27 (s, 1H, OH), 6.76 ( d , 2H, J = 8.0 Hz), 6.59 (d, 2H, J = 8.0 Hz), 3.86 (t, 1H, J = 5.0 Hz, methine H), 3.14 (d, 2H, J = 5.0 Hz, benzylic H ₂ ), 2.98 (s, 6H, 2×NCH ₃ ).

2) 5-(3,4-2) 5-(3,4- 디하이드록시벤질dihydroxybenzyl )-1,3-디메틸피리미딘-2,4,6() -1,3-dimethylpyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3,4-Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1)-trione [5-(3,4-Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Hb (MHY5193)])-trione; compound Hb (MHY5193)]

수율: 58%; ¹H NMR (500 MHz, DMSO-d ₆) δ 8.83 (s, 1H, OH), 8.70 (s, 1H, OH), 6.54 (d, 1H, J = 7.5 Hz), 6.37 (d, 1H, J = 2.0 Hz), 6.20 (dd, 1H, J = 7.5, 2.0 Hz), 3.82 (t, 1H, J = 5.0 Hz, methine H), 3.08 (d, 2H, J = 5.0 Hz, benzylic H₂), 2.99(s, 6H, 2×NCH₃).Yield: 58%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 8.83 (s, 1H, OH), 8.70 (s, 1H, OH), 6.54 (d, 1H, J = 7.5 Hz), 6.37 (d, 1H, J = 2.0 Hz), 6.20 (dd, 1H, J = 7.5, 2.0 Hz), 3.82 (t, 1H, J = 5.0 Hz, methine H), 3.08 (d, 2H, J = 5.0 Hz, benzylic H ₂ ), 2.99(s, 6H, 2×NCH ₃ ).

3) 5-(4-3) 5-(4- 하이드록시hydroxy -3-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3--3- methoxybenzylmethoxybenzyl )-1,3-)-1,3- dimethylpyrimidinedimethylpyrimidine -2,4,6(-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-trione; 화합물 Hd (MHY5190)])-trione; Compound Hd (MHY5190)]

수율: 61%; ¹H NMR (500 MHz, DMSO-d ₆) δ 8.85 (s, 1H, OH), 6.60 (d, 1H, J = 8.0 Hz), 6.49 (d, 1H, J = 2.0 Hz), 6.36 (dd, 1H, J = 8.0, 2.0 Hz), 3.88 (t, 1H, J = 5.0 Hz, methine H), 3.65 (s, 3H, OCH₃), 3.16(d, 2H, J=5.0Hz, benzylic H₂), 2.99(s, 6H, 2×NCH₃).Yield: 61%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 8.85 (s, 1H, OH), 6.60 ( d , 1H, J = 8.0 Hz), 6.49 (d, 1H, J = 2.0 Hz), 6.36 (dd, 1H, J = 8.0, 2.0 Hz), 3.88 (t, 1H, J = 5.0 Hz, methine H), 3.65 (s, 3H, OCH ₃ ), 3.16(d, 2H, J=5.0Hz, benzylic H ₂ ) , 2.99(s, 6H, 2×NCH ₃ ).

4) 5-(3-4) 5-(3- 에톡시ethoxy -4--4- 하이드록시벤질hydroxybenzyl )-1,3-디메틸피리미딘-2,4,6() -1,3-dimethylpyrimidine-2,4,6 ( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-)-trion [5-(3- EthoxyEthoxy -4--4- hydroxybenzylhydroxybenzyl )-1,3-)-1,3- dimethylpyrimidinedimethylpyrimidine -2,4,6(-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-trione; 화합물 He (MHY5192)])-trione; compound He (MHY5192)]

수율: 50%; ¹H NMR (500 MHz, DMSO-d ₆) δ 8.77 (s, 1H, OH), 6.61 (d, 1H, J = 8.0 Hz), 6.47 (d, 1H, J = 1.5 Hz), 6.36 (dd, 1H, J = 8.0, 1.5 Hz), 3.90 - 3.86 (m, 3H, OCH ₂ CH₃, methine H), 3.14(d, 2H, J=5.0Hz, benzylic H₂), 2.98(s, 6H, 2×NCH₃), 1.28(t, 3H, OCH₂CH ₃ ).Yield: 50%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 8.77 (s, 1H, OH), 6.61 ( d , 1H, J = 8.0 Hz), 6.47 (d, 1H, J = 1.5 Hz), 6.36 (dd, 1H, J = 8.0, 1.5 Hz), 3.90 - 3.86 (m, 3H, OCH ₂ CH ₃ , methine H ), 3.14 (d, 2H, J=5.0Hz, benzylic H ₂ ), 2.98(s, 6H, 2×NCH ₃ ), 1.28(t, 3H, OCH ₂ CH ₃ ).

5) 5-(3-5) 5-(3- 하이드록시hydroxy -4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(3-)-trion [5-(3- HydroxyHydroxy -4--4- methoxybenzylmethoxybenzyl )-1,3-)-1,3- dimethylpyrimidinedimethylpyrimidine -2,4,6(-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-trione; 화합물 Hf (MHY5191)])-trione; compound Hf (MHY5191)]

수율: 58%; ¹H NMR (500 MHz, DMSO-d ₆) δ 8.90 (s, 1H), 6.73 (d, 1H, J = 8.0 Hz), 6.43 (d, 1H, J = 2.0 Hz), 6.36 (dd, 1H, J = 8.0, 2.0 Hz), 3.88 (t, 1H, J = 5.0 Hz, methine H), 3.67 (s, 3H, OCH₃), 3.12(d, 2H, J=5.0Hz, benzylic H₂), 3.00(s, 6H, 2×NCH₃).Yield: 58%; 1H NMR (500 MHz, DMSO ^- _d6 ) δ 8.90 (s, 1H), 6.73 ( d , 1H, J = 8.0 Hz), 6.43 (d, 1H, J = 2.0 Hz), 6.36 (dd, 1H, J = 8.0, 2.0 Hz), 3.88 (t, 1H, J = 5.0 Hz, methine H), 3.67 (s, 3H, OCH ₃ ), 3.12(d, 2H, J=5.0Hz, benzylic H ₂ ), 3.00 (s, 6H, 2×NCH ₃ ).

6) 5-(4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(6) 5-(4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6( 1One HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-Methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1)-trione [5-(4-Methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Hg (MHY5188)])-trione; compound Hg (MHY5188)]

수율: 82%; ¹H NMR (500 MHz, CDCl₃) δ 6.94 (d, 2H, J = 8.0 Hz), 6.75 (d, 2H, J = 8.0 Hz), 3.76 (s, 3H, OCH₃), 3.73(t, 1H, J=5.0Hz, methine H), 3.41(d, 2H, J=5.0Hz, benzylic H₂), 3.14(s, 6H, 2×NCH₃).Yield: 82%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 6.94 (d, 2H, J = 8.0 Hz), 6.75 (d, 2H, J = 8.0 Hz), 3.76 (s, 3H, OCH ₃ ), 3.73(t, 1H , J=5.0 Hz, methine H), 3.41 (d, 2H, J=5.0 Hz, benzylic H ₂ ), 3.14 (s, 6H, 2×NCH ₃ ).

7) 5-(4-7) 5-(4- 하이드록시yhydroxyy -3,5--3,5- 디메톡시벤질dimethoxybenzyl )-1,3-디메틸피리미딘-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-트리온 [5-(4-)-trion [5-(4- HydroxyHydroxy -3,5--3,5- dimethoxybenzyldimethoxybenzyl )-1,3-dimethylpyrimidine-2,4,6(1)-1,3-dimethylpyrimidine-2,4,6(1 HH ,3,3 HH ,5,5 HH )-trione; 화합물 Hk (MHY5170)])-trione; Compound Hk (MHY5170)]

수율: 96%; ¹H NMR (500 MHz, DMSO-d ₆) δ 8.25 (brs, 1H), 6.19 (s, 2H), 3.90 (t, 1H, J = 5.0 Hz, methine H), 3.64 (s, 6H), 3.16 (d, 2H, J = 5.0 Hz, benzylic H₂), 3.00(s, 6H, 2×NCH₃).Yield: 96%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 8.25 (brs, 1H), 6.19 (s, 2H), 3.90 (t, 1H, J = 5.0 Hz, methine H), 3.64 (s, 6H), 3.16 (d, 2H, J = 5.0 Hz, benzylic H ₂ ), 3.00 (s, 6H, 2×NCH ₃ ).

[[ 실시예Example 2] 2] MHY의MHY's 녹농균 ( Pseudomonas aeruginosa ( P. P. aeruginosaaeruginosa )의 )of QSQS 및 독성 인자 생성 억제 효과 and inhibitory effect on the production of toxic factors

화학 라이브러리의 MHY는 리포터 기반 생물 검정 (reporter-based bioassay)에 의해 항 QS 활성에 대해 스크리닝되었다. 이 생물학적 검정은 녹농균 (P. aeruginosa)의 마스터 QS 조절자인 LasR의 활성을 측정하기 위해 설계된 pSC11 (lasI _p-lacZ 융합 플라스미드) 및 pJN105L (LasR-발현 플라스미드)을 포함하는 대장균 (E. coli) 이중 플라스미드 리포터 (dual plasmid reporter)로 수행되었다. 이 리포터는 3OC12-HSL을 첨가하면 매우 높은 베타갈락토시다제 (β-galactosidase) 활성을 나타내지만, 효과적인 LasR 억제제 (inhibitor)를 추가로 첨가하면 감소된 활성을 보이는데, LasR에 대한 3OC12-HSL과 억제제 간의 경쟁을 더 잘 보기 위해, 3OC12-HSL을 LasR을 최대로 활성화 시키는 농도의 절반 (50 nM)을 처리하고 억제제를 3OC12-HSL보다 100배 더 높은 농도인 5 μM로 처리하였다. 이러한 조건에서 126개의 MHY를 스크리닝했으며, 그 결과, 도 2에 따를 때, MHY1387 (화합물 Ck)에서 LasR의 활성을 유의하게 억제하였는데, LasR 활성을 35 % 이상 감소시켰다.MHYs in the chemical library were screened for anti-QS activity by a reporter-based bioassay. This bioassay is a double E. coli ( E. coli ) containing pSC11 ( lasI _p - lacZ fusion plasmid) and pJN105L (LasR-expressing plasmid) designed to measure the activity of LasR, the master QS regulator of P. aeruginosa ( P. aeruginosa ). performed with a dual plasmid reporter. This reporter showed very high β-galactosidase activity when 3OC12-HSL was added, but decreased activity when an effective LasR inhibitor was additionally added. To better see the competition between inhibitors, 3OC12-HSL was treated with half of the concentration that maximally activates LasR (50 nM), and the inhibitor was treated with 5 μM, a concentration 100 times higher than 3OC12-HSL. 126 MHYs were screened under these conditions, and as a result, according to FIG. 2, LasR activity was significantly inhibited in MHY1387 (compound Ck), and LasR activity was reduced by more than 35%.

MHY1387 (화합물 Ck)이 독성 인자 생성을 실제로 억제할 수 있는지 알아보고자, 녹농균 (P. aeruginosa) 세포에 각 MHY를 처리했을 때의 총 세포외 프로테아제 활성을 측정하였다. 스킴 밀크 (Skim milk) 분석 결과, 도 3에 따를 때, MHY1387 (화합물 Ck)에 의해 총 프로테아제 활성이 유의하게 감소됨을 확인했다. To investigate whether MHY1387 (compound Ck) can actually inhibit the production of virulence factors, P. aeruginosa ( P. aeruginosa ) The total extracellular protease activity when each MHY was treated was measured. As a result of skim milk analysis, according to FIG. 3, it was confirmed that total protease activity was significantly reduced by MHY1387 (compound Ck).

갈색거저리 (Tenebrio molitor) 감염 분석을 이용하여 이러한 화합물이 녹농균 (P. aeruginosa)의 독성 효과를 감소시킬 수 있는지 여부를 조사하였다. 그 결과, 도 4에 따를 때, 녹농균 (P. aeruginosa) 배양 상등액의 독성 효과가 MHY1387 (화합물 Ck)에 의해 유의하게 감소되었음을 확인했다.Brown mealworm ( Tenebrio molitor ) infection assay was used to investigate whether these compounds could reduce the toxic effects of P. aeruginosa . As a result, according to FIG. 4, it was confirmed that the toxic effect of the culture supernatant of P. aeruginosa was significantly reduced by MHY1387 (compound Ck).

[실시예 3] 세포내 c-di-GMP 수준을 감소로 인한 생물막 형성 억제 효과[Example 3] Effect of inhibiting biofilm formation by reducing intracellular c-di-GMP levels

녹농균의 또 다른 중요한 병원성 결정 인자인 생물막 형성에 대한 MHY1387 (화합물 Ck)의 억제 효과를 조사하였다. 정적 생물막 분석은 녹농균 (P. aeruginosa)의 생물막 형성이 종종 영양분의 영향을 받기 때문에 두 가지 다른 탄소 공급원 배지에서 각각 수행되었다. 그 결과, 도 5A 및 도 5B에 따를 때, 10 μM MHY1387 (화합물 Ck)이 M63-cit+CAA 배지에서 생물막 형성을 각각 33 %, M63-gly 배지에서 각각 46 %까지 유의하게 억제하는 것을 확인했다. 한편, 나이트로프루사이드나트륨 (sodium nitroprusside; 이하, SNP라함)은 잘 알려진 생물막 억제제로, 억제 효능 비교를 위해 5 μM SNP를 처리하였을 때, M63-cit+CAA 배지에서 생물막 형성이 33 % 감소하고, M63-gly 배지에서 65 % 감소를 보였다. SNP는 두 종류의 배지에서 생물막 억제 효과에 큰 차이를 보인 반면, MHY1387 (화합물 Ck)은 적은 차이를 보였고, 탄소원으로 시트르산염 (citrate) + CAA가 주어졌을 때보다 글리세롤 (glycerol)이 주어졌을 때, 생물막 형성이 더 잘 억제되었음을 확인했다. The inhibitory effect of MHY1387 (compound Ck) on biofilm formation, another important pathogenic determinant of Pseudomonas aeruginosa, was investigated. Static biofilm analysis was performed on two different carbon source media, respectively, as P. aeruginosa biofilm formation is often influenced by nutrients. As a result, according to Figures 5A and 5B, it was confirmed that 10 μM MHY1387 (compound Ck) significantly inhibited biofilm formation by 33% in M63-cit + CAA medium and by 46% in M63-gly medium, respectively. . On the other hand, sodium nitroprusside (hereinafter referred to as SNP) is a well-known biofilm inhibitor, and when treated with 5 μM SNP for comparison of inhibitory efficacy, biofilm formation in M63-cit + CAA medium was reduced by 33% and , showing a 65% reduction in M63-gly medium. While SNP showed a large difference in the biofilm inhibitory effect in the two types of media, MHY1387 (compound Ck) showed a small difference, and when glycerol was given as a carbon source than when citrate + CAA was given , confirmed that biofilm formation was better inhibited.

MHY1387 (화합물 Ck)이 생물막 형성을 억제하는 방법을 다루기 위해 많은 그람 음성균에서 생물막 형성을 조절하는 데 중요한 역할을 하는 세포내 신호 전달 분자인 c-di-GMP의 수준을 조사하였다. cdrA는 세포내 c-di-GMP 수준에 대응하는 FleQ에 의해 엄격하게 조절되므로, cdrA _p-lacZ는 c-di-GMP를 정량화하기 위한 리포터로 사용되었다. 그 결과, 도 5C에 따를 때, cdrA _p-lacZ를 포함하는 세포를 MHY로 처리했을 때, MHY1387 (화합물 Ck)로 처리된 세포는 약 31 %까지 c-di-GMP 수준의 감소를 확인했다. SNP는 세포내 c-di-GMP 수준을 감소시키는 것으로 이미 보고되었기 때문에 동일한 조건에서 리포터 세포를 5 μM SNP로 처리하였고, c-di-GMP를 47 % 감소시켰다. 이러한 결과는 생물막 억제제에 의한 생물막 형성 억제와 양적으로 상관관계가 있었다. 따라서, SNP와 마찬가지로 MHY1387 (화합물 Ck)은 세포내 c-di-GMP를 감소시켜, 생물막 형성을 억제하는 것을 알 수 있었다. 또한, 도 8A에 따를 때, MHY1387 (화합물 Ck)이 10 μM에서 박테리아 성장에 영향을 미치지 않았음을 확인했다.To address how MHY1387 (compound Ck) inhibits biofilm formation, we investigated the level of c-di-GMP, an intracellular signaling molecule that plays an important role in regulating biofilm formation in many Gram-negative bacteria. Since cdrA is tightly regulated by FleQ corresponding to intracellular c-di-GMP levels, cdrA _p - lacZ was used as a reporter to quantify c-di-GMP. As a result, according to Fig. 5C, when cells containing cdrA _p - lacZ were treated with MHY, the c-di-GMP level of cells treated with MHY1387 (compound Ck) was reduced by about 31%. Since SNPs have already been reported to reduce intracellular c-di-GMP levels, reporter cells were treated with 5 μM SNPs under the same conditions, and c-di-GMP was reduced by 47%. These results were positively correlated with the inhibition of biofilm formation by the biofilm inhibitor. Therefore, like the SNP, it was found that MHY1387 (compound Ck) reduces intracellular c-di-GMP and inhibits biofilm formation. Also, according to Fig. 8A, it was confirmed that MHY1387 (compound Ck) did not affect bacterial growth at 10 μM.

[실시예 5] 낮은 농도에서의 생물막 형성 억제 효과[Example 5] Biofilm formation inhibitory effect at low concentration

최소한의 농도에서 생물막 형성 억제 여부를 실험하였다. 더 낮은 농도 범위에서 MHY1387 (화합물 Ck)의 항독성 효과를 측정하였고, MHY1387 (화합물 Ck)이 1 nM보다 낮은 농도에서 LasR 활성을 억제하기 시작하였고, 1 nM보다 높은 농도에서는 억제가 안정화되었음을 확인했다. 이러한 결과를 확인하기 위해 pJN101 (PA1897 _p-lacZ) 및 pJN105Q를 포함하는 대장균 (E. coli) 이중 플라스미드 리포터를 사용하여, 또 다른 3OC12-HSL 수용체인 QscR에 대한 MHY1387 (화합물 Ck)의 억제 효과를 조사하였다. 이 실험에서, 3OC12-HSL은 100 nM, 즉 QscR을 최대로 활성화 시키는 농도의 절반을 처리하였다. 그 결과, 도 6A에 따를 때, LasR의 결과와 유사하게, MHY1387 (화합물 Ck)은 1 nM 미만의 농도에서 QscR을 억제하기 시작하였고 1 nM보다 높은 농도에서 안정화 되었다. 녹농균 (P. aeruginosa)에서 MHY1387 (화합물 Ck)이 이와 같은 낮은 농도에서 QS 활성을 억제할 수 있는지 확인하기 위해 특정 프로모터-lacZ 융합 (lasI _p-,PA1897 _p-,rhlA _p-및 pqsA _p-lacZ)을 사용하여 녹농균 (P. aeruginosa)에서 주요 QS 조절자인 LasR, QscR, RhlR 및 PqsR의 활성을 측정하였다. 그 결과, 도 6B에 따를 때, 각 리포터 플라스미드를 보유하는 녹농균 (P. aeruginosa) 세포를 MHY1387 (화합물 Ck)로 처리한 경우, MHY1387 (화합물 Ck)은 100 pM 미만의 농도에서 LasR, QscR 및 RhlR을 억제하기 시작했고, 100 pM보다 높은 농도에서는 안정화 되었다. 또한, 도 6C에 따를 때, MHY1387 (화합물 Ck)이 100 pM에서 녹농균 배양 상등액의 독성을 유의하게 감소시킬 수 있음을 확인하였다. 이러한 결과는 MHY1387 (화합물 Ck)이 매우 낮은 농도에서도 효과를 발휘할 수 있다는 장점이 있음을 알 수 있었다.Whether or not to inhibit biofilm formation at the minimum concentration was tested. The anti-toxic effect of MHY1387 (compound Ck) was measured at a lower concentration range, and it was confirmed that MHY1387 (compound Ck) began to inhibit LasR activity at concentrations lower than 1 nM, and the inhibition stabilized at concentrations higher than 1 nM. . In order to confirm these results, the inhibitory effect of MHY1387 (compound Ck) on QscR, another 3OC12-HSL receptor, was examined using an E. coli double plasmid reporter containing pJN101 ( PA1897 _p - lacZ ) and pJN105Q. investigated. In this experiment, 3OC12-HSL was treated at 100 nM, that is, half of the concentration that maximally activates QscR. As a result, according to FIG. 6A, similar to the results of LasR, MHY1387 (compound Ck) began to inhibit QscR at a concentration of less than 1 nM and stabilized at a concentration higher than 1 nM. To determine if MHY1387 (compound Ck) can inhibit QS activity at such low concentrations in P. aeruginosa , specific promoter- lacZ fusions ( lasI _p- , PA1897 _p- , rhlA _p- and pqsA _p - lacZ ) was used to measure the activities of LasR, QscR, RhlR and PqsR, which are major QS regulators, in P. aeruginosa . As a result, according to Figure 6B, when P. aeruginosa cells having each reporter plasmid were treated with MHY1387 (compound Ck), MHY1387 (compound Ck) was LasR, QscR and RhlR at a concentration of less than 100 pM. and stabilized at concentrations higher than 100 pM. In addition, according to FIG. 6C, it was confirmed that MHY1387 (compound Ck) can significantly reduce the toxicity of the P. aeruginosa culture supernatant at 100 pM. These results indicate that MHY1387 (compound Ck) has the advantage of being effective even at very low concentrations.

저농도에서 생물막 형성을 억제할 수 있는지 알아보기 위해 저농도 범위에서 MHY1387 (화합물 Ck)을 처리하여 생물막 형성을 측정하였다. 그 결과, 도 7A 및 도 7B에 따를 때, 생물막 형성은 M63-cit+CAA 및 M63-gly 배지 모두에서 1 pM MHY1387 (화합물 Ck)에 의해 거의 최대로 억제되었고, 1 pM보다 높은 농도에서는 억제가 안정화 되었다. 도 7C에 따를 때, 세포 내 c-di-GMP 수준은 0.1 pM MHY1387 (화합물 Ck)에서 최대로 감소되었으며, 0.1 pM보다 높은 농도에서는 감소가 안정화 되었다. 한편, 도 8B 및 도 8C에 따를 때, MHY1387 (화합물 Ck)이 M63-cit+CAA 및 M63-gly 배지에서 박테리아 성장에 영향을 미치지 않았다는 점을 확인했다. Biofilm formation was measured by treating MHY1387 (compound Ck) in a low concentration range to see if biofilm formation could be inhibited at low concentrations. As a result, according to Figures 7A and 7B, biofilm formation was inhibited almost to the maximum by 1 pM MHY1387 (compound Ck) in both M63-cit + CAA and M63-gly media, and inhibition was inhibited at concentrations higher than 1 pM. has been stabilized According to Fig. 7C, intracellular c-di-GMP levels were maximally reduced at 0.1 pM MHY1387 (compound Ck), and the reduction was stabilized at concentrations higher than 0.1 pM. On the other hand, according to Figs. 8B and 8C, it was confirmed that MHY1387 (compound Ck) did not affect bacterial growth in M63-cit+CAA and M63-gly media.

이러한 결과를 종합해 보면, MHY1387 (화합물 Ck)은 약 100 pM의 매우 낮은 농도에서 QS와 독성 인자 생성을 억제하였다. MHY1387 (화합물 Ck)은 SNP에 비해 약간 약한 생물막 억제 수준을 나타냈지만, 유효한 효과를 나타내는 SNP에 비해 10⁶배 낮음을 알 수 있었다.Taken together, MHY1387 (compound Ck) inhibited QS and toxic factor production at a very low concentration of about 100 pM. MHY1387 (compound Ck) showed a slightly weaker biofilm inhibition level compared to the SNP, but it was found to be 10 ⁶ times lower than the SNP showing an effective effect.

[[ 실시예Example 6] 6] MHY1387MHY1387 (화합물 (compound CkCk )의 구조 유사체들에서도 ) in the structural analogues of QSQS 및 and 생물막biofilm 형성을 억제 확인 check to inhibit formation

MHY1387 (화합물 Ck) 구조를 기반으로 하는 구조 유사체들이 상기 실시예들에서 설명한 방법과 동일한 방식으로 항QS 활성 및 생물막 형성에 대해 스크리닝되었다. LasR에 대한 3OC12-HSL과 억제제 간의 경쟁을 더 잘 보기 위해, 3OC12-HSL을 LasR을 최대로 활성화 시키는 농도의 절반 (50 nM)을 처리하고, 억제제를 3OC12-HSL보다 100배 더 높은 농도인 5 μM로 처리하였다. 총 67개의 MHY1387 구조 유사체들을 스크리닝했으며, 47개의 MHY 화합물이 LasR 활성을 유의하게 억제하였고, LasR 활성을 15 % 이상 감소시켰다.Structural analogs based on the MHY1387 (compound Ck) structure were screened for anti-QS activity and biofilm formation in the same manner as described in the above Examples. To better see the competition between 3OC12-HSL and the inhibitor for LasR, 3OC12-HSL was treated at half the concentration that maximally activates LasR (50 nM), and the inhibitor was treated at a concentration 100 times higher than 3OC12-HSL, 5 treated with μM. A total of 67 MHY1387 structural analogues were screened, and 47 MHY compounds significantly inhibited LasR activity and reduced LasR activity by more than 15%.

이들 중에 녹농균 (P. aeruginosa)의 또 다른 중요한 병원성 결정 인자인 생물막 형성에 대한 억제효과를 확인하였다. 그 결과, 표 2에 따를 때, 10 μM 농도에서 MHY5134 (화합물 Cc), MHY5135 (화합물 Cb), MHY5136 (화합물 Cd), MHY5137 (화합물 Ce), MHY5140 (화합물 Cg), MHY5152 (화합물 Du), MHY5154 (화합물 Db), MHY5170 (화합물 Hk), MHY5171 (화합물 Cw), MHY5172 (화합물 Dj) 및 MHY5174 (화합물 Ap)의 11개 MHY들이 생물막을 의미있게 억제한다는 것을 확인하였다. 이들 11개 MHY는 M63-cit+CAA 배지에서 6 % 이상, M63-gly 배지에서 11 % 이상 유의하게 생물막 형성을 억제하였다. 즉, 이 11개의 MHY들은 녹농균 병독인자 발현에 가장 중요한 조절인자인 LasR과 생물막 형성을 동시에 억제하는 효과를 가지는 것을 확인했다.Among them, P. aeruginosa ( P. aeruginosa ) The inhibitory effect on biofilm formation, which is another important pathogenic determinant, was confirmed. As a result, according to Table 2, MHY5134 (Compound Cc), MHY5135 (Compound Cb), MHY5136 (Compound Cd), MHY5137 (Compound Ce), MHY5140 (Compound Cg), MHY5152 (Compound Du), MHY5154 at 10 μM concentration. (Compound Db), MHY5170 (Compound Hk), MHY5171 (Compound Cw), MHY5172 (Compound Dj) and MHY5174 (Compound Ap) were found to significantly inhibit biofilm. These 11 MHY inhibited biofilm formation significantly by more than 6% in M63-cit+CAA medium and by more than 11% in M63-gly medium. That is, it was confirmed that these 11 MHYs have the effect of simultaneously inhibiting LasR and biofilm formation, which are the most important regulators for the expression of Pseudomonas aeruginosa virulence factors.

전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술 분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. The above description of the present invention is for illustrative purposes, and those skilled in the art can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting.

본 발명의 범위는 후술하는 청구범위에 의하여 나타내어지며, 청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is indicated by the following claims, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts should be interpreted as being included in the scope of the present invention.

Claims

하기 화학식 I로 표시되는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물:
[화학식 I]

상기

은 단일결합 또는 이중결합이고;
상기 X는 산소 또는 황이고;
상기 R⁵가 수소 또는 (C1~C4)알킬이고;
1) 상기 R⁴가 수소이고, i) 상기 R¹ 내지 R³ 중 어느 하나는 (C1~C4)알킬, 나이트로 또는 페녹시이고, 나머지는 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬 또는 (C1~C4)알콕시, 또는 ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있거나,
2) 상기 R⁴가 (C1~C4)알킬 또는 (C1~C4)알콕시페닐이고, i) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시, 또는 ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있음.A compound selected from a compound represented by Formula I, a stereoisomer thereof, a racemate thereof, or a pharmaceutically acceptable salt thereof:
[Formula I]

remind

is a single bond or a double bond;
X is oxygen or sulfur;
wherein R ⁵ is hydrogen or (C1~C4)alkyl;
1) R ⁴ is hydrogen, i) any one of R ¹ to R ³ is (C1-C4) alkyl, nitro or phenoxy, the others may be the same or different, and hydrogen, hydroxy, halogen , (C1~C4)alkyl or (C1~C4)alkoxy, or ii) wherein R ¹ is hydrogen, and R ² and R ³ are connected to each other to form a dioxol or benzene ring;
2) wherein R ⁴ is (C1~C4)alkyl or (C1~C4)alkoxyphenyl, i) wherein R ¹ to R ³ may be the same as or different from each other, and hydrogen, hydroxy, halogen, (C1~C4) Alkyl, (C1~C4) alkoxy, nitro, benzyloxy or phenoxy unsubstituted or substituted with halogen, or ii) wherein R ¹ is hydrogen, and R ² and R ³ are connected to each other to form dioxol or May form benzene rings.

청구항 1에 있어서, 상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고, 상기 X는 산소 또는 황이고; 상기 R⁴는 수소이고; 상기 R⁵가 수소이고; i) 상기 R¹ 내지 R³ 중 어느 하나는 (C1~C4)알킬, 나이트로 또는 페녹시이고, 나머지는 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬 또는 (C1~C4)알콕시, 또는 ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있는 것을 특징으로 하는 화합물. The method according to claim 1, wherein in the formula I

청구항 1에 있어서, 상기 화학식 I에서 상기

은 단일결합 또는 이중결합이고, 상기 X는 산소 또는 황이고; 상기 R⁴는 (C1~C2)알킬 또는 (C1~C2)알콕시페닐이고; 상기 R⁵가 수소 또는 메틸이고; i) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, ii) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있는 것을 특징으로 하는 화합물.The method according to claim 1, wherein in the formula I

청구항 1에 있어서, 상기 화합물은 화합물 Az 내지 화합물 Hk로 이루어진 군에서 선택되는 것을 특징으로 하는 화합물:
(화합물 Az) 5-(나프탈렌-1-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 AB) 5-(4-하이드록시-3,5-디아이소프로필벤질리덴)-2-티옥소하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-diisopropylbenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Bq) 5-(4-플루오로벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Fluorobenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Bu) 5-(4-((4-플루오로벤질)옥시)벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Bx) 5-(벤조[d][1,3]디옥솔-5-일메틸렌)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 BA) 5-(나프탈렌-2-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Cn) 5-(3,5-디-tert-부틸-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,5-Di-tert-butyl-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cq) 5-(4-플루오로벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cr) 5-(2-나이트로벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cv) 5-(4-((4-클로로벤질)옥시)벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-((4-Chlorobenzyl)oxy)benzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cw) 5-(3-페녹시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cx) 5-(벤조[d][1,3]디옥솔-5-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cz) 5-(나프탈렌-1-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 CB) 5-(4-하이드록시-3,5-디아이소프로필벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Dq) 5-(4-플루오로벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Fluorobenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Du) 5-(4-((4-플루오로벤질)옥시)벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Dx) 5-(벤조[d][1,3]디옥솔-5-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Dy) 5-((2-하이드록시나프탈렌-1-일)메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-((2-Hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 DA) 5-(나프탈렌-2-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ef-1) (E)-5-(3-하이드록시-4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ef-2) (Z)-5-(3-하이드록시-4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ep-1) (E)-5-(4-하이드록시-3,5-디메틸벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ep-2) (Z)-5-(4-하이드록시-3,5-디메틸벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ex-1) (E)-5-(벤조[d][1,3]디옥솔-5-일메틸렌)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ex-2) (Z)-5-(벤조[d][1,3]디옥솔-5-일메틸렌)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fa) 5-(4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fb) 5-(3,4-디하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fc) 5-(2,4-디하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fd) 5-(4-하이드록시-3-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fe) 5-(3-에톡시;-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ff) 5-(3-하이드록시-4-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fg) 5-(4-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fh) 5-(3,4-디메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fi) 5-(2,4-디메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fj) 1-(4-메톡시페닐)-5-(3,4,5-트리메톡시벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fk) 5-(4-하이드록시-3,5-디메톡시벤질)-1-(4메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fl) 5-(3,5-디브로모-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,5-Dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fm) 5-(3-브로모-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fp) 5-(4-하이드록시-3,5-디메틸벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fx) 5-(벤조[d][1,3]디옥솔-5-일메틸)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ga) 5-(4-하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gb) 5-(3,4-디하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gd) 5-(4-하이드록시-3-메톡시벤지리딘)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ge) 5-(3-에톡시-4-하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gf) 5-(3-하이드록시-4-메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gg) 5-(4-메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gk) 5-(4-하이드록시-3,5-디메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ha) 5-(4-하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hb) 5-(3,4-디하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hd) 5-(4-하이드록시-3-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 He) 5-(3-에톡시-4-하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hf) 5-(3-하이드록시-4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hg) 5-(4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione]; 및
(화합물 Hk) 5-(4-하이드록시y-3,5-디메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione].The compound according to claim 1, characterized in that the compound is selected from the group consisting of Compound Az to Compound Hk:
(Compound Az) 5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine -4,6( 1H , 5H )-dione];
(Compound AB) 5-(4-hydroxy-3,5-diisopropylbenzylidene)-2-thioxohydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy -3,5-diisopropylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Bq) 5-(4-fluorobenzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Fluorobenzylidene)pyrimidine-2,4,6 ( 1H , 3H , 5H )-trione];
(Compound Bu) 5-(4-((4-fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-( (4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Bx) 5-(benzo[ d ][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione [5-(Benzo [ d ][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6( 1H , 3H ,5H) -trione ];
(Compound BA) 5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6( 1H,3H,5H)-trione];
(Compound Cn) 5-(3,5-di- tert -butyl-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3 ,5- Ditert -butyl-4-hydroxybenzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Cq) 5-(4-fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cr) 5-(2-nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cv) 5-(4-((4-chlorobenzyl)oxy)benzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(( 4-Chlorobenzyl)oxy)benzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Cw) 5-(3-phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione [5-( Benzo[ d ][1,3]dioxol-5-ylmethyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Cz) 5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine -4,6( 1H , 5H )-dione];
(Compound CB) 5-(4-hydroxy-3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy -3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Dq) 5-(4-fluorobenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Fluorobenzyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Du) 5-(4-((4-fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-(( 4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Dx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Benzo [ d ][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6( 1H , 3H ,5H) -trione ];
(Compound Dy) 5-((2-hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione [5-((2- Hydroxynaphthalen- 1-yl)methyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound DA) 5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4 ,6( 1H , 3H ,5H) -trione ];
(Compound Ef-1) ( E )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H)-trione [ (E ) -5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione] ;
(Compound Ef-2) ( Z )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H)-trione [( Z )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H ) -trione ] ;
(Compound Ep-1) ( E )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H )-trione [( E )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(Compound Ep-2) ( Z )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H )-trione [( Z )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(Compound Ex-1) ( E )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3H ,5H)-trione [ (E ) -5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Ex-2) ( Z )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3H ,5H) -trione [( Z )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Fa) 5-(4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4- Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fb) 5-(3,4-dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Fc) 5-(2,4-dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (2,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fd) 5-(4-hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(4-Hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fe) 5-(3-ethoxy;-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3-Ethoxy-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Ff) 5-(3-hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(3-Hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fg) 5-(4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4- Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fh) 5-(3,4-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-( 3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fi) 5-(2,4-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-( 2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fj) 1-(4-methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fk) 5-(4-hydroxy-3,5-dimethoxybenzyl)-1-(4methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fl) 5-(3,5-dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )- trione [5-(3,5-Dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fm) 5-(3-bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(3-Bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fp) 5-(4-hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )- trione];
(Compound Ga) 5-(4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxybenzylidene) -1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Gb) 5-(3,4-dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 ,4-Dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Gd) 5-(4-hydroxy-3-methoxybenziridine)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (4-Hydroxy-3-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Ge) 5-(3-ethoxy-4-hydroxybenzyridene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3-Ethoxy-4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Gf) 5-(3-hydroxy-4-methoxybenzyridene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3-Hydroxy-4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Gg) 5-(4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzylidene) -1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Gk) 5-(4-hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Ha) 5-(4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxybenzyl)-1 ,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hb) 5-(3,4-dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4 -Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hd) 5-(4-hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4 -Hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound He) 5-(3-ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 -Ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hf) 5-(3-hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 -Hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hg) 5-(4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzyl)-1 ,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione]; and
(Compound Hk) 5-(4-hydroxyy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5 -(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione].

하기 화학식 I로 표시되는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물:
[화학식 I]

상기

은 단일결합 또는 이중결합이고;
상기 X는 산소 또는 황이고;
1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고;
상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며,
상기 R⁵가 수소 또는 (C1~C4)알킬임.A composition for inhibiting biofilm formation or virulence of pathogenic microorganisms, comprising a compound selected from a compound represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof:
[Formula I]

remind

is a single bond or a double bond;
X is oxygen or sulfur;
1) The R ¹ to R ³ may be the same or different, respectively, and are hydrogen, hydroxy, halogen, (C1~C4)alkyl, (C1~C4)alkoxy, nitro, benzyloxy which is optionally substituted with halogen, or phenoxy, or 2) wherein R ¹ is hydrogen, and R ² and R ³ are connected to form a dioxol or benzene ring;
Wherein R ⁴ is hydrogen, (C1~C4)alkyl or (C1~C4)alkoxyphenyl;
R ⁵ is hydrogen or (C1~C4)alkyl.

청구항 5에 있어서, 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소 또는 황이고; 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 브롬, 플루오르, 메틸, 아이소프로필 (iso-Pr), 털트-부틸 (tert-Bu), 메톡시, 에톡시, 나이트로, 플로오르 또는 염소로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고, 상기 R⁴는 수소이며, 상기 R⁵가 수소인 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물.The method according to claim 5, wherein the

is a single bond or a double bond; X is oxygen or sulfur; The R ¹ to R ³ may be the same or different, respectively, and are selected from hydrogen, hydroxy, bromine, fluorine, methyl, isopropyl (iso-Pr), tert-butyl (tert-Bu), methoxy, ethoxy, nitro , benzyloxy or phenoxy, substituted or unsubstituted with fluorine or chlorine, wherein R ¹ is hydrogen, R ² and R ³ may be connected to each other to form a dioxol or benzene ring, and the R ⁴ is hydrogen, and the R ⁵ is characterized in that hydrogen, biofilm formation or virulence (virulence) inhibitory composition of pathogenic microorganisms.

청구항 6에 있어서, 상기 화합물은 화합물 Aa 내지 화합물 BA로 이루어진 군에서 선택되는 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물:
(화합물 Aa) 5-(4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Ab) 5-(3,4-디하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H, 5H)-디온 [5-(3, 4-Dihydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ac) 5-(2,4-디하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H, 5H)-디온 [5-(2,4-Dihydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione];
(화합물 Ad) 5-(4-하이드록시-3-메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3-methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione];
(화합물 Ae) 5-(3-에톡시-4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Ethoxy-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Af) 5-(3-하이드록시-4-메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온[5-(3-Hydroxy-4-methoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ag) 5-(4-메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ah) 5-(3, 4-디메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ai) 5-(2, 4-디메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2, 4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Aj) 2-티옥소-5-(3, 4, 5-트리메톡시벤질리덴)디하이드로피리미딘-4, 6(1H, 5H)-디온 [2-Thioxo-5-(3, 4, 5-trimethoxybenzylidene)dihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ak) 5-(4-하이드록시-3, 5-디메톡시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온[5-(4-Hydroxy-3, 5-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Am) 5-(3-브로모-4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Bromo-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 An) 5-(3, 5-디-tert-부틸-4-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ao) 5-(2-하이드록시벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ap) 5-(4-하이드록시-3, 5-디메틸벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Aq) 5-(4-플루오로벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H,5H)-디온 [5-(4-Fluorobenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Ar) 5-(2-니트로벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H,5H)-디온 [5-(2-Nitrobenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 As) 5-(4-(벤질옥시)벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-(Benzyloxy)benzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Av) 5-(4-(4-클로로벤질옥시)벤질리덴)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-(4-Chlorobenzyloxy)benzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Aw) 5-(3-페녹시벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3-Phenoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Ax) 5-(벤조[d][1,3]디옥솔-5-일메틸렌)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(Benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Az) 5-(나프탈렌-1-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 AB) 5-(4-하이드록시-3,5-디아이소프로필벤질리덴)-2-티옥소하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-diisopropylbenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Ba) 5-(4-하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bb) 5-(3,4-디하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3,4-Dihydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bc) 5-(2,4-디하이드록시벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Bd) 5-(4-하이드록시-3-메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Be) 5-(3-에톡시-4-하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bf) 5-(3-하이드록시-4-메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Hydroxy-4-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bg) 5-(4-메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bh) 5-(3, 4-디메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4-Dimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bi) 5-(2, 4-디메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H) -트리온 [5-(2, 4-Dimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bj) 5-(3, 4, 5-트리메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4, 5-Trimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bk) 5-(4-하이드록시-3, 5-디메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3, 5-dimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bl) 5-(3, 5-디브로모-4-하이드록시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 5-Dibromo-4-hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Bq) 5-(4-플루오로벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Fluorobenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Bs) 5-(4-(벤질옥시)벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Bt) 5-(3-(벤질옥시)벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-(Benzyloxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Bu) 5-(4-((4-플루오로벤질)옥시)벤질리덴)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Bx) 5-(벤조[d][1,3]디옥솔-5-일메틸렌)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 By) 5-((2-하이드록시나프탈렌-1-일)메틸렌)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온[5-((2-Hydroxynaphthalen-1-yl)methylene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 BA) 5-(나프탈렌-2-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ca) 5-(4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cb) 5-(3, 4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cc) 5-(2, 4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2, 4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cd) 5-(4-하이드록시-3-메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ce) 5-(3-에톡시-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cf) 5-(3-하이드록시-4-메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Hydroxy-4-methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cg) 5-(4-메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ch) 5-(3, 4-디메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ci) 5-(2, 4-디메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(2, 4-Dimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cj) 5-(3, 4, 5-트리메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3, 4, 5-Trimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Ck) 5-(4-하이드록시-3, 5-디메톡시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(4-Hydroxy-3, 5-dimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cl) 5-(3,5-디브로모-4-하이드록시)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,5-Dibromo-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cm) 5-(3-브로모-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4, 6(1H, 5H)-디온 [5-(3-Bromo-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cn) 5-(3,5-디-tert-부틸-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,5-Di-tert-butyl-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Co) 5-(2-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H, 5H)-디온 [5-(2-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(화합물 Cp) 5-(4-하이드록시-3,5-디메틸벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-dimethylbenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cq) 5-(4-플루오로벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cr) 5-(2-나이트로벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cs) 5-(4-(벤질옥시)벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-(Benzyloxy)benzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cv) 5-(4-((4-클로로벤질)옥시)벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-((4-Chlorobenzyl)oxy)benzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cw) 5-(3-페녹시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cx) 5-(벤조[d][1,3]디옥솔-5-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cz) 5-(나프탈렌-1-일메틸)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 CB) 5-(4-하이드록시-3,5-디아이소프로필벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Da) 5-(4-하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Db) 5-(3, 4-디하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4-Dihydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dc) 5-(2, 4-디하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(2, 4-Dihydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dd) 5-(4-하이드록시-3-메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 De) 5-(3-에톡시-4-하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Df) 5-(3-하이드록시-4-메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dg) 5-(4-메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Methoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dh) 5-(3, 4-디메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4-Dimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Di) 5-(2, 4-디메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(2, 4-Dimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dj) 5-(3, 4, 5-트리메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 4, 5-Trimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dk) 5-(4-하이드록시-3, 5-디메톡시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(4-Hydroxy-3, 5-dimethoxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dl) 5-(3, 5-디브로모-4-하이드록시벤질)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [5-(3, 5-Dibromo-4-hydroxybenzyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Dq) 5-(4-플루오로벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Fluorobenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Dt) 5-(3-(벤질옥시)벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-(Benzyloxy)benzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Du) 5-(4-((4-플루오로벤질)옥시)벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Dx) 5-(벤조[d][1,3]디옥솔-5-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Dy) 5-((2-하이드록시나프탈렌-1-일)메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-((2-Hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; 및
(화합물 DA) 5-(나프탈렌-2-일메틸)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione].The method according to claim 6, wherein the compound is characterized in that selected from the group consisting of compound Aa to compound BA, biofilm formation or virulence (virulence) inhibiting composition of pathogenic microorganisms:
(Compound Aa) 5-(4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(4-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6 (1H,5H)-dione];
(Compound Ab) 5-(3,4-dihydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3,4-Dihydroxybenzylidene)-2- thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(Compound Ac) 5-(2,4-dihydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione [5-(2,4-Dihydroxybenzylidene)-2- thioxodihydropyrimidine-4,6(1H, 5H)-dione];
(Compound Ad) 5-(4-hydroxy-3-methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(4-Hydroxy-3-methoxybenzylidene )-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione];
(Compound Ae) 5-(3-ethoxy-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3-Ethoxy-4-hydroxybenzylidene )-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(Compound Af) 5-(3-hydroxy-4-methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione[5-(3-Hydroxy-4-methoxybenzylidene )-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(Compound Ag) 5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(4-Methoxybenzylidene)-2-thioxodihydropyrimidine-4,6 (1H, 5H)-dione];
(Compound Ah) 5-(3,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine -4, 6(1H, 5H)-dione];
(Compound Ai) 5-(2,4-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(2,4-Dimethoxybenzylidene)-2-thioxodihydropyrimidine -4, 6(1H, 5H)-dione];
(Compound Aj) 2-thioxo-5-(3,4,5-trimethoxybenzylidene)dihydropyrimidine-4,6(1H,5H)-dione [2-Thioxo-5-(3,4 , 5-trimethoxybenzylidene)dihydropyrimidine-4,6(1H,5H)-dione];
(Compound Ak) 5-(4-hydroxy-3,5-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione[5-(4-Hydroxy-3 , 5-dimethoxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(Compound Am) 5-(3-Bromo-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3-Bromo-4-hydroxybenzylidene )-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(Compound An) 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4, 6(1H, 5H)-dione];
(Compound Ao) 5-(2-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione [5-(2-Hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6 (1H, 5H)-dione];
(Compound Ap) 5-(4-hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy- 3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Aq) 5-(4-fluorobenzylidene)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione [5-(4-Fluorobenzylidene)-2-thioxodihydropyrimidine-4 ,6( 1H , 5H )-dione];
(Compound Ar) 5-(2-nitrobenzylidene)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione [5-(2-Nitrobenzylidene)-2-thioxodihydropyrimidine-4 ,6( 1H , 5H )-dione];
(Compound As) 5-(4-(benzyloxy)benzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(Benzyloxy)benzylidene)- 2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Av) 5-(4-(4-chlorobenzyloxy)benzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(4-) Chlorobenzyloxy)benzylidene)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Aw) 5-(3-phenoxybenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Phenoxybenzylidene)-2-thioxodihydropyrimidine-4 ,6( 1H , 5H )-dione];
(Compound Ax) 5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione [5-( Benzo[ d ][1,3]dioxol-5-ylmethylene)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Az) 5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine -4,6( 1H , 5H )-dione];
(Compound AB) 5-(4-hydroxy-3,5-diisopropylbenzylidene)-2-thioxohydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy -3,5-diisopropylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Ba) 5- (4-hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (4-Hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H)-trione];
(Compound Bb) 5-(3,4-dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(3,4-Dihydroxybenzylidene)pyrimidine-2,4 , 6(1H, 3H, 5H)-trione];
(Compound Bc) 5-(2,4-dihydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(2,4-Dihydroxybenzylidene)pyrimidine-2,4 ,6(1H,3H,5H)-trione];
(Compound Bd) 5-(4-hydroxy-3-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione [5-(4-Hydroxy-3-methoxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];
(Compound Be) 5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione [5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];
(Compound Bf) 5-(3-hydroxy-4-methoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione [5-(3-Hydroxy-4-methoxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];
(Compound Bg) 5-(4-Methoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(4-Methoxybenzylidene)pyrimidine-2,4,6(1H, 3H, 5H)-trione];
(Compound Bh) 5-(3,4-dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(3,4-Dimethoxybenzylidene)pyrimidine-2,4, 6(1H, 3H, 5H)-trione];
(Compound Bi) 5- (2, 4-dimethoxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (2, 4-Dimethoxybenzylidene) pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(Compound Bj) 5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(3,4,5-Trimethoxybenzylidene)pyrimidine -2, 4, 6 (1H, 3H, 5H) -trione];
(Compound Bk) 5-(4-hydroxy-3,5-dimethoxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(4-Hydroxy-3,5 -dimethoxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H)-trione];
(Compound Bl) 5- (3, 5-dibromo-4-hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (3, 5-Dibromo- 4-hydroxybenzylidene) pyrimidine-2, 4, 6 (1H, 3H, 5H)-trione];
(Compound Bq) 5-(4-fluorobenzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Fluorobenzylidene)pyrimidine-2,4,6 ( 1H , 3H , 5H )-trione];
(Compound Bs) 5-(4-(benzyloxy)benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-(Benzyloxy)benzylidene)pyrimidine- 2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Bt) 5-(3-(benzyloxy)benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3-(Benzyloxy)benzylidene)pyrimidine- 2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Bu) 5-(4-((4-fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-( (4-Fluorobenzyl)oxy)benzylidene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Bx) 5-(benzo[ d ][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione [5-(Benzo [ d ][1,3]dioxol-5-ylmethylene)pyrimidine-2,4,6( 1H , 3H ,5H) -trione ];
(Compound By) 5-((2-hydroxynaphthalen-1-yl)methylene)pyrimidine-2,4,6( 1H , 3H ,5H)-trione[5-((2- Hydroxynaphthalen- 1-yl) methylene) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];
(Compound BA) 5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1H,3H,5H)-trione [5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6( 1H,3H,5H)-trione];
(Compound Ca) 5-(4-hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione [5-(4-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cb) 5-(3,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];
(Compound Cc) 5-(2,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];
(Compound Cd) 5-(4-hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy-3- methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione];
(Compound Ce) 5-(3-ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Ethoxy-4- hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione];
(Compound Cf) 5-(3-hydroxy-4-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Hydroxy-4- methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione];
(Compound Cg) 5-(4-methoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Ch) 5-(3,4-dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4-Dimethoxybenzyl)-2- thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];
(Compound Ci) 5-(2,4-dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2,4-Dimethoxybenzyl)-2- thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];
(Compound Cj) 5-(3,4,5-trimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4,5- Trimethoxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H ,5 H )-dione];
(Compound Ck) 5-(4-hydroxy-3,5-dimethoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy- 3, 5-dimethoxybenzyl) -2-thioxodihydropyrimidine-4, 6 (1 H , 5 H ) -dione];
(Compound Cl) 5-(3,5-dibromo-4-hydroxy)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,5- Dibromo-4-hydroxybenzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Cm) 5-(3-bromo-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Bromo-4- hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6(1 H , 5 H )-dione];
(Compound Cn) 5-(3,5-di- tert -butyl-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3 ,5- Ditert -butyl-4-hydroxybenzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Co) 5-(2-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H , 5 H )-dione [5-(2-Hydroxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cp) 5-(4-hydroxy-3,5-dimethylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy-3 ,5-dimethylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Cq) 5-(4-fluorobenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Fluorobenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cr) 5-(2-nitrobenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(2-Nitrobenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cs) 5-(4-(benzyloxy)benzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(Benzyloxy)benzyl)-2 -thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Cv) 5-(4-((4-chlorobenzyl)oxy)benzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-(( 4-Chlorobenzyl)oxy)benzyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Cw) 5-(3-phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione [5-( Benzo[ d ][1,3]dioxol-5-ylmethyl)-2- thioxodihydropyrimidine -4,6( 1H ,5H)-dione];
(Compound Cz) 5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(Naphthalen-1-ylmethyl)-2-thioxodihydropyrimidine -4,6( 1H , 5H )-dione];
(Compound CB) 5-(4-hydroxy-3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy -3,5-diisopropylbenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Da) 5- (4-hydroxybenzyl) pyrimidine-2, 4, 6 (1H, 3H, 5H) -trione [5- (4-Hydroxybenzyl) pyrimidine-2, 4, 6 (1 H , 3H , 5H )-trione];
(Compound Db) 5-(3,4-dihydroxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4-Dihydroxybenzyl)pyrimidine-2 , 4, 6 (1 H , 3 H , 5 H )-trione];
(Compound Dc) 5- (2, 4-dihydroxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione [5- (2, 4-Dihydroxybenzyl) pyrimidine-2 , 4, 6 (1 H , 3 H , 5 H )-trione];
(Compound Dd) 5-(4-hydroxy-3-methoxybenzyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione [5-(4-Hydroxy-3-methoxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];
(Compound De) 5-(3-ethoxy-4-hydroxybenzyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [5-(3-Ethoxy-4-hydroxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];
(Compound Df) 5-(3-hydroxy-4-methoxybenzyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione [5-(3-Hydroxy-4-methoxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];
(Compound Dg) 5-(4-Methoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzyl)pyrimidine-2,4,6( 1 H , 3 H , 5 H )-trione];
(Compound Dh) 5- (3, 4-dimethoxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione [5- (3, 4-Dimethoxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H )-trione];
(Compound Di) 5-(2,4-dimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(2,4-Dimethoxybenzyl)pyrimidine-2, 4, 6 (1 H , 3 H , 5 H )-trione];
(Compound Dj) 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4,5-Trimethoxybenzyl ) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];
(Compound Dk) 5-(4-hydroxy-3,5-dimethoxybenzyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [5-(4-Hydroxy-3 , 5-dimethoxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];
(Compound Dl) 5-(3,5-dibromo-4-hydroxybenzyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [5-(3,5- Dibromo-4-hydroxybenzyl) pyrimidine-2, 4, 6 (1 H , 3 H , 5 H ) -trione];
(Compound Dq) 5-(4-fluorobenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Fluorobenzyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Dt) 5-(3-(benzyloxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3-(Benzyloxy)benzyl)pyrimidine-2 ,4,6( 1H , 3H , 5H )-trione];
(Compound Du) 5-(4-((4-fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-(( 4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Dx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Benzo [ d ][1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6( 1H , 3H ,5H) -trione ];
(Compound Dy) 5-((2-hydroxynaphthalen-1-yl)methyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione [5-((2- Hydroxynaphthalen- 1-yl)methyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione]; and
(Compound DA) 5-(naphthalen-2-ylmethyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Naphthalen-2-ylmethyl)pyrimidine-2,4 ,6( 1H , 3H ,5H) -trione ].

청구항 5에 있어서, 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소이고; 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 브롬, 플루오르, 메틸, 아이소프로필 (iso-Pr), 털트-부틸 (tert-Bu), 메톡시, 에톡시, 나이트로, 플로오르 또는 염소로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고, 상기 R⁴는 메톡시페닐이며, 상기 R⁵가 수소인 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물.The method according to claim 5, wherein the

is a single bond or a double bond; wherein X is oxygen; The R ¹ to R ³ may be the same or different, respectively, and are selected from hydrogen, hydroxy, bromine, fluorine, methyl, isopropyl (iso-Pr), tert-butyl (tert-Bu), methoxy, ethoxy, nitro , benzyloxy or phenoxy, substituted or unsubstituted with fluorine or chlorine, wherein R ¹ is hydrogen, R ² and R ³ may be connected to each other to form a dioxol or benzene ring, and the R ⁴ is methoxyphenyl, wherein R ⁵ is hydrogen, characterized in that, biofilm formation or virulence of pathogenic microorganisms (virulence) inhibitory composition.

청구항 8에 있어서, 상기 화합물은 화합물 Ea-1 내지 화합물 Fx로 이루어진 군에서 선택되는 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물:
(화합물 Ea-1) (E)-5-(4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ea-2) (Z)-5-(4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Eb-1) (E)-5-(3, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Eb-2) (Z)-5-(3, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ec-1) (E)-5-(2, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(2, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ec-2) (Z)-5-(2, 4-디하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(2, 4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ed-1) (E)-5-(4-하이드록시-3-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ed-2) (Z)-5-(4-하이드록시-3-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ee-1) (E)-5-(3-에톡시-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ee-2) (Z)-5-(3-에톡시-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ef-1) (E)-5-(3-하이드록시-4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ef-2) (Z)-5-(3-하이드록시-4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Eg-1) (E)-5-(4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Eg-2) (Z)-5-(4-메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Eh-1) (E)-5-(3, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Eh-2) (Z)-5-(3, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ei-1) (E)-5-(2, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(2, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ei-2) (Z)-5-(2, 4-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(2, 4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ej-1) (E)-1-(4-메톡시페닐)-5-(3, 4, 5-트리메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-1-(4-Methoxyphenyl)-5-(3, 4, 5-trimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ej-2) (Z)-1-(4-메톡시페닐)-5-(3, 4, 5-트리메톡시벤질리덴)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-1-(4-Methoxyphenyl)-5-(3, 4, 5-trimethoxybenzylidene)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ek-1) (E)-5-(4-하이드록시-3, 5-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(4-Hydroxy-3, 5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ek-2) (Z)-5-(4-하이드록시-3, 5-디메톡시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(4-Hydroxy-3, 5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 El-1) (E)-5-(3, 5-디브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3, 5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 El-2) (Z)-5-(3, 5-디브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3, 5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Em-1) (E)-5-(3-브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(E)-5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Em-2) (Z)-5-(3-브로모-4-하이드록시벤질리덴)-1-(4-메톡시페닐)피리미딘-2, 4, 6(1H, 3H, 5H)-트리온 [(Z)-5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1H, 3H, 5H)-trione];
(화합물 Ep-1) (E)-5-(4-하이드록시-3,5-디메틸벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ep-2) (Z)-5-(4-하이드록시-3,5-디메틸벤질리덴)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ex-1) (E)-5-(벤조[d][1,3]디옥솔-5-일메틸렌)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(E)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ex-2) (Z)-5-(벤조[d][1,3]디옥솔-5-일메틸렌)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [(Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fa) 5-(4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fb) 5-(3,4-디하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fc) 5-(2,4-디하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fd) 5-(4-하이드록시-3-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fe) 5-(3-에톡시;-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ff) 5-(3-하이드록시-4-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fg) 5-(4-메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fh) 5-(3,4-디메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fi) 5-(2,4-디메톡시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fj) 1-(4-메톡시페닐)-5-(3,4,5-트리메톡시벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fk) 5-(4-하이드록시-3,5-디메톡시벤질)-1-(4메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fl) 5-(3,5-디브로모-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,5-Dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fm) 5-(3-브로모-4-하이드록시벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Fp) 5-(4-하이드록시-3,5-디메틸벤질)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; 및
(화합물 Fx) 5-(벤조[d][1,3]디옥솔-5-일메틸)-1-(4-메톡시페닐)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(Benzo[d][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione].The method according to claim 8, wherein the compound is characterized in that selected from the group consisting of compound Ea-1 to compound Fx, biofilm formation or virulence (virulence) inhibiting composition of pathogenic microorganisms:
(Compound Ea-1) ( E )-5-(4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( E )-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];
(Compound Ea-2) ( Z )-5-(4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( Z )-5-(4-Hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];
(Compound Eb-1) ( E )-5-(3,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( E )-5-(3,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Eb-2) ( Z )-5-(3,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( Z )-5-(3,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Ec-1) ( E )-5-(2,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( E )-5-(2,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Ec-2) ( Z )-5-(2,4-dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-trione [( Z )-5-(2,4-Dihydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Ed-1) ( E )-5-(4-hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [ (E ) -5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;
(Compound Ed-2) ( Z )-5-(4-hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H )-trione [( Z )-5-(4-Hydroxy-3-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;
(Compound Ee-1) ( E )-5-(3-ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [(E ) -5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;
(Compound Ee-2) ( Z )-5-(3-ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H )-trione [( Z )-5-(3-Ethoxy-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;
(Compound Ef-1) ( E )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H)-trione [ (E ) -5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione] ;
(Compound Ef-2) ( Z )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H)-trione [( Z )-5-(3-hydroxy-4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H ) -trione ] ;
(Compound Eg-1) ( E )-5-(4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( E )-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];
(Compound Eg-2) ( Z )-5-(4-methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H )-tri one [( Z )-5-(4-Methoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];
(Compound Eh-1) ( E )-5-(3,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)- trione [( E )-5-(3,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione];
(Compound Eh-2) ( Z )-5-(3,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)- trione [( Z )-5-(3,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H ,5H)-trione];
(Compound Ei-1) ( E )-5-(2,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H ) -trione [( E )-5-(2,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];
(Compound Ei-2) ( Z )-5-(2,4-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5 H ) -trione [( Z )-5-(2,4-Dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6(1 H , 3 H , 5 H )-trione];
(Compound Ej-1) ( E )-1-(4-methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1 H , 3 H , 5H) -trione [(E ) -1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6( 1H , 3H , 5H )-trione] ;
(Compound Ej-2) ( Z )-1-(4-methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [( Z )-1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzylidene)pyrimidine-2,4,6( 1H , 3H , 5H ) -trione ] ;
(Compound Ek-1) ( E )-5-(4-hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H ,3 H , 5H )-trione [( E )-5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Ek-2) ( Z )-5-(4-hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H ,3 H , 5H )-trione [( Z )-5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound El-1) ( E )-5-(3,5-dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3 H ,5 H )-trione [( E )-5-(3,5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound El-2) ( Z )-5-(3,5-dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3 H ,5 H )-trione [( Z )-5-(3,5-Dibromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Em-1) ( E )-5-(3-bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H)-trione [ (E ) -5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;
(Compound Em-2) ( Z )-5-(3-bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3 H , 5H )-trione [( Z )-5-(3-Bromo-4-hydroxybenzylidene)-1-(4-methoxyphenyl)pyrimidine-2, 4, 6( 1H , 3H , 5H) -trione ] ;
(Compound Ep-1) ( E )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H )-trione [( E )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(Compound Ep-2) ( Z )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H )-trione [( Z )-5-(4-hydroxy-3,5-dimethylbenzylidene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(Compound Ex-1) ( E )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3H ,5H)-trione [ (E ) -5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Ex-2) ( Z )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H , 3H ,5H) -trione [( Z )-5-(benzo[ d ][1,3]dioxol-5-ylmethylene)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Fa) 5-(4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4- Hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fb) 5-(3,4-dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Fc) 5-(2,4-dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (2,4-Dihydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fd) 5-(4-hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(4-Hydroxy-3-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fe) 5-(3-ethoxy;-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3-Ethoxy-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Ff) 5-(3-hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(3-Hydroxy-4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fg) 5-(4-methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4- Methoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fh) 5-(3,4-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-( 3,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fi) 5-(2,4-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-( 2,4-Dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fj) 1-(4-methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fk) 5-(4-hydroxy-3,5-dimethoxybenzyl)-1-(4methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fl) 5-(3,5-dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )- trione [5-(3,5-Dibromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fm) 5-(3-bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(3-Bromo-4-hydroxybenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Fp) 5-(4-hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxy-3,5-dimethylbenzyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione]; and
(Compound Fx) 5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(Benzo[ d ][1,3]dioxol-5-ylmethyl)-1-(4-methoxyphenyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )- trione].

청구항 5에 있어서, 상기

은 단일결합 또는 이중결합이고; 상기 X는 산소이고; 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 브롬, 플루오르, 메틸, 아이소프로필 (iso-Pr), 털트-부틸 (tert-Bu), 메톡시, 에톡시, 나이트로, 플로오르 또는 염소로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고, 상기 R⁴는 메틸이며, 상기 R⁵가 메틸인 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물.The method according to claim 5, wherein the

is a single bond or a double bond; wherein X is oxygen; The R ¹ to R ³ may be the same or different, respectively, and are selected from hydrogen, hydroxy, bromine, fluorine, methyl, isopropyl (iso-Pr), tert-butyl (tert-Bu), methoxy, ethoxy, nitro , benzyloxy or phenoxy, substituted or unsubstituted with fluorine or chlorine, wherein R ¹ is hydrogen, R ² and R ³ may be connected to each other to form a dioxol or benzene ring, and the R ⁴ is methyl, and the R ⁵ is characterized in that methyl, biofilm formation or virulence (virulence) inhibitory composition of pathogenic microorganisms.

청구항 10에 있어서, 상기 화합물은 화합물 Ga 내지 화합물 Hk로 이루어진 군에서 선택되는 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물:
(화합물 Ga) 5-(4-하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gb) 5-(3,4-디하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gd) 5-(4-하이드록시-3-메톡시벤지리딘)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ge) 5-(3-에톡시-4-하이드록시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gf) 5-(3-하이드록시-4-메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gg) 5-(4-메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Gk) 5-(4-하이드록시-3,5-디메톡시벤지리덴)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Ha) 5-(4-하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hb) 5-(3,4-디하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hd) 5-(4-하이드록시-3-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 He) 5-(3-에톡시-4-하이드록시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hf) 5-(3-하이드록시-4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3-Hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Hg) 5-(4-메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione]; 및
(화합물 Hk) 5-(4-하이드록시y-3,5-디메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione].The method according to claim 10, characterized in that the compound is selected from the group consisting of compound Ga to compound Hk, biofilm formation or virulence (virulence) inhibiting composition of pathogenic microorganisms:
(Compound Ga) 5-(4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxybenzylidene) -1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Gb) 5-(3,4-dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 ,4-Dihydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Gd) 5-(4-hydroxy-3-methoxybenziridine)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (4-Hydroxy-3-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Ge) 5-(3-ethoxy-4-hydroxybenzyridene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3-Ethoxy-4-hydroxybenzylidene)-1,3-dimethylpyrimidine-2,4,6( 1H , 3H , 5H )-trione];
(Compound Gf) 5-(3-hydroxy-4-methoxybenzyridene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (3-Hydroxy-4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Gg) 5-(4-methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzylidene) -1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Gk) 5-(4-hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [ 5-(4-Hydroxy-3,5-dimethoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Ha) 5-(4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Hydroxybenzyl)-1 ,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hb) 5-(3,4-dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4 -Dihydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hd) 5-(4-hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4 -Hydroxy-3-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound He) 5-(3-ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 -Ethoxy-4-hydroxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hf) 5-(3-hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3 -Hydroxy-4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Hg) 5-(4-methoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-Methoxybenzyl)-1 ,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione]; and
(Compound Hk) 5-(4-hydroxyy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5 -(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione].

청구항 5에 있어서, 상기 화합물은 화합물 Ap 내지 화합물 Hk로 이루어진 군에서 선택되는 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물:
(화합물 Ap) 5-(4-하이드록시-3,5-디메틸벤질리덴)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cb) 5-(3,4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cc) 5-(2,4-디하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H, 5H)-디온 [5-(2,4-Dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione];
(화합물 Cd) 5-(4-하이드록시-3-메톡시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Ce) 5-(3-에톡시-4-하이드록시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(3-Ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cg) 5-(4-메톡시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-디온 [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Cw) 5-(3-페녹시벤질)-2-티옥소디하이드로피리미딘-4,6(1H,5H)-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione];
(화합물 Db) 5-(3,4-디하이드록시벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4-Dihydroxybenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Dj) 5-(3,4,5-트리메톡시벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4,6(1H,3H,5H)-trione];
(화합물 Du) 5-(4-((4-플루오로벤질)옥시)벤질)피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-((4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1H,3H,5H)-trione]; 및
(화합물 Hk) 5-(4-하이드록시-3,5-디메톡시벤질)-1,3-디메틸피리미딘-2,4,6(1H,3H,5H)-트리온 [5-(4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione].The method according to claim 5, wherein the compound is characterized in that selected from the group consisting of compound Ap to compound Hk, biofilm formation or virulence (virulence) inhibiting composition of pathogenic microorganisms:
(Compound Ap) 5-(4-hydroxy-3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy- 3,5-dimethylbenzylidene)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Cb) 5-(3,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Cc) 5-(2,4-dihydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H , 5 H )-dione [5-(2,4-Dihydroxybenzyl)-2 -thioxodihydropyrimidine-4,6(1 H , 5 H )-dione];
(Compound Cd) 5-(4-hydroxy-3-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Hydroxy-3- methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Ce) 5-(3-ethoxy-4-hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Ethoxy-4- hydroxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione];
(Compound Cg) 5-(4-methoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(4-Methoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Cw) 5-(3-phenoxybenzyl)-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione [5-(3-Phenoxybenzyl)-2-thioxodihydropyrimidine-4, 6( 1H , 5H )-dione];
(Compound Db) 5-(3,4-dihydroxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4-Dihydroxybenzyl)pyrimidine-2 ,4,6( 1H , 3H , 5H )-trione];
(Compound Dj) 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(3,4,5-Trimethoxybenzyl) ) pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione];
(Compound Du) 5-(4-((4-fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5-(4-(( 4-Fluorobenzyl)oxy)benzyl)pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione]; and
(Compound Hk) 5-(4-hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione [5- (4-Hydroxy-3,5-dimethoxybenzyl)-1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione].

청구항 5에 있어서, 상기 화합물은 병원성 미생물의 세포사멸 없이 생물막 또는 균막 형성을 억제하는 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물.The method according to claim 5, characterized in that the compound inhibits the formation of a biofilm or biofilm without apoptosis of pathogenic microorganisms, biofilm formation or virulence (virulence) inhibitory composition of pathogenic microorganisms.

청구항 5에 있어서, 상기 화합물은 조성물 내에 30 내지 3,500,000 pg/L의 농도로 첨가되는 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물.The method according to claim 5, characterized in that the compound is added at a concentration of 30 to 3,500,000 pg / L in the composition, biofilm formation or virulence (virulence) inhibiting composition of pathogenic microorganisms.

청구항 5에 있어서, 상기 병원성 미생물은 녹농균 (Pseudomonas aeruginosa), 대장균 (Escherichia coli), 살모넬라균 (Salmonella enterica) 및 고초균 (Bacillus subtilis)으로 이루어진 군에서 하나 이상 선택되는 것을 특징으로 하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제용 조성물.The method according to claim 5, wherein the pathogenic microorganism Pseudomonas aeruginosa ( Pseudomonas aeruginosa ), Escherichia coli ( Escherichia coli ), Salmonella enterica ( Salmonella enterica ) and Bacillus subtilis ( Bacillus subtilis ) Characterized in that one or more selected from the group consisting of, biofilm formation or virulence (virulence) inhibition composition of pathogenic microorganisms.

하기 화학식 I로 표시되는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 치료용 약학 조성물:
[화학식 I]

상기

은 단일결합 또는 이중결합이고;
상기 X는 산소 또는 황이고;
1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고;
상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며,
상기 R⁵가 수소 또는 (C1~C4)알킬임.A pharmaceutical composition for preventing or treating infectious diseases caused by pathogenic microorganisms, comprising a compound selected from a compound represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof:
[Formula I]

remind

청구항 16에 있어서, 상기 병원성 미생물에 의한 감염성 질환은 피부염, 육아종, 구내염, 질염, 귀두염, 요도염, 장염, 수막염, 심내막염, 패혈증 및 손발톱염으로 이루어진 군으로부터 선택된 것을 특징으로 하는 약학 조성물.The pharmaceutical composition according to claim 16, wherein the infectious disease caused by the pathogenic microorganism is selected from the group consisting of dermatitis, granuloma, stomatitis, vaginitis, balanitis, urethritis, enteritis, meningitis, endocarditis, sepsis and nailitis.

청구항 16에 있어서, 상기 화합물은 병원성 미생물의 세포사멸 없이 생물막 또는 균막 형성을 억제하는 것을 특징으로 하는 약학 조성물.The pharmaceutical composition according to claim 16, wherein the compound inhibits biofilm or biofilm formation without apoptosis of pathogenic microorganisms.

하기 화학식 I로 표시되는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 개선용 건강기능식품 조성물:
[화학식 I]

상기

은 단일결합 또는 이중결합이고;
상기 X는 산소 또는 황이고;
1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고;
상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며,
상기 R⁵가 수소 또는 (C1~C4)알킬임.A health functional food composition for preventing or improving infectious diseases caused by pathogenic microorganisms, comprising a compound selected from a compound represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof:
[Formula I]

remind

하기 화학식 I로 표시되는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물에 의한 감염성 질환 예방 또는 개선용 화장료 조성물:
[화학식 I]

상기

은 단일결합 또는 이중결합이고;
상기 X는 산소 또는 황이고;
1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고;
상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며,
상기 R⁵가 수소 또는 (C1~C4)알킬임.A cosmetic composition for preventing or improving infectious diseases caused by pathogenic microorganisms, comprising a compound selected from a compound represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof:
[Formula I]

remind

하기 화학식 I로 표시되는 화합물, 이의 입체이성질체, 이의 라세미체 또는 이의 약학적으로 허용가능한 염에서 선택된 화합물을 포함하는, 병원성 미생물의 생물막 형성 또는 병독성 (virulence) 억제방법:
[화학식 I]

상기

은 단일결합 또는 이중결합이고;
상기 X는 산소 또는 황이고;
1) 상기 R¹ 내지 R³은 각각 동일하거나 다를 수 있고, 수소, 하이드록시, 할로겐, (C1~C4)알킬, (C1~C4)알콕시, 나이트로, 할로겐으로 치환되거나 치환되지 않은 벤질옥시 또는 페녹시이거나, 2) 상기 R¹은 수소이고, R²와 R³가 서로 연결되어 디옥솔 (dioxol) 또는 벤젠고리를 형성할 수 있고;
상기 R⁴는 수소, (C1~C4)알킬 또는 (C1~C4)알콕시페닐이며,
상기 R⁵가 수소 또는 (C1~C4)알킬임.A method for inhibiting biofilm formation or virulence of pathogenic microorganisms, comprising a compound selected from a compound represented by Formula I, a stereoisomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof:
[Formula I]

remind