KR101518980B1 - Anticancer agents containing selenophene-fused aromatic compounds - Google Patents

Abstract

To an anticancer agent comprising a selenophene-fused aromatic compound.

Description

ANTICANCER AGENTS CONTAINING SELENOPHENE-FUSED AROMATIC COMPOUNDS <br> <br> <br> Patents - stay tuned to the technology ANTICANCER AGENTS CONTAINING SELENOPHENE-FUSED AROMATIC COMPOUNDS

The present invention relates to an anticancer agent comprising a selenophene-fused aromatic compound.

'Benzoselenophen', which is a kind of a compound containing a selenium (Se) element in an aromatic ring, is a substance having a structure similar to indole, benzothiophene and benzofuran, and the 'selenophene-conjugated aromatic compound' Naphen, pyridoselenophene, thiazoloselenophene, and furanoselenophene. That is, the benzoselenophene is a substance belonging to 'selenophen-conjugated aromatic compound'. The selenophene-conjugated aromatic compound containing benzoselenophene has a high utilization potential in various fields, but according to the conventional art, it is difficult to synthesize a derivative and it is difficult to commercialize it as an intermediate or material of pharmaceuticals.

Many synthetic methods have already been developed for indole or benzothiophene structurally similar to benzoselenophene and have been commercialized as therapeutic agents for various diseases such as anticancer agents, hormone replacement agents, immunomodulation, and obesity diabetes treatment. In the case of benzoselenophene, the anticancer effect is expected to be excellent due to the structural similarity with indole or benzothiophene, and the possibility of being used as a photochemotherapeutic agent for treatment of alveoli or psoriasis is highly evaluated, And has not yet reached the stage of commercialization.

Several methods have been known for the synthesis of derivatives of selenophene-conjugated aromatic compounds, including benzocelenophene, for example, "substituted benzodithiophenes and benzodiselenophenes (Korean Patent Laid-Open No. 10-2009-0033909 ) "And so on. However, when benzoselenophene derivatives are synthesized using methods known in the art, benzoselenophene derivatives can be synthesized by various steps, and in particular, derivatives of benzoselenophenes containing a substituent in the aromatic part of benzoselenophene There is a problem that the kinds of synthesizable derivatives are very limited.

The present invention provides a selenophene-conjugated aromatic compound having various substituents and a method for easily and economically preparing the selenophene-conjugated aromatic compound.

Further, the present invention provides an anticancer composition comprising the selenophene-conjugated aromatic compound.

However, the problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned can be clearly understood by those skilled in the art from the following description.

A first aspect of the present invention provides a selenophene-fused aromatic compound represented by formula (1): &lt; EMI ID =

[Chemical Formula 1]

이고, R¹⁷ 및 R²⁰은 각각 독립적으로 H, 또는 치환될 수 있는 알킬기이고, R²¹은 C, O, N, 또는 S이고, R³는 할로기이고, R⁴ 및 R⁵는 각각 독립적으로 C, O, N, S, 결합(bond) 또는 비결합이고, R⁶는 H, -NO₂, -NHCOR, CX₃, -OR, -diOR, 치환될 수 있는 알킬기, 치환될 수 있는 알콕시기, 치환될 수 있는 알킬렌-디옥시기, 치환될 수 있는 아미노기, 할로기, 또는 하기 화학식 A로써 표시되는 치환기이고, X는 할로기이고, R은 H, 치환될 수 있는 알킬기, 치환될 수 있는 아미노기, 치환될 수 있는 아미노산기, 치환될 수 있는 펩타이드기, 치환될 수 있는 C_{1 -7}의 알콕시기, 또는 치환될 수 있는 탄수화물 또는 탄수화물 유도체의 잔기일 수 있으나, 이에 제한되는 것은 아니다: Wherein R ¹ is H or an alkoxy group which may be substituted, R ² is H, -CONR ¹⁷ R ²⁰ , or

, R ¹⁷ and R ²⁰ are each independently H or an alkyl group which may be substituted, R ²¹ is C, O, N, or S, R ³ is a halo group, R ⁴ and R ⁵ are each independently R ⁶ is H, -NO ₂ , -NHCOR, CX ₃ , -OR, -diOR, an alkyl group which may be substituted, an alkoxy group which may be substituted , An alkylene-dioxy group which may be substituted, an amino group which may be substituted, a halo group, or a substituent group represented by the following formula A, X is a halo group, R is H, an alkyl group which may be substituted, an amino group, can cup date of amino group which may be substituted with a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or which may be substituted with a carbohydrate or carbohydrate derivative which may be substituted, but are not limited to:

(A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

A second aspect of the invention provides a selenophene-conjugated aromatic compound represented by Formula 2:

(2)

Wherein R ⁹ is H or an alkoxy group which may be substituted, R ¹⁰ and R ¹¹ are each independently C, O, N, S, bond or non-bond, R ¹² is H, -NO _{2, -NHCOR, CX 3, -OR} , -diOR, alkyl group which may be substituted, be an alkoxy group, may be substituted, which may be substituted with alkylene-dioxolanyl group, an optionally substituted amino group, a haloalkyl group, or the formula A and the substituents represented as, X is a halo group and, R is H, which may be optionally substituted alkyl group, a substituted amino group, an optionally substituted amino group, which may be substituted with a peptide group, a C _{1 -7} which may be substituted Alkoxy group, or a residue of a carbohydrate or carbohydrate derivative that may be substituted, but is not limited thereto:

(A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

A third aspect of the invention provides a selenophene-conjugated aromatic compound represented by the following Formula 3:

(3)

이고, R¹⁷ 및 R²⁰은 각각 독립적으로 H, 또는 치환될 수 있는 알킬기이고, R²¹은 C, O, N, 또는 S이고, R³는 할로기이고, R⁴ 및 R⁵는 각각 독립적으로 C, O, N, S, 결합(bond) 또는 비결합이고, R¹³은 링커(linker)일 수 있으나, 이에 제한되는 것은 아니다.
Wherein R ¹ is H or an alkoxy group which may be substituted, R ² is H, -CONR ¹⁷ R ²⁰ , or

, R ¹⁷ and R ²⁰ are each independently H or an alkyl group which may be substituted, R ²¹ is C, O, N, or S, R ³ is a halo group, R ⁴ and R ⁵ are each independently C, O, N, S, a bond or a non-bond, and R ¹³ may be a linker, but is not limited thereto.

A fourth aspect of the invention includes an anti-cancer composition comprising a selenophen-conjugated aromatic compound according to any one of the first to third aspects of the present application.

A fifth aspect of the present invention is a compound represented by the following general formula (Ia): (7-methoxy-1,2,9,9a-tetrahydrocyclopropa [c] benz [e] indol- There is provided a process for preparing a selenophene-conjugated aromatic compound represented by the following general formula (1) of the first aspect of the present invention, which comprises reacting a selenium-containing aromatic compound:

[Formula 1a]

[Chemical Formula 1b]

[Chemical Formula 1]

이고, R¹⁷ 및 R²⁰은 각각 독립적으로 H, 또는 치환될 수 있는 알킬기이고, R²¹은 C, O, N, 또는 S이고, R³는 할로기이고, R⁴ 및 R⁵는 각각 독립적으로 C, O, N, S, 결합(bond) 또는 비결합이고, R⁶는 H, -NO₂, -NHCOR, CX₃, -OR, -diOR, 치환될 수 있는 알킬기, 치환될 수 있는 알콕시기, 치환될 수 있는 알킬렌-디옥시기, 치환될 수 있는 아미노기, 할로기, 또는 하기 화학식 A로써 표시되는 치환기이고, X는 할로기이고, R은 H, 치환될 수 있는 알킬기, 치환될 수 있는 아미노기, 치환될 수 있는 아미노산기, 치환될 수 있는 펩타이드기, 치환될 수 있는 C_{1 -7}의 알콕시기, 또는 치환될 수 있는 탄수화물 또는 탄수화물 유도체의 잔기일 수 있으나, 이에 제한되는 것은 아니다: In the above formulas, R ¹ is H or an alkoxy group which may be substituted, R ² is H, -CONR ¹⁷ R ²⁰ , or

, R ¹⁷ and R ²⁰ are each independently H or an alkyl group which may be substituted, R ²¹ is C, O, N, or S, R ³ is a halo group, R ⁴ and R ⁵ are each independently R ⁶ is H, -NO ₂ , -NHCOR, CX ₃ , -OR, -diOR, an alkyl group which may be substituted, an alkoxy group which may be substituted , An alkylene-dioxy group which may be substituted, an amino group which may be substituted, a halo group, or a substituent group represented by the following formula A, X is a halo group, R is H, an alkyl group which may be substituted, an amino group, can cup date of amino group which may be substituted with a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or which may be substituted with a carbohydrate or carbohydrate derivative which may be substituted, but are not limited to:

(A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

A sixth aspect of the invention is a process for the preparation of a selenophene compound represented by the following Formula 2 of the second aspect of the present invention, which comprises reacting an MCBI compound represented by the following formula (2a) and a selenium-containing aromatic compound represented by the following formula A process for producing a conjugated aromatic compound is provided:

(2a)

(2b)

(2)

Wherein R ⁹ is an optionally substituted alkoxy group, R ¹⁰ and R ¹¹ are each independently C, O, N, S, a bond or a non-bond, R ¹² is H, -NO ₂ , as shown dioxolanyl group, an amino group, a haloalkyl group, or the formula A which may be substituted _{- -NHCOR, CX 3, -OR,} -diOR, an alkyl group, an alkylene which may be substituted, which may be substituted, which may be substituted and substituents, X is a halo group and, R is selected from H, optionally substituted alkyl, optionally substituted amino group, an optionally substituted amino group, which may be substituted with a peptide group, an alkoxy group which may be substituted with a C _{1 -7} Or a residue of a carbohydrate or a carbohydrate derivative that may be substituted, but is not limited thereto:

 (A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

By the present invention, selenophene-conjugated aromatic compounds having various substituents can be produced more easily and economically. In addition, since the selenophene-conjugated aromatic compound can be easily and economically manufactured by the present invention, the possibility that the selenophene-conjugated aromatic compound can be commercialized as an anticancer agent can be increased.

Meanwhile, when the selenophene-conjugated aromatic compound is prepared according to the present invention, the kind of the selenophene-conjugated aromatic compound obtained may be diversified by diversifying the kind of the aromatic starting material used as a starting material. At this time, the kinds of MCBIs can be varied or the types of benzoselenophen-2-carboxylic acids having substituents can be diversified. The selenophene-conjugated aromatic compound prepared according to the present invention may have various useful properties depending on its specific formula.

In particular, the selenophene-conjugated aromatic compound prepared according to the present invention can be usefully utilized as an anticancer agent or a precursor thereof. The selenophene-conjugated aromatic compound can exhibit an anti-cancer effect through DNA alkylating. As a result of the cytotoxicity test on various cancer cells, the IC ₅₀ shows an extremely strong anti-cancer effect as nM or pM unit . Also, the types of cancer that can be applied are various, such as breast cancer, central nervous system cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, etc. The selenophene- And the like.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. It should be understood, however, that the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In the drawings, the same reference numbers are used throughout the specification to refer to the same or like parts.

Throughout this specification, when an element is referred to as "including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise.

The terms "about "," substantially ", etc. used to the extent that they are used herein are intended to be taken as a reference to either the numerical value or to the numerical value when the manufacturing and material tolerance inherent in the stated meaning is presented, Accurate or absolute numbers are used to prevent unauthorized exploitation by unauthorized intruders of the mentioned disclosure. Also, throughout the present specification, the phrase " step "or" step "does not mean" step for.

Throughout this specification, when a member is "on " another member, it includes not only when the member is in contact with the other member, but also when there is another member between the two members.

Throughout this specification, the term "combination thereof" included in the expression of the machine form means one or more combinations or combinations selected from the group consisting of the constituents described in the expression of the machine form, And the like.

Throughout this specification, "halo" or "halo group" may be, but is not limited to, F, Cl, Br, or I.

As used throughout this specification, "alkyl" or "alkyl group" may be a linear or branched, saturated or unsaturated, alkyl group of 1 to 10 carbon atoms or 1 to 7 carbon atoms, or 1 to 5 carbon atoms, But are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, or isomers thereof. When substituted, the alkyl group may be substituted with up to four substituents as listed below at any particular point of attachment (at any given carbon atom). (E.g., F, Cl, Br, I), haloalkyl (e.g., CCl ₃ or CF ₃ ), alkyloxycarbonyl (-C (O) R), alkylcarbamoyl (C ₁ -C ₆ alkylthio, arylthio, C ₁ -C ₆ alkylthio, arylthio, arylthio, heteroarylthio, arylthio, heteroarylthio, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, aryloxy, alkylcarbonyloxy, arylcarbonyloxy, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyloxy, C ₂ -C ₆ alkenyl , C ₃ -C ₆ alkynyl, aryl, aminocarbonyl, C ₁ -C ₆ alkylcarbonyl, C ₃ -C ₆ cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, aryloxycarbonyl, C ₁ -C ₆ alkoxycarbonyl, C ₃ -C ₆ cycloalkyloxy-carbonyl, heterocyclyl-oxy-carbonyl, C ₁ -C ₆ optionally substituted by one or more components such as alkylsulfonyl, arylsulfonyl, heterocyclyl group- . On the other hand, when the alkyl group is substituted with an alkyl group, it is used in the same way as the "branched alkyl group &quot;. Preferred alkyl groups contain 1 to 6 carbon atoms. Alkylene as used herein means a bridged alkyl group of the formula (CH ₂ ) n. For example, CH ₂ , -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ -, and the like.

Throughout this specification, the term "aryl" or "aryl group ", alone or as part of another group, refers to a monocyclic or bicyclic aromatic ring such as phenyl, For example, naphthyl, phenanthrenyl, indenyl, tetrahydronaphthyl, indanyl, and the like. For example, the "aryl" or "aryl group" includes one or more rings having 6 or more atoms, up to 5 rings containing up to 22 atoms may be present, Double bonds between suitable heteroatoms can alternately (resonate) exist. The "aryl" or "aryl group" may optionally be substituted with one or more substituents selected from halogen, such as F, Br, Cl or I, alkyl such as methyl, ethyl, propyl, alkoxy such as methoxy or ethoxy, Including but not limited to alkyloxycarbonyl, nitro, alkenyloxy, trifluoromethyl, amino, cycloalkyl, aryl, heteroaryl, cyano, alkyl S (O) m (m = 0,1,2) And may be substituted with one or more groups not limited thereto. For example, the "aryl" or "aryl group" may be phenyl, phenyl substituted as described above, phenyl, naphthyl, or naphthyl substituted as described above, but is not limited thereto.

Throughout this specification, "alkoxy" or "alkoxy group" may include, but is not limited to, an "alkyl group" as defined above and an alkoxy group bonded to an oxygen atom. The alkoxy group is bonded to the main chain, the aryl or the heteroaryl group through an oxygen bridge. The alkoxy group may be linear or branched, but is preferably straight-chain. Examples include methoxy, ethyloxy, propoxy, butyloxy, t-butyloxy, i-propoxy and the like. Preferred alkoxy groups contain 1 to 6 carbon atoms, particularly preferred alkoxy groups contain 1 to 3 carbon atoms.

In the present specification, the term "alkylene-dioxy group" may be an alkylene group positioned between two oxygen atoms, and the "alkylene group" is an alkylene group having 1 to 10 carbon atoms, 1 to 7 or 1 to 5 carbon atoms But are not limited to, for example, methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, octylene, nonylene, decylene, or isomers thereof .

The term "amine group" or "amino group" as used herein alone or as part of another group means -NH ₂ , and the "amine group" or "amino group" may be the same or different Alkyl, aryl, arylalkyl, alkenyl, alkynyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkyl, Alkoxyalkyl, thioalkyl, carbonyl or carboxyl.

Throughout this specification, the term "amino acid group" means an amino acid comprising an alpha -amino acid, a beta -amino acid and a gamma -amino acid, and the amino acid may be an L- or D- It is an isomer. For example, amino acids include glycine, alanine, valine, leucine, isoleucine, methionine, proline, phenylalanine, tryptophan, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartic acid, glutamic acid, lysine, arginine, histidine, - alanine and ornithine. &Lt; / RTI &gt; The term "peptide group" means a group generated by the reaction between many natural and / or non-natural amino acids.

Throughout this specification, the term " carbohydrate "or" carbohydrate derivative "is an organic group derived from or derived from, for example, polyhydroxy aldehyde, polyhydroxyketone, or polyol, Quot; refers to a compound that can be converted to such groups by hydrolysis, oxidation, or reduction. Such groups may include, but are not limited to, sugars, starches, cellulose and gums.

또는

을 포함한다.Throughout this specification, the term "diOR"

or

.

Throughout this specification, the term " substituted "means to include all permissible substituents of organic compounds. Acceptable substituents may include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds, and the permissible substituents may be one or more. The term "substituted" when used in combination with any of the above groups refers to an acyl, amino (including simple amino, mono and dialkylamino, mono and diarylamino and alkylarylamino), acylamino Aryl, arylcarbonyloxy, alkoxycarbonyloxy, alkoxycarbonyl, carboxy, carboxylate, aminocarbonyl, mono and dialkylaminocarbonyl, aryloxy, Lower alkyl, lower alkenyl, cycloalkyl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, Aryl, heteroaryl, lower alkoxy, aryloxy, aryloxycarbonyloxy, benzyloxy, benzyl, sulfinyl, alkylsulfinyl, sulfonyl, sulfate, sulfonate, sulfonamide, phosphate, Ney soil, force Pinero Ito, oxo, guanidine, already but can be to mean a group substituted with a substituent such as a furnace, formyl, without being limited thereto. Any of the above substituents may be further substituted, for example, but not limited to, when they contain, for example, a gig alkyl group, an aryl group, or the like.

A first aspect of the present invention provides a selenophene-fused aromatic compound represented by formula (1): &lt; EMI ID =

[Chemical Formula 1]

이고, R¹⁷ 및 R²⁰은 각각 독립적으로 H, 또는 치환될 수 있는 알킬기이고, R²¹은 C, O, N, 또는 S이고, R³는 할로기이고, R⁴ 및 R⁵는 각각 독립적으로 C, O, N, S, 결합(bond) 또는 비결합이고, R⁶는 H, -NO₂, -NHCOR, CX₃, -OR, -diOR, 치환될 수 있는 알킬기, 치환될 수 있는 알콕시기, 치환될 수 있는 알킬렌-디옥시기, 치환될 수 있는 아미노기, 할로기, 또는 하기 화학식 A로써 표시되는 치환기이고, X는 할로기이고, R은 H, 치환될 수 있는 알킬기, 치환될 수 있는 아미노기, 치환될 수 있는 아미노산기, 치환될 수 있는 펩타이드기, 치환될 수 있는 C_{1 -7}의 알콕시기, 또는 치환될 수 있는 탄수화물 또는 탄수화물 유도체의 잔기일 수 있으나, 이에 제한되는 것은 아니다:Wherein R ¹ is H or an alkoxy group which may be substituted, R ² is H, -CONR ¹⁷ R ²⁰ , or

, R ¹⁷ and R ²⁰ are each independently H or an alkyl group which may be substituted, R ²¹ is C, O, N, or S, R ³ is a halo group, R ⁴ and R ⁵ are each independently R ⁶ is H, -NO ₂ , -NHCOR, CX ₃ , -OR, -diOR, an alkyl group which may be substituted, an alkoxy group which may be substituted , An alkylene-dioxy group which may be substituted, an amino group which may be substituted, a halo group, or a substituent group represented by the following formula A, X is a halo group, R is H, an alkyl group which may be substituted, an amino group, can cup date of amino group which may be substituted with a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or which may be substituted with a carbohydrate or carbohydrate derivative which may be substituted, but are not limited to:

 (A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

A second aspect of the invention provides a selenophene-conjugated aromatic compound represented by Formula 2:

(2)

Wherein R ⁹ is H or an alkoxy group which may be substituted, R ¹⁰ and R ¹¹ are each independently C, O, N, S, bond or non-bond, R ¹² is H, -NO _{2, -NHCOR, CX 3, -OR} , -diOR, alkyl group which may be substituted, be an alkoxy group, may be substituted, which may be substituted with alkylene-dioxolanyl group, an optionally substituted amino group, a haloalkyl group, or the formula A and the substituents represented as, X is a halo group and, R is H, which may be optionally substituted alkyl group, a substituted amino group, an optionally substituted amino group, which may be substituted with a peptide group, a C _{1 -7} which may be substituted Alkoxy group, or a residue of a carbohydrate or carbohydrate derivative that may be substituted, but is not limited thereto:

(A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

A third aspect of the invention provides a selenophene-conjugated aromatic compound represented by the following Formula 3:

(3)

이고, R¹⁷ 및 R²⁰은 각각 독립적으로 H, 또는 치환될 수 있는 알킬기이고, R²¹은 C, O, N, 또는 S이고, R³는 할로기이고, R⁴ 및 R⁵는 각각 독립적으로 C, O, N, S, 결합(bond) 또는 비결합이고, R¹³은 링커(linker)일 수 있으나, 이에 제한되는 것은 아니다.Wherein R ¹ is H or an alkoxy group which may be substituted, R ² is H, -CONR ¹⁷ R ²⁰ , or

, R ¹⁷ and R ²⁰ are each independently H or an alkyl group which may be substituted, R ²¹ is C, O, N, or S, R ³ is a halo group, R ⁴ and R ⁵ are each independently C, O, N, S, a bond or a non-bond, and R ¹³ may be a linker, but is not limited thereto.

According to one embodiment of the invention, the linker as comprising a -NHCO-R ¹⁹ -CONH-, the formula of R ¹⁹ may be a alkyl group of C _{1 -7} which may be substituted, without being limited thereto. For example, the linker _{-NHCO-CH 2 -CONH-, -NHCO-} CH 2 CH 2 -CONH-, -NHCO-CH 2 CH 2 CH 2 -CONH-, -NHCO-CH 2 CH 2 CH 2 CH _{2 -CONH-, -NHCO-CH 2 CH} 2 CH 2 CH 2 CH 2 -CONH-, -NHCO-CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 -CONH-, or -NHCO-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -CONH-, but is not limited thereto.

For example, the selenophene-conjugated aromatic compound represented by Formula 3 according to the third aspect of the present invention can be obtained by reacting two selenophene-conjugated aromatic compounds represented by Formula 1 according to the first aspect of the present invention, Structure, and linking them by the linker. However, the present invention is not limited thereto.

A fourth aspect of the invention includes an anti-cancer composition comprising a selenophen-conjugated aromatic compound according to any one of the first to third aspects of the present application.

The selenophene-conjugated aromatic compound prepared according to the present invention can be usefully utilized as an anticancer agent or a precursor thereof. The selenophene-conjugated aromatic compound can exhibit an anti-cancer effect through DNA alkylating. As a result of the cytotoxicity test on various cancer cells, the IC ₅₀ shows an extremely strong anti-cancer effect as nM or pM unit . This is specifically described in the examples of the present application. Also, the types of cancer that can be applied are various, such as breast cancer, central nervous system cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, etc. The selenophene- And the like.

A fifth aspect of the present invention is a compound represented by the following general formula (Ia): (7-methoxy-1,2,9,9a-tetrahydrocyclopropa [c] benz [e] indol- There is provided a process for preparing a selenophene-conjugated aromatic compound represented by the following general formula (1) of the first aspect of the present invention, which comprises reacting a selenium-containing aromatic compound:

[Formula 1a]

[Chemical Formula 1b]

[Chemical Formula 1]

이고, R¹⁷ 및 R²⁰은 각각 독립적으로 H, 또는 치환될 수 있는 알킬기이고, R²¹은 C, O, N, 또는 S이고, R³는 할로기이고, R⁴ 및 R⁵는 각각 독립적으로 C, O, N, S, 결합(bond) 또는 비결합이고, R⁶는 H, -NO₂, -NHCOR, CX₃, -OR, -diOR, 치환될 수 있는 알킬기, 치환될 수 있는 알콕시기, 치환될 수 있는 알킬렌-디옥시기, 치환될 수 있는 아미노기, 할로기, 또는 하기 화학식 A로써 표시되는 치환기이고, X는 할로기이고, R은 H, 치환될 수 있는 알킬기, 치환될 수 있는 아미노기, 치환될 수 있는 아미노산기, 치환될 수 있는 펩타이드기, 치환될 수 있는 C_{1 -7}의 알콕시기, 또는 치환될 수 있는 탄수화물 또는 탄수화물 유도체의 잔기일 수 있으나, 이에 제한되는 것은 아니다:In the above formulas, R ¹ is H or an alkoxy group which may be substituted, R ² is H, -CONR ¹⁷ R ²⁰ , or

, R ¹⁷ and R ²⁰ are each independently H or an alkyl group which may be substituted, R ²¹ is C, O, N, or S, R ³ is a halo group, R ⁴ and R ⁵ are each independently R ⁶ is H, -NO ₂ , -NHCOR, CX ₃ , -OR, -diOR, an alkyl group which may be substituted, an alkoxy group which may be substituted , An alkylene-dioxy group which may be substituted, an amino group which may be substituted, a halo group, or a substituent group represented by the following formula A, X is a halo group, R is H, an alkyl group which may be substituted, an amino group, can cup date of amino group which may be substituted with a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or which may be substituted with a carbohydrate or carbohydrate derivative which may be substituted, but are not limited to:

 (A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

For example, the selenophene-conjugated aromatic compound represented by Formula 1 in the first aspect of the present invention is a compound wherein the NH moiety of MCBI represented by Formula 1a and the carboxy moiety of the selenium-containing aromatic compound represented by Formula 1b EDCI, and a solvent, but the present invention is not limited thereto. Thus, by easily and economically producing the selenophene-conjugated aromatic compound according to the present invention, commercialization of the selenophene-conjugated aromatic compound can be promoted.

According to one embodiment of the present invention, the MCBI compound represented by Formula 1a may be one prepared from MCBI compound represented by Formula 1c below, but is not limited thereto:

[Chemical Formula 1c]

Wherein R ¹ , R ² , and R ³ are as defined in Formula (1a). The MCBI compound represented by Formula 1c is included in the " Boc-MCBI compound &quot;, and the MCBI compound represented by Formula 1a is included in the "seco-MCBI compound &quot;. For example, the seco-MCBI compound can be prepared by a conventional method using the Boc-MCBI compound as a starting material, but is not limited thereto. For example, the seco-MCBI compound can be easily prepared by reacting the Boc-MCBI compound with HCl and EtOAc, but is not limited thereto.

According to one embodiment of the present invention, the process for preparing the MCBI compound represented by the formula (1a) from the MCBI compound represented by the formula (1c) may be carried out under acidic conditions, but is not limited thereto. For example, the acidic condition may be prepared by treating an organic acid such as HCl, but is not limited thereto.

According to an embodiment of the present invention, the selenium-containing aromatic compound represented by Formula 1b may be prepared from a selenium-containing aromatic compound represented by Formula 1d, but is not limited thereto:

&Lt; RTI ID = 0.0 &

Wherein R ⁴ , R ⁵ , and R ⁶ are as defined in Formula 1b, R ¹⁸ is an optionally substituted alkyl group, an optionally substituted alkoxy group, -NO ₂ , or -NHCO ₂ H But is not limited thereto. For example, the selenium-containing aromatic compound represented by Formula 1b can be easily produced by hydrolyzing the -CO ₂ R ¹⁸ portion of the selenium-containing aromatic compound represented by Formula 1d, It is not. For example, LiOH and THF-H ₂ O-MeOH may be treated to effect the hydrolysis, but not limited thereto.

According to one embodiment of the present invention, the process for preparing the selenium-containing aromatic compound represented by Formula 1b from the selenium-containing aromatic compound represented by Formula 1d may be performed under basic conditions, but is not limited thereto . For example, the basic condition may be prepared by treating a basic substance such as LiOH, but is not limited thereto.

According to one embodiment of the present invention, the reaction between the MCBI compound represented by Formula 1a and the selenium-containing aromatic compound represented by Formula 1b may be performed in the presence of EDCI, but the present invention is not limited thereto.

According to an embodiment of the present invention, the reaction of the MCBI compound represented by Formula 1a and the selenium-containing aromatic compound represented by Formula 1b may be performed after dissolving the MCBI compound in a solvent, But is not limited thereto.

According to one embodiment of the present application, the solvent is selected from the group consisting of dimethylformaldehyde (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), CH ₂ Cl ₂ , CH ₃ CN, CH ₃ NO ₂ , CHCl ₃ , ₂ CH ₂ Cl, alcohols, aromatic solvents, and combinations thereof. However, the present invention is not limited thereto. For example, the alcohols may include methanol, ethanol, propanol, or butanol, and the aromatic solvent may include, but is not limited to, benzene, toluene, or derivatives thereof. The solvent may be selected and used as long as it can dissolve the MCBI compound easily.

A sixth aspect of the invention is a process for the preparation of a selenophene compound represented by the following Formula 2 of the second aspect of the present invention, which comprises reacting an MCBI compound represented by the following formula (2a) and a selenium-containing aromatic compound represented by the following formula A process for producing a conjugated aromatic compound is provided:

(2a)

(2b)

(2)

Wherein R ⁹ is an optionally substituted alkoxy group, R ¹⁰ and R ¹¹ are each independently C, O, N, S, a bond or a non-bond, R ¹² is H, -NO ₂ , as shown dioxolanyl group, an amino group, a haloalkyl group, or the formula A which may be substituted _{- -NHCOR, CX 3, -OR,} -diOR, an alkyl group, an alkylene which may be substituted, which may be substituted, which may be substituted and substituents, X is a halo group and, R is selected from H, optionally substituted alkyl, optionally substituted amino group, an optionally substituted amino group, which may be substituted with a peptide group, an alkoxy group which may be substituted with a C _{1 -7} Or a residue of a carbohydrate or a carbohydrate derivative that may be substituted, but is not limited thereto:

 (A)

In the formula, R ⁷ is O, NH, S, or Se, and, R ⁸ is an alkoxy group, a halo group, -NO _2, or -NHCOR ^15, which may be optionally substituted alkyl, optionally substituted, R ¹⁵ is H , the balance of which may be substituted with alkyl group which may be substituted, an amino group, an optionally substituted amino group, a peptide group, a C _{1 -7} which may be substituted with an alkoxy group, or a carbohydrate or carbohydrate derivative which may be substituted with may be substituted with But is not limited thereto.

For example, the selenophene-conjugated aromatic compound represented by Formula 2 in the second aspect of the present invention is a compound wherein the NH moiety of MCBI represented by Formula 2a and the carboxyl moiety of the selenium-containing aromatic compound represented by Formula 2b EDCI, and a solvent, but the present invention is not limited thereto. Thus, by easily and economically producing the selenophene-conjugated aromatic compound according to the present invention, commercialization of the selenophene-conjugated aromatic compound can be promoted.

According to one embodiment of the present invention, the MCBI compound represented by formula (2a) may include, but is not limited to, those prepared from an MCBI compound represented by formula (2c)

[Chemical Formula 2c]

Wherein R &lt; ⁹ &gt; is as defined in Formula 2a above. The MCBI compound represented by Formula 2c is included in the " Boc-MCBI compound " and the MCBI compound represented by Formula 2a is included in the "seco-MCBI compound &quot;. For example, the seco-MCBI compound can be prepared by a conventional method using the Boc-MCBI compound as a starting material, but is not limited thereto. For example, the seco-MCBI compound can be easily prepared by reacting the Boc-MCBI compound with HCl and EtOAc, but is not limited thereto.

According to an embodiment of the present invention, the process for preparing the MCBI compound represented by Formula 2a above from the MCBI compound represented by Formula 2c may be performed under acidic conditions, but is not limited thereto. For example, the acidic condition may be prepared by treating an organic acid such as HCl, but is not limited thereto.

According to one embodiment of the present invention, the selenium-containing aromatic compound represented by Formula 2b may be prepared from a selenium-containing aromatic compound represented by Formula 2d, but is not limited thereto:

(2d)

Wherein R ¹⁰ , R ¹¹ , and R ¹² are as defined in Formula 2b, R ¹⁸ is an optionally substituted alkyl group, an optionally substituted alkoxy group, -NO ₂ , or -NHCO ₂ H But is not limited thereto. For example, the selenium-containing aromatic compound represented by Formula 2b can be easily produced by hydrolyzing the -CO ₂ R ¹⁸ portion of the selenium-containing aromatic compound represented by Formula 2d, It is not. For example, LiOH and THF-H ₂ O-MeOH may be treated to effect the hydrolysis, but not limited thereto.

According to one embodiment of the present invention, the process for preparing the selenium-containing aromatic compound represented by Formula 2b from the selenium-containing aromatic compound represented by Formula 2d may be performed under basic conditions, but is not limited thereto . For example, the basic condition may be prepared by treating a basic substance such as LiOH, but is not limited thereto.

According to one embodiment of the present invention, the reaction between the MCBI compound represented by Formula 2a and the selenium-containing aromatic compound represented by Formula 2b may be performed in the presence of EDCI, but the present invention is not limited thereto.

According to one embodiment of the present invention, the reaction of the MCBI compound represented by Formula 2a and the selenium-containing aromatic compound represented by Formula 2b may be performed after dissolving the MCBI compound in a solvent, But is not limited thereto.

According to one embodiment of the present application, the solvent is selected from the group consisting of dimethylformaldehyde (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), CH ₂ Cl ₂ , CH ₃ CN, CH ₃ NO ₂ , CHCl ₃ , ₂ CH ₂ Cl, alcohols, aromatic solvents, and combinations thereof. However, the present invention is not limited thereto. For example, the alcohols may include methanol, ethanol, propanol, or butanol, and the aromatic solvent may include, but is not limited to, benzene, toluene, or derivatives thereof. The solvent may be selected and used as long as it can dissolve the MCBI compound easily.

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

[Example]

All of the reagents used in the present embodiment are generally commercially available, and in the absence of specific description, they are used without special purification.

Hereinafter, the method for producing the selenophene-bonded aromatic compound according to the fifth aspect of the present invention is described in detail as an example, but the present invention is not limited thereto.

1. For entries 1 through 26 Selenophene - Preparation of conjugated aromatic compounds:

(+) - Boc-MCBI and (+) - Boc-CBI are described in J. Org. Chem. 1996, 61, 1710), and 30 mg or 50 mg of the starting material was mixed with 3 mL of 4 N HCl-EtOAc, stirred at -40 ° C for 30 minutes, and then stirred for 30 minutes And allowed to stand at room temperature. The reaction solution was then concentrated by blowing with nitrogen gas, The remaining material was dried under reduced pressure for at least 15 minutes.

1.1 equivalents of benzoselenophene-2-carboxylic acid and 3.0 equivalents of EDCI were added to prepare the reaction mixture. The reaction mixture was stirred at 25 &lt; 0 &gt; C for 10 hours. After stirring, 3 mL of water was added to the reaction mixture and extracted with 4 x 5 mL of EtOAc. In this process, the organic layers were combined and dried with Na ₂ SO ₄ and concentrated under reduced pressure.

The resulting selenophene-conjugated aromatics of entries 1 to 26 were purified using purified thin layer chromatography (methanol-methylene chloride eluting solvent) to give 15-55% yield. The structures of the compounds are shown in Table 1 below It was like. In addition, NMR experiments were also performed for each of the above compounds, and the data are listed at the bottom of Table 1:

<Compounds of Comparative Example 1 in Table 1 and Entries 1 to 26 NMR  Data>

[Comparative Example 1] seco-MCBI-TMI:

^{1 H NMR (DMSO- d 6,} 500 MHz) ∂ 11.41 (s, 1H, NH) , 10.35 (s, 1H, OH), 8.02 (d, J = 9.0 Hz, 1H), 7.72 (br s, 1H), 7.10 (d, J = 2.5 Hz, 1H), 7.05 (d, J = 2.0 Hz , 1H), 6.99 (dd, J = 9.2, 2.4 Hz, 1H), 6.96 (s, 1H), 4.71 (t, J = 10 Hz, 1H), 4.46 (d, J = 10 Hz, 1H), 4.15-4.10 (m, 1H), 4.05 (dd, J = 11.0, 3.5 Hz, 1H), 3.94 (s, 3H, OCH 3), 3.91 (s, 3H, OCH 3), _{3.82 (s, 3H, OCH 3} ), 3.80 (s, 3H, OCH 3), 3.78 - 3.80 (m, 1H); LCMS, m / e 497.1 (M &lt; ⁺ & gt ^; + H).

Entry 1. seco-MCBI-Nitro-Selenophene:

^{1 H NMR (DMSO- d 6,} 500 MHz) ∂ 8.03 (dd, J = 9.0, 2.5 Hz, 1H), 8.45 (d, J = , 1H), 8.03 (d, J = 9.5 Hz, 1H), 7.72 (br s, 1H), 7.13 (d, J = 2.0 Hz, 1H), 7.02 (dd, J = 9.5, 2.5 Hz, 1H), 4.72 (m, 1H), 4.47 (d, J = 10 Hz, 1H), 4.22 (m, 1H), 4.04 (dd, J = 11.0, 3.0 Hz, 1H), 3.92 (s, 3H, OCH 3), 3.92 - 3.88 (m, 1 H); LCMS, m / e 517.1 (M &lt; ⁺ & gt ^; + H).

Entry 2. seco-MCBI-Methoxy-Selenophene:

^{1 H NMR (DMSO- d 6,} 500 MHz) ∂ (S, 1H), 8.02 (d, J = 9.0 Hz, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.67 d, J = 2.5 Hz, 1H ), 7.12 (d, J = 2.0 Hz, 1H), 7.08 (dd, J = 9.0, 2.5 Hz, 1H), 7.01 (dd, J = 9.0, 2.0 Hz, 1H), 4.73 (t, J = 9.5 Hz , 1H), 4.48 (m, 1H), 4.18 (m, 1H), 4.04 (dd, J = 14.5, 7.0 Hz, 1H), 3.91 (s, 3H, OCH 3), _{3.82 (s, 3H, OCH 3} ), 3.85 - 3.81 (m, 1H); LCMS, m / e 502.2 (M &lt; ⁺ & gt ^; + H).

Entry 3. seco-MCBI-Acetamino-Selenophene:

^{1 H NMR (DMSO- d 6,} 500 MHz) ∂ (D, J = 4.5 Hz, 1H), 8.01 (d, 4.5 Hz, 1H), 8.07 (s, , 1H), 7.68 (br s , 1H), 7.46 (dd, J = 8.5, 2 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 7.01 (dd, J = 9.0, 2.5 Hz, 1H ), 4.77 (t, J = 9.5 Hz, 1H), 4.45 (d, J = 11.5 Hz, 1H), 4.17 (m, 1H), 4.03 (dd, J = 11.5, 3.5 Hz, 1H), 3.91 (s _{, 3H, OCH 3), 3.89} - 3.80 (dd, J = 11.0, 4.0 Hz, 1H); LCMS m / e 529.2 (M &lt; ⁺ & gt ^; + H).

Entry 4

^{1 H NMR (500.1 MHz, ACETONE} -d 6) ∂ 9.32 (s, 1H), 8.508 (d, 1H, J = 2.0 Hz), 8.22 (s, 1H), 8.025 (d, 1H, J = 8.5 Hz) , 7.98 (d, 1H, J = 9.0 Hz), 7.509 (dd, 1H, J = 2,8.5 Hz), 6.98 (dd, 1H, J = 2.5,9 Hz), 6.765 (s, 1H), 6.68 ( dd, 1H, J = 2.5Hz) , 4.6 (dd, 1H, J = 5.0, 10.0 Hz), 4.44 (d, 1H, J = 10.5 Hz), 3.9 (s, 3H), 3.18 (m, 1H), 2.08 (s, 3H), 1.82 (dd, 2H, J = 4 Hz , 7.5 Hz)

Entry 5

^{1 H NMR (500.1 MHz, CDCl} 3) ∂ 3.43 (t, 1H, J = 11.3), 3.88 (m, 1H), 3.90 (s, 3H), 3.98 (m, 1H), 4.56 (m, 1H), 1H, J = 11.3), 6.85 (d, 1H, J = 2.8), 7.02 (dd, 1H, J = 2.8,9.4), 7.31 (s, IH), 8.07 (s, IH), 8.21 (d, IH, J = 9.4), 8.94 (s, IH); ¹³ C NMR (125.7 MHz, CDCl ₃ )? 42.82, 45.60, 55.35, 56.17, 99.07, 100.93, 106.39, 114.97, 115.60, 118.20, 125.78, 130.77, 131.22, 134.63, 136.11, 138.80, 141.81, 148.50, 149.76, , 164.30.

Entry 6

^{1 H NMR (500.1 MHz, CDCl} 3) ∂ 3.48 (t, 1H, J = 11.3), 3.90 (m, 1H), 3.91 (s, 3H), 3.95 (s, 3H), 4.00 (m, 1H), 4.60 (t, 1H, J = 9.4), 4.69 (d, 1H, J = 10.7), 6.92 (s, 1H), 7.05 (m, 2H), 7.43 (d, 1H, J = 1.6), 7.79 (d , 1H, J = 8.8), 7.82 (m, 1H), 7.97 (s, 1H), 8.17 (d, 1H, J = 10.1)

Entry 7

^{1 H NMR (500.1 MHz, CDCl} 3) ∂ 1.05 (t, 3H, J = 7.6), 1.81 (m, 2H), 2.39 (t, 2H, J = 7.9), 3.36 (m, 1H), 3.79 (m , 1H), 3.86 (m, 1H), 3.91 (s, 3H), 4.18 (m, 1H), 4.38 (d, 1H, J = 7.8), 6.7 (dd, 1H, J = 2.8, 36.5), 7.02 (m, 1H), 7.34 ( d, 1H, J = 8.8), 7.49 (s, 1H) 7.75 (d, 1H, J = 9.1), 7.87 (s, 1H), 8.11 (s, 1H), 8.21 ( d, 1 H, J = 9.4)

Entry 8

^{1 H NMR (500.1 MHz, CDCl} 3) ∂ 0.94 (t, 3H, J = 7.6), 1.40 (m, 4H), 1.79 (m, 2H), 2.41 (t, 2H, J = 8.1), 3.35 (m , 1H), 3.66 (m, 1H), 3.80 (d, 1H, J = 12.6), 3.91 (s, 3H), 4.39 (m, 2H), 6.76 (s, 1H), 7.03 (d, 1H, J = 9.4), 7.34 (d, 1H, J = 8.5), 7.49 (m, 1H) 7.74 (d, 1H, J = 11.9), 7.88 (s, 1H), 8.13 (s, 1H), 8.20 (d, 1H, J = 9.4)

Entry 9

^{1 H NMR (500.1 MHz, CDCl} 3) ∂ 3.46 (t, 1H, J = 11.3), 3.90 (d, 1H, J = 3.1), 3.93 (s, 3H), 3.96 (s, 3H), 3.97 (m , 1H), 3.99 (s, 3H), 4.58 (m, 1H), 4.67 (dd, 1H, J = 1.6, 11.0), 6.89 (d, 1H, J = 2.8), 7.04 (dd, 1H, J = 2.8, 9.4), 7.32 (s , 1H), 7.36 (s, 1H), 7.97 (s, 1H), 7.98 (d, 1H, J = 9.4), 8.20 (d, 1H, J = 9.4)

Entry 10

^{1 H NMR (500.1 MHz, ACETONE} -d 6) ∂ 9.4 (s, 1H), 8.605 (dd, 1H, J = 4.5,1Hz), 8.32 (dd, 1H, J = 1,8 Hz), 8.162 (d , 1H, J = 2Hz), 7.65 (brs, 1H), 7.492 (dd, 1H, J = 4.5, 8.0Hz), 7.187 (d, 1H, J = 2.5 Hz), 7.035 (dd, 1H, J = 2.5 , 9), 4.717 (t, 1H, J = 10.0 Hz), 4.635 (d, 1H, J = 11.0 Hz), 4.18 (m, 1H), 4.048 (dd, 1H, J = 3.5, 11.5Hz), 3.9 (s, 3 H), 3.832 (m, 1 H). ¹³ C NMR (125.7 MHz, ACETONE-d ₆ )? 42.85, 47.39, 55.76, 56.50, 99.50, 102.27,116.01,116.28,116.67,118.73,121.43,125.99,128.31,132.80,135.29,137.25,143.53,149.03,155.34 , 160.19, 162.83, 163.08, 166.26

Entry 11

^{1 H NMR (500.1 MHz, CDCl} 3) ∂ 3.47 (m, 1H), 3.92 (m, 1H), 3.94 (s, 3H), 4.02 (t, 1H, J = 11.0), 4.60 (m, 1H), 4.68 (d, 1H, J = 11.0), 6.88 (d, 1H, J = 2.2), 6.91 (d, 1H, J = 2.8), 7.05 (m, 1H), 7.66 (d, 1H, J = 2.5) , 7.79 (s, 1 H), 7.93 (s, 1 H), 8.15 (d, 1 H, J = 9.1)

Entry 12

¹ H NMR (500.1 MHz, DMSO)? 10.46 (s, 1H, OH), 8.12 (d, 1H, J = 8.5 Hz, C6H), 7.90 (S, 1H, J = 8.5 Hz, C9H), 7.52 (t, 1H, J = 8.0Hz, C8H), 7.36 H), 4.74 (d, 1H, J = 11.2 Hz, C2-H) ), 4.17 (m, 1H, C1-H), 4.01 (d, 1H, J = 10.6 Hz, CHHCl), 3.94 (s, 3H, OCH 3), 3.83 (s, 3H, OCH 3), 3.82 (d , 1H, J = 11.2 Hz, CHHCl), 3.79 (s, 3H, OCH 3)

Entry 13

^{1 H NMR (500.1 MHz, DMSO} ) ∂ 10.4 (s, 1H), 10.0 (s, 1H), 8.48 (s, 1H), 8.3 (s, 1H), 8.15 (d, 1H, J = 8.5 Hz), 8.05 (d, 1H, J = 8.5 Hz), 7.88 (d, 1H, J = 8 Hz), 7.86 (brs, 1H), 7.56 (t, 1H, J = 8 Hz), 7.5 (dd, 1H, J = 8.5,2 Hz), 7.4 (t , 1H, J = 8.0 Hz), 7.4 (t, 1H, J = 8.0 Hz), 4.8 (t, 1H, J = 9.5 Hz), 4.45 (dd, 1H, J 1H), 4.0 (dd, 1H, 3.0, J = 11.0 Hz ), 3.89 (m, 1H), 2.3 (td, 2H, J = 7.5 , 1.5 Hz ), 1.6 (qr, 2H, J = 7.5 Hz), 0.9 (t, 1H, J = 3.0,11.0 Hz), ¹³ C NMR (125.7 MHz, Acetone)? 13.96,14.11,19.72,24.41,42.75,47.91,54.67,101.58 , 115.48, 117.07, 118.01, 120.03, 123.35, 123.62, 123.76, 124.34, 128.21, 128.40, 143.0, 130.92, 137.44, 143.66, 155.22, 163.58, 169.85, 172.13

Entry 14

^{1 H NMR (500.1 MHz, ACETONE} -d 6) ∂ 9.26 (s, 1H), 8.537 (d, 1H, J = 8.5Hz), 8.23 (s, 1H), 8.1 (d, 1H, J = 1.0 Hz) , 7.98 (d, 1H, J = 8.5 Hz), 7.55 (m, 2H), 7.4 (m, 1H), 7.2 (d, 1H, J = 8 Hz), 6.834 (s, 1H), 4.621 (dd, 1H, J = 10.5, 5 Hz ), 4.46 (d, 1H, J = 10. 5Hz), 3.17 (m, 1H), 2.366 (t, 1H, J = 7.5 Hz), 1.81 (t, 2H, J = 2 Hz), 1.69 (m, 2H), 0.96 (t, 3H, J = 7.5 Hz) 13 C NMR (125.7 MHz, Acetone) ∂ 14.14, 19.75, 25.32, 33.60, 39.78, 55.72, 112.31, 117.57, 118.22, 120.52, 123.00, 123.22, 126.71, 126.95, 127.04, 127.30, 132.56, 132.93, 133.79, 138.55, 141.74, 143.13, 143.45, 161.44, 165.22, 172.15, 185.56

Entry 15

^{1 H NMR (500.1 MHz, Acetone} ) ∂ 10.4 (s, 1H), 8.2 (s, 1H), 8.1 (d, 1H, J = 8.0 Hz), 8.0 (d, 1H, J = 8.5 Hz), 7.8 ( d, 1H, J = 8.5 Hz ), 7.58 (s, 1H), 7.56 (t, 1H, J = 8.5 Hz), 7.4 (t, 1H, J = 8 Hz), 7.1 (d, 1H, J = 9.0 Hz), 4.8 (t, 1H , J = 10.0 Hz), 4.45 (d, 1H, J = 11.0 Hz), 4.2 (m, 1H), 4.01 (qr, 1H, J = 7 Hz), 3.89 (m, 1H), 3.80 (s, 3H). ¹³ C NMR (125.7 MHz, Acetone)? 43.14, 47.72, 55.96, 56.77, 101.64, 110.34, 117.54, 123.67, 123.75, 124.38, 124.40, 127.26, 128.49, 130.74, 131.43, 143.29, 144.36, 155.24, 159.34, 163.57

Entry 16

^{1 H NMR (500.1 MHz, Acetone} ) ∂ 9.4 (s, 1H), 8.25 (d, 1H, J = 8.5 Hz), 8.2 (s, 1H), 7.9 (m, 4H), 7.68 (s, 1H), 7.54 (td, 1H, J = 6.5, 1 Hz), 7.4 (td 1H, J = 10, 1 Hz), 7.01 (dd, 1H, J = 2, 8.5 Hz), 4.8 (t, 1H, J = 10.0 Hz), 4.7 (dd, 1H , J = 1.5, 10.5 Hz), 4.2 (m, 1H), 4.01 (dd, 1H, J = 3.5, 11.5 Hz), 3.90 (s, 3H), 3.80 (m, 1H ). ¹³ C NMR (125.7 MHz, Acetone)? 43.21, 47.73, 56.13, 56.17, 101.69, 109.18, 115.93, 116.92, 123.64, 124.30, 124.38, 128.45, 129.05, 130.77, 137.13, 137.39, 143.46, 145.4, 155.19, 160.16, 163.49

Entry 17

^{1 H NMR (500.1 MHz, Acetone} ) ∂ 9.5 (s, 1H), 8.25 (d, 1H, J = 5Hz), 8.23 (s, 1H), 7.9 (s, 1H), 7.9 (d, 1H, J = 8.5 Hz), 7.6 (d, 1H, J = 7.5 Hz), 7.5 (t, 1H, J = 8.0 Hz), 7.43 (t, 1H, J = 8.0 Hz) 7.4 (t, 1H, J = 7.0 Hz) , 4.8 (t, 1H, J = 10.5 Hz), 4.68 (dd, 1H, J = 1.5, 10.5 Hz), 4.25 (m, 1H) 4.01 (dd, 1H, J = 3.5, 11.5Hz), 4.01 (s , 3H), 3.82 (dd, 1H, J = 8.5,11 Hz). ¹³ C NMR (125.7 MHz, Acetone) δ 43.14, 47.74, 56.47, 56.79, 107.13, 117.13, 120.72, 123.69, 124.41, 127.89, 128.50, 131.05, 131.44, 131.89, 143.28, 144.67, 155.25, 157.31, 163.55

Entry 18

^{1 H NMR (500.1 MHz, Acetone} ) ∂ 9.25 (s, 1H), 8.3 (d, 1H, J = 8.5Hz), 8.2 (s, 1H), 7.9 (s, 1H), 7.8 (d, 1H, J = 8.5 Hz), 7.68 (s , 1H), 7.55 (m, 1H), 7.52 (s, 1H) 7.4 (m, 1H), 4.8 (t, 1H, J = 11.0 Hz), 4.7 (dd, 1H, J = 2,11.0 Hz), 4.3 ( m, 1H) 4.05 (dd, 1H, J = 3.5, 11.5Hz), 3.94 (s, 3H), 3.89 (s, 3H), 3.8 (dd, 1H, J = 9, 11.5 Hz). ¹³ C NMR (125.7 MHz, Acetone) 41.71, 46.17, 54.77, 54.88, 54.93, 100.18, 101.99, 106.74, 108.12, 115.32, 122.08, 122.73, 122.84, 126.9, 129.46, 135.08, 141.98, 148.55, 149.86, 153.65, 162.01

Entry 19

^{1 H NMR (500.1 MHz, ACETONE} -d 6) ∂ 8.17 (s, 1H), 8.099 (dd, 1H, J = 7.5,1Hz), 7.64 (s, 1H), 7.60 (m, 1H), 7.489 (s , 1H), 7.422 (m, 1H), 7.18 (d, 1H, 7.5Hz), 6.78 (s, 1H), 4.58 (dd, 1H, J = 10.5, 5 Hz), 4.42 (d, 1H, J = 1H), 1.802 (m, 2H), 3.92 (s, 3H)

Entry 20

^{1 H NMR (500.1 MHz, Acetone} ) ∂ 9.3 (s, 1H), 8.5 (s, 1H), 8.22 (d, 1H, J = 8.5 Hz), 8.2 (s, 1H), 7.98 (d, 1H, J = 9 Hz), 7.9 (d , 1H, J = 8.5 Hz), 7.58 (m, 2H), 7.4 (t, 1H, J = 8.0 Hz), 4.8 (t, 1H, J = 11.0 Hz), 4.7 ( dd, 1H, J = 2, 11.0 Hz), 4.24 (m, 1H) 4.05 (dd, 1H, J = 3.5, 11.5 Hz), 3.85 (dd, 3H,, J = 9, 11.5 Hz), 2.1 (s , 3H). ¹³ C NMR (125.7 MHz, Acetone) 24.11, 43.53, 48.13, 57.17, 102.99, 117.18, 118.39, 120.64, 123.30, 124.38, 126.45, 128.45, 131.05, 132.77, 137.13, 138.39, 143.46, 144.4, 155.29, 164.16, 168.49

Entry 21

^{1 H NMR (505.1 MHz, ACETONE} -d 6) ∂ 9.32 (d, 1H, J = 7), 8.51 (s, 1H), 8.24 (s, 1H), 8.09 (d, 1H, J = 8.0), 7.98 (d, 1H, 8.5 Hz) , 7.581 (t, 1H, J = 7.5 Hz), 7.51 (d, 1H, J = 8.5 Hz), 7.428 (t, 1H, 7.5Hz), 7.198 (d, 1H, J = 8Hz), 6.82 (s, 1H), 4.63 (dd, 1H, J = 5.5, 10.5 Hz), 4.47 (d, 1H, J = 10.5 Hz), 3.175 (d, 1H, J = 5.5 Hz), 2.109 (s, 3H), 1.8 (d, 2H, J = 5.5 Hz)

Entry 22

^{1 H NMR (500.1 MHz, Acetone} ) ∂ 9.8 (bs, 1H), 9.3 (s, 1H), 8.5 (s, 1H), 8.2 (d, 2H, J = 9.5 Hz), 8.0 (d, 1H, J = 8.5 Hz), 7.9 (s , 1H), 7.85 (d, 2H, J = 8.5 Hz), 7.7 (dd, 1H, J = 2,8.5 Hz), 7.4 (t, 1H, J = 8 Hz), 4.8 (t, 1H, J = 11.0 Hz), 4.7 (dd, 1H, J = 2, 11.0 Hz), 4.24 (m, 1H) 4.05 (dd, 1H, J = 3.5, 11.5 Hz), 3.85 (m, 1H), 3.25 (s, 2H), 2.5 (s, 6H).

Entry 23

¹ H NMR (500.1 MHz, Acetone)? 9.3 (s, 1H), 8.32 (s, J = 8.5 Hz), 8.18 ( s, 1H), 8.10 (s, 1H), 7.9 (dd, 3H, J = 4, 9 Hz), 7.53 (t, 1H, J = 7 Hz), 7.52 (m, 1H), 5.85 (bs, 1H ), 4.8 (t, 1H, J = 11.0 Hz), 4.68 (dd, 1H, J = 2, 11.0 Hz), 4.24 (m, 1H), 4.05 (dd, 1H, J = 3.5, 11.5 Hz), 3.8 (dd, 1H, J = 8.5, 11.5 Hz), 3.25 (q, 2H, J = 7 Hz), 1.5 (m, 2H), 1.38 , 3H, J = 7.5 Hz)

Entry 24

^{1 H NMR (500.1 MHz, Acetone} ) ∂ 9.3 (s, 1H), 8.92 (s, 1H), 8.86 (s, 1H), 8.37 (s, 1H), 8.25 (d, 1H, J = 8.5Hz), 8.20 (s, 1H), 7.94 (d, 1H, J = 8.5Hz), 7.88 (d, 1H, J = 8.5Hz), 7.618 (dd, 3H, J = 5, 9 Hz), 7.542 (m, 2H ), 7.4 (t, 1H, J = 7 Hz), 7.043 (t, 1H, 9Hz) 4.8 (t, 1H, J = 11.0 Hz), 4.67 (d, 1H, J = 11.5 Hz), 4.24 (t, 1H, J = 8.5 Hz), 4.05 (dd, 1H, J = 3, 11 Hz), 3.848 (dd, 1H, J = 8.5, 11 Hz).

Entry 25

^{1 H NMR (500.1 MHz, ACETONE} -d 6) ∂ 9.25 (s, 1H), 8.527 (s, 1H), 8.25 (d, 1H, J = 8.5 Hz), 8.21 (s, 1H), 7.97 (d, 1H, J = 9 Hz), 7.88 (d, 1H, J = 8.5Hz), 7.54 (t, 2H, J = 8 Hz), 7.40 (t, 1H, J = 8 Hz), 4.8 (t, 1H, J = 11.0Hz), 4.67 (d , 1H, J = 11.0 Hz), 4.23 (m, 1H), 4.04 (dd, 1H, J = 3, 11 Hz), 3.82 (dd, 1H, J = 8.5, 11 Hz), (t, 2H, J = 7.5 Hz), 1.7 (t, 2H, J = 7.0 Hz), 1.4 (m, 4H), 0.9 (m, 3H)

Entry 26

^{1 H NMR (500.1 MHz, ACETONE} -d 6) ∂ 9.6 (s, 1H), 8.44 (s, 1H), 8.238 (d, 1H, J = 8.5 Hz), 8.19 (s, 1H), 7.97 (d, 1H, J = 8.5Hz), 7.87 (d, 1H, J = 8.5Hz), 7.597 (d, 1H, J = 1.5 Hz), 7.53 (d, 1H, J = 7 Hz), 7.4 (d, 1H, J = 7.5 Hz), 7.2 ( s, 1H), 4.87 (t, 1H, J = 11.0Hz), 4.65 (d, 1H, J = 11.0 Hz), 4.523 (dd, 1H, J = 8, 13 Hz) , 4.21 (t, 1H, J = 8.5 Hz), 4.03 (dd, 1H, J = 3.5, 11 Hz), 3.8 (m, 1H), 3.76 (t, 1H, J = 6.5 Hz), 3.183 (m, 2H), 2.08 (s, 3H), 1.99 (s, 3H), 1.51 - 1.44 (m, 6 H)

2. The effect of the synthesized compounds on the growth of cancer cells

On the other hand, in this example, the proliferation inhibitory effect of SK-OV-3 cancer cells on the compounds of Comparative Example 1 and some of the compounds of Entry 1 to 26 was confirmed, and the results are shown in Table 2.

Experimental method of inhibiting proliferation

The 10% FBS and 1% P / S in which the addition of the SK-OV-3 cells suspended in McCoy's 5A Medium was inoculated in a 96-well plate by 3 × 10 ^4/100 ㎕ per well. After incubation at 37 ° C for 4 hours, the compounds were treated with 100 μl to a final concentration of 10 nM and cultured at 37 ° C for 72 hours. In the control group, DMSO, which is a solvent of the compound, was treated to a final concentration of 0.1%. WST-1 assay reagent (iTSBio, Korea) was treated with 10 μl of each well, incubated at 37 ° C for 2 hours, and then absorbance was measured at 450 nm with an automatic microplate reader. The degree of cell growth inhibition was calculated as {(A450 _control- A450 _compound ) / A450 _{control group} } * 100 '.

It will be understood by those of ordinary skill in the art that the foregoing description of the embodiments is for illustrative purposes and that those skilled in the art can easily modify the invention without departing from the spirit or essential characteristics thereof. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be interpreted as being included in the scope of the present invention .

Claims (16)

(7-methoxy-1,2,9,9a-tetrahydrocyclopropa [c] benz [e] indol-4-one) compound represented by the following formula (1a) and a selenium-containing aromatic compound represented by the following formula &Lt; / RTI &gt;
A process for producing a selenophene-bonded aromatic compound represented by the following formula 1:
[Formula 1a]

[Chemical Formula 1b]

[Chemical Formula 1]

Among the above equations,
R ¹ is H or a C _1-7 alkoxy group which may be substituted,
R ² is H, -CONR ¹⁷ R ²⁰ , or

ego,
R ¹⁷ and R ²⁰ are each independently H or a C _1-7 alkyl group which may be substituted,
R &lt; ²¹ &gt; is C, O, N, or S,
R ³ is a halo group,
R ⁴ and R ⁵ are each independently C, O, N, S, a bond or a non-
R ⁶ is _{H, -NO 2, -NHCOR, CX} 3, -OR, -diOR, C 1-7 alkoxy, C _1-7 which may be substituted, which may be optionally substituted C _1-7 alkyl group, a substituted An alkylene-dioxy group, an amino group which may be substituted, a halo group, or a substituent group represented by the following formula (A)
X is a halo group,
R is H, a C _1-7 alkyl group which may be substituted, an amino group which may be substituted or a C _1-7 alkoxy group which may be substituted;
(A)

Wherein,
R &lt; ⁷ &gt; is O, NH, S, or Se,
R ⁸ is a C _1-7 alkyl group which may be substituted, a C _1-7 alkoxy group which may be substituted, a halo group, -NO ₂ or -NHCOR ¹⁵ ,
R ¹⁵ is H, a C _1-7 alkyl group which may be substituted, an amino group which may be substituted or a C _1-7 alkoxy group which may be substituted,
When these groups are substituted, at one or more positions, C _1-7 acyl, amino, C _1-7 acylamino, C _1-7 alkylcarbonyloxy, C _6-10 aryl, C _6-10 arylcarbonyloxy, C _1-7 alkoxycarbonyl, C _1-7 alkoxycarbonyl, carboxy, carboxylate, aminocarbonyl, C _1-7 monoalkylaminocarbonyl, C _1-7 dialkylaminocarbonyl, cyano, azido, halogen, hydroxyl, nitro, trifluoromethyl, thio, C _1-7 alkylthio, C _6-10 arylthio, C _1-7 alkylthio-carbonyl, thio-carboxylate, C _1-7 lower alkyl, C _2-7 lower alkenyl, C _2-7 lower alkynyl, C _3-6 cycloalkyl, C _3-6 heterocycloalkyl, C _6-10 heteroaryl, C _1-7 lower alkoxy, C _{6- 10} aryloxy, C _6-10 aryloxy carbonyloxy, benzyloxy, benzyl, sulfinyl, C _1-7 alkyl sulfinyl, sulfonyl, sulfate, sulfonate, sulfonamide, phosphate, phosphonato, phosphinato Pinero Ito, oxo, No Dean, will have already been replaced by a formyl or no wheat substituent.
The method according to claim 1,
The method for producing a selenophene-bonded aromatic compound represented by Formula 1, wherein the MCBI compound represented by Formula 1a is prepared from an MCBI compound represented by Formula 1c:
[Chemical Formula 1c]

Wherein,
R ¹ , R ² , and R ³ are as defined in Formula (1a).
3. The method of claim 2,
The process for producing a selenophene-bonded aromatic compound represented by Chemical Formula (1), wherein the process for preparing the MCBI compound represented by Formula (1a) from the MCBI compound represented by Formula (1c) is carried out under acidic conditions.
The method according to claim 1,
The selenophene-containing aromatic compound represented by Formula 1b is prepared from a selenium-containing aromatic compound represented by Formula 1d, wherein the selenophene-
&Lt; RTI ID = 0.0 &

Wherein,
R ⁴ , R ⁵ , and R ⁶ are as defined in Formula 1b above,
R ¹⁸ is C _{1 -7} alkyl group, C _{1 -7} alkoxy, -NO _2, or -NHCO ₂ H, which may be substituted, which may be substituted,
If the above groups are substituted, in one or more positions with one or more C _{1 -7} acyl, amino, C _{1 -7} acyl amino, C _{1 -7} alkylcarbonyloxy, C _{6 -10} aryl, C _{6 -10} aryl-carbonyl-oxy, C _{1 -7} alkoxycarbonyloxy, C _{1 -7} alkoxycarbonyl, carboxy, carboxylate, aminocarbonyl, C _{1 -7} monoalkyl amino carbonyl, C _{1 -7} dialkyl-aminocarbonyl, cyano, azido, halogen, hydroxyl, nitro, trifluoromethyl, alkylthio, C _{1 -7} alkylthio, C _{6 -10} aryl thio, C _{1 -7} alkylthio-carbonyl, thio-carboxylate, C _{1 -7} lower alkyl, C _{2 -7-lower} alkenyl, C _{2 -7-lower} alkynyl, C _{3 -6} cycloalkyl, C _{3 -6} heterocycloalkyl, C _{6 -10} heteroaryl, C _{1 -7} lower alkoxy, C _{6 - 10} aryloxy, C _6-10 aryloxy carbonyloxy, benzyloxy, benzyl, sulfinyl, C _{1 -7} alkyl sulfinyl, sulfonyl, sulfate, sulfonate, sulfonamide, phosphate, phosphonato, phosphinato Ney soil, oxo, guanidine, will have already been replaced by a formyl or no wheat substituent.
5. The method of claim 4,
The process for producing the selenium-containing aromatic compound represented by Formula 1b from the selenium-containing aromatic compound represented by Formula 1d is carried out under basic conditions, wherein the process for preparing the selenophene-containing aromatic compound represented by Formula 1 Way.
The method according to claim 1,
The process for producing a selenophene-conjugated aromatic compound represented by Formula 1, wherein the MCBI compound represented by Formula 1a is reacted with the selenium-containing aromatic compound represented by Formula 1b in the presence of EDCI .
The method according to claim 1,
Wherein the reaction of the MCBI compound represented by Formula 1a and the selenium-containing aromatic compound represented by Formula 1b is performed after dissolving the MCBI compound in a solvent, wherein the selenophene- A method for producing a conjugated aromatic compound.
8. The method of claim 7,
The solvent is selected from the group consisting of dimethylformaldehyde (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), CH ₂ Cl ₂ , CH ₃ CN, CH ₃ NO ₂ , CHCl ₃ , ClCH ₂ CH ₂ Cl, Aromatic solvents, and combinations thereof. 2. The process according to claim 1, wherein the selenophene-conjugated aromatic compound is selected from the group consisting of aromatic solvents, aromatic solvents, and combinations thereof.
Reacting a selenium-containing aromatic compound represented by the following formula (2b) with an MCBI compound represented by the following formula (2a)
A process for producing a selenophene-bonded aromatic compound represented by the following formula (2)
(2a)

(2b)

(2)

Among the above equations,
R ⁹ is a C _1-7 alkoxy group which may be substituted,
R ¹⁰ and R ¹¹ are each independently C, O, N, S, a bond or a non-
R ¹² is _{H, -NO 2, -NHCOR, CX} 3, -OR, -diOR, C 1-7 alkoxy, C _1-7 which may be substituted, which may be optionally substituted C _1-7 alkyl group, a substituted An alkylene-dioxy group, an amino group which may be substituted, a halo group, or a substituent group represented by the following formula (A)
X is a halo group,
R is H, a C _1-7 alkyl group which may be substituted, an amino group which may be substituted or a C _1-7 alkoxy group which may be substituted;
(A)

Wherein,
R &lt; ⁷ &gt; is O, NH, S, or Se,
R ⁸ is a C _1-7 alkyl group which may be substituted, a C _1-7 alkoxy group which may be substituted, a halo group, -NO ₂ or -NHCOR ¹⁵ ,
R ¹⁵ is H, a C _1-7 alkyl group which may be substituted, an amino group which may be substituted or a C _1-7 alkoxy group which may be substituted,
When these groups are substituted, at one or more positions, C _1-7 acyl, amino, C _1-7 acylamino, C _1-7 alkylcarbonyloxy, C _6-10 aryl, C _6-10 arylcarbonyloxy, C _1-7 alkoxycarbonyl, C _1-7 alkoxycarbonyl, carboxy, carboxylate, aminocarbonyl, C _1-7 monoalkylaminocarbonyl, C _1-7 dialkylaminocarbonyl, cyano, azido, halogen, hydroxyl, nitro, trifluoromethyl, thio, C _1-7 alkylthio, C _6-10 arylthio, C _1-7 alkylthio-carbonyl, thio-carboxylate, C _1-7 lower alkyl, C _2-7 lower alkenyl, C _2-7 lower alkynyl, C _3-6 cycloalkyl, C _3-6 heterocycloalkyl, C _6-10 heteroaryl, C _1-7 lower alkoxy, C _{6- 10} aryloxy, C _6-10 aryloxy carbonyloxy, benzyloxy, benzyl, sulfinyl, C _1-7 alkyl sulfinyl, sulfonyl, sulfate, sulfonate, sulfonamide, phosphate, phosphonato, phosphinato Pinero Ito, oxo, No Dean, will have already been replaced by a formyl or no wheat substituent.
10. The method of claim 9,
The method for producing a selenophene-bonded aromatic compound represented by Formula 2, wherein the MCBI compound represented by Formula 2a is prepared from an MCBI compound represented by Formula 2c:
[Chemical Formula 2c]

Wherein,
R ⁹ is as defined in Formula (2a).
11. The method of claim 10,
A process for producing a selenophene-bonded aromatic compound represented by Formula 2, wherein the process for preparing the MCBI compound represented by Formula 2a above from the MCBI compound represented by Formula 2c is performed under acidic conditions.
10. The method of claim 9,
Wherein the selenium-containing aromatic compound represented by Formula 2b comprises a selenium-containing aromatic compound represented by Formula 2d: &lt; EMI ID =
(2d)

Wherein,
R ¹⁰ , R ¹¹ , and R ¹² are as defined in Formula 2b above,
R ¹⁸ is C _{1 -7} alkyl group, C _{1 -7} alkoxy, -NO _2, or -NHCO ₂ H, which may be substituted, which may be substituted,
If the above groups are substituted, in one or more positions with one or more C _{1 -7} acyl, amino, C _{1 -7} acyl amino, C _{1 -7} alkylcarbonyloxy, C _{6 -10} aryl, C _{6 -10} aryl-carbonyl-oxy, C _{1 -7} alkoxycarbonyloxy, C _{1 -7} alkoxycarbonyl, carboxy, carboxylate, aminocarbonyl, C _{1 -7} monoalkyl amino carbonyl, C _{1 -7} dialkyl-aminocarbonyl, cyano, azido, halogen, hydroxyl, nitro, trifluoromethyl, alkylthio, C _{1 -7} alkylthio, C _{6 -10} aryl thio, C _{1 -7} alkylthio-carbonyl, thio-carboxylate, C _{1 -7} lower alkyl, C _{2 -7-lower} alkenyl, C _{2 -7-lower} alkynyl, C _{3 -6} cycloalkyl, C _{3 -6} heterocycloalkyl, C _{6 -10} heteroaryl, C _{1 -7} lower alkoxy, C _{6 - 10} aryloxy, C _6-10 aryloxy carbonyloxy, benzyloxy, benzyl, sulfinyl, C _{1 -7} alkyl sulfinyl, sulfonyl, sulfate, sulfonate, sulfonamide, phosphate, phosphonato, phosphinato Ney soil, oxo, guanidine, will have already been replaced by a formyl or no wheat substituent.
13. The method of claim 12,
The process for producing a selenium-containing aromatic compound represented by Formula 2b from the selenium-containing aromatic compound represented by Formula 2d is carried out under basic conditions, wherein the process for producing a selenophene-bonded aromatic compound represented by Formula 2 Way.
10. The method of claim 9,
The process for producing a selenophene-bonded aromatic compound represented by Formula 2, wherein the MCBI compound represented by Formula 2a is reacted with the selenium-containing aromatic compound represented by Formula 2b in the presence of EDCI .
10. The method of claim 9,
Wherein the reaction of the MCBI compound represented by Formula 2a and the selenium-containing aromatic compound represented by Formula 2b is performed after dissolving the MCBI compound in a solvent, wherein the selenophene- A method for producing a conjugated aromatic compound.
16. The method of claim 15,
The solvent is selected from the group consisting of dimethylformaldehyde (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), CH ₂ Cl ₂ , CH ₃ CN, CH ₃ NO ₂ , CHCl ₃ , ClCH ₂ CH ₂ Cl, An aromatic solvent, and combinations thereof. 2. The method according to claim 1, wherein the selenophene-bonded aromatic compound is selected from the group consisting of an aromatic solvent, and combinations thereof.