KR20010006487A - Indole Derivatives Having Combined 5HT1A, 5HT1B and 5HT1D Receptor Antagonist Activity - Google Patents

Indole Derivatives Having Combined 5HT1A, 5HT1B and 5HT1D Receptor Antagonist Activity Download PDF

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KR20010006487A
KR20010006487A KR1019997009577A KR19997009577A KR20010006487A KR 20010006487 A KR20010006487 A KR 20010006487A KR 1019997009577 A KR1019997009577 A KR 1019997009577A KR 19997009577 A KR19997009577 A KR 19997009577A KR 20010006487 A KR20010006487 A KR 20010006487A
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dihydro
methylpiperazin
indole
chloro
phenylaminocarbonyl
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KR1019997009577A
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레이러미 메어리 개스터
하쉐이드 칸틸랄 레이미
폴 애드리언 위먼
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피터 기딩스
스미스클라인비이참피이엘시이
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Priority claimed from GBGB9801882.3A external-priority patent/GB9801882D0/en
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    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

화학식(I)의 화합물, 그의 제조 방법 및 CNS 제로서의 용도를 개시하고 있다.The compounds of formula (I), their preparation and their use as CNS agents are disclosed.

＜화학식 I＞<Formula I>

상기 식에서, Ra는 화학식(I-a)를 갖는 기이거나,Wherein R a is a group having formula (Ia), or

＜화학식 I-a＞<Formula I-a>

(여기서, P1은 페닐, 바이사이클릭 아릴, 산소, 질소 및 황으로부터Wherein P 1 is selected from phenyl, bicyclic aryl, oxygen, nitrogen and sulfur

선택된 1 내지 3개의 헤테로원자를 포함하는 5 내지 7 원 헤테로사이클릭5-7 membered heterocyclic containing 1 to 3 heteroatoms selected

고리, 또는 산소, 질소 및 황으로부터 선택된 1 내지 3개의 헤테로원자를Ring or 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur

포함하는 바이사이클릭 헤테로사이클릭 고리이며;A bicyclic heterocyclic ring comprising;

R1은 수소, 할로겐, C1-6알킬, C3-6시클로알킬, COC1-6알킬, C1-6알콕시,R 1 is hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, COC 1-6 alkyl, C 1-6 alkoxy,

히드록시, 히드록시C1-6알킬, 히드록시C1-6알콕시, C1-6알콕시C1-6알콕시,Hydroxy, hydroxyC 1-6 alkyl, hydroxyC 1-6 alkoxy, C 1-6 alkoxyC 1-6 alkoxy,

C1-6알카노일, 니트로, 트리플루오로메틸, 시아노, SR9, SOR9, SO2R9,C 1-6 alkanoyl, nitro, trifluoromethyl, cyano, SR 9 , SOR 9 , SO 2 R 9 ,

SO2NR10R11, CO2R10, CONR10R11, CO2NR10R11, CONR10(CH2)cCO2R11, (CH2)cNR10R11,SO 2 NR 10 R 11 , CO 2 R 10 , CONR 10 R 11 , CO 2 NR 10 R 11 , CONR 10 (CH 2 ) c CO 2 R 11 , (CH 2 ) c NR 10 R 11 ,

(CH2)cCONR10R11, (CH2)cNR10COR11, (CH2)cCO2C1-6알킬, CO2(CH2)cOR10, NR10R11,(CH 2 ) c CONR 10 R 11 , (CH 2 ) c NR 10 COR 11 , (CH 2 ) c CO 2 C 1-6 alkyl, CO 2 (CH 2 ) c OR 10 , NR 10 R 11 ,

NR10CO2R11, NR10CONR10R11, CR10=NOR11, NR10COOR11, CNR10=NOR11이고(여기서,NR 10 CO 2 R 11 , NR 10 CONR 10 R 11 , CR 10 = NOR 11 , NR 10 COOR 11 , CNR 10 = NOR 11 , where

R9, R10및 R11은 각각 수소 또는 C1-6알킬이며 c는 1 내지 4임);R 9 , R 10 and R 11 are each hydrogen or C 1-6 alkyl and c is 1-4;

R2는 수소, 할로겐, C1-6알킬, C3-6시클로알킬, C3-6시클로알케닐,R 2 is hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl,

C1-6알콕시, C1-6알카노일, 아릴, 아실옥시, 히드록시, 니트로,C 1-6 alkoxy, C 1-6 alkanoyl, aryl, acyloxy, hydroxy, nitro,

트리플루오로메틸, 시아노, CO2R10, CONR10R11, NR10R11이며(여기서, R10및 Trifluoromethyl, cyano, CO2R10, CONR10R11, NR10R11Where R is10And

R11은 R1에 대해 정의된 대로임);R 11 is as defined for R 1 ;

a는 1, 2 또는 3임);a is 1, 2 or 3);

또는 Ra는 하기 화학식(ii)를 갖는 기이며Or R a is a group of formula (ii)

＜화학식 I-b＞<Formula I-b>

(여기서, P2및 P3는 각각 페닐, 바이사이클릭 아릴, 산소, 질소 및Wherein P 2 and P 3 are each phenyl, bicyclic aryl, oxygen, nitrogen and

황으로부터 선택된 1 내지 3개의 헤테로원자를 갖는 5- 내지 7- 원5- to 7-membered having 1 to 3 heteroatoms selected from sulfur

헤테로사이클릭 고리 또는 산소, 질소 또는 황으로부터 선택된 1 내지Heterocyclic ring or 1 to 1 selected from oxygen, nitrogen or sulfur

3개의 헤테로원자를 포함하는 바이사이클릭 헤테로사이클릭기이며;Bicyclic heterocyclic groups containing three heteroatoms;

A는 결합 또는 산소, S(O)m(여기서, m은 0 내지 2임), 카르보닐, CH2,A is a bond or oxygen, S (O) m where m is 0 to 2, carbonyl, CH 2 ,

-CH2-CH2-, 또는 NR4이고(여기서, R4는 수소 또는 C1-6알킬임);-CH 2 -CH 2- , or NR 4 , wherein R 4 is hydrogen or C 1-6 alkyl;

R1은 상기에서 정의한 대로이거나 R1은 산소, 질소 또는R 1 is as defined above or R 1 is oxygen, nitrogen or

황으로부터 선택된 1 내지 3의 헤테로원자를 포함하는 5 내지 7-원5-7 membered containing 1 to 3 heteroatoms selected from sulfur

헤테로사이클릭 고리로 C1-6알킬, 할로겐 또는 C1-6알카노일에 의해 임의로Optionally by C 1-6 alkyl, halogen or C 1-6 alkanoyl to a heterocyclic ring

치환되어 있으며;Substituted;

R2및 R3는 각각 수소, 할로겐, C1-6알킬, C3-6시클로알킬, C3-6시클로R 2 and R 3 are each hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cyclo

알케닐, C1-6알콕시, C1-6알카노일, 아릴, 아실옥시, 히드록시, 니트로,Alkenyl, C 1-6 alkoxy, C 1-6 alkanoyl, aryl, acyloxy, hydroxy, nitro,

트리플루오로메틸, 시아노, CO2R10, CONR10R11, NR10R11이고(여기서, R10 Trifluoromethyl, cyano, CO 2 R 10 , CONR 10 R 11 , NR 10 R 11 , wherein R 10

및 R11은 R1에 대해 정의된 대로임);And R 11 is as defined for R 1 ;

a 및 b는 각각 0, 1, 2 또는 3임);a and b are each 0, 1, 2 or 3);

Y는 -NH-, -NR5-이며(여기서, R5는 C1-6알킬이거나 Y는 -CH2- 또는 -O-임);Y is -NH-, -NR 5- , wherein R 5 is C 1-6 alkyl or Y is -CH 2 -or -O-;

V는 산소 또는 황이고;V is oxygen or sulfur;

D는 질소, 탄소 또는 CH기이며; W는 (CR16R17)t이거나(여기서, t는 2, 3 또는 4이고 R16및 R17은 각각 수소 또는 C1-6알킬임) W는 (CR16R17)u-J이며(여기서, u는 0, 1, 2 또는 3이고 J는 산소, 황, CR16=CR17, CR16=N, =CR16O, =CR16S 또는 =CR16-NR17임); X는 질소 또는 탄소이고;D is nitrogen, carbon or CH group; W is (CR 16 R 17 ) t (where t is 2, 3 or 4 and R 16 and R 17 are each hydrogen or C 1-6 alkyl) W is (CR 16 R 17 ) u -J ( Wherein u is 0, 1, 2 or 3 and J is oxygen, sulfur, CR 16 = CR 17 , CR 16 = N, = CR 16 O, = CR 16 S or = CR 16 -NR 17 ); X is nitrogen or carbon;

Rb는 수소, 할로겐, 히드록시, C1-6알킬, 트리플루오로메틸, C1-6알콕시, C2-6알케닐, C1-4알킬에 의해 임의로 치환된 C3-7시클로알킬, 또는 아릴이며;R b is C 3-7 cycloalkyl optionally substituted by hydrogen, halogen, hydroxy, C 1-6 alkyl, trifluoromethyl, C 1-6 alkoxy, C 2-6 alkenyl, C 1-4 alkyl Or aryl;

Rc는 수소 또는 C1-6알킬이고;R c is hydrogen or C 1-6 alkyl;

은 X가 질소일 때는 단일 결합이고 또는 X가 탄소일 때는 단일 또는 이중 결합이다. Is a single bond when X is nitrogen or a single or double bond when X is carbon.

Description

조합된 5ＨＴ1Ａ, 5ＨＴ1Ｂ 및 5ＨＴ1Ｄ 수용체 길항 활성을 갖는 인돌 유도체{Indole Derivatives Having Combined 5HT1A, 5HT1B and 5HT1D Receptor Antagonist Activity}Indole derivatives having combined 5HT1A, 5HT1B and 5HT1D Receptor Antagonist Activity

본 발명은 신규의 피페라진 유도체, 이들의 제조 방법 및 이들을 포함하는 약학 조성물에 관한 것이다.The present invention relates to novel piperazine derivatives, methods for their preparation and pharmaceutical compositions comprising them.

WO 95/06637, WO 95/06044 및 WO 95/04729에서는 5HTID수용체 길항 활성 작용을 한다고 알려진 일련의 피페라진 유도체를 개시하고 있다. 이들 화합물이 다양한 CNS 질병, 예를 들면 우울증의 치료에 사용될 수 있다고 주장되고 있다. EPA 0533266/7/8에서는 5HTID수용체 길항 활성 작용을 한다고 알려진 일련의 벤즈아닐리드 유도체를 개시하고 있다.WO 95/06637, WO 95/06044 and WO 95/04729 disclose a series of piperazine derivatives known to have 5HT ID receptor antagonistic activity. It is claimed that these compounds can be used for the treatment of various CNS diseases such as depression. EPA 0533266/7/8 discloses a series of benzanilide derivatives known to have 5HT ID receptor antagonistic activity.

현재 구조적으로 특수한 부류의 화합물이 조합된 5HTIA, 5HTIB및 5HTID수용체 길항 활성 작용을 나타낸다고 알려지고 있다. 그러한 화합물은 비교적 빠르게 작용이 개시된다는 잇점이 있어 다양한 CNS 질병의 치료 및 예방에 유용할 것이라고 예상된다. 그러므로, 우선, 본 발명은 화학식(I)의 화합물 또는 그의 염을 제공한다:It is currently known that structurally specific classes of compounds exhibit a combination of 5HT IA , 5HT IB and 5HT ID receptor antagonist activity. Such compounds are expected to be useful for the treatment and prophylaxis of various CNS diseases because of the advantage that their action begins relatively quickly. Therefore, firstly, the present invention provides a compound of formula (I) or a salt thereof:

상기 식에서, Ra는 화학식(I-a)를 갖는 기이거나,Wherein R a is a group having formula (Ia), or

(여기서, P1은 페닐, 바이사이클릭 아릴, 산소, 질소 및 황으로부터Wherein P 1 is selected from phenyl, bicyclic aryl, oxygen, nitrogen and sulfur

선택된 1 내지 3개의 헤테로원자를 포함하는 5 내지 7 원 헤테로사이클릭5-7 membered heterocyclic containing 1 to 3 heteroatoms selected

고리, 또는 산소, 질소 및 황으로부터 선택된 1 내지 3개의 헤테로원자를Ring or 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur

포함하는 바이사이클릭 헤테로사이클릭 고리이며;A bicyclic heterocyclic ring comprising;

R1은 수소, 할로겐, C1-6알킬, C3-6시클로알킬, COC1-6알킬, C1-6알콕시,R 1 is hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, COC 1-6 alkyl, C 1-6 alkoxy,

히드록시, 히드록시C1-6알킬, 히드록시C1-6알콕시, C1-6알콕시C1-6알콕시,Hydroxy, hydroxyC 1-6 alkyl, hydroxyC 1-6 alkoxy, C 1-6 alkoxyC 1-6 alkoxy,

C1-6알카노일, 니트로, 트리플루오로메틸, 시아노, SR9, SOR9, SO2R9,C 1-6 alkanoyl, nitro, trifluoromethyl, cyano, SR 9 , SOR 9 , SO 2 R 9 ,

SO2NR10R11, CO2R10, CONR10R11, CO2NR10R11, CONR10(CH2)cCO2R11, (CH2)cNR10R11,SO 2 NR 10 R 11 , CO 2 R 10 , CONR 10 R 11 , CO 2 NR 10 R 11 , CONR 10 (CH 2 ) c CO 2 R 11 , (CH 2 ) c NR 10 R 11 ,

(CH2)cCONR10R11, (CH2)cNR10COR11, (CH2)cCO2C1-6알킬, CO2(CH2)cOR10, NR10R11,(CH 2 ) c CONR 10 R 11 , (CH 2 ) c NR 10 COR 11 , (CH 2 ) c CO 2 C 1-6 alkyl, CO 2 (CH 2 ) c OR 10 , NR 10 R 11 ,

NR10CO2R11, NR10CONR10R11, CR10=NOR11, NR10COOR11, CNR10=NOR11이고(여기서,NR 10 CO 2 R 11 , NR 10 CONR 10 R 11 , CR 10 = NOR 11 , NR 10 COOR 11 , CNR 10 = NOR 11 , where

R9, R10및 R11은 각각 수소 또는 C1-6알킬이며 c는 1 내지 4임);R 9 , R 10 and R 11 are each hydrogen or C 1-6 alkyl and c is 1-4;

R2는 수소, 할로겐, C1-6알킬, C3-6시클로알킬, C3-6시클로알케닐,R 2 is hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl,

C1-6알콕시, C1-6알카노일, 아릴, 아실옥시, 히드록시, 니트로,C 1-6 alkoxy, C 1-6 alkanoyl, aryl, acyloxy, hydroxy, nitro,

트리플루오로메틸, 시아노, CO2R10, CONR10R11, NR10R11이며(여기서, R10및 Trifluoromethyl, cyano, CO2R10, CONR10R11, NR10R11Where R is10And

R11은 R1에 대해 정의된 대로임);R 11 is as defined for R 1 ;

a는 1, 2 또는 3임);a is 1, 2 or 3);

또는 Ra는 하기 화학식(ii)를 갖는 기이며Or R a is a group of formula (ii)

(여기서, P2및 P3는 각각 페닐, 바이사이클릭 아릴, 산소, 질소 및Wherein P 2 and P 3 are each phenyl, bicyclic aryl, oxygen, nitrogen and

황으로부터 선택된 1 내지 3개의 헤테로원자를 갖는 5- 내지 7- 원5- to 7-membered having 1 to 3 heteroatoms selected from sulfur

헤테로사이클릭 고리 또는 산소, 질소 또는 황으로부터 선택된 1 내지Heterocyclic ring or 1 to 1 selected from oxygen, nitrogen or sulfur

3개의 헤테로원자를 포함하는 바이사이클릭 헤테로사이클릭기이며;Bicyclic heterocyclic groups containing three heteroatoms;

A는 결합 또는 산소, S(O)m(여기서, m은 0 내지 2임), 카르보닐, CH2,A is a bond or oxygen, S (O) m where m is 0 to 2, carbonyl, CH 2 ,

-CH2-CH2-, 또는 NR4이고(여기서, R4는 수소 또는 C1-6알킬임);-CH 2 -CH 2- , or NR 4 , wherein R 4 is hydrogen or C 1-6 alkyl;

R1은 상기 화학식(I)에서 정의한 대로이거나 R1은 산소, 질소 또는R 1 is as defined in formula (I) or R 1 is oxygen, nitrogen or

황으로부터 선택된 1 내지 3의 헤테로원자를 포함하는 5 내지 7-원5-7 membered containing 1 to 3 heteroatoms selected from sulfur

헤테로사이클릭 고리로 C1-6알킬, 할로겐 또는 C1-6알카노일에 의해 임의로Optionally by C 1-6 alkyl, halogen or C 1-6 alkanoyl to a heterocyclic ring

치환되어 있으며;Substituted;

R2및 R3는 각각 수소, 할로겐, C1-6알킬, C3-6시클로알킬, C3-6시클로R 2 and R 3 are each hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cyclo

알케닐, C1-6알콕시, C1-6알카노일, 아릴, 아실옥시, 히드록시, 니트로,Alkenyl, C 1-6 alkoxy, C 1-6 alkanoyl, aryl, acyloxy, hydroxy, nitro,

트리플루오로메틸, 시아노, CO2R10, CONR10R11, NR10R11이고(여기서, R10 Trifluoromethyl, cyano, CO 2 R 10 , CONR 10 R 11 , NR 10 R 11 , wherein R 10

및 R11은 R1에 대해 정의된 대로임);And R 11 is as defined for R 1 ;

a 및 b는 각각 0, 1, 2 또는 3임);a and b are each 0, 1, 2 or 3);

Y는 -NH-, -NR5-이며(여기서, R5는 C1-6알킬이거나 Y는 -CH2- 또는 -O-임);Y is -NH-, -NR 5- , wherein R 5 is C 1-6 alkyl or Y is -CH 2 -or -O-;

V는 산소 또는 황이고;V is oxygen or sulfur;

D는 질소, 탄소 또는 CH기이며; W는 (CR16R17)t이거나(여기서, t는 2, 3 또는 4이고 R16및 R17은 각각 수소 또는 C1-6알킬임) W는 (CR16R17)u-J이며(여기서, u는 0, 1, 2 또는 3이고 J는 산소, 황, CR16=CR17, CR16=N, =CR16O, =CR16S 또는 =CR16-NR17임); X는 질소 또는 탄소이고;D is nitrogen, carbon or CH group; W is (CR 16 R 17 ) t (where t is 2, 3 or 4 and R 16 and R 17 are each hydrogen or C 1-6 alkyl) W is (CR 16 R 17 ) u -J ( Wherein u is 0, 1, 2 or 3 and J is oxygen, sulfur, CR 16 = CR 17 , CR 16 = N, = CR 16 O, = CR 16 S or = CR 16 -NR 17 ); X is nitrogen or carbon;

Rb는 수소, 할로겐, 히드록시, C1-6알킬, 트리플루오로메틸, C1-6알콕시, C2-6알케닐, C1-4알킬에 의해 임의로 치환된 C3-7시클로알킬, 또는 아릴이며;R b is C 3-7 cycloalkyl optionally substituted by hydrogen, halogen, hydroxy, C 1-6 alkyl, trifluoromethyl, C 1-6 alkoxy, C 2-6 alkenyl, C 1-4 alkyl Or aryl;

Rc는 수소 또는 C1-6알킬이고;R c is hydrogen or C 1-6 alkyl;

은 X가 질소일 때는 단일 결합이고 또는 X가 탄소일 때는 단일 또는 이중 결합이다. Is a single bond when X is nitrogen or a single or double bond when X is carbon.

C1-6알킬기는 단독으로든 또는 다른 기의 일부분으로든 직쇄 또는 분지쇄일 수 있다. 본원에 사용된 용어 ‘아실옥시’는 -OC(O)C1-6알킬기를 나타낸다. 본원에 사용된 용어 ‘아릴’은 다르게 언급된 바가 없으면, 페닐과 같은 기를 나타낸다. 본원에 사용된 용어 ‘아르알킬’은 다르게 언급된 바가 없으면, 벤질과 같은 기를 나타낸다.The C 1-6 alkyl group, alone or as part of another group, may be straight or branched chain. The term 'acyloxy' as used herein refers to an -OC (O) C 1-6 alkyl group. As used herein, the term 'aryl', unless stated otherwise, refers to a group such as phenyl. The term 'aralkyl', as used herein, unless otherwise indicated, refers to a group such as benzyl.

부분적으로 포화될 수 있는, P1, P2및(또는) P3로 표현된 바이사이클릭 아릴 기는 나프틸이 바람직하다.Preferred are bicyclic aryl groups represented by P 1 , P 2 and / or P 3 , which may be partially saturated, naphthyl.

산소, 질소 및 황으로부터 선택된 1 내지 3의 헤테로원자를 포함하는 바이사이클릭 헤테로사이클릭 고리의 예로는 이소퀴놀린, 인돌, 벤조퓨란, 벤조티오펜 및 바람직하게는 퀴놀린이 있다.Examples of bicyclic heterocyclic rings comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur are isoquinoline, indole, benzofuran, benzothiophene and preferably quinoline.

P1, P2및(또는) P3로 표현된 산소, 질소 및 황으로부터 선택된 1 내지 3개의 헤테로원자를 포함하는 5 내지 7 원 헤테로사이클릭 고리의 예로는 티에닐, 퓨릴, 피롤일, 트리아졸일, 이미다졸일, 옥사졸일, 티아졸일, 옥사디아졸일, 이소티아졸일, 이속사졸일, 티아디아졸일, 피리미딜, 피리다지닐 및 피라지닐이 있으며 및 피리딜이 바람직하다.Examples of 5 to 7 membered heterocyclic rings containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur represented by P 1 , P 2 and / or P 3 are thienyl, furyl, pyrroyl, tria Zolyl, imidazolyl, oxazolyl, thiazolyl, oxdiazolyl, isothiazolyl, isoxazolyl, thiadiazoleyl, pyrimidyl, pyridazinyl and pyrazinyl and pyridyl is preferred.

상기에서 정의한 헤테로사이클릭 고리는 탄소 원자나 존재할 경우, 적절한 질소 원자를 통해 분자 내의 나머지 성분들과 연결될 수 있다. 또한 이런 고리는 포화되거나 부분적으로 포화될 수 있다. 포화되거나 부분적으로 포화된 5 내지 7 원 헤테로사이클릭 고리의 예로는 피레리딘, 피롤리딘 및 모르폴린이 있다. 부분적으로 포화된 바이사이클릭 헤테로사이클릭 고리의 예로는 디히드로벤조퓨란, 디히드로벤조티오펜, 테트라히드로퀴놀린 및 테트라히드로이소퀴놀린이 있다.The heterocyclic ring as defined above may be linked with the remaining components in the molecule via a carbon atom or, where present, an appropriate nitrogen atom. Such rings may also be saturated or partially saturated. Examples of saturated or partially saturated 5 to 7 membered heterocyclic rings are pyridine, pyrrolidine and morpholine. Examples of partially saturated bicyclic heterocyclic rings are dihydrobenzofuran, dihydrobenzothiophene, tetrahydroquinoline and tetrahydroisoquinoline.

바람직하게는 R1은 할로겐 원자, 예를 들면, 불소, 염소 또는 브롬이며 R2및(또는) R3는 바람직하게는 각각 수소, 할로겐, 예를 들면 염소기이거나, C1-6알킬기, 예를 들면 메틸기이다. R1이 5 내지 7-원 헤테로사이클릭 고리일 때, 적절한 임의 치환체로는 C1-6알킬, C1-6알카노일 및 할로겐이 있다.Preferably R 1 is a halogen atom, for example fluorine, chlorine or bromine and R 2 and / or R 3 are each preferably hydrogen, halogen, for example chlorine or C 1-6 alkyl groups, eg For example, it is a methyl group. When R 1 is a 5-7 membered heterocyclic ring, suitable optional substituents include C 1-6 alkyl, C 1-6 alkanoyl and halogen.

a 및 b는 각각 1 또는 2가 바람직하다.a and b are preferably 1 or 2, respectively.

A는 결합 또는 산소가 바람직하며, 가장 바람직하게는 결합이다.A is preferably a bond or oxygen, most preferably a bond.

Y는 -NH-가 바람직하다.Y is preferably -NH-.

V는 산소가 바람직하다.V is preferably oxygen.

D는 질소가 바람직하며 W기는 (CR16R17)t기가 바람직하다(여기서, R16및 R17은 각각 수소가 유익하며 t는 2가 적절함).D is preferably nitrogen and the W group is preferably a (CR 16 R 17 ) t group (where R 16 and R 17 are each beneficial for hydrogen and t is 2 is appropriate).

Rb는 수소 또는 할로겐 원자, 예를 들면 염소, C1-6알콕시기, 예를 들면 메톡시 또는 C1-6알킬기, 예를 들면 메틸 또는 에틸이 바람직하다.R b is preferably hydrogen or a halogen atom, for example chlorine, a C 1-6 alkoxy group, for example a methoxy or C 1-6 alkyl group, for example methyl or ethyl.

X는 질소가 바람직하다.X is preferably nitrogen.

Rc는 C1-6알킬기, 예를 들면 메틸이 바람직하다.R c is preferably a C 1-6 alkyl group, for example methyl.

본 발명에 따른 특히 바람직한 화합물로는;Particularly preferred compounds according to the invention include;

1-[(4-브로모-3-메틸페닐)아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1-[(4-bromo-3-methylphenyl) aminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole,

1-[(4-브로모-3-메틸페닐)아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1-[(4-bromo-3-methylphenyl) aminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole,

1-[(2,3-디클로로페닐)아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1-[(2,3-dichlorophenyl) aminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol,

1-[2,3-디클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1- [2,3-dichloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl)- 1H-Indole,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-(퀴놀린-5-일아미노카르보닐)-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- (quinolin-5-ylaminocarbonyl) -1H-indole,

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) phenylaminocarbonyl] -1H-indole,

5-브로모-1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H- Indol,

2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol,

1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌,1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1H-indole ,

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-5-비닐-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -5-vinyl-1H- Indol,

2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol,

1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌,1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1H-indole ,

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-5-트리플루오로메틸-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -5-trifluoromethyl -1H-indole,

1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸-1H-인돌,1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-trifluoromethyl- 1H-Indole,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole ,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole ,

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1-indole

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naph-1-ylacetyl] -1H-indole ,

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-5-비닐-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -5-vinyl-1H-indole,

5-브로모-2,3-디히드로-6-(1-메틸피페리딘-4-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-Bromo-2,3-dihydro-6- (1-methylpiperidin-4-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl]- 1H-Indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole,

2,3-디히드로-1-[4-(t-부톡시카르보닐아미노)페닐아미노카르보닐]-5-클로로-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-1- [4- (t-butoxycarbonylamino) phenylaminocarbonyl] -5-chloro-6- (4-methylpiperazin-1-yl) -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole,

6-브로모-7-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1,2,3,4-테트라히드로퀴놀린,6-bromo-7- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1,2,3,4- Tetrahydroquinoline,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(4-페녹시페닐아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (4-phenoxyphenylaminocarbonyl) -1H-indole,

5-클로로-2,3-디히드로-1-[4-(4-클로로페녹시)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (4-chlorophenoxy) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(3-페녹시페닐아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (3-phenoxyphenylaminocarbonyl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리미딘-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrimidin-2-yl) phenylaminocarbonyl] -1H-indole,

1-(3-벤조일페닐아미노카르보닐)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- (3-benzoylphenylaminocarbonyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole,

1-(4-벤조일페닐아미노카르보닐)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- (4-benzoylphenylaminocarbonyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(2-메틸퀴놀린-6-일아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (2-methylquinolin-6-ylaminocarbonyl) -1H-indole,

5-클로로-2,3-디히드로-1-[4-(퍼-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (per-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티엔-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thien-2-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-2-일)나프트-1-일아세틸]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-2-yl) naphth-1-ylacetyl] -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole ,

5-클로로-2,3-디히드로-1-[4-(1-메틸피페리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (1-methylpiperidin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole,

5-클로로-2,3-디히드로-1-[4-(2-메틸옥사졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2-methyloxazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole ,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(2-메틸피리딘-4-일)페닐아미노-카르보닐]-1H-인돌,5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (2-methylpyridin-4-yl) phenylamino-carbonyl] -1 H- Indol,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(2-메틸피리딘-4-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (2-methylpyridin-4-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol,

5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol,

2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H Indol,

5-클로로-2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol,

5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol,

2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H Indol,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(5-메틸-1,2,4-옥사디아졸-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (5-methyl-1,2,4-oxadiazol-3-yl) phenyl Aminocarbonyl] -1 H-indole,

5-클로로-2,3-디히드로-1-[4-(3-메틸-1,2,4-옥사디아졸-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (3-methyl-1,2,4-oxadiazol-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin- 1-day) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[3-(피리미딘-2-일옥시)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [3- (pyrimidin-2-yloxy) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-{4-[N-메틸-N-(피리미딘-2-일)아미노]페닐아미노카르보닐}-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- {4- [N-methyl-N- (pyrimidin-2-yl) amino] phenylaminocar Carbonyl} -1H-indole,

5-브로모-2,3-디히드로-1-[4-(퍼-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (per-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티엔-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thien-3-yl) phenylaminocarbonyl] -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티아졸-2-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thiazol-2-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티아졸-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thiazol-2-yl) phenylaminocarbonyl] -1H-indole,

1-[4-(5-아세틸티엔-2-일)페닐아미노카르보닐]-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- [4- (5-acetylthien-2-yl) phenylaminocarbonyl] -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole,

1-(5-브로모나프트-1-일아세틸)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- (5-bromonaft-1-ylacetyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(8-페닐퀴놀린-5-일아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (8-phenylquinolin-5-ylaminocarbonyl) -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(8-페닐퀴놀린-5-일아미노카르보닐)-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (8-phenylquinolin-5-ylaminocarbonyl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[2-(2-페닐에틸)퀴놀린-6-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [2- (2-phenylethyl) quinolin-6-ylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(1-메틸피페리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (1-methylpiperidin-4-yl) naphth-1-ylaminocarbox Carbonyl] -1H-indole,

5-브로모-2,3-디히드로-1-[4-(이소퀴놀린-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (isoquinolin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-1-[4-(이소퀴놀린-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (isoquinolin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-3-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-3-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-3-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-메틸-1,2,3,4-테트라히드로이소퀴놀린-7-일)아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl) Aminocarbonyl] -1 H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-메틸-1,2,3,4-테트라히드로이소퀴놀린-7-일)아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl ) Aminocarbonyl] -1 H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-8-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-8-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-8-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-8-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-1-[4-(이미다졸-1-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (imidazol-1-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) phenylaminocarbonyl] -1H-indole,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-5-일)아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-5-yl) aminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole,

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-1-[4-(2,6-디메틸-피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2,6-dimethyl-pyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole,

5-클로로-2,3-디히드로-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl)- 1H-Indole,

5-브로모-2,3-디히드로-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

2,3-디히드로-5-메톡시-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-1-[5-(6-메틸피리딘-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (6-methylpyridin-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

2,3-디히드로-5-메톡시-1-[5-(6-메틸피리딘-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [5- (6-methylpyridin-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole,

5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-ethylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol,

5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-ethylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol,

5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌 히드로클로라이드,5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole hydrochloride ,

5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌 히드로클로라이드,5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole hydrochloride ,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리다진-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridazin-3-yl) phenylaminocarbonyl] -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리다진-3-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridazin-3-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피라진-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrazin-2-yl) phenylaminocarbonyl] -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피라진-2-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrazin-2-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-페닐피리딘-5-일)아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-phenylpyridin-5-yl) aminocarbonyl] -1H-indole,

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-페닐피리딘-5-일)아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-phenylpyridin-5-yl) aminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-1-[4-(6-메틸피리다진-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (6-methylpyridazin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole ,

5-브로모-2,3-디히드로-1-[4-(6-메틸피리다진-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (6-methylpyridazin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-3-yl) phenylaminocarbonyl] -1H-indole,

5-클로로-2,3-디히드로-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole ,

2,3-디히드로-5-메톡시-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol,

5-브로모-2,3-디히드로-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol,

5-클로로-2,3-디히드로-1-[4-(1-메틸피라졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (1-methylpyrazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole ,

5-브로모-2,3-1-[4-(1-메틸피라졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-1- [4- (1-methylpyrazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-1-[4′-시아노-3′-메틸바이페닐-4-아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4'-cyano-3'-methylbiphenyl-4-aminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol,

5-브로모-2,3-디히드로-1-[4′-시아노-3′-메틸바이페닐-4-아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-Bromo-2,3-dihydro-1- [4'-cyano-3'-methylbiphenyl-4-aminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol,

5-클로로-2,3-디히드로-1-[4-(2-메틸피리딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2-methylpyridin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole,

5-브로모-2,3-디히드로-1-[4-(2-메틸피리딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2-methylpyridin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole ,

5-클로로-2,3-디히드로-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- (4 -Methylpiperazin-1-yl) -1H-indole,

2,3-디히드로-5-메톡시-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- ( 4-methylpiperazin-1-yl) -1H-indole,

5-브로모-2,3-디히드로-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- ( 4-methylpiperazin-1-yl) -1H-indole,

5-클로로-2,3-디히드로-1-[5-(5-메틸옥사졸-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (5-methyloxazol-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole,

2,3-디히드로-5-메톡시-1-[5-(5-메틸옥사졸-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [5- (5-methyloxazol-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole,

5-브로모-2,3-디히드로-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol,

2,3-디히드로-5-메톡시-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol,

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -1H- Indol,

5-브로모-2,3-디히드로-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol,

5-클로로-2,3-디히드로-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol,

2,3-디히드로-5-메톡시-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol,

5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole,

2,3-디히드로-5-메톡시-1-[4-(2,6-디메틸피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole,

5-클로로-2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole,

5-브로모-2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1 -Yl) -1H-indole,

2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1 -Yl) -1H-indole,

또는 그의 약학적으로 수용가능한 염이 있다.Or pharmaceutically acceptable salts thereof.

화학식(I)을 갖는 화합물의 바람직한 염은 약학적으로 수용가능한 염이다. 이들에는 산 부가 염, 예를 들면 히드로클로라이드, 히드로브로마이드, 포스페이트, 아세테이트, 퓨마레이트, 말레에이트, 타르트레이트, 시트레이트, 옥살레이트, 메탄술폰에이트 및 p-톨루엔술폰에이트가 포함된다.Preferred salts of compounds of formula (I) are pharmaceutically acceptable salts. These include acid addition salts such as hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, methanesulfonate and p-toluenesulfonate.

화학식(I)을 갖는 어떤 화합물은 입체이성질체 형태로 존재할 수 있다. 본 발명은 화학식(I)의 모든 기하학적 및 광학적 이성질체 및 라세미체를 포함하는 그의 혼합물을 포괄한다고 이해할 수 있다.Certain compounds having formula (I) may exist in stereoisomeric forms. It is to be understood that the present invention encompasses all geometric and optical isomers of formula (I) and mixtures thereof including racemates.

본 발명의 화합물은 공지된 방법으로 제조될 수 있다. 또다른 측면으로, 본 발명은The compounds of the present invention can be prepared by known methods. In another aspect, the invention

(a) 상기 화학식(I)에서 D가 질소이며 Y가 NH일 경우, 화학식(II)의 화합물(a) a compound of formula (II), in which D is nitrogen and Y is NH in formula (I)

Ra-NC(=V) (여기서, Ra및 V는 화학식(I)에서 정의된 대로임)R a -NC (= V), where R a and V are as defined in formula (I)

또는 그의 보호 유도체와 화학식(III)의 화합물Or a protective derivative thereof and a compound of formula (III)

(여기서, W, X, Rb및 Rc는 화학식(I)에서 정의된 대로임)Wherein W, X, R b and R c are as defined in formula (I)

또는 그의 보호 유도체를 결합하거나Or a protective derivative thereof

(b) 상기 화학식(I)에서 D가 질소이며 Y가 NH 또는 NR5일 경우, 적절한 우레아 형성제와 함께 화학식(IV)의 화합물을(b) when D is nitrogen in formula (I) and Y is NH or NR 5 , a compound of formula (IV) with a suitable urea former

Ra-NH2또는 Ra-NR5H (여기서, Ra및 R5는 화학식(I)에서 정의된 대로임)R a -NH 2 or R a -NR 5 H, wherein R a and R 5 are as defined in formula (I)

화학식(III)의 화합물과 반응시키며,Reacts with a compound of formula III

(c) 상기 화학식(I)에서 D가 질소일 경우, 화학식(V)의 화합물을(c) when D in the formula (I) is nitrogen, the compound of formula (V)

Ra-Y-(C=O)-L2(여기서, Ra는 화학식(I)에서 정의된 대로이고, Y는 -CH2- 또는R a -Y- (C = O) -L 2 , wherein R a is as defined in formula (I), and Y is -CH 2 -or

-O-이며 L2는 적절한 이탈기임)-O- and L 2 is a suitable leaving group)

화학식(III)의 화합물과 반응시키고,Reacted with a compound of formula (III),

(d) 상기 화학식(I)에서 D가 탄소 또는 CH일 경우, 화학식(VI)의 화합물을(d) when D in formula (I) is carbon or CH, a compound of formula (VI)

Ra-NH2(여기서, Ra는 화학식(I)에서 정의된 대로임)R a -NH 2 , where R a is as defined in formula (I)

화학식(VII)의 화합물과 반응시키고,Reacted with a compound of formula (VII),

(여기서, D는 탄소 또는 CH이며, W, X, Rb및 Rc는 화학식(I)에서 정의된Wherein D is carbon or CH and W, X, R b and R c are defined in Formula (I)

대로이고 L2는 적절한 이탈기임)L 2 is the appropriate leaving group)

이어서 임의로Then randomly

·임의의 보호기 제거,· Remove any protector,

·화학식(I)의 화합물을 화학식(I)의 또다른 화합물로 전환,Converting a compound of formula (I) to another compound of formula (I),

·약학적으로 수용가능한 염 형성Pharmaceutically acceptable salt formation

을 포함하는 화학식(I)의 화합물 또는 그의 약학적으로 수용가능한 염의 제조 방법을 제공한다.It provides a method of preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof.

과정 (a)의 반응은 편리하게는 유기 용매, 예를 들면 디클로로메탄에서 이루어진다.The reaction of process (a) is conveniently carried out in an organic solvent, for example dichloromethane.

과정 (b)에서, 우레아 형성제는 카르보닐 디이미다졸, 트리포스젠 또는 포스젠이 가능하며, 염기, 예를 들면 트리에틸렌아민 또는 피리딘 존재 하의 상온 또는 상승 온도에서 불활성 유기 용매, 예를 들면 디메틸포름아미드, 테트라히드로퓨란 또는 디클로로메탄에서 반응이 수행될 수 있다.In process (b), the urea former can be carbonyl diimidazole, triphosgene or phosgene, inert organic solvents such as at room or elevated temperatures in the presence of a base, for example triethyleneamine or pyridine, for example The reaction can be carried out in dimethylformamide, tetrahydrofuran or dichloromethane.

과정 (c)에서, 이탈기 L2는 할로겐, 예를 들면 염소기일 수 있으며 반응은 염기, 예를 들면 트리에틸렌아민 또는 피리딘 존재 하의 상온 또는 상승 온도에서 불활성 유기 용매, 예를 들면 테트라히드로퓨란 또는 디클로로메탄에서 반응이 수행될 수 있다.In process (c), the leaving group L 2 may be a halogen, for example a chlorine group and the reaction is carried out at an inert organic solvent such as tetrahydrofuran or at room or elevated temperature in the presence of a base such as triethyleneamine or pyridine or The reaction can be carried out in dichloromethane.

과정 (d)에서, 이탈기 L2는 할로겐, 예를 들면 염소기일 수 있으며 반응은 염기, 예를 들면 트리에틸렌아민 또는 피리딘 존재 하의 상온 또는 상승 온도에서 불활성 유기 용매, 예를 들면 테트라히드로퓨란 또는 디클로로메탄에서 수행될 수 있다.In process (d), the leaving group L 2 may be a halogen, for example a chlorine group and the reaction is carried out at an inert organic solvent such as tetrahydrofuran or at room or elevated temperature in the presence of a base such as triethyleneamine or pyridine or It can be performed in dichloromethane.

화학식(I)의 화합물은 표준 기술을 사용하여 다른 화학식(I)의 화합물로 전환될 수 있다. 예를 들면, Rc가 수소인 경우, 불활성 용매에서 C1-6알킬 할라이드 1몰 당량 및 적절한 염기 1몰 당량을 사용하여 통상적인 알킬화에 의해 C1-6알킬기를 도입할 수 있다.Compounds of formula (I) may be converted to other compounds of formula (I) using standard techniques. For example, when R c is hydrogen, with a C 1-6 alkyl halide and 1 molar equivalent of a suitable base in an inert solvent, one molar equivalent of a C 1-6 alkyl group may be introduced by conventional alkylation.

화학식(II), (III), (IV), (V), (VI) 및 (VII)의 중간체들은 공지된 방법을 사용하여 제조될 수 있다.Intermediates of formulas (II), (III), (IV), (V), (VI) and (VII) can be prepared using known methods.

상기 어느 과정 동안 임의의 반응 치환체를 보호할 필요가 있을 수 있다는 것을 당업자는 인식할 것이다. 표준 보호 및 탈보호 기술이 사용될 수 있다. 예를 들면, 제1 아민이 프탈이미드, 벤질, 벤질옥시카르보닐 또는 트리틸 유도체로써 보호될 수 있다. 이들 기는 일반적인 공지 과정에 의해 제거될 수 있다.Those skilled in the art will appreciate that it may be necessary to protect any reaction substituents during any of these processes. Standard protection and deprotection techniques can be used. For example, the first amine may be protected with phthalimide, benzyl, benzyloxycarbonyl or trityl derivatives. These groups can be removed by common known procedures.

카르복실산기는 에스테르로써 보호될 수 있다. 알데히드 또는 케톤기는 아세탈, 케탈, 티오아세탈 또는 티오케탈로써 보호될 수 있다. 탈보호는 표준 조건을 사용하여 이루어진다.Carboxylic acid groups can be protected with esters. Aldehyde or ketone groups can be protected with acetals, ketals, thioacetals or thioketals. Deprotection is achieved using standard conditions.

5HT1A/1B/1D수용체 길항제 및 특히 본 발명의 화합물은 CNS 질병, 예를 들면 감정 질환, 예를 들면 우울증, 계절성 질환 및 기분 변조; 불안증, 예를 들면 일반화된 불안, 극도의 공포, 광장 공포증, 사회 공포증, 강박 관념 및 외상 후 스트레스 질병; 기억성 질병, 예를 들면 치매, 건망증 및 노인성 기억 손상; 식습관 질환, 예를 들면 신경성 식욕 부진 및 신경성 병적 기아 및 수면성 질병(예를 들면 주기적 리듬의 교란)의 치료에 사용될 수 있다. 다른 CNS 질병에는 그 외 다른 정신 질환과 더불어 운동성 질병, 예를 들면 파키슨 병, 파키슨 병에 의한 치매, 파킨슨증에 의해 유발되는 신경 이완 및 만성 운동 이상이 있다.5HT 1A / 1B / 1D receptor antagonists and in particular the compounds of the present invention include CNS diseases such as emotional disorders such as depression, seasonal diseases and mood modulation; Anxiety, such as generalized anxiety, extreme fear, agoraphobia, social phobia, obsessive and post-traumatic stress diseases; Memory diseases such as dementia, forgetfulness and senile memory impairment; It can be used for the treatment of eating disorders such as anorexia nervosa and neuropathic hunger and sleep disorders (eg disturbances of periodic rhythms). Other CNS diseases include motor disorders such as Parkinson's disease, dementia caused by Parkinson's disease, nerve relaxation caused by Parkinson's disease, and chronic motor abnormalities, along with other mental disorders.

5HT1A/1B/1D수용체 길항제 및 특히 본 발명의 화합물은 운동 및 분비 변화를 포함하는 내장 장애 및 내분비 질병, 예를 들면 과프로락틴과잉혈증의 치료, 혈관경련(특히 중추 맥관계에서) 및 고혈압 치료에 사용될 수도 있다. 또한 이들은 성기능 장애 및 저체온증을 치료하는 데 사용될 수도 있다.5HT 1A / 1B / 1D receptor antagonists and in particular the compounds of the invention are used for the treatment of visceral disorders and endocrine diseases including movement and secretion changes, such as hyperprolactin hyperemia, in the treatment of vasospasm (particularly in central vascular system) and hypertension May be used. They can also be used to treat sexual dysfunction and hypothermia.

또한 본 발명은 상기 질병의 치료에 사용되기 위한 일반식(I)의 화합물 또는 그의 생리학적으로 허용가능한 염 또는 용매화물을 제공한다.The present invention also provides a compound of formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment of the disease.

또다른 측면에서, 본 발명은 치료에 있어 일반식(I)의 화합물 또는 그의 약학적으로 수용가능한 염 또는 용매화물을 필요로 하는 환자에게 효과적인 양으로 투여하는 것을 포함하는 상기 질병 치료 방법을 제공한다.In another aspect, the present invention provides a method for treating a disease comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. .

특히 본 발명은 우울증의 치료 또는 예방에 사용하기 위한 일반식(I)의 화합물 또는 그의 생리학적으로 허용가능한 염 또는 용매화물을 제공한다.In particular, the present invention provides a compound of formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment or prevention of depression.

본 발명에 따른 화합물이 하나 이상의 다른 치료제, 예를 들면 다른 항억제제와 함께 유익하게 사용될 수 있다는 것은 당업자에게 인식되어 있을 것이다.It will be appreciated by those skilled in the art that the compounds according to the invention may be advantageously used in combination with one or more other therapeutic agents, for example other anti-inhibitors.

또한 본 발명은 화학식(I)의 화합물 또는 그의 약학적으로 수용가능한 염을 포함하는 약학 조성물 및 약학적으로 수용가능한 담체를 제공한다.The present invention also provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

적절하게는 상온 및 대기압에서 혼합에 의해 제조될 수 있는 본 발명의 약학 조성물은 보통 경구, 비경구 또는 직장 투여를 하며 이 경우 정제, 캡슐, 경구용 액상 제제, 가루, 과립, 로젠지(lozenge), 재구성될 수 있는 가루, 삽입가능하거나 주입가능한 용액 또는 현탁액 또는 좌약의 형태일 수 있다. 경구로 투여할 수 있는 조성물이 일반적으로 바람직하다.Pharmaceutical compositions of the invention, which may be prepared by mixing at room temperature and atmospheric pressure, are usually administered orally, parenterally or rectally, in which case tablets, capsules, oral liquid preparations, powders, granules, lozenges. , Reconstitutable flour, insertable or injectable solutions or suspensions, or suppositories. Compositions that can be administered orally are generally preferred.

경구 투여용 정제 및 캡슐은 단위 투여량 형태일 수 있으며 통상적인 부형제, 예를 들면 결합제, 충전제, 정제화 윤활제, 분해제 및 수용가능한 습윤제를 포함할 수 있다. 상기 정제는 통상의 제약 기술에서 널리 알려진 방법에 따라 코팅될 수도 있다.Tablets and capsules for oral administration may be in unit dosage form and may include conventional excipients such as binders, fillers, tableting lubricants, disintegrating agents and acceptable wetting agents. The tablets may be coated according to methods well known in the conventional pharmaceutical arts.

경구용 액상 제제는 예를 들면, 수성 또는 유성 현탁액, 용액, 유화액, 시럽 또는 엘릭시르(elixir) 형태이거나 사용하기 전에 물 또는 다른 적절한 비히클 (vehicle)과 재구성되기 위한 건조 제품 형태일 수 있다. 상기 액상 제제는 통상적인 부가물, 예를 들면 현탁제, 유화제, (식용 오일을 포함할 수 있는) 비-수성 비히클, 보존제 및 필요하다면 통상적인 풍미제 또는 착색제를 포함할 수 있다.Oral liquid preparations may, for example, be in the form of aqueous or oily suspensions, solutions, emulsions, syrups or elixirs or in the form of dry products for reconstitution with water or other suitable vehicle prior to use. The liquid preparations may include customary adducts such as suspending agents, emulsifiers, non-aqueous vehicles (which may include edible oils), preservatives and, if desired, conventional flavoring or coloring agents.

비경구 투여를 위해서, 액상 단위 투여량 형태는 본 발명 화합물 또는 그의 약학적으로 수용가능한 염 및 무균 비히클을 사용하여 제조될 수 있다. 상기 화합물은 사용된 비히클 및 농도에 따라, 비히클 내에서 부유되거나 용해될 수 있다. 용액 제조에 있어, 상기 화합물은 적절한 바이알 또는 앰플에 충진하여 밀봉하기 전에 멸균시킨 주사약 및 여과액에 용해시킬 수 있다. 유익하게는, 보조제, 예를 들면 국부 마취제, 보존제 및 완충제가 비히클에 용해된다. 안정성을 증가시키기 위해, 상기 조성물을 바이알 속으로 충진시킨 후에 동결시킨 후, 진공 하에서 물을 제거시킬 수 있다. 비경구용 현탁액은 상기 화합물이 비히클에 용해되는 대신 현탁되는 것을 제외하면 실질적으로 동일한 방법으로 제조되며 멸균은 여과에 의해 달성될 수 없다. 상기 화합물을 무균 비히클 내에 현탁시키기 전에 에틸렌 옥시드에 노출됨으로써 멸균시킬 수 있다. 유익하게는, 상기 화합물이 쉽게 균일한 분포를 이루도록 상기 조성물이 계면활성제 또는 습윤제를 포함한다.For parenteral administration, liquid unit dosage forms can be prepared using the compounds of the present invention or their pharmaceutically acceptable salts and sterile vehicles. The compound may be suspended or dissolved in the vehicle, depending on the vehicle and concentration used. In solution preparation, the compounds may be dissolved in sterile injectables and filtrates before filling and sealing in appropriate vials or ampoules. Advantageously, auxiliaries such as local anesthetics, preservatives and buffers are dissolved in the vehicle. In order to increase the stability, the composition can be filled into vials and then frozen, followed by removal of water under vacuum. Parenteral suspensions are prepared in substantially the same manner except that the compounds are suspended instead of dissolved in the vehicle and sterilization cannot be achieved by filtration. The compound can be sterilized by exposure to ethylene oxide prior to suspension in a sterile vehicle. Advantageously, the composition comprises a surfactant or wetting agent so that the compound is easily and uniformly distributed.

상기 조성물은 투여 방법에 따라 0.1 중량% 내지 99 중량%, 바람직하게는 10 내지 60 중량%의 활성제를 포함할 수 있다.The composition may comprise 0.1 to 99% by weight, preferably 10 to 60% by weight of active agent, depending on the method of administration.

상기 질병을 치료하는 데 사용될 수 있는 화합물의 투여량은 질병의 심각성, 환자의 몸무게 및 다른 유사한 요인들에 의해 일반적으로 변화될 것이다. 그러나, 일반적인 방법으로써, 적절한 단위 투여량은 0.05 내지 1000mg, 더욱 적절하게는 1.0 내지 200mg일 수 있으며 상기 단위 투여량은 하루 한 번 이상, 예를 들면 하루에 두 번 또는 세 번 투여될 수 있다. 상기 치료법은 수 주 또는 수 개월 지속될 수 있다.The dosage of a compound that can be used to treat the disease will generally vary depending on the severity of the disease, the weight of the patient and other similar factors. However, as a general method, a suitable unit dose may be 0.05 to 1000 mg, more suitably 1.0 to 200 mg and the unit dose may be administered one or more times per day, for example twice or three times a day. The therapy can last for weeks or months.

하기 실시예는 본 발명 화합물의 제조 방법을 나타낸다.The following examples show the preparation of the compounds of the invention.

기재 항목 1Article item 1

4-브로모-3-메틸페닐 이소시아네이트4-bromo-3-methylphenyl isocyanate

옥살일 클로라이드(11.94g, 0.094몰) 이후 DMF 3 방울을 디클로로메탄 (300ml) 중의 4-브로모-3-메틸벤조산(10.0g, 0.047몰)의 교반 현탁액에 첨가했다. 상기 혼합물을 실온에서 60시간 동안 교반한 후, 상기 용액을 진공 농축하여 산 클로라이드를 적색 오일로 얻었다. 이 물질을 디클로로메탄(300ml)에 재용해시키고 0℃로 냉각시켰다. 테트라부틸암모늄 아오다이드(0.150g)을 첨가한 후 물(75ml) 중의 소듐 아지드(4.36g, 0.066몰) 용액을 첨가하고 혼합물을 0℃에서 3시간 동안 격렬히 교반한 후 물(200ml)로 희석시키고 상기 디클로로메탄 층을 분리, 건조(Na2SO4) 및 진공 농축시켜(그러나, 완전 건조될 때까지는 아님) 아실 아지드를 연한 오렌지색 고체로 얻었다. 이 물질을 톨루엔(300ml)에 용해시키고 환류 하에 교반하면서 1시간 동안 가열한 후 냉각하고 진공 농축하여 표제 화합물을 적갈색 오일로 얻었다(9.42g, 95%).Three drops of DMF after oxalyl chloride (11.94 g, 0.094 mole) were added to a stirred suspension of 4-bromo-3-methylbenzoic acid (10.0 g, 0.047 mole) in dichloromethane (300 ml). After the mixture was stirred at room temperature for 60 hours, the solution was concentrated in vacuo to give acid chloride as a red oil. This material was redissolved in dichloromethane (300 ml) and cooled to 0 ° C. Tetrabutylammonium aodide (0.150 g) is added followed by a solution of sodium azide (4.36 g, 0.066 mole) in water (75 ml) and the mixture is vigorously stirred at 0 ° C. for 3 h and then with water (200 ml) Diluted and the dichloromethane layer was separated, dried (Na 2 SO 4 ) and concentrated in vacuo (but not until complete drying) to obtain acyl azide as a pale orange solid. This material was dissolved in toluene (300 ml), heated for 1 h with stirring under reflux, cooled and concentrated in vacuo to afford the title compound as a reddish brown oil (9.42 g, 95%).

기재 항목 2Article item 2

4-(피리딘-4-일)나프트-1-일아민4- (pyridin-4-yl) naphth-1-ylamine

소듐 카보네이트(14g)를 포함하는 1,2-디메톡시에탄(400ml) 및 물(100ml) 중의 4-브로모나프트-1-일아민(10g, 45mmole)의 교반 현탁액을 아르곤 하에서 0.3시간 동안 플러쉬(flush)했다. 테트라키스(트리페닐포스핀)팔라듐(O)(2,75g, 2.4mmole)을 첨가 후 4-피리딜보론산(5.7g, 46mmole)을 첨가한 후 혼합물을 5시간 동안 환류 하에 가열했다. 상기 혼합물을 진공 농축시켜 갈색 슬러리로 형성시킨 후 디클로로메탄 및 물 사이로 분배했다. 상기 수용액을 디클로로메탄으로 더욱 추출하고 상기 조합된 유기물을 건조(Na2SO4) 및 진공 농축시켜 갈색 고체(13.2g)를 얻었다. 에틸 아세테이트로 용출시키면서 플래쉬 크로마토그래피에 의해 상기 고체를 정제함으로써 표제 화합물을 황색 결정성 고체로 얻었다(7.8g, 78%).A stirred suspension of 1,2-dimethoxyethane (400 ml) comprising sodium carbonate (14 g) and 4-bromonaft-1-ylamine (10 g, 45 mmol) in water (100 ml) was flushed under argon for 0.3 h. flush). Tetrakis (triphenylphosphine) palladium (O) (2,75 g, 2.4 mmol) was added followed by the addition of 4-pyridylboronic acid (5.7 g, 46 mmol) and the mixture was heated at reflux for 5 hours. The mixture was concentrated in vacuo to form a brown slurry and partitioned between dichloromethane and water. The aqueous solution was further extracted with dichloromethane and the combined organics were dried (Na 2 SO 4 ) and concentrated in vacuo to give a brown solid (13.2 g). Purification of the solid by flash chromatography eluting with ethyl acetate gave the title compound as a yellow crystalline solid (7.8 g, 78%).

기재 항목 3Article item 3

5-(피리딘-4-일)-1-나프토산5- (pyridin-4-yl) -1-naphthoic acid

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 5-브로모-1-나프토산 (EP 547442 A1) 및 4-피리딜보론산으로부터 제조하였다.The title compound was prepared from 5-bromo-1-naphthoic acid (EP 547442 A1) and 4-pyridylboronic acid using a procedure similar to that described in Item 2.

기재 항목 4Article item 4

5-(피리딘-4-일)나프트-1-일 이소시아네이트5- (pyridin-4-yl) naphth-1-yl isocyanate

상기 표제 화합물을 기재 항목 1과 유사한 과정을 사용하여 5-(피리딘-4-일)-1-나프토산(D3)으로부터 제조하였다.The title compound was prepared from 5- (pyridin-4-yl) -1-naphthoic acid (D3) using a procedure similar to that described in Item 1.

기재 항목 5Article item 5

4-(피리딘-4-일)아닐린4- (pyridin-4-yl) aniline

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 4-브로모아닐린 및 4-피리디닐보론산으로부터 백색 고체로 제조하였다(17%).The title compound was prepared as a white solid from 4-bromoaniline and 4-pyridinylboronic acid using a procedure similar to that described in Item 2 (17%).

기재 항목 6Article item 6

3-클로로-4-(피리딘-4-일)아닐린3-chloro-4- (pyridin-4-yl) aniline

3-클로로-4-(피리딘-4-일)아세트아닐리드를 얻기 위하여 기재 항목 2와 유사한 과정을 사용하여 3-클로로-4-브로로아세트아닐리드를 4-피리디닐보론산과 반응시켰다. 2M NaOH 용액 및 에탄올의 혼합물에서 6시간 동안 환류 하에 가열함으로써 이 물질을 가수분해함으로써 상기 표제 화합물을 연한 황색 고체로 얻었다(5.5g, 73%).3-chloro-4-broroacetanilide was reacted with 4-pyridinylboronic acid using a procedure similar to that described in Item 2 to obtain 3-chloro-4- (pyridin-4-yl) acetanilide. The title compound was obtained as a pale yellow solid by hydrolysis of this material by heating under reflux for 6 hours in a mixture of 2M NaOH solution and ethanol (5.5 g, 73%).

기재 항목 7List item 7

2,3-디클로로-4-(피리딘-4-일)아닐린2,3-dichloro-4- (pyridin-4-yl) aniline

상기 표제 화합물을 기재 항목 6과 유사한 과정을 사용하여 4-브로모-2,3-디클로로아세트아닐리드 및 4-피리디닐보론산으로부터 염기 가수분해에 의해 제조하였다.The title compound was prepared by base hydrolysis from 4-bromo-2,3-dichloroacetanilide and 4-pyridinylboronic acid using a procedure similar to that described in Item 6.

기재 항목 8Article item 8

1-아세틸-2,3-디히드로-6-니트로-1H-인돌1-acetyl-2,3-dihydro-6-nitro-1H-indole

실온에서 디클로로메탄(1000ml) 중의 2,3-디히드로-6-니트로-1H-인돌(100g, 0.61몰)의 교반 용액을 아세트산 무수물(62ml, 0.66몰)로 20분간 적하 처리했다. 상기 반응 혼합물을 추가 2시간 동안 교반하고 이어서 10% Na2CO3용액(300ml)으로 세척하고 건조(Na2SO4) 및 진공 농축시켜 표제 화합물을 황색 고체로 얻었다(125g, 100%).A stirred solution of 2,3-dihydro-6-nitro-1H-indole (100 g, 0.61 mol) in dichloromethane (1000 ml) was added dropwise to acetic anhydride (62 ml, 0.66 mol) for 20 minutes at room temperature. The reaction mixture was stirred for an additional 2 hours and then washed with 10% Na 2 CO 3 solution (300 ml), dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a yellow solid (125 g, 100%).

기재 항목 9Article item 9

1-아세틸-6-아미노-2,3-디히드로-1H-인돌1-acetyl-6-amino-2,3-dihydro-1H-indole

THF(5500ml) 중의 1-아세틸-2,3-디히드로-6-니트로-1H-인돌(D8, 125g, 0.61몰)의 교반된 현탁액을 50psi에서 20시간 동안 10% Pd-C(20g)으로 수소화했다. 키이슬레이거(kieselguhr) 플러그를 통한 여과로 상기 촉매를 제거하고 여과액을 진공 농축함으로써 상기 표제 화합물을 베이지색 고체로 얻었다(102g, 95%).A stirred suspension of 1-acetyl-2,3-dihydro-6-nitro-1H-indole (D8, 125 g, 0.61 mol) in THF (5500 ml) was added to 10% Pd-C (20 g) at 50 psi for 20 hours. Hydrogenated. Filtration through a kieselguhr plug removed the catalyst and the filtrate was concentrated in vacuo to afford the title compound as a beige solid (102 g, 95%).

기재 항목 10Article item 10

1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

1-부탄올(1800ml) 중의 1-아세틸-6-아미노-2,3-디히드로-1H-인돌(D9, 37.8g, 0.22몰), 메클로르에타민 히드로클로라이드(46g, 0.24몰) 및 무수 칼륨 카보네이트(80g, 0.58몰)을 8시간 동안 환류 하에 가열한 후 추가의 메클로르에타민 히드로클로라이드(25g, 0.13몰) 및 칼륨 카보네이트(41g, 0.30몰)을 첨가하고 3시간 동안 계속 환류하였다. 상기 반응 혼합물을 냉각시킨 후 물(1000ml)로 세척했다. 상기 수성 세척액을 에틸 아세테이트로 추출하고 상기 추출액을 1-부탄올 용액과 혼합시킨 후 진공에서 농축시켰다. 오렌지색 오일을 얻기 위해 상기 갈색 유성 잔류물(60g)을 0-8% MeOH/DCM으로 용출시키면서 실리카 겔에서 크로마트그래피하고, 이것을 에테르로 연화시켜 상기 표제 화합물을 베이지색 고체로 얻었다(12.2g, 22%).1-acetyl-6-amino-2,3-dihydro-1H-indole (D9, 37.8 g, 0.22 moles), mechlorethamine hydrochloride (46 g, 0.24 moles) in 1-butanol (1800 ml) and potassium anhydride The carbonate (80 g, 0.58 mole) was heated under reflux for 8 hours after which additional mechlorethamine hydrochloride (25 g, 0.13 mole) and potassium carbonate (41 g, 0.30 mole) were added and reflux continued for 3 hours. The reaction mixture was cooled down and washed with water (1000 ml). The aqueous wash was extracted with ethyl acetate and the extract was mixed with 1-butanol solution and concentrated in vacuo. The brown oily residue (60 g) was chromatographed on silica gel eluting with 0-8% MeOH / DCM to give an orange oil, which was triturated with ether to give the title compound as a beige solid (12.2 g, 22%).

기재 항목 11Article item 11

2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 기재 항목 13과 유사한 과정을 사용하여 1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D10)로부터 베이지색 고체로써 제조하였다 (92%).The title compound was prepared as a beige solid from 1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D10) using a procedure similar to that described in Item 13. (92%).

기재 항목 12Article item 12

1-아세틸-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1-acetyl-5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

아르곤 존재 하 -5℃에서 디클로로메탄(100ml) 중의 1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D10, 1,1g, 0.0040몰)의 교반 용액을 DCM(10ml) 중의 N-클로로숙신이미드(0.73g, 0.0054몰)의 용액으로 15분 간 적하 처리한 후 추가 0.5시간 동안 -5℃에서 보관하고 1시간 동안 방치하여 실온으로 되게 했다. 상기 반응 혼합물을 2M HCl 산(60ml)으로 추출하고 상기 산 추출물을 고체 K2CO3를 첨가하여 염기화하고 DCM으로 추출했다. 상기 유기 추출물을 건조(Na2SO4)하고 진공 농축하여 표제 화합물을 베이지색 고체로 얻었다(1.45g, 100%).1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D10, 1,1 g, 0.0040 mol in dichloromethane (100 ml) in the presence of argon ) Was stirred dropwise for 15 minutes with a solution of N-chlorosuccinimide (0.73 g, 0.0054 mol) in DCM (10 ml), and then stored at -5 ° C for an additional 0.5 hours, and left at room temperature for 1 hour. I got it. The reaction mixture was extracted with 2M HCl acid (60 ml) and the acid extract was basified by addition of solid K 2 CO 3 and extracted with DCM. The organic extract was dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a beige solid (1.45 g, 100%).

기재 항목 13Article item 13

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

2M HCl 산(120ml) 중의 1-아세틸-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D12, 1.4g, 0.0048몰)의 교반 용액을 아르곤 존재 하에 환류 하에서 5시간 동안 가열했다. 상기 반응 혼합물을 방치하여 냉각하고 고체 K2CO3를 첨가하여 염기화하며 DCM으로 추출했다. 상기 추출물을 건조(Na2SO4) 및 진공 농축시켜 상기 표제 화합물을 베이지색 고체로 얻었다(0.93g, 78%).Stirring of 1-acetyl-5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D12, 1.4 g, 0.0048 mol) in 2M HCl acid (120 ml) The solution was heated for 5 hours under reflux in the presence of argon. The reaction mixture was left to cool, basified by addition of solid K 2 CO 3 and extracted with DCM. The extract was dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a beige solid (0.93 g, 78%).

기재 항목 14List item 14

1-아세틸-5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1-acetyl-5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

아르곤 존재 하의 -5℃에서 디클로로메탄(100ml) 및 메탄올(50ml)의 혼합물 중의 1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D10, 2.0 g, 0.0077몰)의 교반 혼합물을 벤질트리메틸암모늄 트리브로마이드(3.14g, 0.0081몰)로 20분 간 일부분씩 처리했다. 상기 혼합물을 1시간 동안 방치하여 실온으로 되게 한 후 진공 농축시켰으며 잔류물을 디클로로메탄(150ml)에 용해시키고, 물(2×100ml)로 세척하고 건조(Na2SO4) 및 진공 농축하여 표제 화합물을 베이지색 고체로 얻었다(2.52g, 97%).1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D10) in a mixture of dichloromethane (100 ml) and methanol (50 ml) at -5 ° C in the presence of argon. , 2.0 g, 0.0077 mole) of the stirred mixture was treated in portions with benzyltrimethylammonium tribromide (3.14 g, 0.0081 mole) for 20 minutes. The mixture was left to stand for 1 h, allowed to come to room temperature and concentrated in vacuo, and the residue was dissolved in dichloromethane (150 ml), washed with water (2 × 100 ml), dried (Na 2 SO 4 ) and concentrated in vacuo. The compound was obtained as a beige solid (2.52 g, 97%).

기재 항목 15List item 15

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

2M 히드로브롬산(50ml) 중의 1-아세틸-2,3-디히드로-5-브로모-6-(4-메틸피페라진-1-일)-1H-인돌(D14, 0,60g, 1.8mmole)의 용액을 실온에서 5일 동안 교반한 후 고체 K2CO3를 첨가하여 염기화하고 DCM으로 추출했다. 상기 추출물을 건조(Na2SO4) 및 진공 농축하여 상기 표제 화합물을 갈색 고체로 얻었다(0.31g, 58%).1-acetyl-2,3-dihydro-5-bromo-6- (4-methylpiperazin-1-yl) -1H-indole (D14, 0,60 g, 1.8 mmol) in 2M hydrobromic acid (50 ml) ) Solution was stirred at room temperature for 5 days, then basified by addition of solid K 2 CO 3 and extracted with DCM. The extract was dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a brown solid (0.31 g, 58%).

기재 항목 16List item 16

1-아세틸-2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌1-acetyl-2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 기재 항목 18과 유사한 과정을 사용하여 1-아세틸-2,3-디히드로-5-브로모-6-(4-메틸피페라진-1-일)-1H-인돌(D14) 및 테트라메틸틴으로부터 베이지색 고체로 제조하였다(63%).The title compound was purified using 1-acetyl-2,3-dihydro-5-bromo-6- (4-methylpiperazin-1-yl) -1H-indole (D14) using a procedure similar to that described in Item 18, and Prepared as a beige solid from tetramethyltin (63%).

기재 항목 17List item 17

2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 기재 항목 13과 유사한 과정을 사용하여 1-아세틸-2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌(D16)로부터 베이지색 고체로 제조하였다(89%).The title compound was beige from 1-acetyl-2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1H-indole (D16) using a procedure similar to that described in Item 13. Prepared as a color solid (89%).

기재 항목 18List item 18

1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-비닐-1H-인돌1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-vinyl-1H-indole

건조 DMF(15ml) 중의 1-아세틸-2,3-디히드로-5-브로모-6-(4-메틸피페라진-1-일)-5-비닐-1H-인돌(D14, 600mg, 1.8mmole) 교반 용액을 비닐트리부틸틴(0.78ml, 2.7mmole)으로 처리하고 20분간 아르곤을 거품일게 함으로써 탈기한 후 트리에틸아민(0.50ml, 3.6mmole) 및 테트라키스(트리페닐포스핀)팔라듐(O)(200mg)을 첨가시키고 상기 혼합물을 아르곤 존재 하 100℃에서 7시간 동안 가열했다. 상기 반응 혼합물을 방치하여 냉각시키고, EtOAc(150ml)로 희석시킨 후 0.5M HCl 산(2×100ml)로 추출했다. 상기 산 추출액을 고체 K2CO3를 첨가하여 염기화한 후 DCM(2×100ml)으로 추출하고 상기 추출액을 건조(Na2SO4) 및 진공 농축시켜 상기 표제 화합물을 베이지색 고체로 얻었다(480mg, 95%).1-acetyl-2,3-dihydro-5-bromo-6- (4-methylpiperazin-1-yl) -5-vinyl-1H-indole (D14, 600 mg, 1.8 mmol) in dry DMF (15 ml) ) The stirred solution was treated with vinyltributyltin (0.78ml, 2.7mmole) and degassed by bubbling argon for 20 minutes, followed by triethylamine (0.50ml, 3.6mmole) and tetrakis (triphenylphosphine) palladium (O ) (200 mg) was added and the mixture was heated at 100 ° C. for 7 hours in the presence of argon. The reaction mixture was left to cool, diluted with EtOAc (150 ml) and extracted with 0.5 M HCl acid (2 × 100 ml). The acid extract was basified with addition of solid K 2 CO 3 and extracted with DCM (2 × 100 ml) and the extract was dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a beige solid (480 mg). , 95%).

기재 항목 19List item 19

2,3-디히드로-6-(4-메틸피페라진-1-일)-5-비닐-1H-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-vinyl-1H-indole

에탄올(25ml) 중의 1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-비닐 -1H-인돌(D18, 250mg, 9.0mmole)의 교반 용액을 10% NaOH 용액(45ml)로 처리하고 15분간 아르곤을 거품일게 함으로써 탈기한 후 7시간 동안 환류하에 가열했다. 상기 혼합물을 방치하여 냉각시키고 약 40ml 부피까지 진공에서 농축한 후 DCM으로 추출했다. 상기 추출액을 건조(Na2SO4) 및 진공 농축시켜 표제 화합물을 갈색 고체로 얻었다(170mg, 80%).A stirred solution of 1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-vinyl-1H-indole (D18, 250 mg, 9.0 mmol) in ethanol (25 ml) was prepared. Treated with% NaOH solution (45 ml) and degassed by bubbling argon for 15 minutes followed by heating under reflux for 7 hours. The mixture was left to cool, concentrated in vacuo to about 40 ml volume and extracted with DCM. The extract was dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a brown solid (170 mg, 80%).

기재 항목 20Article item 20

1-아세틸-2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌1-acetyl-2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1H-indole

에탄올(100ml) 중의 1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-비 닐-1H-인돌(D18, 400mg, 1.4mmole)의 교반 용액을 대기압 상온에서 24시간 동안 10% Pd-C(100mg)으로 수소화했다. 상기 촉매를 키이슬레이거를 통해 여과함으로써 제거하고 상기 여과액을 진공 농축시켜 표제 화합물을 베이지색 고체를 얻었다(380mg, 94%).A stirred solution of 1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-vinyl-1H-indole (D18, 400 mg, 1.4 mmol) in ethanol (100 ml) Hydrogenated to 10% Pd-C (100 mg) for 24 h at atmospheric pressure. The catalyst was removed by filtration through a Keithley razer and the filtrate was concentrated in vacuo to yield the title compound as a beige solid (380 mg, 94%).

기재 항목 21List item 21

2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 기재 항목 13과 유사한 과정을 사용하여 1-아세틸-2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌(D20)로부터 베이지색 고체를 제조하였다 (94%).The title compound was beige from 1-acetyl-2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1H-indole (D20) using a procedure similar to that described in Item 13. A colored solid was prepared (94%).

기재 항목 22List item 22

1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸-1H-인돌1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-trifluoromethyl-1H-indole

건조 DMF(16ml) 및 톨루엔(10ml) 중의 1-아세틸-5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D14, 500mg, 1.5mmole), 칼륨 트리플루오로아세테이트(410mg, 2.7mmole) 및 요오드화 구리(I)(572mg, 3.0mmole) 교반 용액을 톨루엔/물을 트랩하기 위해 딘(Dean) 및 스탁(Stark) 헤드를 사용하여 아르곤 존재 하 130℃에서 0.5시간 동안 가열했다. 딘 및 스탁 헤드를 응축기로 대체하고 상기 혼합물을 155℃에서 34시간 동안 가열하고 난 후 추가의 칼륨 트리플루오로아세테이트(410mg) 및 요오드화 구리(I)(570mg)을 첨가하고 155℃에서 3시간 동안 계속 가열하였다. 상기 반응 혼합물을 방치하여 냉각하고 묽은 암모늄 용액(200ml) 및 DCM(150ml)으로 처리하고, 잘 흔든 후 키이슬레이거의 플러그를 통해 여과했다. 상기 유기 층을 분리, 건조(Na2SO4) 및 진공 농축했다. 잔류물을 에틸 아세테이트로 용출시키면서 염기성 암모니아 상에 크로마토그래피로 정제하여 표제 화합물을 베이지색 고체로 얻었다(63%).1-acetyl-5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D14, 500 mg, 1.5 in dry DMF (16 ml) and toluene (10 ml) mmole), potassium trifluoroacetate (410mg, 2.7mmole) and a copper iodide (I) (572mg, 3.0mmole) stirred solution using argon and stark heads to trap toluene / water Heated at 130 ° C. for 0.5 h. Replace the Dean and Stark heads with a condenser and heat the mixture at 155 ° C. for 34 hours, then add additional potassium trifluoroacetate (410 mg) and copper iodide (570 mg) for 3 hours at 155 ° C. Heating continued. The reaction mixture was left to cool, treated with dilute ammonium solution (200 ml) and DCM (150 ml), shaken well and filtered through a plug of a Kiesligger. The organic layer was separated, dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was purified by chromatography on basic ammonia, eluting with ethyl acetate to give the title compound as a beige solid (63%).

기재 항목 23List item 23

2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸-1H-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-trifluoromethyl-1H-indole

2M HCl 산(25ml) 및 에탄올(25ml) 중의 1-아세틸-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸-1H-인돌(D22, 260mg, 1.1mmole) 용액을 실온에서 7일간 보관한 후 부피가 약 25ml가 될 때까지 진공 농축했다. 상기 수성 잔류물을 고체 K2CO3로 염기화한 후 DCM으로 추출하고 상기 추출액을 건조(Na2SO4)하고 진공 농축시켜 표제 화합물을 베이지색 고체로 얻었다(300mg, 91%).1-acetyl-2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-trifluoromethyl-1H-indole (D22, in 2M HCl acid (25 ml) and ethanol (25 ml) 260 mg, 1.1 mmol) solution was stored at room temperature for 7 days and concentrated in vacuo until the volume became about 25 ml. The aqueous residue was basified with solid K 2 CO 3 , extracted with DCM and the extract was dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a beige solid (300 mg, 91%).

기재 항목 24Article item 24

4-(피리딘-4-일)나프트-1-일아세트산4- (pyridin-4-yl) naphth-1-ylacetic acid

1,2-디메톡시에탄(50ml) 중의 4-브로모나프트-1-일아세트산(1g, 3.78mmole, 문헌[J. Org. Chem., 1951, 16, 1588])을 피리딘-4-일보론산(465mg, 3.78mmole), 소듐 히드로젠 카보네이트(952mg, 11.3mmole) 및 물(10ml)로 처리했다. 상기 혼합물을 통해 15분간 아르곤 스트림을 거품 형성하게 한 후 테트라키스(트리페닐포스핀)팔라듐 (O)(200mg, 0.17mmole)을 첨가한 후 상기 혼합물을 환류 하에 18시간 동안 가열했다. 이어서 상기 혼합물을 검이 될 때까지 진공 농축하고 2M 소듐 히드록시드 용액 및 디클로로메탄 사이에 분배했다. 상기 수성 층을 분리하고, 칼륨 카보네이트 수용액을 첨가하여 pH7로 맞추고 디클로로메탄으로 추출했다. 상기 디클로로메탄 추출액을 건조(Na2SO4)하고 진공 농축하여 상기 표제 화합물을 얻고 이것을 에테르로부터 mp210-215℃인 니들로 결정화했다.4-Bromonaph-1-ylacetic acid (1 g, 3.78 mmol, J. Org. Chem., 1951, 16, 1588) in 1,2-dimethoxyethane (50 ml) was pyridine-4-ylboronic acid. (465 mg, 3.78 mmol), sodium hydrogen carbonate (952 mg, 11.3 mmol) and water (10 ml). The argon stream was bubbled through the mixture for 15 minutes, after which tetrakis (triphenylphosphine) palladium (O) (200 mg, 0.17 mmole) was added and the mixture was heated at reflux for 18 hours. The mixture was then concentrated in vacuo until a gum and partitioned between 2M sodium hydroxide solution and dichloromethane. The aqueous layer was separated, adjusted to pH 7 by addition of aqueous potassium carbonate solution and extracted with dichloromethane. The dichloromethane extract was dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound which crystallized from ether with a needle at mp210-215 ° C.

기재 항목 25List item 25

5-(피리딘-4-일)나프트-1-일아세트산5- (pyridin-4-yl) naphth-1-ylacetic acid

상기 표제 화합물을 기재 항목 24와 유사한 과정을 사용하여 5-브로모나프트-1-일아세트산(문헌[Bull. Soc. Chim. Fr., 1968, 7, 2957]) 및 피리딘-4-일보론산으로부터 제조하였다.The title compound was prepared from 5-bromonaft-1-ylacetic acid (Bull. Soc. Chim. Fr., 1968, 7, 2957) and pyridin-4-ylboronic acid using a procedure similar to that described in Item 24. Prepared.

기재 항목 26List item 26

퀴놀린-6-일 이소시아네이트Quinolin-6-yl Isocyanate

상기 표제 화합물을 설명1과 유사한 과정을 사용하여 6-퀴놀린카르복실산으로부터 제조하였다.The title compound was prepared from 6-quinolinecarboxylic acid using a procedure similar to Description 1.

기재 항목 27List item 27

3-(4-메틸피페라진-1-일)-1-니트로벤젠3- (4-methylpiperazin-1-yl) -1-nitrobenzene

K2CO3(52.5g, 0.385몰) 및 메클로르에타민 히드로클로라이드(31.4g, 0.16몰)을 2-부탄올(500ml) 중의 3-니트로아닐린(15.0g, 0.11몰) 용액에 첨가했다. 상기 혼합물을 아르곤 존재 하에 18시간 동안 교반하면서 환류한 후 추가의 메클로르에타민 히드로클로라이드(17.5g, 0.09몰) 및 K2CO3(25.0g, 0.18몰)을 첨가하고 환류 하에 가열을 24시간 동안 계속했다. 상기 2-부탄올을 진공에서 제거하고 잔류물을 H2O(300ml) 및 CH2Cl2(300ml) 사이에 분배시켰다. 상기 CH2Cl2을 분리하고 상기 수용액을 CH2Cl2(3×200ml)로 재-추출했다. 상기 유기물을 혼합하고, 건조(Na2SO4) 및 진공 농축하여 오렌지색 오일을 얻고 이것을 0-4% MeOH/CH2Cl2로 용출시키면서 실리카 겔 상에서 칼럼 크로마토그래피로 정제했다. 표제 화합물은 오렌지색 오일이었다(16.72g, 70%).K 2 CO 3 (52.5 g, 0.385 mol) and mechlorethamine hydrochloride (31.4 g, 0.16 mol) were added to a solution of 3-nitroaniline (15.0 g, 0.11 mol) in 2-butanol (500 ml). The mixture was refluxed with stirring for 18 hours in the presence of argon, followed by the addition of additional mechlorethamine hydrochloride (17.5 g, 0.09 mol) and K 2 CO 3 (25.0 g, 0.18 mol) and heating under reflux for 24 hours. Continued for a while. The 2-butanol was removed in vacuo and the residue was partitioned between H 2 O (300 ml) and CH 2 Cl 2 (300 ml). The CH 2 Cl 2 was separated and the aqueous solution was re-extracted with CH 2 Cl 2 (3 × 200 ml). The organics were mixed, dried (Na 2 SO 4 ) and concentrated in vacuo to give an orange oil which was purified by column chromatography on silica gel eluting with 0-4% MeOH / CH 2 Cl 2 . The title compound was orange oil (16.72 g, 70%).

기재 항목 28List item 28

3-(4-메틸피페라진-1-일)아닐린3- (4-methylpiperazin-1-yl) aniline

3-(4-메틸피페라진-1-일)-1-니트로벤젠(D27, 8.10g, 0.037몰)을 EtOH(250ml)에 용해시키고 실온 및 대기압에서 10% Pd/C(2g)으로 18시간 동안 수소화했다. 상기 촉매를 여과로 제거하고 상기 여과액을 진공 농축시켜 표제 화합물을 연한 황색 오일로 얻었다(6.64g, 95%).3- (4-Methylpiperazin-1-yl) -1-nitrobenzene (D27, 8.10 g, 0.037 mol) was dissolved in EtOH (250 ml) and 18 h at 10% Pd / C (2 g) at room temperature and atmospheric pressure. While hydrogenated. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to afford the title compound as a pale yellow oil (6.64 g, 95%).

기재 항목 29List item 29

7-(4-메틸피페라진-1-일)퀴놀린7- (4-methylpiperazin-1-yl) quinoline

3-(4-메틸피페라진-1-일)아닐린(D28, 6.6g, 0.035몰)을 글리세롤(8ml, 0.1몰)로 커버하고 진한 황산(5.2ml, 0.097몰)을 10분간 교반하면서 조심스럽게 적가했다. 공기 콘덴서를 조절하고 요오드(100mg)를 첨가하고 상기 반응물을 100℃에서 3시간 동안 교반하면서 가열한 후 150℃에서 4시간 동안 교반하면서 가열했다. 상기 반응물을 냉각시키고 물(250ml)에 쏟아 부었다. 상기 수용액을 K2CO3로 pH10으로 염기화하고 CH2Cl2(3×300ml)으로 추출했다. 상기 유기물을 혼합하고, 건조(Na2SO4)하고 진공 농축하여 짙은 갈색 오일을 얻었으며 이것을 2% MeOH/CH2Cl2로 용출시키면서 염기성 암모니아 상에서 칼럼 크로마토그래피로 정제했다. 표제 화합물은 오렌지색 고체였다(4.05g, 52%).Cover 3- (4-methylpiperazin-1-yl) aniline (D28, 6.6 g, 0.035 moles) with glycerol (8 ml, 0.1 moles) and carefully add concentrated sulfuric acid (5.2 ml, 0.097 moles) for 10 minutes while stirring I dropped it. The air condenser was adjusted and iodine (100 mg) was added and the reaction heated with stirring at 100 ° C. for 3 hours and then with stirring at 150 ° C. for 4 hours. The reaction was cooled and poured into water (250 ml). The aqueous solution was basified to pH 10 with K 2 CO 3 and extracted with CH 2 Cl 2 (3 × 300 ml). The organics were combined, dried (Na 2 SO 4 ) and concentrated in vacuo to afford a dark brown oil which was purified by column chromatography on basic ammonia, eluting with 2% MeOH / CH 2 Cl 2 . The title compound was an orange solid (4.05 g, 52%).

기재 항목 30List item 30

7-(4-메틸피페라진-1-일)-1,2,3,4-테트라히드로퀴놀린7- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydroquinoline

7-(4-메틸피페라진-1-일)퀴놀린(D29, 3.71g, 0.016몰)을 EtOH(100ml) 및 AcOH(5ml)에 용해시키고 50psi 및 실온에서 5% Pt/C(1.0g)으로 84시간 동안 수소화했다. 상기 촉매를 여과로 제거하고 용매를 진공에서 제거하며 상기 여과액을 10% Na2CO3(수용액) 및 CH2Cl2사이에서 분배했다. 상기 CH2Cl2를 분리, 건조(Na2SO4) 및 진공 농축하여 표제 화합물을 연한 오렌지/갈색 고체로 얻었다(3.60g, 95%).Dissolve 7- (4-methylpiperazin-1-yl) quinoline (D29, 3.71 g, 0.016 mol) in EtOH (100 ml) and AcOH (5 ml) and 5% Pt / C (1.0 g) at 50 psi and room temperature Hydrogenated for 84 hours. The catalyst was removed by filtration, the solvent was removed in vacuo and the filtrate was partitioned between 10% Na 2 CO 3 (aq) and CH 2 Cl 2 . The CH 2 Cl 2 was separated, dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a pale orange / brown solid (3.60 g, 95%).

기재 항목 31List item 31

7-(4-메틸피페라진-1-일)-1-트리플루오로아세틸-1,2,3,4-테트라히드로퀴놀린7- (4-methylpiperazin-1-yl) -1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline

트리플루오로아세트산 무수물(0.67ml, 4.8mmole)을 아르곤 존재 하에 얼음에서 냉각된 CH2Cl2(30ml) 중의 7-(4-메틸피페라진-1-일)-1,2,3,4-테트라히드로퀴놀린 (D30, 1.0g, 4.3mmole)에 적가했다. 0℃에서 30분 후에 상기 혼합물을 실온으로 30분간 가온한 후 묽은 Na2HCO3(수용액)으로 세척했다. 상기 CH2Cl2을 분리하고 건조(Na2SO4) 및 진공 농축하여 표제 화합물을 점액성의 황색 오일로 얻었다(1.42g, 100%).Trifluoroacetic anhydride (0.67 ml, 4.8 mmole) was added 7- (4-methylpiperazin-1-yl) -1,2,3,4- in CH 2 Cl 2 (30 ml) cooled on ice in the presence of argon. Add dropwise to tetrahydroquinoline (D30, 1.0 g, 4.3 mmol). After 30 minutes at 0 ° C. the mixture was warmed to room temperature for 30 minutes and then washed with dilute Na 2 HCO 3 (aq). The CH 2 Cl 2 was separated, dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a viscous yellow oil (1.42 g, 100%).

기재 항목 32List item 32

6-브로모-7-(4-메틸피페라진-1-일)-1-트리플루오로아세틸-1,2,3,4-테트라히드로퀴놀린6-bromo-7- (4-methylpiperazin-1-yl) -1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline

상기 표제 화합물을 기재 항목 14와 유사한 과정을 사용하여 7-(4-메틸피페라진-1-일)-1-트리플루오로아세틸-1,2,3,4-테트라히드로퀴놀린(D31)로부터 제조하였다.The title compound was prepared from 7- (4-methylpiperazin-1-yl) -1-trifluoroacetyl-1,2,3,4-tetrahydroquinoline (D31) using a procedure similar to that described in Item 14. It was.

기재 항목 33List item 33

6-브로모-7-(4-메틸피페라진-1-일)-1,2,3,4-테트라히드로퀴놀린6-bromo-7- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydroquinoline

K2CO3(고체)(0.50g, 3.6mmole)을 MeOH(30ml) 중의 6-브로모-7-(4-메틸피페라진-1-일)-1-트리플루오로아세틸-1,2,3,4-테트라히드로퀴놀린(D32, 0.74g, 1.8mmole )의 교반된 용액에 첨가했다. 실온에서 18시간 후에 상기 MeOH를 진공에서 제거하고 상기 잔류물을 CH2Cl2및 10% Na2CO3(수용액) 사이에서 분배했다. 상기 CH2Cl2을 분리, 건조(Na2SO4) 및 진공 농축하여 표제 화합물을 오렌지/갈색 고체로 얻었다(0.55g, 98%).K 2 CO 3 (solid) (0.50 g, 3.6 mmol) was added to 6-bromo-7- (4-methylpiperazin-1-yl) -1-trifluoroacetyl-1,2, in MeOH (30 ml). To a stirred solution of 3,4-tetrahydroquinoline (D32, 0.74 g, 1.8 mmole) was added. After 18 hours at room temperature the MeOH was removed in vacuo and the residue was partitioned between CH 2 Cl 2 and 10% Na 2 CO 3 (aq). The CH 2 Cl 2 was separated, dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as an orange / brown solid (0.55 g, 98%).

기재 항목 34List item 34

1-부티릴-2,3-디히드로-6-니트로-1H-인돌1-butyryl-2,3-dihydro-6-nitro-1H-indole

CH2Cl2(200ml) 중의 2,3-디히드로-6-니트로-1H-인돌(16.4g, 100mmole)을 실온에서 2시간 동안 계속적으로 교반하면서 부티릴 클로라이드(10.6g, 100mmole) 및 Et3N(10.1g, 100mmole)로 처리했다. 이어서 상기 반응물을 5N HCl로 세척하고 K2CO3수용액으로 포화시켰다. 이어서 상기 반응물을 건조(Na2SO4)하고 표제 화합물로 얻기 위해 페트롤로부터 니들 형태로 결정화된 검이 될 때까지 진공에서 농축했다(23.4g, 100%).2,3-dihydro-6-nitro-1H-indole (16.4 g, 100 mmol) in CH 2 Cl 2 (200 ml) was mixed with butyryl chloride (10.6 g, 100 mmol) and Et 3 with continuous stirring at room temperature for 2 hours. Treated with N (10.1 g, 100 mmol). The reaction was then washed with 5N HCl and saturated with aqueous K 2 CO 3 solution. The reaction was then dried (Na 2 SO 4 ) and concentrated in vacuo until a gum crystallized in needle form from petrol to obtain as the title compound (23.4 g, 100%).

기재 항목 35List item 35

6-아미노-2,3-디히드로-1-부티릴-1-H-인돌6-amino-2,3-dihydro-1-butyryl-1-H-indole

1-부티릴-2,3-디히드로-6-니트로-1H-인돌(D34, 19.8g, 84.4mmole)을 수소 대기 하 50psi에서 MeOH(200ml) 중의 숯(2g) 상에서 10% 팔라듐으로 온도가 60℃까지 상승되는 속도로 교반하고 수소 흡수를 멈추었다. 이어서 상기 반응물을 셀라이트를 통해 여과하고 반응 생성물이 남지 않도록 뜨거운 MeOH로 상기 셀라이트를 세척했다. 니들 형태로 상기 표제 화합물을 얻기 위해 상기 여과액을 진공에서 증발시켰다(13.3g, 77%).1-butyryl-2,3-dihydro-6-nitro-1H-indole (D34, 19.8 g, 84.4 mmole) was heated to 10% palladium on char (2 g) in MeOH (200 ml) at 50 psi under hydrogen atmosphere. Stirred at a rate rising to 60 ° C. and stopped hydrogen absorption. The reaction was then filtered through celite and the celite was washed with hot MeOH to leave no reaction product. The filtrate was evaporated in vacuo (13.3 g, 77%) to obtain the title compound in needle form.

기재 항목 36List item 36

1-부틸릴-2,3-디히드로-6-아이오도-1H-인돌1-butylyl-2,3-dihydro-6-iodo-1H-indole

0℃에서 진한 H2SO4(3ml) 및 물(35ml)의 혼합물 중의 6-아미노-1-부틸릴-2,3-디히드로-1H-인돌(D35, 3.0g, 0.015몰)을 물(10ml) 중의 소듐 니트리트(1.1g, 0.016몰)의 용액으로 적하(액체 표면에 닿는 첨가 퓨넬의 끝) 처리하고 이 동안 온도를 5℃이하로 유지했다. 이어서 이 혼합물을 0℃에서 물(10ml) 중의 칼륨 아이오다이드(2.66g, 0.016몰)의 용액에 적가하기 전에 3℃ 미만에서 추가 20분간 교반했다. 약간의 비등이 관찰되었고 짙은 오렌지색 현탁액이 형성되었다. 상기 혼합물을 방치하여 실온으로 되게 하는 동안 추가 1.5시간 동안 교반했다. 증발시 표제 화합물을 오렌지색 고체로 얻기 위해 생성물을 EtOAc(3×)로 추출하며 상기 유기물을 세척하고(Na2S2O3용액) 건조(Na2SO4)했다(3.3g, 70%).6-amino-1-butylyl-2,3-dihydro-1H-indole (D35, 3.0 g, 0.015 mol) in a mixture of concentrated H 2 SO 4 (3 ml) and water (35 ml) at 0 ° C 10 ml) was treated dropwise (the end of the addition funnel touching the liquid surface) with a solution of sodium nitrite (1.1 g, 0.016 mol), during which the temperature was kept below 5 ° C. The mixture was then stirred for an additional 20 minutes at <3 ° C. before dropwise addition to a solution of potassium iodide (2.66 g, 0.016 mol) in water (10 ml) at 0 ° C. Some boiling was observed and a dark orange suspension formed. The mixture was stirred for an additional 1.5 hours while left to come to room temperature. On evaporation the product was extracted with EtOAc (3 ×) to afford the title compound as an orange solid, the organics were washed (Na 2 S 2 O 3 solution) and dried (Na 2 SO 4 ) (3.3 g, 70%).

기재 항목 37List item 37

1-부틸릴-2,3-디히드로-6-(피리딘-4-일)-1H-인돌1-butylyl-2,3-dihydro-6- (pyridin-4-yl) -1H-indole

Na2CO3(3.85g, 36.4mmole)을 포함하는 디메톡시에탄(120ml) 및 물(30ml) 중의 1-부티릴-2,3-디히드로-6-아이오도-1H-인돌(D36, 3.28g, 10.4mmole)을 아르곤으로 1시간 동안 플러쉬하였다. 4-피리딜보론산(1.3g, 10.8mmole) 및 테트라키스(트리페닐포스핀)팔라듐(O)(600mg, 0.52mmole)을 상기 혼합물에 첨가하고 상기 혼합물을 1시간 동안 환류 하에 가열했다. 상기 혼합물을 방치하여 냉각시키고 진공 증발시키며 잔류물을 물과 CH2Cl2사이에서 분배했다. 상기 수용액을 CH2Cl2(2×)로 추가 추출하고, 상기 유기물을 혼합하고 건조하여(Na2SO4) 증발시 짙은 갈색 오일을 얻고, 이것을 플래쉬 크로마토그래피(5% MeOH/CH2Cl2용출액)에 의해 정제함으로써 상기 표제 화합물을 갈색 고체로 얻었다(1.5g, 54%).Dimethoxyethane (120 ml) with Na 2 CO 3 (3.85 g, 36.4 mmole) and 1-butyryl-2,3-dihydro-6-iodo-1H-indole (D36, 3.28) in water (30 ml) g, 10.4 mmol) was flushed with argon for 1 hour. 4-pyridylboronic acid (1.3 g, 10.8 mmol) and tetrakis (triphenylphosphine) palladium (O) (600 mg, 0.52 mmol) were added to the mixture and the mixture was heated at reflux for 1 hour. The mixture was left to cool, evaporated in vacuo and the residue partitioned between water and CH 2 Cl 2 . The aqueous solution was further extracted with CH 2 Cl 2 (2 ×), and the organics were mixed and dried (Na 2 SO 4 ) to give a dark brown oil upon evaporation, which was subjected to flash chromatography (5% MeOH / CH 2 Cl 2). Purification by eluent) afforded the title compound as a brown solid (1.5 g, 54%).

기재 항목 38List item 38

1-부티릴-2,3-디히드로-6-(1-메틸피페리딘-4-일)-1H-인돌1-butyryl-2,3-dihydro-6- (1-methylpiperidin-4-yl) -1H-indole

아이오도메탄(1.6g, 11.3mmole)을 아세톤(50ml) 중의 1-부티릴-2,3-디히드로 -6-(피리딘-4-일)-1H-인돌(D37, 1.5g, 5.63mmole) 용액에 첨가하고 상기 혼합물을 철야 보관했다. 여과로 에탄올(25ml) 및 물(25ml)에 용해시킨 오렌지색 고체(1.2g)을 얻었으며 상기 용액을 0℃로 냉각시켰다. 소듐 보로히드라이드(166mg, 4.4mmole)을 상기 용액에 5분에 걸쳐 일부분씩 첨가하고 상기 혼합물을 추가 10분간 교반했다. 2M NaOH 용액(16ml) 및 물(40ml)를 상기 혼합물에 첨가하고 생성물을 CH2Cl2(2×)로 추출하고, 건조(Na2SO4) 및 진공 증발하여 갈색 오일(1.0g)을 얻었다. 이어서 상기 오일을 에탄올(50ml)에 용해시키고 50psi 및 50℃에서 72시간 동안 10% Pd-C(100mg)으로 수소화했다. 여과 및 진공에서 여과액을 증발시킴으로써 상기 표제 화합물을 백색 고체로 얻었다(710mg, 44%).Iodomethane (1.6 g, 11.3 mmol) was converted to 1-butyryl-2,3-dihydro-6- (pyridin-4-yl) -1 H-indole (D37, 1.5 g, 5.63 mmol) in acetone (50 ml). The solution was added and the mixture was stored overnight. Filtration gave an orange solid (1.2 g) dissolved in ethanol (25 ml) and water (25 ml) and the solution was cooled to 0 ° C. Sodium borohydride (166 mg, 4.4 mmole) was added to the solution in portions over 5 minutes and the mixture was stirred for an additional 10 minutes. 2M NaOH solution (16ml) and water (40ml) were added to the mixture and the product was extracted with CH 2 Cl 2 (2 ×), dried (Na 2 SO 4 ) and vacuum evaporated to give a brown oil (1.0 g). . The oil was then dissolved in ethanol (50 ml) and hydrogenated with 10% Pd-C (100 mg) at 50 psi and 50 ° C. for 72 hours. Filtration and evaporation of the filtrate in vacuo gave the title compound as a white solid (710 mg, 44%).

기재 항목 39List item 39

5-브로모-2,3-디히드로-6-(1-메틸피페리딘-4-일)-1H-인돌5-Bromo-2,3-dihydro-6- (1-methylpiperidin-4-yl) -1H-indole

N-브로모숙신이미드(454mg, 2.55mmole)을 아세트산(20ml) 중의 1-부티릴-2,3-디히드로-6-(1-메틸피페리딘-4-일)-1H-인돌(D38, 2.32mmole)의 교반 용액에 첨가하고 상기 혼합물을 실온에서 철야 교반했다. 상기 혼합물을 물로 희석시키고 고체 K2CO3로 염기화했다. 상기 유기물을 CH2Cl2로 추출하고 건조(Na2SO4)하며 진공에서 증발시킴으로써 회백색 고체(890mg)를 얻었다. 에탄올(20ml) 및 2M NaOH용액(30ml) 중의 고체(790mg, 2.16mmole) 일부분을 아르곤 존재 하 80℃에서 72시간 동안 가열했다. 생성물을 CH2Cl2로 추출하고, 유기물을 건조(Na2SO4)하고 진공 증발시켜 상기 표제 화합물을 오렌지색 고체를 얻었다(647mg, 100%).N-bromosuccinimide (454 mg, 2.55 mmol) was dissolved in 1-butyryl-2,3-dihydro-6- (1-methylpiperidin-4-yl) -1H-indole in acetic acid (20 ml). D38, 2.32 mmol) was added and the mixture was stirred overnight at room temperature. The mixture was diluted with water and basified with solid K 2 CO 3 . The organics were extracted with CH 2 Cl 2 , dried (Na 2 SO 4 ) and evaporated in vacuo to yield an off-white solid (890 mg). A portion of solid (790 mg, 2.16 mmol) in ethanol (20 ml) and 2 M NaOH solution (30 ml) was heated at 80 ° C. for 72 h in the presence of argon. The product was extracted with CH 2 Cl 2 and the organics were dried (Na 2 SO 4 ) and evaporated in vacuo to give the title compound as an orange solid (647 mg, 100%).

NH는 발견되지 않음.NH not found.

기재 항목 40List item 40

4-(t-부톡시카르보닐아미노)아닐린4- (t-butoxycarbonylamino) aniline

디-tert-부틸 디카보네이트(4.25ml, 18.5mmole)을 0℃에서 CH2Cl2(50ml) 중의 페닐렌디아민(2.0g, 18.5mmole)의 교반 용액에 첨가하고 상기 혼합물을 교반하였으며 이 때 16시간 동안 실온으로 가온했다. 진공에서 증발시킴으로써 디-Boc 화합물이 잔류물을 형성하도록 하면서 순도 80%의 상기 표제 화합물을 얻었다(3.79g, 98%).Di-tert-butyl dicarbonate (4.25 ml, 18.5 mmol) was added to a stirred solution of phenylenediamine (2.0 g, 18.5 mmol) in CH 2 Cl 2 (50 ml) at 0 ° C. and the mixture was stirred at this time 16 Warmed to RT. Evaporation in vacuo gave the title compound with a purity of 80% (3.79 g, 98%), allowing the di-Boc compound to form a residue.

기재 항목 41List item 41

4-(피리미딘-2-일)벤조산4- (pyrimidin-2-yl) benzoic acid

연한 담황색(buff colored) 가루로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 방법으로 4-카르복시페닐보론산 및 2-브로모피리미딘으로부터 제조하였다(35%).The title compound obtained as a light buff colored powder was prepared from 4-carboxyphenylboronic acid and 2-bromopyrimidine (35%) in a similar manner as described in Item 2.

기재 항목 42List item 42

4-(피리미딘-2-일)페닐 이소시아네이트4- (pyrimidin-2-yl) phenyl isocyanate

연한 노란색 가루로 수득된 상기 표제 화합물을 기재 항목 1와 유사한 방법으로 4-(피리미딘-2-일)벤조산(D41)로부터 제조하였다(83%).The title compound obtained as a pale yellow powder was prepared from 4- (pyrimidin-2-yl) benzoic acid (D41) in a similar manner as described in Item 1 (83%).

(1H NMR-CDCl3에 불용성이므로 관찰되지 않음).(Not observed as insoluble in 1 H NMR-CDCl 3 ).

기재 항목 43List item 43

5-클로로-2,3-디히드로-1-(4-아이오도페닐아미노카르보닐)-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-methylpiperazin-1-yl) -1H-indole

회백색 가루로 수득된 상기 표제 화합물을 실시예 4와 유사한 방법으로 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 4-아이오도아닐린으로부터 제조하였다(54%).The title compound obtained as an off-white powder was subjected to 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) and 4- in a similar manner to Example 4. Prepared from iodoaniline (54%).

기재 항목 44List item 44

N-[4-(피리딘-4-일)나프트-1-일]아세트아미드N- [4- (pyridin-4-yl) naphth-1-yl] acetamide

CH2Cl2(10ml) 중의 아세틸 클로라이드(0.5ml, 7.0mmole) 용액을 0℃에서 CH2Cl2및 트리에틸아민(1.0ml, 7.1mmole) 중의 4-(피리딘-4-일)나프트-1-일아민 (D2, 1.5g, 6.8mmole) 용액에 적가하고 혼합물을 교반했으며, 이 때 1시간 동안 방치하여 실온으로 되게 했다. 상기 용액을 수성의 10% Na2CO3로 세척하고 유기물을 건조(Na2SO4)하고 진공 증발시켜 상기 표제 화합물을 황색 고체로 얻었다(1.9g, 100%).A solution of acetyl chloride (0.5 ml, 7.0 mmol) in CH 2 Cl 2 (10 ml) was washed with 4- (pyridin-4-yl) naphth- in CH 2 Cl 2 and triethylamine (1.0 ml, 7.1 mmol) at 0 ° C. To the 1-ylamine (D2, 1.5 g, 6.8 mmole) solution was added dropwise and the mixture was stirred, at which point it was left to stand for 1 hour to room temperature. The solution was washed with aqueous 10% Na 2 CO 3 and the organics were dried (Na 2 SO 4 ) and evaporated in vacuo to afford the title compound as a yellow solid (1.9 g, 100%).

기재 항목 45List item 45

N-[4-(1-메틸-1,2,5,6-테트라히드로피리딘-4-일)나프트-1-일]아세트아미드N- [4- (1-methyl-1,2,5,6-tetrahydropyridin-4-yl) naphth-1-yl] acetamide

아이오도메탄(1.92g, 13.6mmole)을 아세톤(50ml) 중의 N-[4-(피리딘-4-일)나프트-1-일]아세트아미드(D44, 1.8g, 6.8mmole) 용액에 첨가하고 상기 혼합물을 철야 보관했다. 여과로 에탄올(25ml) 및 물(25ml)에 용해시킨 황색 고체(1.2g)을 얻었으며 0℃로 냉각하고 5분간 소듐 보로히드라이드(166mg, 4.4mmole)로 일부분씩 처리한 후 1시간 동안 교반했다. 수성의 10% NaOH(16ml) 및 물(40ml)를 상기 혼합물에 첨가하고 생성물을 CH2Cl2로 추출하고, 건조(Na2SO4)하고 진공에서 증발시켜 상기 표제 화합물을 갈색 고체로 얻었다(880mg, 44%).Iodomethane (1.92 g, 13.6 mmol) was added to a solution of N- [4- (pyridin-4-yl) naphth-1-yl] acetamide (D44, 1.8 g, 6.8 mmol) in acetone (50 ml) The mixture was stored overnight. Filtration gave a yellow solid (1.2 g) dissolved in ethanol (25 ml) and water (25 ml), cooled to 0 ° C., treated with sodium borohydride (166 mg, 4.4 mmol) for 5 minutes and stirred for 1 hour. did. Aqueous 10% NaOH (16 ml) and water (40 ml) were added to the mixture and the product was extracted with CH 2 Cl 2 , dried (Na 2 SO 4 ) and evaporated in vacuo to afford the title compound as a brown solid ( 880 mg, 44%).

기재 항목 46List item 46

4-(1-메틸피페리딘-4-일)나프트-1-일아민4- (1-methylpiperidin-4-yl) naphth-1-ylamine

에탄올(50ml) 중의 N-[4-(1-메틸-1,2,5,6-테트라히드로피리딘-4-일)나프트-1-일]아세트아미드(D45, 800mg, 2.9mmole) 용액을 50psi 및 50℃에서 192시간 동안 10% Pd-C로 수소화했다. 셀라이트를 통해 여과시키고 여과액을 증발시킴으로써 증발시 백색 고체(683mg)을 얻었다. 상기 고체를 에탄올(10ml) 및 수성의 2M NaOH(16ml)에 용해시키고 아르곤 존재 하에 환류시키면서 72시간 동안 가열했다. 상기 혼합물을 CH2Cl2로 추출하고, 유기물을 건조(Na2SO4)하고 진공 증발시켜 상기 표제 화합물을 오렌지색 오일로 얻었다(520mg, 76%).A solution of N- [4- (1-methyl-1,2,5,6-tetrahydropyridin-4-yl) naphth-1-yl] acetamide (D45, 800 mg, 2.9 mmol) in ethanol (50 ml) Hydrogenated with 10% Pd-C for 192 hours at 50 psi and 50 ° C. Filtration through celite and evaporation of the filtrate gave a white solid (683 mg) upon evaporation. The solid was dissolved in ethanol (10 ml) and aqueous 2M NaOH (16 ml) and heated for 72 hours while refluxing in the presence of argon. The mixture was extracted with CH 2 Cl 2 , the organics were dried (Na 2 SO 4 ) and evaporated in vacuo to afford the title compound as an orange oil (520 mg, 76%).

기재 항목 47List item 47

4-(4-아미노페닐)-2-메틸옥사졸4- (4-aminophenyl) -2-methyloxazole

THF(70ml) 중의 2-메틸-4-(4-니트로페닐)옥사졸(1.70g, 8.2mmole, 문헌[J. Het. Chem. 1981, 18,885]) 및 탄소 상의 10% 팔라듐(0.20g) 혼합물을 대기압 하의 수소 존재 하에서 42시간 동안 교반했다. 상기 혼합물을 여과시키고 진공에서 건조 농축시켰다. 잔류물을 CH2Cl2중의 2% MeOH로 용출시키면서 실리카 겔 상에서 크로마토그래피에 의해 정제했다. 상기 표제 화합물은 황색 가루로 얻었다 (0.92g).A mixture of 2-methyl-4- (4-nitrophenyl) oxazole (1.70 g, 8.2 mmol, J. Het. Chem. 1981, 18,885) in THF (70 ml) and 10% palladium (0.20 g) on carbon Was stirred for 42 h in the presence of hydrogen under atmospheric pressure. The mixture was filtered and concentrated to dryness in vacuo. The residue was purified by chromatography on silica gel eluting with 2% MeOH in CH 2 Cl 2 . The title compound was obtained as a yellow powder (0.92 g).

기재 항목 48List item 48

4-(2-메틸-피리딘-4-일)벤조산4- (2-Methyl-pyridin-4-yl) benzoic acid

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 4-브로모-2-메틸피리딘(문헌[J. Org. Chem. 1985, 50, 4410]) 및 4-카르복시페닐보론산으로부터 백색 고체로 제조하였다(84%).The title compound was prepared as a white solid from 4-bromo-2-methylpyridine (J. Org. Chem. 1985, 50, 4410) and 4-carboxyphenylboronic acid using a procedure similar to that described in Item 2. (84%).

기재 항목 49List item 49

4-(2-메틸-피리딘-4-일)아닐린4- (2-methyl-pyridin-4-yl) aniline

아민을 베이지색 고체로 얻기 위해 상기 표제 화합물을 이소시아네이트를 형성한 후 NaOH를 사용하여 염기성 가수분해를 함으로써 기재 항목 1과 유사한 과정을 사용하여 4-(2-메틸-피리딘-4-일)벤조산(D48)로부터 제조하였다(31%).To obtain the amine as a beige solid, the title compound formed an isocyanate followed by basic hydrolysis with NaOH to give 4- (2-methyl-pyridin-4-yl) benzoic acid ( D48) (31%).

기재 항목 50List item 50

N-(tert-부틸로옥시카르보닐)-4-아이오도아닐린N- (tert-butylooxycarbonyl) -4-iodoaniline

디-tert-부틸 디카보네이드(2.99g, 0.014몰)을, 이 후 4-디메틸아미노피리딘을 촉매로 작용할 수 있는 양으로 건조 디클로로메탄(20ml) 중의 4-아이오도아닐린(3g, 0.014몰) 용액에 첨가했다. 상기 반응물을 상온에서 철야 교반한 후 물(2×20ml)로 세척하고 건조(MgSO4)하였다. 여과 및 증발로 회백색 고체를 얻었다(1.90g, 43%).4-iodoaniline (3 g, 0.014 mole) in dry dichloromethane (20 ml) in an amount capable of catalyzing di-tert-butyl dicarbonide (2.99 g, 0.014 mole) followed by 4-dimethylaminopyridine Added to solution. The reaction was stirred overnight at room temperature, washed with water (2 x 20ml) and dried (MgSO 4 ). Filtration and evaporation gave an off-white solid (1.90 g, 43%).

기재 항목 51List item 51

N-(tert-부틸옥시카르보닐)-4-(티아졸-2-일)아닐린N- (tert-butyloxycarbonyl) -4- (thiazol-2-yl) aniline

건조 DMF(6ml) 중의 N-(tert-부틸옥시카르보닐)-4-아이오도아닐린(D50, 319mg, 1mmole), 비스(피나콜라토)디보론(279mg, 1.1mole), DCM(1:1)(24mg, 0.029mmole)과 1,1′-비스(디페닐포스피노)퍼로센 디클로로팔라듐(II) 복합체 및 칼륨 아세테이트(294mg, 3mmole)을 80℃에서 2시간 동안 가열했다. 냉각 후에 2-브로모티아졸(328mg, 2mmole), 2M 소듐 카보네이트(2.5ml) 및 DCM(1:1)(24mg, 0.029mmole)과 1,1′-비스(디페닐포스피노)퍼로센 디클로로팔라듐(II) 복합체를 첨가하고 반응물을 80℃에서 18시간 동안 가열했다. 냉각 후에 상기 용액을 물(20ml)로 희석시켰다. 에틸 아세테이트(2×20ml)로 추출한 후 건조(MgSO4)시키고 감소된 압력 하에서 여과시키고 증발시켜 오일을 얻었다. 이것을 헥산 중의 10% 에틸 아세테이트로 용출시키면서 실리카 겔 상에서 크로마토그래피하여 상기 표제 화합물을 오일(137mg, 50%)로 얻었다.N- (tert-butyloxycarbonyl) -4-iodoaniline (D50, 319 mg, 1 mmol), bis (pinacolato) diboron (279 mg, 1.1 mole), DCM (1: 1) in dry DMF (6 ml) ) (24 mg, 0.029 mmol) and 1,1′-bis (diphenylphosphino) perrocene dichloropalladium (II) complex and potassium acetate (294 mg, 3 mmole) were heated at 80 ° C. for 2 hours. 2-bromothiazole (328 mg, 2 mmole), 2M sodium carbonate (2.5 ml) and DCM (1: 1) (24 mg, 0.029 mmol) and 1,1′-bis (diphenylphosphino) perrocene dichloropalladium after cooling (II) The complex was added and the reaction heated at 80 ° C. for 18 hours. After cooling the solution was diluted with water (20 ml). Extract with ethyl acetate (2 × 20 ml), then dry (MgSO 4 ), filter under reduced pressure and evaporate to give an oil. This was chromatographed on silica gel eluting with 10% ethyl acetate in hexanes to give the title compound as an oil (137 mg, 50%).

기재 항목 52List item 52

4-(티아졸-2-일)아닐린4- (thiazol-2-yl) aniline

디클로로메탄(2ml) 및 트리플루오로아세트산(0.1ml) 중의 N-(tert-부틸옥시카르보닐)-4-(티아졸-2-일)아닐린(D51, 122mg, 0.44mmole)용액을 상온에서 18시간 동안 교반한 후 물(20ml)를 첨가했다. 상기 수용액 상을 디클로로메탄(2×10ml)로 추출하고 상기 추출액을 10% 수성 소듐 히드로젠 카보네이트(2×20ml)로 세척한 후 건조(MgSO4)시키고, 밝은 황색 오일을 얻기 위해 감소된 압력 하에서 증발시켰으며 이를 가만히 두면서 고체화 했다(70mg, 90%).N- (tert-butyloxycarbonyl) -4- (thiazol-2-yl) aniline (D51, 122mg, 0.44mmole) solution in dichloromethane (2ml) and trifluoroacetic acid (0.1ml) After stirring for hours water (20 ml) was added. The aqueous phase was extracted with dichloromethane (2 × 10 ml) and the extract was washed with 10% aqueous sodium hydrogen carbonate (2 × 20 ml) and then dried (MgSO 4 ) under reduced pressure to obtain a light yellow oil. Evaporated and solidified while leaving still (70 mg, 90%).

기재 항목 53List item 53

4-(이소퀴놀린-2-일)벤조산4- (isoquinolin-2-yl) benzoic acid

회백색 고체로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 4-카르복시페닐보론산 및 4-브로모이소퀴놀린으로부터 제조하였다(58%).The title compound obtained as an off-white solid was prepared from 4-carboxyphenylboronic acid and 4-bromoisoquinoline (58%) using a procedure similar to that described in Item 2.

기재 항목 54List item 54

4-(이소퀴놀린-4-일)페닐 이소시아네이트4- (isoquinolin-4-yl) phenyl isocyanate

상기 표제 화합물을 기재 항목 1과 유사한 과정을 사용하여 4-(이소퀴놀린-4-일)벤조산(D53)으로부터 제조하였다. 상기 이소시아네이트는 순수 화합물로 농축하지 않고 톨루엔 용액으로 사용하였다.The title compound was prepared from 4- (isoquinolin-4-yl) benzoic acid (D53) using a procedure similar to that described in Item 1. The isocyanate was used as a toluene solution without concentrating as a pure compound.

기재 항목 55List item 55

4-(퀴놀린-3-일)벤조산4- (quinolin-3-yl) benzoic acid

회백색 고체(72%)로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 4-카르복시페닐보론산 및 3-브로모퀴놀린으로부터 제조하였다.The title compound obtained as an off-white solid (72%) was prepared from 4-carboxyphenylboronic acid and 3-bromoquinoline using a similar procedure as described in Item 2.

기재 항목 56List item 56

4-(퀴놀린-3-일)페닐 이소시아네이트4- (quinolin-3-yl) phenyl isocyanate

상기 표제 화합물을 기재 항목 51과 유사한 과정을 사용하여 4-(퀴놀린-3-일)벤조산(D55)으로부터 제조하였다. 상기 이소시아네이트는 순수 화합물로 농축시키기 않고 톨루엔 용액으로 사용되었다.The title compound was prepared from 4- (quinolin-3-yl) benzoic acid (D55) using a procedure similar to that described in Item 51. The isocyanate was used as a toluene solution without concentrating to pure compound.

기재 항목 57List item 57

4-(퀴놀린-8-일)벤조산4- (quinolin-8-yl) benzoic acid

회백색 고체로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 4-카르복시페닐보론산 및 8-브로모퀴놀린으로부터 제조하였다(65%).The title compound obtained as an off-white solid was prepared from 4-carboxyphenylboronic acid and 8-bromoquinoline (65%) using a procedure similar to that described in Item 2.

기재 항목 58List item 58

4-(퀴놀린-8-일)페닐 이소시아네이트4- (quinolin-8-yl) phenyl isocyanate

상기 표제 화합물을 기재 항목 51과 유사한 과정을 사용하여 4-(퀴놀린-8-일)벤조산(D57)로부터 제조하였다. 상기 이소시아네이트는 순수 화합물로 농축시키기 않고 톨루엔 용액으로 사용되었다.The title compound was prepared from 4- (quinolin-8-yl) benzoic acid (D57) using a procedure similar to that described in Item 51. The isocyanate was used as a toluene solution without concentrating to pure compound.

기재 항목 59List item 59

3-브로모-2,6-디메틸피리딘(D59a) 및 4-브로모-2,6-디메틸피리딘 (D59b)3-bromo-2,6-dimethylpyridine (D59a) and 4-bromo-2,6-dimethylpyridine (D59b)

아르곤 존재 하의 실온에서 1,2-디클로로에탄(250ml) 중의 옥시브롬화인 (25g, 0.085몰)의 교반 용액을 2,6-루티딘-N-옥시드(10g, 0.081몰)로 처리한 후 환류 하에 6시간 동안 가열했다. 상기 혼합물을 방치하여 냉각시킨 후 잘 교반된 얼음/물(400ml) 속으로 서서히 쏟아 붓고 고체 K2CO3를 첨가하여 염기화했다. 상기 수성 혼합물을 디클로로메탄으로 추출하고 추출액을 건조(Na2SO4)하고 진공 농축시켰다. 상기 잔류물을 4개의 성분으로 분리하기 위해서 1:1 에테르/60-80 페트롤로 용출시키면서 실리카 겔 상에서 크로마토그래피했다. 제2 성분이 황색 오일인 3-브로모-2,6-디메틸피리딘이었고(2.5g, 21%);A stirred solution of phosphorus oxybromide (25 g, 0.085 mol) in 1,2-dichloroethane (250 ml) at room temperature in the presence of argon was treated with 2,6-lutidine-N-oxide (10 g, 0.081 mol) and then refluxed. Under heating for 6 hours. The mixture was left to cool and then poured slowly into well stirred ice / water (400 ml) and basified by addition of solid K 2 CO 3 . The aqueous mixture was extracted with dichloromethane and the extract was dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 1: 1 ether / 60-80 petrol to separate into four components. The second component was 3-bromo-2,6-dimethylpyridine, a yellow oil (2.5 g, 21%);

제3 성분이 연한 황색 오일로 4-브로모-2,6-디메틸피리딘이었다(1.5g, 12%).The third component was 4-bromo-2,6-dimethylpyridine as a pale yellow oil (1.5 g, 12%).

기재 항목 60List item 60

4-(2,6-디메틸-피리딘-4-일)벤조산4- (2,6-Dimethyl-pyridin-4-yl) benzoic acid

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 4-브로모-2,6-디메틸피리딘(D59b)와 4-카르복시페닐보론산으로부터 백색 고체로 제조하였다(76%).The title compound was prepared as a white solid (76%) from 4-bromo-2,6-dimethylpyridine (D59b) and 4-carboxyphenylboronic acid using a procedure similar to that described in Item 2.

산 양성자는 발견되지 않음.Acid protons not found.

기재 항목 61List item 61

4-(2,6-디메틸-피리딘-3-일)벤조산4- (2,6-Dimethyl-pyridin-3-yl) benzoic acid

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 3-브로모-2,6-디메틸피리딘(D59a)와 4-카르복시페닐보론산으로부터 베이지색 고체로 제조하였다 (76%).The title compound was prepared as a beige solid from 3-bromo-2,6-dimethylpyridine (D59a) and 4-carboxyphenylboronic acid using a procedure similar to that described in Item 2 (76%).

산 양성자는 발견되지 않음.Acid protons not found.

기재 항목 62List item 62

4-(2,6-디메틸-피리딘-4-일)페닐 이소시아네이트4- (2,6-dimethyl-pyridin-4-yl) phenyl isocyanate

상기 표제 화합물을 기재 항목 1과 유사한 과정을 사용하여 4-(2,6-디메틸-피리딘 -4-일)벤조산(D60)으로부터 제조하였다. 상기 이소시아네이트는 순수 화합물로 농축시키지 않고 톨루엔 용액으로 사용했다.The title compound was prepared from 4- (2,6-dimethyl-pyridin-4-yl) benzoic acid (D60) using a procedure similar to that described in Item 1. The isocyanate was used as a toluene solution without concentrating the pure compound.

기재 항목 63List item 63

4-(2,6-디메틸-피리딘-3-일)페닐 이소시아네이트4- (2,6-dimethyl-pyridin-3-yl) phenyl isocyanate

상기 표제 화합물을 기재 항목 1과 유사한 과정을 사용하여 4-(2,6-디메틸-피리딘 -3-일)벤조산(D61)으로부터 제조하였다. 상기 이소시아네이트는 순수 화합물로 농축시키지 않고 톨루엔 용액으로 사용했다.The title compound was prepared from 4- (2,6-dimethyl-pyridin-3-yl) benzoic acid (D61) using a procedure similar to that described in Item 1. The isocyanate was used as a toluene solution without concentrating the pure compound.

기재 항목 64List item 64

8-브로모-5-니트로퀴놀린8-bromo-5-nitroquinoline

8-브로모퀴놀린(1.5g, 7.2mmole)을 잘 교반된 진한 H2SO4(5ml), 진한 HNO3(10ml) 및 발연 HNO3(2ml) 용액에 적가하고 얼음에서 냉각시켰다. 상기 혼합물을 65℃에서 30시간 동안 가열하고 난 후 냉각시키고 교반하면서 H2O(350ml) 속으로 쏟아 부었다. 형성된 침전물을 여과시키고 H2O로 세척하며 진공 건조시켜 상기 표제 화합물을 연한 우유빛 고체로 얻었다(1.10g, 60%).8-bromoquinoline (1.5 g, 7.2 mmole) was added dropwise to well stirred concentrated H 2 SO 4 (5 ml), concentrated HNO 3 (10 ml) and fuming HNO 3 (2 ml) solutions and cooled on ice. The mixture was heated at 65 ° C. for 30 h and then poured into H 2 O (350 ml) with cooling and stirring. The precipitate formed was filtered off, washed with H 2 O and dried in vacuo to afford the title compound as a pale milky solid (1.10 g, 60%).

기재 항목 65List item 65

5-니트로-8-페닐퀴놀린5-nitro-8-phenylquinoline

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 8-브로모-5-니트로퀴놀린(D64) 및 페닐보론산으로부터 오렌지/갈색 고체로 제조하였다(99%).The title compound was prepared as an orange / brown solid (99%) from 8-bromo-5-nitroquinoline (D64) and phenylboronic acid using a procedure similar to that described in Item 2.

기재 항목 66List item 66

5-아미노-8-페닐퀴놀린5-amino-8-phenylquinoline

상기 표제 호합물을 기재 항목 20과 유사한 과정을 사용하여 5-니트로-8-페닐퀴놀린(D65)으로부터 오렌지/갈색 고체로 제조하였다(97%).The title compound was prepared as an orange / brown solid (97%) from 5-nitro-8-phenylquinoline (D65) using a similar procedure as described in Item 20.

기재 항목 67List item 67

6-아세트아미도-2-메틸퀴놀린6-acetamido-2-methylquinoline

상기 표제 화합물을 기재 항목 8과 유사한 과정을 사용하여 6-아미노-2-메틸퀴놀린 및 아세트산 무수물을 사용하여 녹색 고체로 제조하였다(95%).The title compound was prepared as a green solid using 6-amino-2-methylquinoline and acetic anhydride (95%) using a procedure similar to that described in Item 8.

설명68Description68

6-아미노-2-(2-페닐에테닐)퀴놀린6-amino-2- (2-phenylethenyl) quinoline

아세트산 무수물(6ml) 중의 6-아세트아미도-2-메틸퀴놀린(D67, 600mg, 3.0mmole)현탁액을 벤즈알데히드(954mg, 9.0mmole)로 처리하고 혼합물을 120℃에서 40시간 동안 가열한 후 냉각시키며 상기 아세트산 무수물을 진공에서 제거했다. 잔류물을 2M NaOH(30ml) 및 EtOH(10ml)에 용해시키고 교반하면서 환류 하에 가열하였다. 18시간 후에 EtOH를 진공에서 제거하고 잔류물을 EtOAc (3×100ml)로 추출했다. 상기 유기물을 혼합하고 건조(Na2SO4)하고 진공 농축시켜 탁한 갈색 오일을 얻었으며 이것을 EtOAc로 용출시키면서 염기성 알루미나 상에서 크로마토그래피로 정제했다. 상기 표제 화합물은 갈색 고체(210mg, 28%)로 수득되었으며 부분적으로 벤질 알코올로 부분적으로 혼탁되었다.The 6-acetamido-2-methylquinoline (D67, 600 mg, 3.0 mmol) suspension in acetic anhydride (6 ml) was treated with benzaldehyde (954 mg, 9.0 mmol) and the mixture was heated at 120 ° C. for 40 hours before cooling Acetic anhydride was removed in vacuo. The residue was dissolved in 2M NaOH (30 ml) and EtOH (10 ml) and heated under reflux with stirring. After 18 h EtOH was removed in vacuo and the residue was extracted with EtOAc (3 × 100 ml). The organics were combined, dried (Na 2 SO 4 ) and concentrated in vacuo to afford a cloudy brown oil which was purified by chromatography on basic alumina eluting with EtOAc. The title compound was obtained as a brown solid (210 mg, 28%) and partly cloudy with benzyl alcohol.

기재 항목 69List item 69

6-아미노-2-(2-페닐에틸)퀴놀린6-amino-2- (2-phenylethyl) quinoline

상기 표제 화합물을 기재 항목 20과 유사한 과정을 사용하여 6-아미노-2-(2-페닐에테닐)퀴놀린(D68)으로부터 부분적으로 벤젠 알코올로 혼탁된 황색 오일로 제조하였다(41%).The title compound was prepared from a 6-amino-2- (2-phenylethenyl) quinoline (D68) as a yellow oil partially clouded with benzene alcohol using a procedure similar to that described in Item 20 (41%).

기재 항목 70List item 70

2-(3-니트로페녹시)피리미딘2- (3-nitrophenoxy) pyrimidine

건조 DMF 중의 3-니트로페놀(2.08g, 15mmole), 2-브로모피리미딘(2.38g, 15mmole) 및 무수 칼륨 카보네이트(2.76g, 20mmole)의 교반된 혼합물을 80℃에서 4시간 동안 가열했다. 상기 냉각 혼합물을 진공에서 건조 농축시키고 잔류물을 CH2Cl2(75ml) 및 물(50ml) 사이에서 분배했다. 상기 유기 상을 분리하고, 물로 세척하며 건조(Na2SO4)하고 진공에서 건조 농축시켰다. 잔류물을 CH2Cl2으로 용출시키면서 실리카 겔 상에서 크로마토그래피로 정제했다. 상기 표제 화합물은 연한 황색 가루(1.94g, 60%)로 단리되었다.A stirred mixture of 3-nitrophenol (2.08 g, 15 mmol), 2-bromopyrimidine (2.38 g, 15 mmol) and anhydrous potassium carbonate (2.76 g, 20 mmol) in dry DMF was heated at 80 ° C. for 4 hours. The cold mixture was concentrated to dryness in vacuo and the residue was partitioned between CH 2 Cl 2 (75 ml) and water (50 ml). The organic phase was separated, washed with water, dried (Na 2 SO 4 ) and concentrated to dryness in vacuo. The residue was purified by chromatography on silica gel eluting with CH 2 Cl 2 . The title compound was isolated as pale yellow powder (1.94 g, 60%).

기재 항목 71List item 71

3-(피리미딘-2-일옥시)아닐린3- (pyrimidin-2-yloxy) aniline

진한 HCl(0.7ml)을 메탄올(30ml) 중의 2-(3-니트로페녹시)피리미딘(D70, 0.65g, 3mmole) 및 염화 주석(II)(2.28g, 12mmole)의 교반 용액에 첨가했다. 혼합물을 환류 하에 2시간 동안 가열하고 냉각하며 거의 건조되도록 진공 농축했다. 잔류물을 CH2Cl2(50ml) 및 물(25ml)로 처리하고 pH를 12로 맞추기 위해 2N NaOH 용액을 첨가했다. 상기 혼합물을 여과시키고 유기상을 분리하고, 물로 세척하며 건조(Na2SO4)하고 건조를 위해 진공 농축시켜 표제 화합물을 황색 가루로 얻었다 (0.50g, 89%).Concentrated HCl (0.7 ml) was added to a stirred solution of 2- (3-nitrophenoxy) pyrimidine (D70, 0.65 g, 3 mmoles) and tin (II) chloride (2.28 g, 12 mmoles) in methanol (30 ml). The mixture was heated at reflux for 2 h, cooled and concentrated in vacuo to dryness. The residue was treated with CH 2 Cl 2 (50 ml) and water (25 ml) and 2N NaOH solution was added to adjust pH to 12. The mixture was filtered, the organic phase was separated, washed with water, dried (Na 2 SO 4 ) and concentrated in vacuo to dryness to afford the title compound as a yellow powder (0.50 g, 89%).

기재 항목 72List item 72

N-메틸-4-니트로-N-(피리미딘-2-일)아닐린N-methyl-4-nitro-N- (pyrimidin-2-yl) aniline

칼륨 tert-부톡시드(1.79g, 16mmole)을 건조 DMF(25ml) 중의 N-메틸-4-니트로아닐린(2.20g, 14.5mmole)의 교반 용액에 첨가했다. 실온에서 1시간 동안 교반한 후, 2-브로모피리미딘(2.30g, 14.5mmole)을 첨가하고 상기 혼합물을 80℃에서 6시간 동안 가온한 후 실온에서 철야 저장했다. 진공에서 건조 농축시킨 후, 잔류물을 CH2Cl2(100ml) 및 물(30ml)로 분배했다. 상기 유기 상을 물로 세척하고 건조(Na2SO4)하며 건조 농축시켰다. 디에틸 에테르에서 잔류물을 연화시킴으로써 연한 황색-오렌지색 가루의 표제 화합물을 얻었다(1.24g, 37%).Potassium tert-butoxide (1.79 g, 16 mmol) was added to a stirred solution of N-methyl-4-nitroaniline (2.20 g, 14.5 mmol) in dry DMF (25 ml). After stirring for 1 hour at room temperature, 2-bromopyrimidine (2.30 g, 14.5 mmole) was added and the mixture was warmed at 80 ° C. for 6 hours and then stored at room temperature overnight. After concentrated to dryness in vacuo, the residue was partitioned between CH 2 Cl 2 (100 ml) and water (30 ml). The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated to dryness. The residue was triturated in diethyl ether to give the title compound as a pale yellow-orange powder (1.24 g, 37%).

기재 항목 73List item 73

4-[N-메틸-N-(피리미딘-2-일)아미노]아닐린4- [N-methyl-N- (pyrimidin-2-yl) amino] aniline

메탄올(70ml) 및 에틸 아세테이트(70ml) 중의 N-메틸-4-니트로-N-(피리미딘-2-일)아닐린(D72, 1.30g, 5.6mmole)용액을 탄소(0.25g) 상에서 10% 팔라듐으로 처리하고 수소 존재 하 1기압 하에서 48시간 동안 진동시켰다. 여과된 혼합물을 건조 농축시키고 잔류물을 디에틸 에테르에서 연화시켜 연한 오렌지-갈색 가루의 표제 화합물을 얻었다(0.78g, 68%).N-methyl-4-nitro-N- (pyrimidin-2-yl) aniline (D72, 1.30 g, 5.6 mmole) solution in methanol (70 ml) and ethyl acetate (70 ml) was dissolved in 10% palladium on carbon (0.25 g). And oscillated for 48 hours under 1 atmosphere in the presence of hydrogen. The filtered mixture was concentrated to dryness and the residue was triturated in diethyl ether to give the title compound as a pale orange-brown powder (0.78 g, 68%).

기재 항목 74List item 74

5-(피리딘-4-일)나프트-1-일아민5- (pyridin-4-yl) naphth-1-ylamine

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 5-브로모-1-나프틸아민(JP 08151353 A2) 및 4-피리딜보론산을 사용하여 제조하였다.The title compound was prepared using 5-bromo-1-naphthylamine (JP 08151353 A2) and 4-pyridylboronic acid using a procedure similar to that described in Item 2.

기재 항목 75List item 75

N-[5-(피리딘-4-일)나프트-1-일]아세트아미드N- [5- (pyridin-4-yl) naphth-1-yl] acetamide

상기 표제 화합물을 기재 항목 44와 유사한 방법으로 5-(피리딘-4-일)나프트-1-일아민(D74)으로부터 제조하였다. MH+263.The title compound was prepared from 5- (pyridin-4-yl) naphth-1-ylamine (D74) in a similar manner as described in Item 44. MH + 263.

기재 항목 76List item 76

N-[5-(1-메틸-1,2,5,6-테트라히드로피리딘-4-일)나프트-1-일]아세트아미드N- [5- (1-methyl-1,2,5,6-tetrahydropyridin-4-yl) naphth-1-yl] acetamide

상기 표제 화합물을 기재 항목 45와 유사한 방법으로 N-[5-(피리딘-4-일)나프트-1-일]아세트아미드(D75)로부터 제조하였다. MH+281.The title compound was prepared from N- [5- (pyridin-4-yl) naphth-1-yl] acetamide (D75) in a similar manner as described in Item 45. MH + 281.

기재 항목 77List item 77

5-(1-메틸피페리딘-4-일)나프트-1-일아민5- (1-methylpiperidin-4-yl) naphth-1-ylamine

상기 표제 화합물을 기재 항목 46과 유사한 방법으로 N-[5-(1-메틸-1,2,5,6-테트라히드로피리딘-4-일)나프트-1-일]아세트아미드(D76)로부터 제조하였다.The title compound was obtained from N- [5- (1-methyl-1,2,5,6-tetrahydropyridin-4-yl) naphth-1-yl] acetamide (D76) in a similar manner as described in Item 46. Prepared.

기재 항목 78List item 78

N-2-(4-니트로페닐)에틸-트리플루오로아세트아미드N-2- (4-nitrophenyl) ethyl-trifluoroacetamide

디클로로메탄(100ml) 중의 트리플루오로아세트산 무수물(10.6ml) 용액을 0℃에서 2,6-루티딘(17.4ml) 및 4-니트로펜에틸아민 히드로클로라이드(15.2g, 75mmole)의 교반 용액에 적가했다. 상기 혼합물을 아르곤 존재 하 25℃에서 철야 교반한 후 묽은 시트르산(x2), 염수로 세척하고 건조(Na2SO4)했다. 유기 상의 물질로부터 상기 표제 화합물을 연한 황색 고체로 얻었다(19.04g).A solution of trifluoroacetic anhydride (10.6 ml) in dichloromethane (100 ml) was added dropwise to a stirred solution of 2,6-lutidine (17.4 ml) and 4-nitrophenethylamine hydrochloride (15.2 g, 75 mmol) at 0 ° C. did. The mixture was stirred overnight at 25 ° C. in the presence of argon and then washed with dilute citric acid (× 2), brine and dried (Na 2 SO 4 ). The title compound was obtained as a pale yellow solid from the material of the organic phase (19.04 g).

기재 항목 79List item 79

7-니트로-1,2,3,4-테트라히드로-2-트리플루오로아세틸이소퀴놀린7-nitro-1,2,3,4-tetrahydro-2-trifluoroacetylisoquinoline

아세트산(10ml) 및 진한 H2SO4(15ml) 중의 N-2-(4-니트로페닐)에틸-트리플루오로아세트아미드(D78, 2.26g, 9.15mmole)을 문헌[G.E.Stokker, Tet. Lett., 1996, 37, 5453]의 과정에 따라 25℃에서 20시간 동안 교반했다. 마무리 작업으로 상기 표제 화합물을 백색 고체(2.17g)로 얻었다.N-2- (4-nitrophenyl) ethyl-trifluoroacetamide (D78, 2.26 g, 9.15 mmol) in acetic acid (10 ml) and concentrated H 2 SO 4 (15 ml) is described in GEStokker, Tet. Lett., 1996, 37, 5453] was stirred for 20 hours at 25 ℃. Finishing gave the title compound as a white solid (2.17 g).

기재 항목 80List item 80

7-니트로-1,2,3,4-테트라히드로이소퀴놀린7-nitro-1,2,3,4-tetrahydroisoquinoline

7-니트로-1,2,3,4-테트라히드로-2-트리플루오로아세틸이소퀴놀린(D79, 17.2g; 63mmole)을 10% 수성 메탄올(660ml) 중의 칼륨 카보네이트 용액(46.6g)을 사용하여 실온에서 가수분해했다. 디클로로메탄으로 마무리 작업을 하여 상기 표제 화합물을 얻었다(11g).7-nitro-1,2,3,4-tetrahydro-2-trifluoroacetylisoquinoline (D79, 17.2 g; 63 mmole) using a solution of potassium carbonate (46.6 g) in 10% aqueous methanol (660 ml) Hydrolysis at room temperature. Finishing with dichloromethane gave the title compound (11 g).

기재 항목 81List item 81

2-메틸-7-니트로-1,2,3,4-테트라히드로이소퀴놀린2-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

7-니트로-1,2,3,4-테트라히드로이소퀴놀린(D80, 2.08g; 11.7mmole)을 문헌[G. M. Carrera 및 D. S. Garvey, J. Het. Chem., 1992, 29, 847]의 과정에 따라 80℃에서 2시간 동안 88% 포름산(3.45ml) 및 37% 수성 포름알데히드(5.88ml)로 처리했다. 10% 소듐 히드록시드로 먼저 염기화시킨 후 에틸 아세테이트로 추출함으로써 오렌지색 검(2.3g)을 얻었다. 0-3% 메탄올/에틸 아세테이트 중의 실리카겔 상에서 크로마토그래피를 함으로써 오렌지색 고체(1.7g)로 상기 표제 화합물을 얻었다. MH+193.7-nitro-1,2,3,4-tetrahydroisoquinoline (D80, 2.08 g; 11.7 mmoles) is described by GM Carrera and DS Garvey, J. Het. Chem., 1992, 29, 847] were treated with 88% formic acid (3.45 ml) and 37% aqueous formaldehyde (5.88 ml) at 80 ° C. for 2 hours. An orange gum (2.3 g) was obtained by basifying first with 10% sodium hydroxide and then extracting with ethyl acetate. Chromatography on silica gel in 0-3% methanol / ethyl acetate gave the title compound as an orange solid (1.7 g). MH + 193.

기재 항목 82List item 82

7-아미노-2-메틸-1,2,3,4-테트라히드로이소퀴놀린7-amino-2-methyl-1,2,3,4-tetrahydroisoquinoline

메탄올(40ml) 중의 2-메틸-7-니트로-1,2,3,4-테트라히드로이소퀴놀린(D81, 0.25g; 1.3mmole)을 대기압 하에서 철야로 탄소 상의 10% 팔라듐(100mg)으로 수소화했다. 상기 촉매를 키이슬레이거 패드를 통해 여과시킴으로써 제거하고 진공 증발시켜 상기 표제 화합물을 백색 고체(213mg)로 얻었다. MH+163.2-Methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline (D81, 0.25 g; 1.3 mmoles) in methanol (40 ml) was hydrogenated overnight at 10% palladium on carbon (100 mg) under atmospheric pressure. . The catalyst was removed by filtration through a Keisligger pad and evaporated in vacuo to yield the title compound as a white solid (213 mg). MH + 163.

기재 항목 83List item 83

8-브로모퀴놀린-2,4-디카르복실산8-bromoquinoline-2,4-dicarboxylic acid

7-브로로이사틴(10g, 0.044몰, 문헌[Proc. Royal Soc., 1958, 148, 481])을 1분 동안, 이후 피루브산(5.35ml, 0.077몰)을 1분 동안 H2O(64ml) 중의 KOH(21.3g, 0.38몰)의 교반 용액에 첨가했다. 잔여 용액을 실온에서 1시간 동안 교반한 후 환류 하에 1.5시간 동안 가열하고 실온으로 냉각시킨 후 H2O(100ml)로 희석시키고 여과시켰다. 여과액을 pH1이 될 때까지 진한 염산으로 산성화시키고 여과시키며 고체를 H2O로 세척하고 진공 하에서 건조했다. 상기 표제 화합물은 갈색 고체(10.1g, 77%)였다.7-Broisatin (10 g, 0.044 moles, Proc. Royal Soc., 1958, 148, 481) for 1 minute followed by pyruvic acid (5.35 ml, 0.077 moles) for 1 minute H 2 O (64 ml). To a stirred solution of KOH (21.3 g, 0.38 mol) in water. The remaining solution was stirred at room temperature for 1 hour, then heated to reflux for 1.5 hours, cooled to room temperature, diluted with H 2 O (100 ml) and filtered. The filtrate was acidified with concentrated hydrochloric acid until pH1 and filtered, the solid was washed with H 2 O and dried under vacuum. The title compound was a brown solid (10.1 g, 77%).

산 양성자는 발견되지 않음.Acid protons not found.

기재 항목 84List item 84

8-브로모퀴놀린-4-카르복실산8-bromoquinoline-4-carboxylic acid

니트로벤젠(40ml) 중의 8-브로모퀴놀린-2,4-디카르복실산(D83, 10g, 34mmole) 용액을 환류 하에 2시간 동안 가열한 후 방치하여 실온으로 냉각시키고 헥산(60ml)로 희석시킨 후 상기 표제 화합물을 갈색 고체로써 여과해 냈다(8.5g, 100%).A solution of 8-bromoquinoline-2,4-dicarboxylic acid (D83, 10 g, 34 mmole) in nitrobenzene (40 ml) was heated under reflux for 2 hours, then left to cool to room temperature and diluted with hexane (60 ml). The title compound was then filtered off as a brown solid (8.5 g, 100%).

산 양성자는 발견되지 않음Acid protons not found

기재 항목 85List item 85

8-페닐퀴놀린-4-카르복실산8-phenylquinoline-4-carboxylic acid

상기 표제 화합물은 기재 항목 2와 유사한 과정을 사용하여 8-브로모퀴놀린-4-카르복실산(D84) 및 페닐보론산으로부터 갈색 고체로 제조되었다(63%).The title compound was prepared as a brown solid (63%) from 8-bromoquinoline-4-carboxylic acid (D84) and phenylboronic acid using a procedure similar to that described in Item 2.

산 양성자는 발견되지 않음.Acid protons not found.

기재 항목 86List Item 86

8-페닐퀴놀린-4-일 이소시아네이트8-phenylquinolin-4-yl isocyanate

상기 표제 화합물을 기재 항목 1과 유사한 과정을 사용하여 8-페닐퀴놀린-4-카르복실산(D85)로부터 제조하였다. 이소시아네이트를 순수 화합물로 농축시키지 않고 톨루엔 용액으로서 사용하였다.The title compound was prepared from 8-phenylquinoline-4-carboxylic acid (D85) using a procedure similar to that described in Item 1. Isocyanate was used as toluene solution without concentrating to pure compound.

기재 항목 87List item 87

4-아미노-2-메틸페닐보론산4-Amino-2-methylphenylboronic acid

아르곤 하 0℃의 디클로로메탄(250ml) 중의 4-브로모-3-메틸아닐린(20g, 0.107몰) 및 트리에틸아민(33ml, 0.237몰) 교반 용액을 디클로로메탄(100ml) 중의 비스(클로로디메틸실릴)에탄(25.3g, 0.12몰) 용액으로 15분에 걸쳐 적하 처리하였다. 혼합물을 실온으로 가온하고 20시간 교반한 후, 여과 및 진공 농축하였다. 잔류물을 60-80 페트롤(400ml)로 추출하고 여과물을 진공 농축하여 스타베이스 (stabas)를 오렌지색 오일로서 남겼다(35g, 100%). 이를 건조 THF(400ml)에 용해시키고 아르곤 하에 -65℃로 냉각시킨 후 헥산 중의 2.5M n-부틸리튬(52ml, 0.13몰)으로 15분에 걸쳐 적하 처리하였다. 혼합물을 -65℃에서 1시간 교반한 후, 트리이소프로필붕산염(30ml, 0.13몰)으로 10분에 걸쳐 적하 처리하고 -65℃에서 추가 1.5시간 동안 교반한 후, NH4Cl 포화 수용액(100ml)으로 처리하고 방치하여 실온이 되게 하였다. 혼합물을 물(200ml)로 희석하고 진한 염산(50ml)으로 산성화하고 20분간 교반한 후, 진공 하에 농축하여 부피가 약 400ml가 되게 하였다. 수성 잔류물을 에틸 아세테이트로 세척한 후 고체 K2CO3를 첨가하여 염기화하였다. 염기성 혼합물을 에틸 아세테이트로 추출하고 추출물을 건조시키고(Na2SO4) 진공 농축하여 부피가 약 150ml가 될 때 고체가 침전되어 나오기 시작하였다. 혼합물을 8℃로 냉각시키고 고체를 여과해 내고 건조시켜 상기 표제 화합물을 백색 고체로서 생성하였다(9.2g, 51%).A stirred solution of 4-bromo-3-methylaniline (20 g, 0.107 mol) and triethylamine (33 ml, 0.237 mol) in dichloromethane (250 ml) at 0 ° C. under argon was added bis (chlorodimethylsilyl in dichloromethane (100 ml). The solution was added dropwise over 15 minutes with a ethane (25.3 g, 0.12 mol) solution. The mixture was allowed to warm to rt and stirred for 20 h, then filtered and concentrated in vacuo. The residue was extracted with 60-80 petrol (400 ml) and the filtrate was concentrated in vacuo to leave the star base as an orange oil (35 g, 100%). It was dissolved in dry THF (400 ml) and cooled to -65 ° C. under argon and then dropwise treated with 2.5 M n-butyllithium (52 ml, 0.13 mol) in hexane over 15 minutes. The mixture was stirred at −65 ° C. for 1 hour, then treated dropwise with triisopropylborate (30 ml, 0.13 mol) over 10 minutes and stirred at −65 ° C. for an additional 1.5 hours, followed by saturated aqueous NH 4 Cl solution (100 ml). And left to stand at room temperature. The mixture was diluted with water (200 ml), acidified with concentrated hydrochloric acid (50 ml) and stirred for 20 minutes, then concentrated in vacuo to a volume of about 400 ml. The aqueous residue was washed with ethyl acetate and then basified by addition of solid K 2 CO 3 . The basic mixture was extracted with ethyl acetate, the extract was dried (Na 2 SO 4 ) and concentrated in vacuo to precipitate a solid when the volume reached about 150 ml. The mixture was cooled to 8 ° C. and the solid was filtered off and dried to give the title compound as a white solid (9.2 g, 51%).

산 양성자는 발견되지 않음.Acid protons not found.

기재 항목 88List item 88

4-(2,6-디메틸-피리딘-4-일)-3-메틸아닐린4- (2,6-dimethyl-pyridin-4-yl) -3-methylaniline

상기 표제 화합물은 기재 항목 2에서와 유사한 과정을 사용하여 4-클로로-2,6-디메틸피리딘 (문헌[Chem. Abs. 1952, 46, 4541]) 및 4-아미노-2-메틸페닐보론산 (D87)으로부터 베이지색 고체로서 제조되었다(4%).The title compound was prepared using a procedure similar to that described in Item 2, 4-chloro-2,6-dimethylpyridine (Chem. Abs. 1952, 46, 4541) and 4-amino-2-methylphenylboronic acid (D87 ) As a beige solid (4%).

기재 항목 89Listed Items 89

3-메틸-4-(6-메틸-피리딘-2-일)아닐린3-methyl-4- (6-methyl-pyridin-2-yl) aniline

상기 표제 화합물을 기재 항목 2에서와 유사한 과정을 사용하여 2-브로모-6-메틸피리딘 및 4-아미노-2-메틸페닐보론산(D87)으로부터 베이지색 고체로서 제조하였다(100%).The title compound was prepared as a beige solid from 2-bromo-6-methylpyridine and 4-amino-2-methylphenylboronic acid (D87) using a procedure similar to that described in Item 2 (100%).

기재 항목 90List item 90

5-카르복시-나프트-1-일보론산5-carboxy-naphth-1-ylboronic acid

아르곤 하 -60℃의 건조 THF(1000ml) 중의 5-브로모-1-나프토산(문헌[Bull. Soc. Chim. Fr., 1968, 7, 2957], 22.3g, 0.089몰) 교반 용액을 헥산 중의 1.6M n-부틸리튬(125ml, 0.20몰)으로 15분에 걸쳐 적하 처리하였다. 제1 당량을 가하자 초기의 갈색 용액에서 베이지색 침전이 형성되었으며 제2 당량을 가하자 다시 용해되었다. 생성된 용액을 -60℃에서 40분간 교반한 후, 트리이소프로필붕산염(51ml, 0.22몰)을 가하고, 혼합물을 -60℃에서 추가 1시간 동안 교반한 후 점진적으로 -10℃까지 가열하였다. NH4Cl 포화 수용액을 가하고(300ml), 이어 물(400ml), 그 후 5M 염산(200ml)을 첨가하였다. 생성된 혼합물을 진공 농축하여 부피가 약 1000ml가 되게 한 후, 40% NaOH 용액을 첨가하여 염기화하고 에틸 아세테이트로 세척하였다. 상기 수용액을 과량의 5M 염산에 첨가하고 침전되어 나오는 고체를 여과해 내고 물로 세척 및 건조하여 백색 고체(9.67g)를 생성하였으며, 이는 1-나프토산과 함께 약 50%의 표제 화합물을 함유하였다.A stirred solution of 5-bromo-1-naphthoic acid (Bull. Soc. Chim. Fr., 1968, 7, 2957), 22.3 g, 0.089 mol) in dry THF (1000 ml) at -60 ° C. under argon was added with hexane. The dropwise treatment was performed with 1.6 M n-butyllithium (125 ml, 0.20 mol) in 15 minutes. Beige precipitate formed in the initial brown solution upon the addition of the first equivalent and dissolved again when the second equivalent was added. The resulting solution was stirred at −60 ° C. for 40 minutes, then triisopropylborate (51 ml, 0.22 mol) was added and the mixture was stirred at −60 ° C. for an additional 1 hour and then gradually heated to −10 ° C. NH 4 Cl saturated aqueous solution was added (300 ml) followed by water (400 ml) followed by 5M hydrochloric acid (200 ml). The resulting mixture was concentrated in vacuo to a volume of about 1000 ml, then basified by addition of 40% NaOH solution and washed with ethyl acetate. The aqueous solution was added to excess 5M hydrochloric acid and the precipitated solid was filtered off, washed with water and dried to give a white solid (9.67 g) which contained about 50% of the title compound with 1-naphthoic acid.

기재 항목 91List item 91

5-(6-메틸-피리딘-2-일)-1-나프토산5- (6-Methyl-pyridin-2-yl) -1-naphthoic acid

상기 표제 화합물을 기재 항목 2에서와 유사한 과정을 사용하여 2-브로모-6-메틸피리딘 및 5-카르복시-나프트-1-일보론산(D90)으로부터 베이지색 고체로 제조하였다(46%).The title compound was prepared as a beige solid from 2-bromo-6-methylpyridine and 5-carboxy-naphth-1-ylboronic acid (D90) using a procedure similar to that described in Item 2 (46%).

산 양성자는 발견되지 않음.Acid protons not found.

기재 항목 92List item 92

5-(6-메틸-피리딘-2-일)나프트-1-일 이소시아네이트5- (6-methyl-pyridin-2-yl) naphth-1-yl isocyanate

상기 표제 화합물을 기재 항목 1에서와 유사한 과정을 사용하여 5-(6-메틸-피리딘-2-일)-1-나프토산(D 91)으로부터 제조하였다. 상기 이소시아네이트를 단리하지 않고 톨루엔 용액으로서 다음 단계에 사용하였다.The title compound was prepared from 5- (6-methyl-pyridin-2-yl) -1-naphthoic acid (D 91) using a procedure similar to that described in Item 1. The isocyanate was used in the next step as a toluene solution without isolation.

기재 항목 93List item 93

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-트리플루오로아세틸-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-trifluoroacetyl-1H-indole

상기 표제 화합물을 기재 항목 31에서와 유사한 과정을 사용하여 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 베이지색 고체로 제조하였다 (96%).The title compound was converted from 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) to a beige solid using a procedure similar to that described in Item 31. Prepared (96%).

기재 항목 94List item 94

5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-트리플루오로아세틸-1H-인돌5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1-trifluoroacetyl-1H-indole

아르곤 하 1,2-디클로로에탄(200ml) 중의 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)트리플루오로아세틸-1H-인돌(D93, 7.0g, 10mmole) 교반 용액에 디이소프로필에틸아민(3.50ml, 20mmole)에 이어 1-클로로에틸 클로로포름산염 (4.35ml, 40mmole)을 첨가하였다. 1시간 후 혼합물을 묽은 NaHCO3수용액으로 세척한 후 건조하고(Na2SO4) 진공 농축하여 갈색 고체를 생성하였다(8.86g, 100%). MeOH(200ml) 중의 현탁액을 3시간 환류하며 교반한 후 냉각시키고 MeOH를 진공에서 제거하였다. 잔류물을 묽은 NaHCO3수용액 및 CH2Cl2사이에 분배하였다. CH2Cl2를 분리하고 상기 수용액을 CH2Cl2(2x50ml)로 재추출하였다. 유기층을 혼합, 건조(Na2SO4)하고 진공 농축하여 표제 화합물을 갈색 고체로서 생성하였다(4.79g, 72%).5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) trifluoroacetyl-1H-indole (D93, 7.0 g, in argonol 1,2-dichloroethane (200 ml) Diisopropylethylamine (3.50 ml, 20 mmol) was added followed by 1-chloroethyl chloroformate (4.35 ml, 40 mmol). After 1 h the mixture was washed with dilute NaHCO 3 aqueous solution, dried (Na 2 SO 4 ) and concentrated in vacuo to yield a brown solid (8.86 g, 100%). The suspension in MeOH (200 ml) was stirred at reflux for 3 hours, then cooled and MeOH was removed in vacuo. The residue was partitioned between dilute NaHCO 3 aqueous solution and CH 2 Cl 2 . CH 2 Cl 2 was separated and the aqueous solution was reextracted with CH 2 Cl 2 ( 2 × 50 ml). The organic layer was mixed, dried (Na 2 SO 4 ) and concentrated in vacuo to yield the title compound as a brown solid (4.79 g, 72%).

NH는 발견되지 않음.NH not found.

기재 항목 95List item 95

6-(4-아세틸피페라진-1-일)-5-클로로-2,3-디히드로-1-트리플루오로아세틸-1H-인돌6- (4-acetylpiperazin-1-yl) -5-chloro-2,3-dihydro-1-trifluoroacetyl-1H-indole

얼음에서 냉각된 CH2Cl2(50ml) 중의 5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-트리플루오로아세틸-1H-인돌(D94, 1.0g, 3.0mmole) 교반 용액을 아세트산 무수물(0.34g, 3.3mmole)로 처리한 후 실온이 될 때까지 가온했다. 6시간 후 혼합물을 묽은 NaHCO3(수용액)으로 세척하고 건조(Na2SO4)하고 진공 농축하여 표제 화합물을 갈색 고체로서 생성하였다(1.10g, 97%).5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1-trifluoroacetyl-1H-indole (D94, 1.0 g, in ice-cold CH 2 Cl 2 (50 ml) 3.0 mmol) The stirred solution was treated with acetic anhydride (0.34 g, 3.3 mmol) and then warmed to room temperature. After 6 h the mixture was washed with dilute NaHCO 3 (aq), dried (Na 2 SO 4 ) and concentrated in vacuo to yield the title compound as a brown solid (1.10 g, 97%).

기재 항목 96List item 96

6-(4-아세틸피페라진-1-일)-5-클로로-2,3-디히드로-1H-인돌6- (4-acetylpiperazin-1-yl) -5-chloro-2,3-dihydro-1H-indole

상기 표제 화합물은 기재 항목 33과 유사한 과정을 사용하여 6-(4-아세틸피페라진-1-일)-5-클로로-2,3-디히드로-1-트리플루오로아세틸-1H-인돌(D95)로부터 갈색 기포로 제조되었다(81%).The title compound was prepared in the same manner as described in Item 33 using 6- (4-acetylpiperazin-1-yl) -5-chloro-2,3-dihydro-1-trifluoroacetyl-1H-indole (D95). ) As a brown bubble (81%).

NH는 발견되지 않음.NH not found.

기재 항목 97List item 97

5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-6- (4-ethylpiperazin-1-yl) -1H-indole

아르곤 하 실온에서 THF(30ml) 중의 6-(4-아세틸피페라진-1-일)-5-클로로-2,3-디히드로-1H-인돌(D96, 0.65g, 2.3mmole) 교반 용액을 THF(9.3ml, 9.3mmole)중의 1M 보란-THF 복합체로 처리한 후 환류 하에서 5시간 동안 가열했다. 상기 혼합물을 0℃로 냉각시킨 후 메탄올(25ml) 중의 진한 염산(6ml)으로 적하 처리했다. 30분 후, 상기 용액을 2시간 동안 가열하여 환류시킨 후 진공 농축시켰다. 상기 잔류물을 에틸 아세테이트(50ml) 및 2M 염산(40ml)으로 처리하고 잘 진동시킨 후 수성 층을 분리하고 K2CO3로 염기화시킨 후 디클로로메탄으로 추출했다. 상기 추출액을 건조(Na2SO4)하고, 진공 농축시킨 후 잔류물을 2-10% 메탄올/디클로로에메탄으로 용출시키면서 실리카 겔 상에서 크로마토그래피로 정제하여 상기 표제 화합물을 베이지색 고체로 얻었다(0.31g, 50%).Agitated a 6- (4-acetylpiperazin-1-yl) -5-chloro-2,3-dihydro-1H-indole (D96, 0.65 g, 2.3 mmole) stirred solution in THF (30 ml) at room temperature under argon to THF. Treated with 1M borane-THF complex in (9.3ml, 9.3mmole) and heated under reflux for 5 hours. The mixture was cooled to 0 ° C. and then dropwise treated with concentrated hydrochloric acid (6 ml) in methanol (25 ml). After 30 minutes, the solution was heated to reflux for 2 hours and then concentrated in vacuo. The residue was treated with ethyl acetate (50 ml) and 2M hydrochloric acid (40 ml) and shaken well, the aqueous layer was separated, basified with K 2 CO 3 and extracted with dichloromethane. The extract was dried (Na 2 SO 4 ), concentrated in vacuo and the residue purified by chromatography on silica gel, eluting with 2-10% methanol / dichloromethane to afford the title compound as a beige solid (0.31). g, 50%).

기재 항목 98Article item 98

6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1-트리플루오로아세틸-1H-인돌6- [4- (tert-butyloxycarbonyl) piperazin-1-yl] -5-chloro-2,3-dihydro-1-trifluoroacetyl-1H-indole

상기 표제 화합물을 기재 항목 95와 유사한 과정을 사용하여 5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-트리플루오로아세틸-1H-인돌(D94) 및 디-tert-부틸 디카보네이트로부터 갈색 기포로 제조하였다(100%).The title compound was prepared using a procedure similar to that described in Item 95, using 5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1-trifluoroacetyl-1H-indole (D94) and di Prepared as brown foam from -tert-butyl dicarbonate (100%).

기재 항목 99List item 99

6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1H-인돌6- [4- (tert-butyloxycarbonyl) piperazin-1-yl] -5-chloro-2,3-dihydro-1H-indole

상기 표제 화합물을 기재 항목 33과 유사한 과정을 사용하여 6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1-트리플루오로아세틸-1H-인돌(D98)로부터 갈색 고체로 제조하였다(84%).The title compound was purified using 6- [4- (tert-butyloxycarbonyl) piperazin-1-yl] -5-chloro-2,3-dihydro-1-trifluoro using a procedure similar to that described in Item 33. Prepared as a brown solid from acetyl-1H-indole (D98) (84%).

기재 항목 100Article item 100

6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌6- [4- (tert-butyloxycarbonyl) piperazin-1-yl] -5-chloro-2,3-dihydro-1- [4- (pyridin-4-yl) naphth-1-yl Aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1H-인돌(D99)로부터 황색/갈색 고체로 제조하였다(67%).The title compound was subjected to 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 6- [4- (tert-butyloxycarbonyl) piperazine-1 using a procedure similar to Example 4. Prepared as a yellow / brown solid from -yl] -5-chloro-2,3-dihydro-1H-indole (D99) (67%).

기재 항목 101List item 101

6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌6- [4- (tert-butyloxycarbonyl) piperazin-1-yl] -5-chloro-2,3-dihydro-1- [5- (pyridin-4-yl) naphth-1-yl Aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일아민(D74) 및 6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1H-인돌(D99)로부터 황색/갈색 고체로 제조하였다(74%).The title compound was subjected to a procedure similar to Example 4 using 5- (pyridin-4-yl) naphth-1-ylamine (D74) and 6- [4- (tert-butyloxycarbonyl) piperazine-1 Prepared as a yellow / brown solid from -yl] -5-chloro-2,3-dihydro-1H-indole (D99) (74%).

기재 항목 102List item 102

4-(피리다진-3-일)벤조산4- (pyridazin-3-yl) benzoic acid

상기 표제 화합물을 기재 항목 24와 유사한 과정을 사용하여 3-클로로피리다진 및 4-카르복시페닐보론산으로부터 갈색 고체(87%)로 제조하였다. MS:m/z=199(M-H).The title compound was prepared as a brown solid (87%) from 3-chloropyridazine and 4-carboxyphenylboronic acid using a procedure similar to that described in Item 24. MS: m / z = 199 (M-H).

기재 항목 103List item 103

4-(피리다진-2-일)벤조산4- (pyridazin-2-yl) benzoic acid

상기 표제 화합물을 기재 항목 24와 유사한 과정을 사용하여 2-클로로피라진 및 4-카르복시보론산으로부터 백색 고체로 제조하였다(88%). MS:m/z=156(M-CO2).The title compound was prepared as a white solid from 2-chloropyrazine and 4-carboxyboronic acid using a procedure similar to that described in Item 24 (88%). MS: m / z = 156 (M-CO 2 ).

기재 항목 104List item 104

6-페닐니코틴산6-phenylnicotinic acid

상기 표제 화합물을 기재 항목 24와 유사한 과정을 사용하여 6-클로로니코틴산 및 페닐보론산으로부터 회백색 고체(54%)로 제조하였다. MS:m/z=200(MH+).The title compound was prepared as an off-white solid (54%) from 6-chloronicotinic acid and phenylboronic acid using a procedure similar to that described in Item 24. MS: m / z = 200 (MH + ).

기재 항목 105List item 105

4-(6-메틸-피리다진-3-일)벤조산4- (6-Methyl-pyridazin-3-yl) benzoic acid

상기 표제 화합물을 기재 항목 24와 유사한 과정을 사용하여 3-클로로-6-메틸피리다진 및 4-카르복시페닐보론산으로부터 황색 고체로 제조하였다(52%). MS:m/z=213(M-H).The title compound was prepared as a yellow solid from 3-chloro-6-methylpyridazine and 4-carboxyphenylboronic acid using a similar procedure as described in Item 24 (52%). MS: m / z = 213 (M-H).

기재 항목 106List item 106

4-(4-시아노-3-메틸페닐)벤조산4- (4-cyano-3-methylphenyl) benzoic acid

상기 표제 화합물을 기재 항목 24와 유사한 과정을 사용하여 4-브로모-2-메틸벤조니트릴 및 4-카르복시페닐보론산으로부터 백색 고체로 제조하였다(75%). MS:m/z=236(M-H).The title compound was prepared as a white solid from 4-bromo-2-methylbenzonitrile and 4-carboxyphenylboronic acid using a procedure similar to that described in Item 24 (75%). MS: m / z = 236 (M-H).

기재 항목 107Article item 107

4-(5-메틸-옥사졸-2-일)아닐린4- (5-methyl-oxazol-2-yl) aniline

THF(75ml) 중의 5-메틸-2-(4-니트로페닐)옥사졸(문헌[Chim. Ther. 1973, 8(4), 437])(3.0g, 15mmole) 및 탄소 상의 10% 팔라듐(0.25g)을 수소 대기 하에서 24시간 동안 교반했다. 상기 혼합물을 여과시키고 건조를 위해 진공 농축시켜 상기 표제 화합물을 연한 담황색 가루로 얻었다(2.29g, 89%).5-Methyl-2- (4-nitrophenyl) oxazole in THF (75 ml) (Chim. Ther. 1973, 8 (4), 437] (3.0 g, 15 mmole) and 10% palladium (0.25 on carbon) g) was stirred for 24 h under a hydrogen atmosphere. The mixture was filtered and concentrated in vacuo for drying to afford the title compound as a pale pale yellow powder (2.29 g, 89%).

기재 항목 108List item 108

5-니트로-나프트-1-일카르복사미드5-nitro-naphth-1-ylcarboxamide

CH2Cl2(200ml) 중의 5-니트로-나프트-1-일카르복실산(문헌[Chem. Pharm. Bull 1984, 32(10), 3968)(3.50g, 16mmole) 교반 용액을 옥살일 클로라이드(2.1ml, 24mmole) 및 DMF(2방울)로 처리했다. 상기 혼합물을 실온에서 5시간 동안 교반했다. 상기 용액을 건조를 위해 진공 농축하고 잔류물을 건조 THF(200ml)에 용해시켰다. 암모니아를 0.5시간 동안 상기 용액을 통해 서서히 거품을 형성시켰다. 상기 혼합물을 건조를 위해 진공 농축하고 잔류물을 물에서 연화시키고 고체를 여과 해 내고 진공 건조시켜 상기 표제 화합물을 연한 갈색 가루로 얻었다(3.34g, 95%).5-nitro-naphth-1-ylcarboxylic acid (Chem. Pharm. Bull 1984, 32 (10), 3968) (3.50 g, 16 mmol) stirred solution in CH 2 Cl 2 (200 ml) was converted to oxalyl chloride. (2.1 ml, 24 mmol) and DMF (2 drops). The mixture was stirred at rt for 5 h. The solution was concentrated in vacuo for drying and the residue was dissolved in dry THF (200 ml). Ammonia was bubbled slowly through the solution for 0.5 h. The mixture was concentrated in vacuo for drying and the residue was softened in water and the solids were filtered off and dried in vacuo to afford the title compound as a light brown powder (3.34 g, 95%).

기재 항목 109Article item 109

N-[1-(디메틸아미노)에틸리덴]-5-니트로나프트-1-일카르복사미드N- [1- (dimethylamino) ethylidene] -5-nitronaphth-1-ylcarboxamide

5-니트로-나프트-1-일카르복사미드(D108, 1.50g, 7mmole) 및 N,N-디메틸아세트아미드 디메틸아세탈(3ml) 교반 혼합물을 110℃에서 2시간 동안 가열했다. 냉각 혼합물을 물(20ml)로 희석시키고 침전 고체를 여과해 내고 물로 세척한 후 진공 건조하여 상기 표제 화합물을 연한 갈색 가루로 얻었다(1.60g, 80%).The stirring mixture of 5-nitro-naphth-1-ylcarboxamide (D108, 1.50 g, 7 mmol) and N, N-dimethylacetamide dimethylacetal (3 ml) was heated at 110 ° C. for 2 hours. The cold mixture was diluted with water (20 ml) and the precipitated solid was filtered off, washed with water and dried in vacuo to afford the title compound as a light brown powder (1.60 g, 80%).

기재 항목 110Article item 110

3-메틸-5-(5-니트로-나프트-1-일)-1,2,4-옥사디아졸3-methyl-5- (5-nitro-naphth-1-yl) -1,2,4-oxadiazole

N-[1-(디메틸아미노)에틸리덴]-5-니트로나프트-1-일카르복사미드(D109, 1.55g, 5.4mmole)을 히드록실아민 히드로클로라이드(0.47g, 6.75mmole) 및 5M NaOH 용액(1.35ml, 6.75mmole) 교반 용액에 첨가했다. 상기 혼합물을 4시간 동안 80℃로 가온한 후 냉각하고 물(50ml)로 희석했다. 침전 고체를 여과해 내고 물로 세척하고 진공 건조하여 상기 표제 화합물을 연한 담황색 가루로 남겼다(1.11g, 80%).N- [1- (dimethylamino) ethylidene] -5-nitronaphth-1-ylcarboxamide (D109, 1.55 g, 5.4 mmoles) was converted to hydroxylamine hydrochloride (0.47 g, 6.75 mmoles) and 5 M NaOH. Solution (1.35 ml, 6.75 mmol) was added to the stirred solution. The mixture was warmed to 80 ° C. for 4 h, then cooled and diluted with water (50 ml). The precipitated solid was filtered off, washed with water and dried in vacuo to leave the title compound as a pale pale yellow powder (1.11 g, 80%).

기재 항목 111List item 111

5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아민5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylamine

상기 표제 화합물을 기재 항목 71과 유사한 과정을 사용하여 3-메틸-5-(5-니트로-나프트-1-일)-1,2,4-옥사디아졸(D110)으로부터 연한 황색 가루로 제조하였다(54%).The title compound was prepared as a pale yellow powder from 3-methyl-5- (5-nitro-naphth-1-yl) -1,2,4-oxadiazole (D110) using a procedure similar to that described in item 71. (54%).

기재 항목 112List item 112

5-니트로-N-프로파질나프트-1-일카르복사미드5-nitro-N-propazylnaph-1-ylcarboxamide

CH2Cl2(50ml) 중의 5-니트로나프트-1-일카르복실산(문헌[Chem. Pharm. Bull 1984, 32(10), 3968)(1.10g, 5mmole) 교반 용액을 옥살일 클로라이드(0.5ml, 6mmole) 및 DMF(1방울)로 처리했다. 실온에서 3시간 후 상기 혼합물을 진공 농축하여 건조시켰다. 잔류물을 CH2Cl2(30ml)에 용해시키고, 트리에틸아민(1.4nl, 10mmole)로 처리하고 이 후 CH2Cl2(10ml) 중의 프로파질아민(0.28g, 5mmole) 용액을 적가하였다. 실온에서 18시간 동안 교반한 후, 상기 혼합물을 물로 세척하고 건조(Na2SO4)하고 진공 농축하여 건조시켰다. 상기 표제 화합물을 연한 황색 가루로 얻기 위해 잔류물을 디에틸 에테르로 연화시켰다(0.79g, 61%).A stirring solution of 5-nitronaphth-1-ylcarboxylic acid (Chem. Pharm. Bull 1984, 32 (10), 3968) (1.10 g, 5 mmol) in CH 2 Cl 2 (50 ml) was added to oxalyl chloride ( 0.5 ml, 6 mmoles) and DMF (1 drop). After 3 hours at room temperature the mixture was concentrated in vacuo and dried. The residue was dissolved in CH 2 Cl 2 (30 ml), treated with triethylamine (1.4nl, 10 mmol) and then a solution of propazylamine (0.28 g, 5 mmol) in CH 2 Cl 2 (10 ml) was added dropwise. After stirring for 18 hours at room temperature, the mixture was washed with water, dried (Na 2 SO 4 ) and concentrated in vacuo to dryness. The residue was triturated with diethyl ether (0.79 g, 61%) to afford the title compound as a pale yellow powder.

기재 항목 113List item 113

5-메틸-2-(5-니트로나프트-1-일)옥사졸5-methyl-2- (5-nitronaphth-1-yl) oxazole

빙초산(10ml) 중의 5-니트로-N-프로파질나프트-1-일카르복사미드(D112, 0.75g, 3mmole) 및 아세트화 수은(0.04g, 0.12mmole) 교반 혼합물을 4시간 동안 가열하여 환류하였다. 냉각된 혼합물을 진공 농축하여 건조시키고 잔류물을 CH2Cl2에 용해시키고 K2CO3수용액으로 세척하고 건조(Na2SO4)하며 진공 농축하여 건조시켰다. 잔류물을 CH2Cl2로 용출시키면서 실리카 겔 상에서 플래쉬 크로마토그래피하여 상기 표제 화합물을 황색 가루로 얻었다(0.50g, 66%).5-nitro-N-propazylnaph-1-ylcarboxamide (D112, 0.75g, 3mmole) and acetonitrile (0.04g, 0.12mmole) stirring mixture in glacial acetic acid (10ml) was heated to reflux for 4 hours. It was. The cooled mixture was concentrated in vacuo to dryness and the residue was dissolved in CH 2 Cl 2 , washed with aqueous K 2 CO 3 aqueous solution, dried (Na 2 SO 4 ) and concentrated in vacuo to dryness. The residue was flash chromatographed on silica gel eluting with CH 2 Cl 2 to afford the title compound as a yellow powder (0.50 g, 66%).

기재 항목 114List item 114

5-(5-메틸옥사졸-2-일)나프트-1-일아민5- (5-methyloxazol-2-yl) naphth-1-ylamine

상기 표제 화합물을 기재 항목 28과 유사한 과정을 사용하여 5-메틸-2-(5-니트로나프트-1-일)옥사졸(D113)로부터 황색/녹색 검으로 제조하였다(95%).The title compound was prepared as a yellow / green gum from 5-methyl-2- (5-nitronaphth-1-yl) oxazole (D113) using a procedure similar to that described in Item 28 (95%).

기재 항목 115List item 115

3-메틸-4-(피리미딘-2-일)아닐린3-methyl-4- (pyrimidin-2-yl) aniline

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 2-브로모피리미딘 및 4-아미노-2-메틸페닐 보론산(D87)으로부터 황색 고체로 제조하였다(46%).The title compound was prepared as a yellow solid from 2-bromopyrimidine and 4-amino-2-methylphenyl boronic acid (D87) using a procedure similar to that described in Item 2 (46%).

기재 항목 116List item 116

3-메틸-4-(피리미딘-5-일)아닐린3-methyl-4- (pyrimidin-5-yl) aniline

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 5-브로모피리미딘 및 4-아미노-2-메틸페닐보론산(D87)로부터 담황색 고체로 제조하였다(91%).The title compound was prepared as a pale yellow solid from 5-bromopyrimidine and 4-amino-2-methylphenylboronic acid (D87) using a procedure similar to that described in Item 2 (91%).

기재 항목 117Article item 117

2,6-디메틸-4-아이오도피리딘2,6-dimethyl-4-iodopyridine

2-부타논(250ml) 중의 4-클로로-2,6-디메틸피리딘(문헌[Chem. Abs. 1952, 46, 4541])(2.6g, 18mmole) 교반 용액을 소듐 아오다이드(17.6g, 120mmole) 및 4-톨루엔술폰산(3.4g, 18mmole)로 처리하고 상기 혼합물을 아르곤 하에서 72시간 동안 환류 하에 가열했다. 상기 반응 혼합물을 냉각한 후 진공 농축하고 잔류물을 물(200ml)로 처리하고 에틸 아세테이트로 추출했다. 추출액을 소듐 티오설페이트 수용액으로 세척한 후 건조(Na2SO4)하고 진공 농축하여 상기 표제 화합물이 백색 고체로 얻었고 이는 아세톤을 사용하여 백색 고체로써 그의 히드로클로라이드 염으로 전환되었다(3.44g, 69%).4-chloro-2,6-dimethylpyridine (Chem. Abs. 1952, 46, 4541) (2.6 g, 18 mmol) stirring solution in 2-butanone (250 ml) was added sodium aodide (17.6 g, 120 mmol). ) And 4-toluenesulfonic acid (3.4 g, 18 mmol) and the mixture was heated under reflux for 72 h under argon. The reaction mixture was cooled and then concentrated in vacuo and the residue was treated with water (200 ml) and extracted with ethyl acetate. The extract was washed with aqueous sodium thiosulfate solution, dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a white solid which was converted to its hydrochloride salt as a white solid using acetone (3.44 g, 69% ).

기재 항목 118Article item 118

5-(2,6-디메틸-피리딘-4-일)-1-나프토산5- (2,6-dimethyl-pyridin-4-yl) -1-naphthoic acid

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 2,6-디메틸-4-아이오도피리딘(D117) 및 5-카르복시나프트-1-일보론산(D90)으로부터 백색 고체로 제조하였다(70%).The title compound was prepared as a white solid from 2,6-dimethyl-4-iodopyridine (D117) and 5-carboxynaph-1-ylboronic acid (D90) using a procedure similar to that described in Item 2 (70%). ).

산 양성자는 발견되지 않음.Acid protons not found.

기재 항목 119Article item 119

5-(2,6-디메틸-피리딘-4-일)나프트-1-일 이소시아네이트5- (2,6-dimethyl-pyridin-4-yl) naphth-1-yl isocyanate

상기 표제 화합물을 기재 항목 1과 유사한 과정을 사용하여 5-(2,6-디메틸-피리딘-4-일)-1-나프토산(D118)으로부터 제조하였다. 상기 이소시아네이트를 단리하지 않고 톨루엔 용액으로서 다음 단계에 사용했다.The title compound was prepared from 5- (2,6-dimethyl-pyridin-4-yl) -1-naphthoic acid (D118) using a procedure similar to that described in Item 1. The isocyanate was used in the next step as a toluene solution without isolation.

기재 항목 120Article item 120

4-(2,6-디메틸피리딘-3-일)-3-메틸아닐린4- (2,6-dimethylpyridin-3-yl) -3-methylaniline

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 3-브로모-2,6-디메틸피리딘(D59a) 및 4-아미노-2-메틸페닐보론산(D87)로부터 연한 황색 오일로 제조하였다(6.5%).The title compound was prepared as a pale yellow oil from 3-bromo-2,6-dimethylpyridine (D59a) and 4-amino-2-methylphenylboronic acid (D87) using a procedure similar to that described in Item 2 (6.5%). ).

기재 항목 121List item 121

3-메틸-4-(티아졸-2-일)아닐린3-methyl-4- (thiazol-2-yl) aniline

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 2-브로모티아졸 및 4-아미노-2-메틸페닐보론산(D87)로부터 연한 황색/갈색 오일로 제조하였다 (65%).The title compound was prepared as a light yellow / brown oil from 2-bromothiazole and 4-amino-2-methylphenylboronic acid (D87) using a procedure similar to that described in Item 2 (65%).

기재 항목 122List Item 122

5-(피리미딘-5-일)-1-나프토산5- (pyrimidin-5-yl) -1-naphthoic acid

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 5-브로모피리미딘 및 5-카르복시나프트-1-일보론산(D90)으로부터 베이지색 오일로 제조하였다 (78%).The title compound was prepared as a beige oil from 5-bromopyrimidine and 5-carboxynaft-1-ylboronic acid (D90) using a procedure similar to that described in Item 2 (78%).

기재 항목 123Article item 123

5-(피리미딘-5-일)나프트-1-일 이소시아네이트5- (pyrimidin-5-yl) naphth-1-yl isocyanate

상기 표제 화합물을 기재 항목 1과 유사한 과정을 사용하여 5-(피리미딘-5-일)-1-나프토산(D122)으로부터 제조하였다. 상기 이소시아네이트를 단리하지 않고 톨루엔 용액으로 다음 단계에 사용했다.The title compound was prepared from 5- (pyrimidin-5-yl) -1-naphthoic acid (D122) using a procedure similar to that described in Item 1. The isocyanate was used in the next step as a toluene solution without isolation.

기재 항목 124Article item 124

5-아세틸나프트-1-일아민5-acetylnaphth-1-ylamine

메탄올(75ml) 중의 1-아세틸-5-니트로나프탈렌(문헌[Aust. J. Chem. 1995, 48(12), 1969)], 10% Pd-C(0.20g) 및 시클로헥센(10ml) 교반 용액을 환류 하에 6시간 동안 가열했다. 냉각된 혼합물을 여과하고 진공 농축했다. 잔류물을 CH2Cl2(50ml)에 용해시키고 물로 세척하며 건조(Na2SO4)하고 건조 농축했다. 잔류물을 에테르/헥산으로 연화함으로써 상기 표제 화합물을 황색/갈색 가루(0.52g, 80%)로 얻었다.1-acetyl-5-nitronaphthalene (Aust. J. Chem. 1995, 48 (12), 1969), 10% Pd-C (0.20 g) and cyclohexene (10 ml) stirred solution in methanol (75 ml) Was heated under reflux for 6 h. The cooled mixture was filtered and concentrated in vacuo. The residue was dissolved in CH 2 Cl 2 (50 ml), washed with water, dried (Na 2 SO 4 ) and concentrated to dryness. The residue was triturated with ether / hexanes to give the title compound as a yellow / brown powder (0.52 g, 80%).

기재 항목 125List item 125

5-(피리미딘-2-일옥시)나프트-1-일아민5- (pyrimidin-2-yloxy) naphth-1-ylamine

상기 표제 화합물을 기재 항목 70과 유사한 과정을 사용하여 5-히드록시나프트-1-일아민 및 2-브로모피리미딘으로부터 연한 담황색 가루로 제조하였다(58%).The title compound was prepared as a light pale yellow powder from 5-hydroxynaphth-1-ylamine and 2-bromopyrimidine (58%) using a procedure similar to that described in Item 70.

기재 항목 126Article item 126

5-시아노나프트-1-일아민5-cyanonaph-1-ylamine

철 가루(0.21g, 3.7mmole) 및 암모늄 클로라이드(0.02g, 0.4mmole)을 에탄올(10ml) 및 물(5ml) 중의 5-니트로나프트-1-일카르보니트릴(D128, 0.15g, 0.76mmole)교반 용액에 첨가한 후 혼합물을 환류 하에 0.5시간 동안 가열했다. 상기 혼합물을 약간 냉각시키고 여과시키고 진공 농축했다. 잔류물을 에틸 아세테이트(25ml) 및 물(15ml) 사이에 분배했다. 상기 유기 층을 분리하고 건조(Na2SO4)하고 진공 농축하여 상기 표제 화합물을 황색/녹색 가루로 얻었다(0.11g, 85%).Iron powder (0.21 g, 3.7 mmole) and ammonium chloride (0.02 g, 0.4 mmole) were added to 5-nitronaphth-1-ylcarbonitrile (D128, 0.15 g, 0.76 mmol) in ethanol (10 ml) and water (5 ml). After addition to the stirred solution, the mixture was heated at reflux for 0.5 h. The mixture was cooled slightly, filtered and concentrated in vacuo. The residue was partitioned between ethyl acetate (25 ml) and water (15 ml). The organic layer was separated, dried (Na 2 SO 4 ) and concentrated in vacuo to afford the title compound as a yellow / green powder (0.11 g, 85%).

기재 항목 127Article item 127

5-니트로나프트-1-일카르보니트릴5-nitronaphth-1-ylcarbonitrile

CH2Cl2(5ml) 중의 트리메틸실릴포스페이트 2.5M 용액(문헌[Synthesis, 1982, 591])을 5-니트로나프트-1-일카르복사미드(D108, 0.20g, 0.93mmole) 교반 용액 첨가하고 혼합물을 2시간 동안 가열하여 환류했다. 냉각된 혼합물을 물(10ml)로 처리하고 10분간 교반한 후 상기 유기 상을 분리, 염수로 세척하고 건조(Na2SO4)하고 진공 농축하여 건조시켰다. 잔류물을 CH2Cl2로 용출시키면서 실리카 겔 상에서 플래쉬 크로마토그래피하여 상기 표제 화합물을 무색 가루로 얻었다(0.12g, 66%).A trimethylsilylphosphate 2.5M solution (Synthesis, 1982, 591) in CH 2 Cl 2 (5 ml) was added a stirring solution of 5-nitronaphth-1-ylcarboxamide (D108, 0.20 g, 0.93 mmol) The mixture was heated to reflux for 2 hours. The cooled mixture was treated with water (10 ml) and stirred for 10 minutes, after which the organic phase was separated, washed with brine, dried (Na 2 SO 4 ) and concentrated in vacuo to dryness. The residue was flash chromatographed on silica gel eluting with CH 2 Cl 2 to afford the title compound as a colorless powder (0.12 g, 66%).

기재 항목 128Article item 128

5-니트로나프트-1-일아미독심5-nitronaph-1-ylamidoxim

히드록실아민 히드로클로라이드(1.23g, 1.78mmole)을 메탄올(100ml) 중의 소듐 히드록시드(0.71g, 17.8mmole) 용액에 첨가했다. 혼합물을 5-니트로나프트-1-일카르보니트릴(D127, 1.60g, 8.1mmole)로 처리하고 48시간 동안 가열하여 환류했다. 냉각된 혼합물을 증발시켜 10ml로 농축한 후 물(50ml)로 처리했다. 침전물을 수거하고 물로 세척한 후 진공 건조하여 상기 표제 화합물을 연한 황색 가루로 얻었다(1.65g, 88%).Hydroxylamine hydrochloride (1.23 g, 1.78 mmol) was added to a solution of sodium hydroxide (0.71 g, 17.8 mmol) in methanol (100 ml). The mixture was treated with 5-nitronaphth-1-ylcarbonitrile (D127, 1.60 g, 8.1 mmole) and heated to reflux for 48 hours. The cooled mixture was evaporated to concentration to 10 ml and treated with water (50 ml). The precipitate was collected, washed with water and dried in vacuo to afford the title compound as a pale yellow powder (1.65 g, 88%).

기재 항목 129Listed Items 129

5-메틸-3-(5-니트로나프트-1-일)-1,2,4-옥사디아졸5-methyl-3- (5-nitronaphth-1-yl) -1,2,4-oxadiazole

아세틸 클로라이드(0.78ml, 11mmole)을 피리딘(10ml) 중의 5-니트로나프트-1-일아미독심(D128, 1.28g, 5.5mmole) 교반 용액에 적가했다. 혼합물을 실온에서 0.5시간 동안 교반한 후 24시간 동안 가열하여 환류하였다. 냉각된 혼합물을 물(100ml)로 처리하고 에틸 아세테이트(3x25ml)로 추출했다. 혼합된 유기 추출물을 묽은 HCl, 물로 세척하고 건조(Na2SO4)하고 건조 농축했다. 잔류물을 CH2Cl2로 용출시키면서 실리카 겔 상에서 플래쉬 크로마토그래피하여 상기 표제 화합물을 연한 황색 가로 얻었다(0.86g, 61%).Acetyl chloride (0.78 ml, 11 mmol) was added dropwise to a stirring solution of 5-nitronaphth-1-ylamidosim (D128, 1.28 g, 5.5 mmol) in pyridine (10 ml). The mixture was stirred at rt for 0.5 h and then heated to reflux for 24 h. The cooled mixture was treated with water (100 ml) and extracted with ethyl acetate (3 × 25 ml). The combined organic extracts were washed with dilute HCl, water, dried (Na 2 SO 4 ) and concentrated to dryness. The residue was flash chromatographed on silica gel eluting with CH 2 Cl 2 to afford the title compound in pale yellow color (0.86 g, 61%).

기재 항목 130List item 130

5-(5-메틸-1,2,4-옥사디아졸-3-일)나프트-1-일아민5- (5-methyl-1,2,4-oxadiazol-3-yl) naphth-1-ylamine

상기 표제 화합물을 기재 항목 126에 개시된 과정에 따라 갈색 검으로 제조하였다. 이것은 회색 가루를 얻기 위해 그의 히드로클로라이드 염으로 전환되었다.The title compound was prepared as a brown gum following the procedure described in entry item 126. This was converted to its hydrochloride salt to get gray flour.

실시예 1Example 1

1-[(4-브로모-3-메틸페닐)아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)인돌1-[(4-bromo-3-methylphenyl) aminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) indole

칼륨 t-부톡시드(59mg, 0.50mmole)을 아르곤 하 무수 THF(10ml) 중의 5-메톡시-6-(4-메틸피페라진-1-일)인돌 (130mg, 0.50mmole, WO 95/06637의 중간체 2)에 첨가하고 혼합물을 15분가 교반했다. 여기에 무수 THF(10ml) 중의 4-브로모-3-메틸페닐 이소시아네이트(D1, 127mg, 0.60mmole) 용액을 첨가했다. 잔류 혼합물을 아르곤 하 실온에서 16시간 동안 교반한 후 진공 농축했다. 잔류물을 0-6% MeOH/CH2Cl2로 용출시키면서 실리카 겔 상에서 칼럼 크로마토그래피로 정제하여 상기 표제 화합물을 연한 황색 고체로 얻었다(108mg, 45%).Potassium t-butoxide (59 mg, 0.50 mmole) of 5-methoxy-6- (4-methylpiperazin-1-yl) indole (130 mg, 0.50 mmole, WO 95/06637) in dry THF (10 ml) under argon Was added to intermediate 2) and the mixture was stirred for 15 minutes. To this was added a solution of 4-bromo-3-methylphenyl isocyanate (D1, 127 mg, 0.60 mmol) in dry THF (10 ml). The residual mixture was stirred at rt under argon for 16 h and then concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with 0-6% MeOH / CH 2 Cl 2 to afford the title compound as a pale yellow solid (108 mg, 45%).

실시예 2Example 2

1-[(4-브로모-3-메틸페닐)아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)인돌1-[(4-bromo-3-methylphenyl) aminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) indole

디클로로메탄(10ml) 중의 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(0.10g, 0.40mmole, WO 95/06627의 중간체 3)을 디클로로메탄(10ml) 중의 4-브로모-3-메틸페닐 이소시아네이트(D1, 0.11g, 0.50mmole)에 첨가했다. 혼합물을 실온에서 17시간 동안 교반한 후 진공 농축하여 짙은 황색 오일을 얻었다. 이 오일을 디에틸 에테르로 교반한 후 고체를 여과해 내고 건조하여 상기 표제 화합물을 황색 고체로 얻었다(0.17g, 92%).2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole (0.10 g, 0.40 mmol, Intermediate 3 of WO 95/06627) in dichloromethane (10 ml) Was added to 4-bromo-3-methylphenyl isocyanate (D1, 0.11 g, 0.50 mmol) in dichloromethane (10 ml). The mixture was stirred at rt for 17 h and then concentrated in vacuo to give a dark yellow oil. The oil was stirred with diethyl ether and then the solid was filtered off and dried to afford the title compound as a yellow solid (0.17 g, 92%).

실시예 3Example 3

1-[(2,3-디클로로페닐)아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌1-[(2,3-dichlorophenyl) aminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정에 따라 2,3-디클로로페닐 이소시아네이트 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 제조하였다.The title compound was prepared using 2,3-dichlorophenyl isocyanate and 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole ( From intermediate 3) of WO 95/06627.

실시예 4Example 4

2,3-히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌2,3-hydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indole

아르곤 하 CH2Cl2(10ml) 중의 트리포스진(84mg, 0.28mmole)교반 용액을 CH2Cl2(10ml) 중의 4-(피리딘-4-일)나프트-1-일아민(D2, 196mg, 0.89mmole) 및 NEt3(90mg, 0.89mmole)에 30분에 걸쳐 적가했다. 첨가 완료 후, 혼합물을 실온에서 15분간 교반한 후 CH2Cl2(10ml) 중의 2,3-디히드로-5-메톡시-6-(4-메틸피레라진-1-일)-1H-인돌(WO 95/06627의 중간체 3, 200mg, 0.81mmole) 용액을 첨가했다. 6시간 후, 혼합물을 10% Na2CO3(수용액)으로 세척하고 건조(Na2SO4)하고 진공 농축하여 탁한 녹색 오일을 얻고 이를 2-5% MeOH/CH2Cl2로 용출시키면서 실리카 겔 상에서 크로마토그래피로 정제하였다. 상기 표제 화합물을 베이지색 고체로 얻었다(292mg, 73%).Ar and CH 2 Cl 2 (10ml) of the binary tree Force 4- (pyridin-4-yl) naphth-1-yl amine in (84mg, 0.28mmole) was added to CH 2 Cl 2 (10ml) ( D2, 196mg , 0.89 mmole) and NEt 3 (90 mg, 0.89 mmole) dropwise over 30 minutes. After the addition was completed, the mixture was stirred at room temperature for 15 minutes and then 2,3-dihydro-5-methoxy-6- (4-methylpyrazin-1-yl) -1H-indole in CH 2 Cl 2 (10 ml). (Intermediate 3 of WO 95/06627, 200 mg, 0.81 mmole) was added. After 6 hours, the mixture was washed with 10% Na 2 CO 3 (aq), dried (Na 2 SO 4 ) and concentrated in vacuo to give a cloudy green oil which was eluted with 2-5% MeOH / CH 2 Cl 2 with silica gel. Purify by chromatography on. The title compound was obtained as a beige solid (292 mg, 73%).

실시예 5Example 5

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[5-(4-피리딘)나프트-1-일아미노카르보닐]-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [5- (4-pyridine) naphth-1-ylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일 이소시아네이트(D4) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일) -1H-인돌(WO 95/06627의 중간체 3)로부터 제조하였다.The title compound was purified using a procedure similar to Example 2 using 5- (pyridin-4-yl) naphth-1-yl isocyanate (D4) and 2,3-dihydro-5-methoxy-6- (4- Methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627).

실시예 6Example 6

1-[2,3-디클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌1- [2,3-dichloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl)- 1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 2,3-디클로로-4-(피리딘-4-일)아닐린(D7) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌 (WO 95/06627의 중간체 3)으로부터 오렌지/갈색 고체로 제조하였다(54%).The title compound was prepared in a similar manner to Example 4 using 2,3-dichloro-4- (pyridin-4-yl) aniline (D7) and 2,3-dihydro-5-methoxy-6- (4- Prepared as an orange / brown solid from methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (54%).

실시예 7Example 7

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-(퀴놀린-5-일아미노카르보닐)-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- (quinolin-5-ylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-아미노퀴놀린 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3 )으로부터 제조하였다.The title compound was purified using 5-aminoquinoline and 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole (WO 95) using a procedure similar to Example 4. / 06627 intermediate 3).

실시예 8Example 8

2,3-디히드로-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌2,3-dihydro- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D11)로부터 베이지색 고체로 제조하였다(50%).The title compound was prepared in a similar manner to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 2,3-dihydro-6- (4-methylpiperazin-1 Prepared as a beige solid from -yl) -1H-indole (D11) (50%).

실시예 9Example 9

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D13)로부터 제조하였다(38%). 이것을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared in a similar manner to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 5-chloro-2,3-dihydro-6- (4-methyl Prepared from piperazin-1-yl) -1H-indole (D13) (38%). This was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 10Example 10

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol

상기 표제 화합물을 기재 항목 14와 유사한 과정을 사용하여 2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌(E8) 및 벤질트리메틸암모늄 트리브로마이드로부터 베이지색 고체로 제조하였다(86%). 이 물질을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1 using a procedure similar to that described in Item 14. Prepared as a beige solid from -ylaminocarbonyl] -1H-indole (E8) and benzyltrimethylammonium tribromide (86%). This material was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 11Example 11

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)페닐아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)아닐린(D5) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 백색 고체로 제조하였다(24%).The title compound was purified using 4- (pyridin-4-yl) aniline (D5) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1- using a similar procedure as in Example 4. Prepared as a white solid from I) -1H-indole (D15) (24%).

실시예 12Example 12

5-브로모-1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-클로로-4-(피리딘-4-일)아닐린(D6) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진 -1-일)-1H-인돌(D15)로부터 백색 고체로 제조하였다(13%).The title compound was purified using 3-chloro-4- (pyridin-4-yl) aniline (D6) and 5-bromo-2,3-dihydro-6- (4-methylpipepe using a similar procedure to Example 4. Prepared as a white solid from razin-1-yl) -1H-indole (D15) (13%).

실시예 13Example 13

2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌 (D17)로부터 제조하였다(52%). 이 물질을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 2,3-dihydro-5-methyl-6- (4-methyl Prepared from piperazin-1-yl) -1H-indole (D17) (52%). This material was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 14Example 14

1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-클로로-4-(피리딘-4-일)아닐린(D6) 및 2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌 (D17)로부터 백색 고체로 제조하였다(67%).The title compound was purified using 3-chloro-4- (pyridin-4-yl) aniline (D6) and 2,3-dihydro-5-methyl-6- (4-methylpiperazin using a similar procedure as in Example 4. Prepared as a white solid from -1-yl) -1H-indole (D17) (67%).

실시예 15Example 15

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-5-비닐-1H-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -5-vinyl-1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 2,3-디히드로-6-(4-메틸피페라진-1-일)-5-비닐-1H-인돌 (D19)로부터 제조하였다(50%). 이 물질을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared in a similar manner to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 2,3-dihydro-6- (4-methylpiperazin-1 Prepared from -yl) -5-vinyl-1H-indole (D19) (50%). This material was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 16Example 16

2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌 (D21)로부터 베이지색 고체로 제조하였다(43%). 이 물질을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared in a similar manner to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 2,3-dihydro-5-ethyl-6- (4-methyl Prepared as a beige solid from piperazin-1-yl) -1H-indole (D21) (43%). This material was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 17Example 17

1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-클로로-4-(피리딘-4-일)아닐린(D6) 및 2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌 (D21)로부터 백색 고체로 제조하였다(33%).The title compound was purified using 3-chloro-4- (pyridin-4-yl) aniline (D6) and 2,3-dihydro-5-ethyl-6- (4-methylpiperazin using a similar procedure to Example 4. Prepared as a white solid from -1-yl) -1H-indole (D21) (33%).

실시예 18Example 18

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-5-트리플루오로메틸-1H-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -5-trifluoromethyl -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸-1H-인돌(D23)로부터 베이지색 고체로 제조하였다(42%). 이 물질을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared in a similar manner to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 2,3-dihydro-6- (4-methylpiperazin-1 Prepared as a beige solid from -yl) -5-trifluoromethyl-1H-indole (D23) (42%). This material was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 19Example 19

1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸-1H-인돌1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-trifluoromethyl- 1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-클로로-4-(피리딘-4-일)아닐린(D6) 및 2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸 -1H-인돌(D23)로부터 베이지색 고체로 제조하였다(17%).The title compound was purified using 3-chloro-4- (pyridin-4-yl) aniline (D6) and 2,3-dihydro-6- (4-methylpiperazin-1-yl using a similar procedure as in Example 4. Prepared as a beige solid from) -5-trifluoromethyl-1H-indole (D23) (17%).

실시예 20Example 20

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole

옥살일 클로라이드(206mg, 1.6mmole) 이후 DMF(1방울)을 CH2Cl2(30ml) 중의 4-(피리딘-4-일)나프트-1-일아세트산(D24, 213mg, 0.81mmole) 교반 현탁액에 첨가했다. 2시간 후, 용매 및 과량의 옥살일클로라이드를 진공에서 제거하여 산 클로라이드를 연한 황색 고체로서 얻었다. 이것을 CH2Cl2(15ml)에 용해시키고 아르곤 존재 하 0℃에서 10분에 걸쳐 CH2Cl2(15ml) 중의 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3, 200mg, 0.81mmole) 및 NEt3(164mg, 1.6mmole)에 일부분씩 첨가했다. 0℃에서 30분 후, 상기 혼합물을 실온에서 5시간 동안 교반한 후 10% Na2CO3(수용액)으로 세척하고 건조(Na2SO4)하고 진공 농축했다. 탁한 녹색/갈색 오일을 2-5% MeCH/CH2Cl2로 용출시키면서 실리카 상에서 크로마토그래피에 의해 정제하여 상기 표제 화합물을 황색 고체로 얻었다(340mg, 85%).Oxalyl chloride (206 mg, 1.6 mmol) followed by one drop of DMF (4- (pyridin-4-yl) naphth-1-ylacetic acid (D24, 213 mg, 0.81 mmol) stirred suspension in CH 2 Cl 2 (30 ml) Added to. After 2 hours, the solvent and excess oxalylchloride were removed in vacuo to give the acid chloride as a pale yellow solid. This CH 2 Cl 2 (15ml) 2,3- dihydro-5-methoxy-dissolved in the presence of argon at 0 ℃ over 10 minutes, CH 2 Cl 2 (15ml) to the 6- (4-methylpiperazin-l- 1-day) -1H-indole (intermediate 3 of WO 95/06627, 200 mg, 0.81 mmole) and NEt 3 (164 mg, 1.6 mmole) were added in portions. After 30 minutes at 0 ° C., the mixture was stirred at room temperature for 5 hours, then washed with 10% Na 2 CO 3 (aq), dried (Na 2 SO 4 ) and concentrated in vacuo. The turbid green / brown oil was purified by chromatography on silica eluting with 2-5% MeCH / CH 2 Cl 2 to afford the title compound as a yellow solid (340 mg, 85%).

실시예 21Example 21

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole

상기 표제 화합물을 실시예 20과 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일아세트산(D25) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 제조하였다.The title compound was prepared in a similar manner to Example 20 using 5- (pyridin-4-yl) naphth-1-ylacetic acid (D25) and 2,3-dihydro-5-methoxy-6- (4- Prepared from methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627).

실시예 22Example 22

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole

상기 표제 화합물을 실시예 20와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아세트산(D24) 및 2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D11)로부터 에틸 아세테이트로부터 형성된 베이지색 고체로 제조하였다(72%).The title compound was purified using 4- (pyridin-4-yl) naphth-1-ylacetic acid (D24) and 2,3-dihydro-6- (4-methylpiperazin-1 using a procedure similar to Example 20. Prepared as a beige solid formed from ethyl acetate from -yl) -1H-indole (D11) (72%).

실시예 23Example 23

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole

상기 표제 화합물을 실시예 20과 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아세트산(D24) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)으로부터 황색 오일로써 제조하였다(50%). 이 물질을 에틸 아세테이트로부터 형성된 베이지색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 20 using 4- (pyridin-4-yl) naphth-1-ylacetic acid (D24) and 5-chloro-2,3-dihydro-6- (4-methyl Prepared as a yellow oil from piperazin-1-yl) -1H-indole (D13) (50%). This material was converted to its hydrochloride salt as a beige solid formed from ethyl acetate.

실시예 24Example 24

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naph-1-ylacetyl] -1H-indole

상기 표제 화합물을 기재 항목 14와 유사한 과정을 사용하여 2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌(E22) 및 벤질트리메틸암모늄 트리브로마이드로부터 제조하였다(62%). 이 물질을 에틸 아세테이트로부터 베이지색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1 using a procedure similar to that described in Item 14. Prepared from -ylacetyl] -1H-indole (E22) and benzyltrimethylammonium tribromide (62%). This material was converted from ethyl acetate to its hydrochloride salt as a beige solid.

실시예 25Example 25

2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-5-비닐-1H-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -5-vinyl-1H-indole

상기 표제 화합물을 실시예 20과 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아세트산(D24) 및 2,3-디히드로-6-(4-메틸피페라진-1-일)-5-비닐-1H-인돌 (D19)로부터 제조하였다(45%). 이 물질을 아세톤/에틸 아세테이트로부터 백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was subjected to 4- (pyridin-4-yl) naphth-1-ylacetic acid (D24) and 2,3-dihydro-6- (4-methylpiperazin-1 using a procedure similar to Example 20. Prepared from -yl) -5-vinyl-1H-indole (D19) (45%). This material was converted from acetone / ethyl acetate to its hydrochloride salt as a white solid.

실시예 26Example 26

5-브로모-2,3-디히드로-6-(1-메틸피페라진-4-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌5-bromo-2,3-dihydro-6- (1-methylpiperazin-4-yl) -1- [4- (pyridin-4-yl) naph-1-ylacetyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 5-브로모-2,3-디히드로-6-(1-메틸피페리딘-4-일)-1H-인돌 (D39)로부터 제조하였다(11%).The title compound was prepared using a procedure similar to that of Example 4, using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 5-bromo-2,3-dihydro-6- (1- Prepared from methylpiperidin-4-yl) -1H-indole (D39) (11%).

실시예 27Example 27

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일 이소시아네이트(D4) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1- 일)-1H-인돌(D13)로부터 제조하였다.The title compound was purified using a procedure similar to Example 2 5- (pyridin-4-yl) naphth-1-yl isocyanate (D4) and 5-chloro-2,3-dihydro-6- (4-methyl Prepared from piperazin-1-yl) -1H-indole (D13).

실시예 28Example 28

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일 이소시아네이트(D4) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1- 일)-1H-인돌(D15)로부터 제조하였다.The title compound was prepared using a procedure similar to Example 2, using 5- (pyridin-4-yl) naphth-1-yl isocyanate (D4) and 5-bromo-2,3-dihydro-6- (4- Prepared from methylpiperazin-1-yl) -1H-indole (D15).

실시예 29Example 29

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 퀴놀린-6-일 이소시아네이트(D26) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 제조하였다.The title compound was subjected to quinolin-6-yl isocyanate (D26) and 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H using a procedure similar to Example 2. Prepared from indole (Intermediate 3 of WO 95/06627).

실시예 30Example 30

1-[4-(t-부톡시카르보닐아미노)페닐아미노카르보닐]-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1- [4- (t-butoxycarbonylamino) phenylaminocarbonyl] -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(t-부톡시카르보닐아미노)아닐린(D40) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D13)로부터 제조하였다(29%).The title compound was purified using 4- (t-butoxycarbonylamino) aniline (D40) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1 using a similar procedure as in Example 4. Prepared from -yl) -1H-indole (D13) (29%).

실시예 31Example 31

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 퀴놀린-6-일 이소시아네이트(D26) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 제조하였다.The title compound was subjected to quinolin-6-yl isocyanate (D26) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H using a procedure similar to Example 2. Prepared from indole (D15).

실시예 32Example 32

6-브로모-2,3-디히드로-7-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1,2,3,4-테트라히드로퀴놀린6-bromo-2,3-dihydro-7- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1 , 2,3,4-tetrahydroquinoline

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 6-브로모-7-(4-메틸피페라진-1-일)-1,2,3,4-테트라히드로퀴놀린(D33)으로부터 제조하였다.The title compound was prepared in a similar manner to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 6-bromo-7- (4-methylpiperazin-1-yl ), 1,2,3,4-tetrahydroquinoline (D33).

실시예 33Example 33

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(4-페녹시페닐아미노카르보닐)-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (4-phenoxyphenylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 4-페녹시페닐 이소시아네이트로부터 제조하였다.The title compound was prepared using a procedure similar to that of Example 2, using 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) and 4-phenoxyphenyl Prepared from isocyanates.

실시예 34Example 34

5-클로로-1-[4-(4-클로로페녹시)페닐아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-1- [4- (4-chlorophenoxy) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 4-(4-클로로페녹시)아닐린으로부터 제조하였다.The title compound was prepared using a procedure similar to that of Example 4, using 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) and 4- (4- From chlorophenoxy) aniline.

실시예 35Example 35

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 퀴놀린-6-일 이소시아네이트(D26) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다.The title compound was prepared using a procedure similar to that of Example 2, using quinolin-6-yl isocyanate (D26) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H- Prepared from indole (D13).

실시예 36Example 36

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(3-페녹시페닐아미노카르보닐)-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (3-phenoxyphenylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 3-페녹시아닐린으로부터 제조하였다.The title compound was prepared using a procedure similar to that of Example 4, using 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) and 3-phenoxyaniline Prepared from.

실시예 37Example 37

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리미딘-2-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrimidin-2-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 4-(피리미딘-2-일)페닐 이소시아네이트(D42)로부터 연한 우유빛 가루로 제조하였다(69%).The title compound was prepared using a procedure similar to that of Example 2, using 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) and 4- (pyrimidine). Prepared as a pale milky powder from -2-yl) phenyl isocyanate (D42) (69%).

실시예 38Example 38

1-(3-벤조일페닐아미노카르보닐)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1- (3-benzoylphenylaminocarbonyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-아미노벤조페논 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다.The title compound was prepared using a procedure similar to Example 4 using 3-aminobenzophenone and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13). Prepared from.

실시예 39Example 39

1-(4-벤조일페닐아미노카르보닐)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1- (4-benzoylphenylaminocarbonyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-아미노벤조페논 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다.The title compound was prepared in the same manner as in Example 4 using 4-aminobenzophenone and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) Prepared from.

실시예 40Example 40

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(2-메틸퀴놀린-6-일아미노카르보닐)-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (2-methylquinolin-6-ylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 6-아미노-2-메틸퀴놀린 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다.The title compound was purified using 6-amino-2-methylquinoline and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole using a procedure similar to that of Example 4. Prepared from (D13).

실시예 41Example 41

5-클로로-2,3-디히드로-1-[4-(퍼-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (per-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

연한 담황색 가루로 수득된 상기 표제 화합물을 5-클로로-2,3-디히드로-1-(4-아이오도페닐아미노카르보닐)-6-(4-메틸피페라진-1-일)-1H-인돌(D43) 및 2-퓨릴보론산으로부터 제조하였다(64%).The title compound obtained as a light pale yellow powder was obtained from 5-chloro-2,3-dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-methylpiperazin-1-yl) -1H- Prepared from indole (D43) and 2-furylboronic acid (64%).

DMSO 시그널에 의해 2×CH2시그널은 발견되지 않음.2 × CH 2 signal not found by DMSO signal.

실시예 42Example 42

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티엔-2-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thien-2-yl) phenylaminocarbonyl] -1H-indole

연한 우유빛 가루로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 과정으로 5-클로로-2,3-디히드로-1-(4-아이오도페닐아미노카르보닐)-6-(4-메틸피페라진 -1-일)-1H-인돌(D43) 및 2-티에닐보론산으로부터 제조하였다(56%).The title compound obtained as a pale milky powder was subjected to 5-chloro-2,3-dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-methylpiperazin in a similar manner as described in Item 2. Prepared from -1-yl) -1H-indole (D43) and 2-thienylboronic acid (56%).

실시예 43Example 43

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole

상기 표제 화합물을 실시예 20과 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일아세트산(D25) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다.The title compound was prepared in a similar manner to Example 20 using 5- (pyridin-4-yl) naphth-1-ylacetic acid (D25) and 5-chloro-2,3-dihydro-6- (4-methyl Prepare from piperazin-1-yl) -1H-indole (D13).

실시예 44Example 44

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole

상기 표제 화합물을 실시예 20과 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일아세트산(D25) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 제조하였다.The title compound was prepared using a procedure similar to Example 20, using 5- (pyridin-4-yl) naphth-1-ylacetic acid (D25) and 5-bromo-2,3-dihydro-6- (4- Prepared from methylpiperazin-1-yl) -1H-indole (D15).

실시예 45Example 45

5-클로로-2,3-디히드로-1-[4-(1-메틸피페리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (1-methylpiperidin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(1-메틸피페리딘-4-일)나프트-1-일아민(D46) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다.The title compound was prepared in a similar manner to Example 4 using 4- (1-methylpiperidin-4-yl) naphth-1-ylamine (D46) and 5-chloro-2,3-dihydro-6 Prepared from-(4-methylpiperazin-1-yl) -1H-indole (D13).

실시예 46Example 46

5-클로로-2,3-디히드로-1-[4-(2-메틸로옥사졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (2-methylloxazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(4-아미노페닐)-2-메틸옥사졸(D47) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D13)로부터 연한 황색 가루로 제조하였다(67%).The title compound was prepared using a procedure similar to that of Example 4, using 4- (4-aminophenyl) -2-methyloxazole (D47) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin Prepared as a pale yellow powder from -1-yl) -1H-indole (D13) (67%).

H2O 시그널에 의해 2×CH2시그널은 발견되지 않음.2 × CH 2 signal not found by H 2 O signal.

실시예 47Example 47

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(2-메틸피리딘-4-일)페닐아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (2-methylpyridin-4-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(2-메틸피리딘-4-일)아닐린(D49) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 백색 고체로 제조하였다(48%).The title compound was prepared using a procedure similar to that of Example 4, using 4- (2-methylpyridin-4-yl) aniline (D49) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin Prepared as a white solid from -1-yl) -1H-indole (D15) (48%).

실시예 48Example 48

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(2-메틸피리딘-4-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (2-methylpyridin-4-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(2-메틸피리딘-4-일)아닐린(D49) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D13)로부터 베이지색 고체로 제조하였다(79%).The title compound was prepared using a procedure similar to that of Example 4, using 4- (2-methylpyridin-4-yl) aniline (D49) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin- Prepared as a beige solid from 1-yl) -1H-indole (D13) (79%).

실시예 49Example 49

5-클로로-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-4-일)페닐 이소시아네이트(D62) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)으로부터 백색 고체로 제조하였다(55%).The title compound was prepared in a similar manner to Example 2 using 4- (2,6-dimethylpyridin-4-yl) phenyl isocyanate (D62) and 5-chloro-2,3-dihydro-6- (4-methyl Prepared as a white solid (55%) from piperazin-1-yl) -1H-indole (D13).

실시예 50Example 50

5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-4-일)페닐 이소시아네이트(D62) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 백색 고체로 제조하였다(36%).The title compound was prepared in a similar manner to Example 2 using 4- (2,6-dimethylpyridin-4-yl) phenyl isocyanate (D62) and 5-bromo-2,3-dihydro-6- (4- Prepared as a white solid (36%) from methylpiperazin-1-yl) -1H-indole (D15).

실시예 51Example 51

2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-4-일)페닐 이소시아네이트(D62) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)인돌(WO 95/06627의 중간체 3)로부터 베이지색 고체로 제조하였다(28%).The title compound was prepared in a similar manner to Example 2 using 4- (2,6-dimethylpyridin-4-yl) phenyl isocyanate (D62) and 2,3-dihydro-5-methoxy-6- (4- Prepared as a beige solid from methylpiperazin-1-yl) indole (Intermediate 3 of WO 95/06627) (28%).

실시예 52Example 52

5-클로로-2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-3-일)페닐 이소시아네이트(D63) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 백색 고체로 제조하였다(21%).The title compound was prepared in a similar manner to Example 2 using 4- (2,6-dimethylpyridin-3-yl) phenyl isocyanate (D63) and 5-chloro-2,3-dihydro-6- (4-methyl Prepared as a white solid from piperazin-1-yl) -1H-indole (D13) (21%).

실시예 53Example 53

5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-3-일)페닐 이소시아네이트(D63) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 백색 고체로 제조하였다(44%).The title compound was prepared in a similar manner to Example 2 using 4- (2,6-dimethylpyridin-3-yl) phenyl isocyanate (D63) and 5-bromo-2,3-dihydro-6- (4- Prepared as a white solid (44%) from methylpiperazin-1-yl) -1H-indole (D15).

실시예 54Example 54

2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-3-일)페닐 이소시아네이트(D63) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 베이지색 고체로 제조하였다(17%).The title compound was prepared in a similar manner to Example 2 using 4- (2,6-dimethylpyridin-3-yl) phenyl isocyanate (D63) and 2,3-dihydro-5-methoxy-6- (4- Prepared as a beige solid from methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (17%).

실시예 55Example 55

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(5-메틸-1,2,4-옥사디아졸-3-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (5-methyl-1,2,4-oxadiazol-3-yl) phenyl Aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 방법으로 4-(5-메틸-1,2,4-옥사디아졸-3-일)아닐린(문헌[Ger. Offen DE 2046928]) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다. 생성물은 연한 우유빛 가루로 단리되었다(44%).The title compound was prepared in a similar manner to Example 4 using 4- (5-methyl-1,2,4-oxadiazol-3-yl) aniline (Ger. Offen DE 2046928) and 5-chloro-2, Prepared from 3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13). The product was isolated as a pale milky powder (44%).

실시예 56Example 56

5-클로로-2,3-디히드로-1-[4-(3-메틸-1,2,4-옥사디아졸-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (3-methyl-1,2,4-oxadiazol-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin- 1-day) -1H-indole

상기 표제 화합물은 실시예 4와 유사한 과정으로 4-(3-메틸-1,2,4-옥사디아졸-5-일)아닐린(문헌[J. Het. Chem. 1980, 17(6), 1273-5]) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 백색 가루로 단리되었다(0.13g, 48%).The title compound was prepared in a similar manner to Example 4 with 4- (3-methyl-1,2,4-oxadiazol-5-yl) aniline (J. Het. Chem. 1980, 17 (6), 1273 -5]) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) as a white powder (0.13 g, 48%).

NH 양성자는 발견되지 않음.NH protons not found.

실시예 57Example 57

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[3-(피리미딘-2-일옥시)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [3- (pyrimidin-2-yloxy) phenylaminocarbonyl] -1H-indole

상기 표제 화합물은 실시예 4와 유사한 방법으로 3-(피리미딘-2-일옥시)아닐린(D71) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조되었다. 생성물은 연한 담황색 가루로 단리되었다(32%).The title compound was prepared in a similar manner to Example 4 using 3- (pyrimidin-2-yloxy) aniline (D71) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl ) -1H-indole (D13). The product was isolated as a light pale yellow powder (32%).

실시예 58Example 58

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-{4-[N-메틸-N-(피리미딘-2-일)아미노]페닐아미노카르보닐}-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- {4- [N-methyl-N- (pyrimidin-2-yl) amino] phenylaminocar Carbonyl} -1H-indole

상기 표제 화합물은 실시예 4와 유사한 방법으로 4-[N-메틸-N-(피리미딘-2-일)아미노]아닐린(D73) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조되었다. 생성물은 연한 우유빛 가루로 단리되었다(54%).The title compound was prepared in a similar manner to Example 4 using 4- [N-methyl-N- (pyrimidin-2-yl) amino] aniline (D73) and 5-chloro-2,3-dihydro-6- (4 -Methylpiperazin-1-yl) -1H-indole (D13). The product was isolated as a pale milky powder (54%).

실시예 59Example 59

5-브로모-2,3-디히드로-1-[4-(퍼-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (per-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 4-(퍼-2-일)아닐린(문헌[Synthesis 1976, 1, 40]) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 제조하였다. 상기 표제 화합물은 우유빛 가루로 단리되었다(38%).The title compound is referred to as 4- (per-2-yl) aniline (Synthesis 1976, 1, 40) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl ) -1H-indole (D15). The title compound was isolated as milky flour (38%).

실시예 60Example 60

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티엔-3-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thien-3-yl) phenylaminocarbonyl] -1H-indole

우유빛 가루로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 방법으로 5-클로로-2,3-디히드로-1-(4-아이오도페닐아미노카르보닐)-6-(4-메틸피페라진-1-일)-1H-인돌(D43)로부터 제조하였다(31%).The title compound obtained as a milky powder was prepared by 5-chloro-2,3-dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-methylpiperazin- Prepared from 1-day) -1H-indole (D43) (31%).

실시예 61Example 61

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티아졸-2-일)페닐아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thiazol-2-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(티아졸-2-일)아닐린(D52) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 제조하였다(19%).The title compound was purified using 4- (thiazol-2-yl) aniline (D52) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1 using a similar procedure as in Example 4. Prepared from -yl) -1H-indole (D15) (19%).

실시예 62Example 62

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티아졸-2-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thiazol-2-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 D51과 유사한 과정을 사용하여 5-클로로-2,3-디히드로-1-(4-아이오도페닐아미노카르보닐)-6-(4-메틸피페라진-1-일)-1H-인돌(D43) 및 2-브로모티아졸로부터 제조하였다(8%).The title compound was purified by 5-chloro-2,3-dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-methylpiperazin-1-yl) -1H using a procedure similar to D51. Prepared from indole (D43) and 2-bromothiazole (8%).

실시예 63Example 63

1-[4-(5-아세틸티엔-2-일)페닐아미노카르보닐]-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1- [4- (5-acetylthien-2-yl) phenylaminocarbonyl] -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

담황색 고체로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 방법으로 5-클로로-2,3-디히드로-1-(4-아이오도페닐아미노카르보닐)-6-(4-메틸피페라진-1-일)-1H-인돌(D43) 및 5-아세틸티엔-2-일보론산으로부터 제조하였다(42%).The title compound obtained as a pale yellow solid was subjected to 5-chloro-2,3-dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-methylpiperazin-1 in a similar manner as described in Item 2. Prepared from -yl) -1H-indole (D43) and 5-acetylthien-2-ylboronic acid (42%).

우레아 NH는 발견되지 않음.Urea NH not found.

실시예 64Example 64

1-(5-브로모나프트-1-일아세틸)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1- (5-bromonaft-1-ylacetyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 20과 유사한 방법을 사용하여 5-브로모나프트-1-일아세트산(문헌[Bull. Soc. Chim. Fr. 1968, 7, 2957]) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 밝은 황색 기포로 제조하였다(62%).The title compound was purified using 5-bromonaft-1-ylacetic acid (Bull. Soc. Chim. Fr. 1968, 7, 2957) and 5-chloro-2,3- using a similar method as in Example 20. Prepared with light yellow foam from dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) (62%).

실시예 65Example 65

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(8-페닐퀴놀린-5-일아미노카르보닐)-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (8-phenylquinolin-5-ylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-아미노-8-페닐퀴놀린(D66) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 우유빛 고체로 제조하였다(40%).The title compound was purified using 5-amino-8-phenylquinoline (D66) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl)-using a procedure similar to that of Example 4. Prepared as a milky solid from 1H-indole (D13) (40%).

실시예 66Example 66

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(8-페닐퀴놀린-5-일아미노카르보닐)-1H-인돌5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (8-phenylquinolin-5-ylaminocarbonyl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-아미노-8-페닐퀴놀린(D66) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 우유빛 고체로 제조하였다(25%).The title compound was purified using 5-amino-8-phenylquinolin (D66) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) using procedures similar to those of Example 4. Prepared as a milky solid from -1H-indole (D15) (25%).

실시예 67Example 67

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[2-(2-페닐에틸)퀴놀린-6-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [2- (2-phenylethyl) quinolin-6-ylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 6-아미노-2-(2-페닐에틸)퀴놀린(D69) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D13)로부터 백색 고체로 제조하였다(77%).The title compound was purified using 6-amino-2- (2-phenylethyl) quinoline (D69) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin- Prepared as a white solid from 1-yl) -1H-indole (D13) (77%).

실시예 68Example 68

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(1-메틸피페리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (1-methylpiperidin-4-yl) naphth-1-ylaminocarbox Carbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(1-메틸피페리딘-4-일)나프트-1-일아민(D77) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 백색 고체로 제조하였다(15%).The title compound was prepared using a procedure similar to Example 4 using 5- (1-methylpiperidin-4-yl) naphth-1-ylamine (D77) and 5-chloro-2,3-dihydro-6 Prepared as a white solid from-(4-methylpiperazin-1-yl) -1H-indole (D13) (15%).

실시예 69Example 69

5-브로모-2,3-디히드로-1-[4-(이소퀴놀린-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (isoquinolin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(이소퀴놀린-4-일)페닐 이소시아네이트(D54) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 백색 고체로 제조하였다(24%).The title compound was prepared using a procedure similar to that of Example 2. 4- (isoquinolin-4-yl) phenyl isocyanate (D54) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin- Prepared as a white solid from 1-yl) -1H-indole (D15) (24%).

실시예 70Example 70

5-클로로-2,3-디히드로-1-[4-(이소퀴놀린-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (isoquinolin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(이소퀴놀린-4-일)페닐 이소시아네이트(D54) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 백색 고체로 제조하였다(25%).The title compound was prepared using a procedure similar to that of Example 2. 4- (isoquinolin-4-yl) phenyl isocyanate (D54) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1 Prepared as a white solid from -yl) -1H-indole (D13) (25%).

실시예 71Example 71

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-3-일)페닐아미노카르보닐]-1H-인돌5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-3-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(퀴놀린-3-일)페닐 이소시아네이트(D56) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 회백색 고체로 제조하였다(6%).The title compound was prepared in a similar manner to Example 2 using 4- (quinolin-3-yl) phenyl isocyanate (D56) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1 Prepared as an off-white solid from -yl) -1H-indole (D15) (6%).

실시예 72Example 72

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-3-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-3-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(퀴놀린-3-일)페닐 이소시아네이트(D56) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 밝은 베이지색 고체로 제조하였다(10%).The title compound was prepared in a similar manner to Example 2 using 4- (quinolin-3-yl) phenyl isocyanate (D56) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1- Prepared as a light beige solid from I) -1H-indole (D13) (10%).

실시예 73Example 73

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-메틸-1,2,3,4-테트라히드로이소퀴놀린-7-일)아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl) Aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 7-아미노-2-메틸-1,2,3,4-테트라히드로이소퀴놀린(D78) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 회백색 고체로 제조하였다(23%).The title compound was purified using 7-amino-2-methyl-1,2,3,4-tetrahydroisoquinoline (D78) and 5-chloro-2,3-dihydro-6- using a procedure similar to that of Example 4. Prepared as an off-white solid from (4-methylpiperazin-1-yl) -1H-indole (D13) (23%).

실시예 74Example 74

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-메틸-1,2,3,4-테트라히드로이소퀴놀린-7-일)아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl Aminocarbonyl] -1 H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 7-아미노-2-메틸-1,2,3,4-테트라히드로이소퀴놀린(D78) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 회백색 고체로 제조하였다(41%).The title compound was purified using 7-amino-2-methyl-1,2,3,4-tetrahydroisoquinoline (D78) and 5-bromo-2,3-dihydro-6 using a procedure similar to Example 4. Prepared as an off-white solid from-(4-methylpiperazin-1-yl) -1H-indole (D13) (41%).

실시예 75Example 75

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-8-일)페닐아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-8-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(퀴놀린-8-일)페닐 이소시아네이트(D58) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 백색 고체로 제조하였다(52%).The title compound was prepared in a similar manner to Example 2 using 4- (quinolin-8-yl) phenyl isocyanate (D58) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1 Prepared as a white solid from -yl) -1H-indole (D15) (52%).

실시예 76Example 76

5-클로로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-8-일)페닐아미노카르보닐]-1H-인돌5-chloro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-8-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 4-(퀴놀린-8-일)페닐 이소시아네이트(D58) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 백색 고체로 제조하였다(71%).The title compound was prepared in a similar manner to Example 2 using 4- (quinolin-8-yl) phenyl isocyanate (D58) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1- Prepared as a white solid from I) -1H-indole (D13) (71%).

실시예 77Example 77

5-클로로-2,3-디히드로-1-[4-(이미다졸-1-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (imidazol-1-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 방법으로 4-(이미다졸-1-일)아닐린(문헌[J. Med. Chem. 1988. 31(11), 2136]) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다. 생성물은 연한 우유빛 가루로 단리되었다(42%).The title compound was prepared in a similar manner to Example 4 with 4- (imidazol-1-yl) aniline (J. Med. Chem. 1988. 31 (11), 2136) and 5-chloro-2,3- Prepared from dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13). The product was isolated as a pale milky powder (42%).

실시예 78Example 78

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) phenylaminocarbonyl] -1H-indole

상기 표제 화합물을 기재 항목 2와 유사한 과정을 사용하여 5-클로로-2,3-디히드로-1-[4-아이오도페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌(D43) 및 4-피리딜보론산(문헌[Med. Chem. 1997, 40(22), 3542])로부터 제조하였다. 생성물은 연한 황색 고체로 단리되었다(46%).The title compound was prepared using a procedure similar to that described in Item 2, using 5-chloro-2,3-dihydro-1- [4-iodophenylaminocarbonyl] -6- (4-methylpiperazin-1-yl). -1H-indole (D43) and 4-pyridylboronic acid (Med. Chem. 1997, 40 (22), 3542). The product was isolated as a pale yellow solid (46%).

DMSO 시그널에 의해 4H는 발견되지 않음.4H not detected by DMSO signal.

실시예 79Example 79

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-5-일)아미노카르보닐]-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-5-yl) aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-아미노-8-페닐퀴놀린(D66) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 황색/갈색 오일로 제조하였다(20%). 이것을 아세톤을 사용하여 황색 고체로써 HCl 염으로 전환하였다.The title compound was prepared using a procedure similar to that of Example 4, using 5-amino-8-phenylquinolin (D66) and 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) Prepared as a yellow / brown oil from -1H-indole (Intermediate 3 of WO 95/06627) (20%). This was converted to HCl salt as a yellow solid using acetone.

실시예 80Example 80

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 8-페닐퀴놀린-4-일 이소시아네이트(D86) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D13)로부터 황색 고체로 제조하였다(75%).The title compound was purified using 8-phenylquinolin-4-yl isocyanate (D86) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) using a procedure similar to that of Example 2. Prepared as a yellow solid from -1H-indole (D13) (75%).

실시예 81Example 81

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 8-페닐퀴놀린-4-일 이소시아네이트(D86) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D15)로부터 황색 고체로 제조하였다(75%).The title compound was subjected to 8-phenylquinolin-4-yl isocyanate (D86) and 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl using a similar procedure as in Example 2. Prepared as a yellow solid from) -1H-indole (D15) (75%).

실시예 82Example 82

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 8-페닐퀴놀린-4-일 이소시아네이트(D86) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌 (WO 95/06627의 중간체 3)로부터 베이지색 오일로 제조하였다(73%).The title compound was subjected to 8-phenylquinolin-4-yl isocyanate (D86) and 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl using a similar procedure as in Example 2. Prepared as a beige oil from) -1H-indole (Intermediate 3 of WO 95/06627) (73%).

실시예 83Example 83

5-클로로-1-[4-(2,6-디메틸피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-1- [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 4-(2,6-디메틸피리딘-4-일)-3-메틸아닐린(D88) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 연한 황색 고체 로 제조하였다(41%).The title compound was converted to 4- (2,6-dimethylpyridin-4-yl) -3-methylaniline (D88) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl Prepared as a pale yellow solid from) -1H-indole (D13) (41%).

실시예 84Example 84

5-클로로-2,3-디히드로-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl)- 1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-메틸-4-(6-메틸피리딘-2-일)아닐린(D89) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 연한 황색 검으로 제조하였다(86%). 이것을 아세톤을 사용하여 연한 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 4 using 3-methyl-4- (6-methylpyridin-2-yl) aniline (D89) and 5-chloro-2,3-dihydro-6- (4- Prepared as a pale yellow gum from methylpiperazin-1-yl) -1H-indole (D13) (86%). This was converted to its hydrochloride salt as a pale yellow solid using acetone.

실시예 85Example 85

5-브로모-2,3-디히드로-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-메틸-4-(6-메틸피리딘-2-일)아닐린(D89) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 황색 기포로 제조하였다(67%). 이것을 아세톤을 사용하여 베이지색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 4 using 3-methyl-4- (6-methylpyridin-2-yl) aniline (D89) and 5-bromo-2,3-dihydro-6- (4 Prepared as a yellow bubble from -methylpiperazin-1-yl) -1H-indole (D15) (67%). This was converted to its hydrochloride salt as a beige solid using acetone.

실시예 86Example 86

2,3-디히드로-5-메톡시-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-메틸-4-(6-메틸피리딘-2-일)아닐린(D89) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)으로부터 연한 황색 기포로 제조하였다(84%). 이것을 아세톤을 사용하여 연한 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 4 using 3-methyl-4- (6-methylpyridin-2-yl) aniline (D89) and 2,3-dihydro-5-methoxy-6- (4 Prepared as pale yellow bubbles from -methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (84%). This was converted to its hydrochloride salt as a pale yellow solid using acetone.

실시예 87Example 87

5-클로로-2,3-디히드로-1-[5-(6-메틸피리딘-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [5- (6-methylpyridin-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(6-메틸피리딘-2-일)나프트-1-일 이소시아네이트(D92) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진 -1-일)-1H-인돌(D13)로부터 연한 황색 고체로 제조하였다(59%). 이것을 아세톤을 사용하여 연한 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using a procedure similar to Example 4 using 5- (6-methylpyridin-2-yl) naphth-1-yl isocyanate (D92) and 5-chloro-2,3-dihydro-6- ( Prepared as a pale yellow solid from 4-methylpiperazin-1-yl) -1H-indole (D13) (59%). This was converted to its hydrochloride salt as a pale yellow solid using acetone.

실시예 88Example 88

2,3-디히드로-5-메톡시-1-[5-(6-메틸피리딘-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [5- (6-methylpyridin-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(6-메틸피리딘-2-일)나프트-1-일 이소시아네이트(D92) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진 -1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 연한 황색 기체로 제조하였다(55%). 이것을 아세톤을 사용하여 연한 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using a procedure similar to Example 4 using 5- (6-methylpyridin-2-yl) naphth-1-yl isocyanate (D92) and 2,3-dihydro-5-methoxy-6- Prepared as a pale yellow gas from (4-methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (55%). This was converted to its hydrochloride salt as a pale yellow solid using acetone.

실시예 89Example 89

5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1-[(4-피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-ethylpiperazin-1-yl) -1-[(4-pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(피리딘-4-일)나프트-1-일아민(D2) 및 5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1H-인돌 (D97)로부터 베이지색 고체로 제조하였다(60%). HCl 염은 아세톤을 사용하여 황색 고체로써 단리되었다.The title compound was prepared in a similar manner to Example 4 using 4- (pyridin-4-yl) naphth-1-ylamine (D2) and 5-chloro-2,3-dihydro-6- (4-ethyl Prepared as a beige solid from piperazin-1-yl) -1H-indole (D97) (60%). HCl salt was isolated as a yellow solid using acetone.

실시예 90Example 90

5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-ethylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(피리딘-4-일)나프트-1-일아민(D74) 및 5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1H-인돌 (D97)로부터 베이지색 고체로 제조하였다(68%). HCl 염은 아세톤을 사용하여 황색 고체로써 단리되었다.The title compound was prepared in a similar manner to Example 4 using 5- (pyridin-4-yl) naphth-1-ylamine (D74) and 5-chloro-2,3-dihydro-6- (4-ethyl Prepared as a beige solid from piperazin-1-yl) -1H-indole (D97) (68%). HCl salt was isolated as a yellow solid using acetone.

실시예 91Example 91

5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌 히드로클로라이드5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole hydrochloride

메탄올(30ml) 중의 6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌(D100, 345mg, 0.59mmole) 교반 용액을 에테르(3ml) 중의 1M HCl로 처리했다. 18시간 후 실온에서 에테르(2.5ml) 중의 추가 HCl을 첨가했다. 24시간 후, 혼합물을 진공 농축시켰으며 잔류물을 아세톤으로 연화시켜 고체화함으로써 상기 표제 화합물을 황색 고체로 얻었다(260mg, 84%).6- [4- (tert-butyloxycarbonyl) piperazin-1-yl] -5-chloro-2,3-dihydro-1- [4- (pyridin-4-yl) in methanol (30 ml) A FT-1-ylaminocarbonyl] -1 H-indole (D100, 345 mg, 0.59 mmole) stirred solution was treated with 1 M HCl in ether (3 ml). After 18 h additional HCl in ether (2.5 ml) was added at room temperature. After 24 hours, the mixture was concentrated in vacuo and the residue was triturated with acetone to solidify to give the title compound as a yellow solid (260 mg, 84%).

실시예 92Example 92

5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌 히드로클로라이드5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole hydrochloride

상기 표제 화합물을 실시예 91과 유사한 과정을 사용하여 6-[4-(tert-부틸옥시카르보닐)피페라진-1-일]-5-클로로-2,3-디히드로-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌(D100)로부터 베이지색 고체로 제조했다(60%).The title compound was purified using 6- [4- (tert-butyloxycarbonyl) piperazin-1-yl] -5-chloro-2,3-dihydro-1- [5- using a similar procedure as in Example 91. Prepared as a beige solid from (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole (D100) (60%).

실시예 93Example 93

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리다진-3-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridazin-3-yl) phenylaminocarbonyl] -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(피리다진-3-일)벤조산(D102)으로부터 그의 이소시아네이트를 형성한 후 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일) -1H-인돌(D13)을 첨가하여 상기 표제 화합물을 연한 황색 고체인 우레아 얻었다(7%).5-Chloro-2,3-dihydro-6- (4-methylpiperazin-) after forming its isocyanate from 4- (pyridazin-3-yl) benzoic acid (D102) using a procedure similar to that described in item 1 1-yl) -1H-indole (D13) was added to afford the title compound urea as a pale yellow solid (7%).

실시예 94Example 94

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리다진-3-일)페닐아미노카르보닐]-1H-인돌5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridazin-3-yl) phenylaminocarbonyl] -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(피리다진-3-일)벤조산(D102)으로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일) -1H-인돌(D15)을 첨가하여 상기 표제 화합물을 회색 고체인 우레아로 얻었다(3%).5-Bromo-2,3-dihydro-6- (4-methylpiperazin after formation of its isocyanate from 4- (pyridazin-3-yl) benzoic acid (D102) using a procedure similar to that described in Item 1 -1-yl) -1H-indole (D15) was added to give the title compound as a gray solid urea (3%).

실시예 95Example 95

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피라진-2-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrazin-2-yl) phenylaminocarbonyl] -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(피라진-2-일)벤조산(D103)으로부터 그의 이소시아네이트를 형성한 후 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)을 첨가하여 상기 표제 화합물을 연한 황색 고체인 우레아로 얻었다(30%).5-chloro-2,3-dihydro-6- (4-methylpiperazin-1) after the formation of its isocyanate from 4- (pyrazin-2-yl) benzoic acid (D103) using a procedure similar to that described in item 1 -Yl) -1H-indole (D13) was added to afford the title compound as a light yellow solid urea (30%).

실시예 96Example 96

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피라진-2-일)페닐아미노카르보닐]-1H-인돌5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrazin-2-yl) phenylaminocarbonyl] -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(피라진-2-일)벤조산(D103)으로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)을 첨가하여 상기 표제 화합물을 황색 고체인 우레아로 얻었다(49%).5-Bromo-2,3-dihydro-6- (4-methylpiperazin- after forming its isocyanate from 4- (pyrazin-2-yl) benzoic acid (D103) using a procedure similar to that described in item 1 1-yl) -1H-indole (D15) was added to afford the title compound as a yellow solid urea (49%).

실시예 97Example 97

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-페닐피리딘-5-일)아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-phenylpyridin-5-yl) aminocarbonyl] -1H-indole

기재 항목 1과 유사한 과정을 사용하여 6-페닐니코틴산(D104)으로부터 그의 이소시아네이트를 형성한 후 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D15)을 첨가하여 상기 표제 화합물을 백색 고체인 우레아로 얻었다(48%).5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H- after forming its isocyanate from 6-phenylnicotinic acid (D104) using a procedure similar to that described in item 1 Indole (D15) was added to afford the title compound as a white solid urea (48%).

실시예 98Example 98

5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-페닐피리딘-5-일)아미노카르보닐]-1H-인돌5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-phenylpyridin-5-yl) aminocarbonyl] -1H-indole

기재 항목 1과 유사한 과정을 사용하여 6-페닐니코틴산(D104)으로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)을 첨가하여 상기 표제 화합물을 회백색 고체인 우레아로 얻었다(46%).5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H after forming its isocyanate from 6-phenylnicotinic acid (D104) using a procedure similar to that described in item 1 -Indole (D15) was added to afford the title compound as an off-white solid urea (46%).

실시예 99Example 99

5-클로로-2,3-디히드로-1-[4-(6-메틸피리다진-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (6-methylpyridazin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(6-메틸피리다진-3-일)벤조산 (D102)으로부터 그의 이소시아네이트를 형성한 후 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)을 첨가하여 상기 표제 화합물을 담황색 고체인 우레아로 얻었다(23%).5-Chloro-2,3-dihydro-6- (4-methyl) after forming its isocyanate from 4- (6-methylpyridazin-3-yl) benzoic acid (D102) using a procedure similar to that described in Item 1 Piperazin-1-yl) -1H-indole (D13) was added to afford the title compound as a pale yellow solid urea (23%).

실시예 100Example 100

5-브로모-2,3-디히드로-1-[4-(6-메틸피리다진-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (6-methylpyridazin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

기재 항목 1과 유사한 과정을 사용하여 4-(6-메틸피리다진-3-일)벤조산 (D102)으로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)을 첨가하여 상기 표제 화합물을 담황색 고체인 우레아로 얻었다(28%)5-bromo-2,3-dihydro-6- (4- after forming its isocyanate from 4- (6-methylpyridazin-3-yl) benzoic acid (D102) using a procedure similar to that described in item 1 Methylpiperazin-1-yl) -1H-indole (D15) was added to afford the title compound as a pale yellow solid urea (28%).

실시예 101Example 101

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-3-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-3-yl) phenylaminocarbonyl] -1H-indole

연한 우유빛 가루로 수득된 상기 표제 화합물을 기재 항목 2와 유사한 방법으로 5-클로로-2,3-디히드로-1-(4-아이오도페닐아미노카르보닐)-6-(4-메틸피페라진 -1-일)-1H-인돌(D43) 및 3-피리딜보론산(문헌[Chem. Pharm. Bull, 1983, 31(12), 4573])으로부터 제조하였다(19%).The title compound obtained as a pale milky powder was prepared by 5-chloro-2,3-dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-methylpiperazin in a similar manner as described in Item 2. -1-yl) -1H-indole (D43) and 3-pyridylboronic acid (Chem. Pharm. Bull, 1983, 31 (12), 4573) (19%).

DMSO 시그널에 의해 2×CH2시그널은 발견되지 않음.2 × CH 2 signal not found by DMSO signal.

실시예 102Example 102

5-클로로-2,3-디히드로-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

연한 우유빛 가루로 수득된 상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 4-(5-메틸옥사졸-2-일)아닐린(D107)으로부터 제조하였다(63%).The title compound obtained as a pale milky powder was obtained using a method similar to that of Example 4, using 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13). ) And 4- (5-methyloxazol-2-yl) aniline (D107) (63%).

실시예 103Example 103

2,3-디히드로-5-메톡시-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

연한 우유빛 가루로 수득된 상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3) 및 4-(5-메틸옥사졸-2-일)아닐린(D107)으로부터 제조하였다(44%).The title compound obtained as a pale milky powder was treated with 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole ( Intermediate 3) and 4- (5-methyloxazol-2-yl) aniline (D107) of WO 95/06627 (44%).

실시예 104Example 104

5-브로모-2,3-디히드로-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

연한 우유빛 가루로 수득된 상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15) 및 4-(5-메틸옥사졸-2-일)아닐린(D107)으로부터 제조하였다(23%).The title compound obtained as a pale milky powder was purified using 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole ( D15) and 4- (5-methyloxazol-2-yl) aniline (D107) (23%).

실시예 105Example 105

5-클로로-2,3-디히드로-1-[4-(1-메틸피라졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (1-methylpyrazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(1-메틸피라졸-4-일)벤조산(WO 97/43262)으로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)을 첨가하여 상기 표제 화합물을 담황색 고체인 우레아로 얻었다(18%).5-Bromo-2,3-dihydro-6- after forming its isocyanate from 4- (1-methylpyrazol-4-yl) benzoic acid (WO 97/43262) using a procedure similar to that described in Item 1 (4-methylpiperazin-1-yl) -1H-indole (D13) was added to afford the title compound as a pale yellow solid urea (18%).

실시예 106Example 106

5-브로모-2,3-디히드로-1-[4-(1-메틸피라졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (1-methylpyrazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

기재 항목 1과 유사한 과정을 사용하여 4-(1-메틸피라졸-4-일)벤조산(WO 97/43262)로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)를 첨가하여 표제 화합물을 담황색 고체인 우레아로 얻었다(30%).5-Bromo-2,3-dihydro-6- after forming its isocyanate from 4- (1-methylpyrazol-4-yl) benzoic acid (WO 97/43262) using a procedure similar to that described in Item 1 (4-Methylpiperazin-1-yl) -1H-indole (D15) was added to afford the title compound as a pale yellow solid urea (30%).

실시예 107Example 107

5-클로로-1-[4′-시아노-3′-메틸바이페닐-4-아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-1- [4'-cyano-3'-methylbiphenyl-4-aminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H- Indole

기재 항목 1과 유사한 과정을 사용하여 4-(4-시아노-3-메틸페닐)벤조산 (D106)으로부터 그의 이소시아네이트를 형성한 후 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)을 첨가하여 상기 표제 화합물을 회색 고체인 우레아로 얻었다(39%).5-Chloro-2,3-dihydro-6- (4-methylpipe) after forming a isocyanate thereof from 4- (4-cyano-3-methylphenyl) benzoic acid (D106) using a procedure similar to that described in Item 1 Razin-1-yl) -1H-indole (D13) was added to afford the title compound as a gray solid urea (39%).

실시예 108Example 108

5-브로모-1-[4′-시아노-3′-메틸바이페닐-4-아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-1- [4'-cyano-3'-methylbiphenyl-4-aminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H Indol

기재 항목 1과 유사한 과정을 사용하여 4-(4-시아노-3-메틸페닐)벤조산 (D106)으로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)을 첨가하여 상기 표제 화합물을 담황색 고체인 우레아로 얻었다(28%).5-Bromo-2,3-dihydro-6- (4-methyl) after forming its isocyanate from 4- (4-cyano-3-methylphenyl) benzoic acid (D106) using a procedure similar to that described in Item 1 Piperazin-1-yl) -1H-indole (D15) was added to afford the title compound as a pale yellow solid urea (28%).

실시예 109Example 109

5-클로로-2,3-디히드로-1-[4-(2-메틸피리딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [4- (2-methylpyridin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(2-메틸피리딘-5-일)벤조산(WO 97/43262)으로부터 그의 이소시아네이트를 형성한 후 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)을 첨가하여 상기 표제 화합물을 담황색 고체인 우레아로 얻었다(2%).A procedure similar to that described in Item 1 was used to form its isocyanate from 4- (2-methylpyridin-5-yl) benzoic acid (WO 97/43262), followed by 5-chloro-2,3-dihydro-6- (4 -Methylpiperazin-1-yl) -1H-indole (D13) was added to afford the title compound as a pale yellow solid urea (2%).

실시예 110Example 110

5-브로모-2,3-디히드로-1-[4-(2-메틸피리딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (2-methylpyridin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole

기재 항목 1과 유사한 과정을 사용하여 4-(2-메틸피리딘-5-일)벤조산(WO 97/43262)으로부터 그의 이소시아네이트를 형성한 후 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)을 첨가하여 상기 표제 화합물을 담황색 고체인 우레아로 얻었다(10%).A procedure similar to that described in Item 1 was used to form its isocyanate from 4- (2-methylpyridin-5-yl) benzoic acid (WO 97/43262), followed by 5-bromo-2,3-dihydro-6- ( 4-methylpiperazin-1-yl) -1H-indole (D15) was added to afford the title compound as a pale yellow solid urea (10%).

실시예 111Example 111

5-클로로-2,3-디히드로-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- (4 Methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아민(D111)으로부터 제조하였다. 상기 표제 화합물은 연한 담황색 가루로써 히드로클로라이드 염으로 전환되었다(59%).The title compound was prepared in a similar manner to Example 4 using 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) and 5- (3- Prepared from methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylamine (D111). The title compound was converted to the hydrochloride salt as a light pale yellow powder (59%).

실시예 112Example 112

2,3-디히드로-5-메톡시-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- ( 4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3) 및 5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아민(D111)으로부터 제조하였다. 상기 표제 화합물은 무색 가루로써 히드로클로라이드 염으로 전환되었다(68%).The title compound was prepared in a similar manner to Example 4 using 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627). ) And 5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylamine (D111). The title compound was converted to the hydrochloride salt as a colorless powder (68%).

실시예 113Example 113

5-브로모-2,3-디히드로-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- ( 4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15) 및 5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아민(D111)으로부터 제조하였다. 상기 표제 화합물은 연한 담황색 가루로써 히드로클로라이드 염으로 전환되었다(36%).The title compound was purified using 5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D15) and 5- (3 using a similar method as in Example 4. Prepared from -methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylamine (D111). The title compound was converted to the hydrochloride salt as a light pale yellow powder (36%).

H20 시그널에 의해 2×CH2가 발견되지 않음.2 × CH 2 not found by H 2 0 signal.

실시예 114Example 114

5-클로로-2,3-디히드로-1-[5-(5-메틸옥사졸-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [5- (5-methyloxazol-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 방법으로 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13) 및 5-(5-메틸옥사졸-2-일)나프트-1-일아민 (D114)으로부터 제조하였으며, 이는 연한 황색 가루로써 히드로클로라이드 염으로 전환되었다(41%).The title compound was purified in a similar manner to Example 4 using 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13) and 5- (5-methyloxa Zol-2-yl) naphth-1-ylamine (D114), which was converted to the hydrochloride salt as a pale yellow powder (41%).

DMSO 시그널에 의해 CH3시그널은 발견되지 않음.CH 3 signal not detected by DMSO signal.

실시예 115Example 115

2,3-디히드로-5-메톡시-1-[5-(5-메틸옥사졸-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [5- (5-methyloxazol-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole

연한 황색 가루로써 히드로클로라이드 염으로 수득된 상기 표제 화합물을 실시예 4와 유사한 방법으로 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3) 및 5-(5-메틸옥사졸-2-일)나프트-1-일아민(D114)으로부터 제조하였다(56%).The title compound obtained as a hydrochloride salt as a pale yellow powder was prepared in the same manner as in Example 4 using 2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) and 5- (5-methyloxazol-2-yl) naphth-1-ylamine (D114) (56%).

실시예 116Example 116

5-브로모-2,3-디히드로-1-[3-메틸-4-(피리미딘-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [3-methyl-4- (pyrimidin-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1 -Work) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 3-메틸-4-(피리미딘-2-일)아닐린(D115) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 베이지색 기포로 제조하였다(34%). 이 기포를 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 3-methyl-4- (pyrimidin-2-yl) aniline (D115) and 5-bromo-2,3-dihydro-6- (4-methyl using a similar method as in Example 4. Prepared as beige bubbles from piperazin-1-yl) -1H-indole (D15) (34%). This bubble was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 117Example 117

2,3-디히드로-5-메톡시-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 3-메틸-4-(피리미딘-2-일)아닐린(D115) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 베이지색 기포로 제조하였다(32%). 이 기포을 아세톤을 사용하여 황갈색 가루로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 3-methyl-4- (pyrimidin-2-yl) aniline (D115) and 2,3-dihydro-5-methoxy-6- (4-methyl using a similar method as in Example 4. Prepared as beige foam from piperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (32%). This bubble was converted to its hydrochloride salt as a tan powder using acetone.

실시예 118Example 118

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 3-메틸-4-(피리미딘-2-일)아닐린(D115) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 베이지색 기포로 제조하였다(47%). 이 기포를 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 3-methyl-4- (pyrimidin-2-yl) aniline (D115) and 5-chloro-2,3-dihydro-6- (4-methylpipepe using a similar method as in Example 4. Prepared as beige bubbles from razin-1-yl) -1H-indole (D13) (47%). This bubble was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 119Example 119

5-브로모-2,3-디히드로-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 3-메틸-4-(피리미딘-5-일)아닐린(D116) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 기포로 제조하였다(82%). 이 기포를 아세톤을 사용하여 회백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 3-methyl-4- (pyrimidin-5-yl) aniline (D116) and 5-bromo-2,3-dihydro-6- (4-methyl using a similar method as in Example 4. Prepared from foam (82%) from piperazin-1-yl) -1H-indole (D15). This bubble was converted to its hydrochloride salt as an off-white solid using acetone.

실시예 120Example 120

5-클로로-2,3-디히드로-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 3-메틸-4-(피리미딘-5-일)아닐린(D116) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 기포로 제조하였다(84%). 이 기포를 아세톤을 사용하여 회백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 3-methyl-4- (pyrimidin-5-yl) aniline (D116) and 5-chloro-2,3-dihydro-6- (4-methylpipepe using a similar method as in Example 4. Prepared as bubbles from razin-1-yl) -1H-indole (D15) (84%). This bubble was converted to its hydrochloride salt as an off-white solid using acetone.

실시예 121Example 121

2,3-디히드로-5-메톡시-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 4와 유사한 방법을 사용하여 3-메틸-4-(피리미딘-5-일)아닐린(D116) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 기포로 제조하였다(97%). 이 기포를 아세톤을 사용하여 회백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using 3-methyl-4- (pyrimidin-5-yl) aniline (D116) and 2,3-dihydro-5-methoxy-6- (4-methyl using a similar method as in Example 4. Prepared from foam (97%) from piperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627). This bubble was converted to its hydrochloride salt as an off-white solid using acetone.

실시예 122Example 122

5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-4-일)-3-메틸아닐린(D88) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 연한 황색 기포로 제조하였다(89%). 이것을 아세톤을 사용하여 연한 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to that of Example 4, using 4- (2,6-dimethylpyridin-4-yl) -3-methylaniline (D88) and 5-bromo-2,3-dihydro-6- Prepared as a pale yellow bubble from (4-methylpiperazin-1-yl) -1H-indole (D15) (89%). This was converted to its hydrochloride salt as a pale yellow solid using acetone.

실시예 123Example 123

2,3-디히드로-5-메톡시-1-[4-(2,6-디메틸피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-4-일)-3-메틸아닐린(D88) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 연한 황색 기포로 제조하였다(95%). 이것을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to that of Example 4, using 4- (2,6-dimethylpyridin-4-yl) -3-methylaniline (D88) and 2,3-dihydro-5-methoxy-6- Prepared as a pale yellow bubble from (4-methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (95%). This was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 124Example 124

5-클로로-2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(2,6-디메틸피리딘-4-일)나프트-1-일 이소시아네이트(D119) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 백색 기포로 제조하였다(83%). 이것을 아세톤을 사용하여 백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using a procedure similar to Example 4 using 5- (2,6-dimethylpyridin-4-yl) naphth-1-yl isocyanate (D119) and 5-chloro-2,3-dihydro-6 Prepared as a white bubble from-(4-methylpiperazin-1-yl) -1H-indole (D13) (83%). This was converted to its hydrochloride salt as a white solid using acetone.

실시예 125Example 125

5-브로모-2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-인돌린5-bromo-2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1 -Day) -indolin

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(2,6-디메틸피리딘-4-일)-1-나프틸 이소시아네이트(D119) 및 5-브로모-6-(4-메틸피페라진-1-일)-1H-인돌(D15)로부터 백색 기포로 제조하였다(64%). 이것을 아세톤을 사용하여 백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to that of Example 4. 5- (2,6-dimethylpyridin-4-yl) -1-naphthyl isocyanate (D119) and 5-bromo-6- (4-methylpiperazin Prepared as white bubbles from -1-yl) -1H-indole (D15) (64%). This was converted to its hydrochloride salt as a white solid using acetone.

실시예 126Example 126

1-[5-(2,6-디메틸-4-피리딜)-1-나프틸아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌1- [5- (2,6-dimethyl-4-pyridyl) -1-naphthylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(2,6-디메틸피리딘-4-일)나프트-1-일 이소시아네이트(D119) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 무색 오일로 제조하였다(88%). 이것을 아세톤을 사용하여 연한 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using a procedure similar to Example 4 using 5- (2,6-dimethylpyridin-4-yl) naphth-1-yl isocyanate (D119) and 2,3-dihydro-5-methoxy- Prepared as a colorless oil from 6- (4-methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (88%). This was converted to its hydrochloride salt as a pale yellow solid using acetone.

실시예 127Example 127

2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)-3-메틸페닐아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) -3-methylphenylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl ) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 4-(2,6-디메틸피리딘-3-일)-3-메틸아닐린(D120) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 연한 황색 오일로 제조하였다(44%). 이것을 아세톤을 사용하여 오렌지색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to that of Example 4, using 4- (2,6-dimethylpyridin-3-yl) -3-methylaniline (D120) and 2,3-dihydro-5-methoxy-6- Prepared as a pale yellow oil from (4-methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (44%). This was converted to its hydrochloride salt as an orange solid using acetone.

실시예 128Example 128

5-브로모-2,3-디히드로-1-[3-메틸-4-(티아졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-bromo-2,3-dihydro-1- [3-methyl-4- (thiazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-메틸-4-(티아졸-2-일)아닐린(D121) 및 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D15)로부터 기포로 제조하였다(64%). 이것을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 4 using 3-methyl-4- (thiazol-2-yl) aniline (D121) and 5-bromo-2,3-dihydro-6- (4-methyl Prepared from foam (64%) from piperazin-1-yl) -1H-indole (D15). This was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 129Example 129

5-클로로-2,3-디히드로-1-[3-메틸-4-(티아졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [3-methyl-4- (thiazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-메틸-4-(티아졸-2-일)아닐린(D121) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌 (D13)로부터 베이지색 기포로 제조하였다(70%). 이것을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 4 using 3-methyl-4- (thiazol-2-yl) aniline (D121) and 5-chloro-2,3-dihydro-6- (4-methylpipepe Prepared as beige bubbles from razin-1-yl) -1H-indole (D13) (70%). This was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 130Example 130

2,3-디히드로-5-메톡시-1-[3-메틸-4-(티아졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌2,3-dihydro-5-methoxy-1- [3-methyl-4- (thiazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 3-메틸-4-(티아졸-2-일)아닐린(D121) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌 (WO 95/06627의 중간체 3)로부터 연한 황색 오일로 제조하였다(68%). 이것을 아세톤을 사용하여 황색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was prepared using a procedure similar to Example 4 using 3-methyl-4- (thiazol-2-yl) aniline (D121) and 2,3-dihydro-5-methoxy-6- (4-methyl Prepared as a light yellow oil from piperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (68%). This was converted to its hydrochloride salt as a yellow solid using acetone.

실시예 131Example 131

1-(5-아세틸나프트-1-일아미노카르보닐)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌1- (5-acetylnaphth-1-ylaminocarbonyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-아세틸나프트-1-일아민(D124) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다. 이것을 담황색 가루로써 그의 히드로클로라이드 염으로 전환하였다(60%).The title compound was purified using 5-acetylnaphth-1-ylamine (D124) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) using procedures similar to those of Example 4. ) -1H-indole (D13). This was converted to its hydrochloride salt as a pale yellow powder (60%).

실시예 132Example 132

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리미딘-2-일옥시)나프트-1-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyrimidin-2-yloxy) naphth-1-ylaminocarbonyl]- 1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(피리미딘-2-일옥시)나프트-1-일아민(D125) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다. 이것을 연한 우유빛 가루로써 그의 히드로클로라이드 염으로 전환하였다(61%).The title compound was prepared in a similar manner to Example 4 using 5- (pyrimidin-2-yloxy) naphth-1-ylamine (D125) and 5-chloro-2,3-dihydro-6- (4 Prepared from -methylpiperazin-1-yl) -1H-indole (D13). This was converted to its hydrochloride salt as a pale milky powder (61%).

실시예 133Example 133

5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리미딘-5-일)나프트-1-일아미노카르보닐]-1H-인돌5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyrimidin-5-yl) naphth-1-ylaminocarbonyl] -1H Indol

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 5-(피리미딘-5-일)나프트-1-일 이소시아네이트(D123) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 백색 기포로 제조하였다(43%). 이것을 아세톤을 사용하여 백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using a procedure similar to Example 2 using 5- (pyrimidin-5-yl) naphth-1-yl isocyanate (D123) and 5-chloro-2,3-dihydro-6- (4- Prepared as white foam from methylpiperazin-1-yl) -1H-indole (D13) (43%). This was converted to its hydrochloride salt as a white solid using acetone.

실시예 134Example 134

2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[5-(피리미딘-5-일)나프트-1-일아미노카르보닐]-1H-인돌2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [5- (pyrimidin-5-yl) naphth-1-ylaminocarbonyl]- 1H-indole

상기 표제 화합물을 실시예 2와 유사한 과정을 사용하여 5-(피리미딘-5-일)나프트-1-일 이소시아네이트(D123) 및 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌(WO 95/06627의 중간체 3)로부터 백색 기포로 제조하였다(50%). 이것을 아세톤을 사용하여 백색 고체로써 그의 히드로클로라이드 염으로 전환하였다.The title compound was purified using a procedure similar to Example 2 using 5- (pyrimidin-5-yl) naphth-1-yl isocyanate (D123) and 2,3-dihydro-5-methoxy-6- (4 Prepared as white foam from -methylpiperazin-1-yl) -1H-indole (Intermediate 3 of WO 95/06627) (50%). This was converted to its hydrochloride salt as a white solid using acetone.

실시예 135Example 135

5-클로로-1-(5-시아노나프트-1-일아미노카르보닐)-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-1- (5-cyanonaph-1-ylaminocarbonyl) -2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-시아노나프트-1-일아민(D126) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다. 이것을 우유빛 가루로써 그의 히드로클로라이드 염으로 전환하였다(81%).The title compound was purified using 5-cyanonaph-1-ylamine (D126) and 5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl using a procedure similar to that of Example 4. ) -1H-indole (D13). This was converted to its hydrochloride salt as a milky powder (81%).

실시예 136Example 136

5-클로로-2,3-디히드로-1-[5-(5-메틸-1,2,4-옥사디아졸-3-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌5-chloro-2,3-dihydro-1- [5- (5-methyl-1,2,4-oxadiazol-3-yl) naphth-1-ylaminocarbonyl] -6- (4 Methylpiperazin-1-yl) -1H-indole

상기 표제 화합물을 실시예 4와 유사한 과정을 사용하여 5-(5-메틸-1,2,4-옥사디아졸-3-일)나프트-1-일아민(D130) 및 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌(D13)로부터 제조하였다. 이것을 담황색 가루로써 그의 히드로클로라이드 염으로 전환하였다(84%).The title compound was prepared using a procedure similar to that of Example 4. 5- (5-methyl-1,2,4-oxadiazol-3-yl) naphth-1-ylamine (D130) and 5-chloro-2 Prepared from, 3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole (D13). This was converted to its hydrochloride salt as a pale yellow powder (84%).

H2O 시그널에의해 2H 시그널은 발견되지 않음.2H signal not found due to H 2 O signal.

약리 데이타Pharmacological data

5-HT1A, 5-HT1B및 5-HT1D수용체 결합5-HT 1A , 5-HT 1B and 5-HT 1D Receptor Binding

5-HT1A수용체(4×107/ml)를 발현시키는 HEK 293 세포는 트리스 완충액에서 균질화되고 1ml 분취량에 보관되었다. 5-HT1B수용체(4×107세포/ml)를 발현시키는 CHO 세포는 트리스 완충액에서 균질화되고 1.5ml 분취량에 보관되었다. 5-HT1D수용체(0.563×108/ml)를 발현시키는 CHO 세포는 트리스 완충액에서 균질화되고 1ml 분취량에 보관되었다.HEK 293 cells expressing 5-HT 1A receptor (4 × 10 7 / ml) were homogenized in Tris buffer and stored in 1 ml aliquots. CHO cells expressing 5-HT 1B receptor (4 × 10 7 cells / ml) were homogenized in Tris buffer and stored in 1.5 ml aliquots. CHO cells expressing 5-HT 1D receptor (0.563 × 10 8 / ml) were homogenized in Tris buffer and stored in 1 ml aliquots.

세포 현탁액 0.4ml를 트리스 Mg HCl 완충액(pH7.7) 중의 5-HT1B/1D수용체를 위한 [3H]-5HT(4nM) 및 5-HT1A수용체를 위한 [3H]-8-OH DPAT(1nM) 및 실험 약물을 함께 37℃에서 45분 간 인큐베이트했다. 0.01mM 5-HT를 사용하여 비-특이적 결합을 한정하면서, 각각의 실험 약물을 10개 농도(0.01mM에서 최종 농도 0.3nM까지)로 실험했다. 총 분석 부피는 0.5ml이다. 인큐베이션은 팩카드 필터메이트(Packard Filtermate)(0.3% 폴리에틸렌이민 중의 예비-침지된 필터)를 사용한 급속 여과에 의해 중지되었으며 방사능은 탑카운트(Topcount) 신틸레이션 카운팅에 의해 측정되었다. pKi값은 반복적인 최소 제곱 곡선 피팅(fitting) 프로그램에 의해 나타난 IC50으로부터 계측되었다.0.4 ml of cell suspension was added to [ 3 H] -5HT (4 nM) for 5-HT 1B / 1D receptor and [ 3 H] -8-OH DPAT for 5-HT 1A receptor in Tris Mg HCl buffer (pH7.7). (1 nM) and the experimental drug were incubated together at 37 ° C. for 45 minutes. Each experimental drug was tested at 10 concentrations (0.01 mM to final concentration 0.3 nM), while limiting non-specific binding using 0.01 mM 5-HT. Total assay volume is 0.5 ml. Incubation was stopped by rapid filtration using Packard Filtermate (pre-soaked filter in 0.3% polyethyleneimine) and radioactivity was measured by Topcount scintillation counting. pKi values were measured from IC 50 shown by an iterative least square curve fitting program.

실시예 5, 9, 10, 15, 21, 24, 25, 27, 28, 43, 44, 45, 47, 48, 49, 50, 52, 53, 67, 68, 69, 70, 71, 72, 76, 78, 80, 81, 82, 83, 89, 97, 98 및 110은 5-HT1A, 5-HT1B및 5-HT1D수용체에서 8.0을 초과한 pKi값을 가졌다.Examples 5, 9, 10, 15, 21, 24, 25, 27, 28, 43, 44, 45, 47, 48, 49, 50, 52, 53, 67, 68, 69, 70, 71, 72, 76, 78, 80, 81, 82, 83, 89, 97, 98 and 110 had pKi values greater than 8.0 at the 5-HT 1A , 5-HT 1B and 5-HT 1D receptors.

Claims (12)

화학식(I)의 화합물 또는 그의 염.Compounds of formula (I) or salts thereof. ＜화학식 I＞<Formula I> 상기 식에서, Ra는 화학식(I-a)를 갖는 기이거나,Wherein R a is a group having formula (Ia), or ＜화학식 I-a＞<Formula I-a> (여기서, P1은 페닐, 바이사이클릭 아릴, 산소, 질소 및 황으로부터Wherein P 1 is selected from phenyl, bicyclic aryl, oxygen, nitrogen and sulfur 선택된 1 내지 3개의 헤테로원자를 포함하는 5 내지 7 원 헤테로사이클릭5-7 membered heterocyclic containing 1 to 3 heteroatoms selected 고리, 또는 산소, 질소 및 황으로부터 선택된 1 내지 3개의 헤테로원자를Ring or 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur 포함하는 바이사이클릭 헤테로사이클릭 고리이며;A bicyclic heterocyclic ring comprising; R1은 수소, 할로겐, C1-6알킬, C3-6시클로알킬, COC1-6알킬, C1-6알콕시,R 1 is hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, COC 1-6 alkyl, C 1-6 alkoxy, 히드록시, 히드록시C1-6알킬, 히드록시C1-6알콕시, C1-6알콕시C1-6알콕시,Hydroxy, hydroxyC 1-6 alkyl, hydroxyC 1-6 alkoxy, C 1-6 alkoxyC 1-6 alkoxy, 아실, 니트로, 트리플루오로메틸, 시아노, SR9, SOR9, SO2R9,Acyl, nitro, trifluoromethyl, cyano, SR 9 , SOR 9 , SO 2 R 9 , SO2NR10R11, CO2R10, CONR10R11, CO2NR10R11, CONR10(CH2)cCO2R11, (CH2)cNR10R11,SO 2 NR 10 R 11 , CO 2 R 10 , CONR 10 R 11 , CO 2 NR 10 R 11 , CONR 10 (CH 2 ) c CO 2 R 11 , (CH 2 ) c NR 10 R 11 , (CH2)cCONR10R11, (CH2)cNR10COR11, (CH2)cCO2C1-6알킬, CO2(CH2)cOR10, NR10R11,(CH 2 ) c CONR 10 R 11 , (CH 2 ) c NR 10 COR 11 , (CH 2 ) c CO 2 C 1-6 alkyl, CO 2 (CH 2 ) c OR 10 , NR 10 R 11 , NR10CO2R11, NR10CONR10R11, CR10=NOR11, NR10COOR11, CNR10=NOR11이고(여기서,NR 10 CO 2 R 11 , NR 10 CONR 10 R 11 , CR 10 = NOR 11 , NR 10 COOR 11 , CNR 10 = NOR 11 , where R10및 R11은 각각 수소 또는 C1-6알킬이며 c는 1 내지 4임);R 10 and R 11 are each hydrogen or C 1-6 alkyl and c is 1-4; R2는 수소, 할로겐, C1-6알킬, C3-6시클로알킬, C3-6시클로알케닐,R 2 is hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, C1-6알콕시, C1-6알카노일, 아릴, 아실옥시, 히드록시, 니트로,C 1-6 alkoxy, C 1-6 alkanoyl, aryl, acyloxy, hydroxy, nitro, 트리플루오로메틸, 시아노, CO2R10, CONR10R11, NR10R11이며(여기서, R10및 Trifluoromethyl, cyano, CO2R10, CONR10R11, NR10R11Where R is10And R11은 R1에 대해 정의된 대로임);R 11 is as defined for R 1 ; a는 1, 2 또는 3임);a is 1, 2 or 3); 또는 Ra는 하기 화학식(ii)를 갖는 기이며Or R a is a group of formula (ii) ＜화학식 I-b＞<Formula I-b> (여기서, P2및 P3는 각각 페닐, 바이사이클릭 아릴, 산소, 질소 및Wherein P 2 and P 3 are each phenyl, bicyclic aryl, oxygen, nitrogen and 황으로부터 선택된 1 내지 3개의 헤테로원자를 갖는 5- 내지 7- 원5- to 7-membered having 1 to 3 heteroatoms selected from sulfur 헤테로사이클릭 고리 또는 산소, 질소 또는 황으로부터 선택된 1 내지Heterocyclic ring or 1 to 1 selected from oxygen, nitrogen or sulfur 3개의 헤테로원자를 포함하는 바이사이클릭 헤테로사이클릭기이며;Bicyclic heterocyclic groups containing three heteroatoms; A는 결합 또는 산소, S(O)m(여기서, m은 0 내지 2임), 카르보닐, CH2,A is a bond or oxygen, S (O) m where m is 0 to 2, carbonyl, CH 2 , -CH2-CH2-, 또는 NR4이고(여기서, R4는 수소 또는 C1-6알킬임);-CH 2 -CH 2- , or NR 4 , wherein R 4 is hydrogen or C 1-6 alkyl; R1은 상기 화학식(I)에서 정의한 대로이거나 R1은 산소, 질소 또는R 1 is as defined in formula (I) or R 1 is oxygen, nitrogen or 황으로부터 선택된 1 내지 3개의 헤테로원자를 포함하는 임의로 치환된Optionally substituted comprising 1 to 3 heteroatoms selected from sulfur 5 내지 7-원 헤테로사이클릭 고리이며;5 to 7-membered heterocyclic ring; R2및 R3는 각각 수소, 할로겐, C1-6알킬, C3-6시클로알킬, C3-6시클로R 2 and R 3 are each hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cyclo 알케닐, C1-6알콕시, C1-6알카노일, 아릴, 아실옥시, 히드록시, 니트로,Alkenyl, C 1-6 alkoxy, C 1-6 alkanoyl, aryl, acyloxy, hydroxy, nitro, 트리플루오로메틸, 시아노, CO2R10, CONR10R11, NR10R11이고(여기서, R10 Trifluoromethyl, cyano, CO 2 R 10 , CONR 10 R 11 , NR 10 R 11 , wherein R 10 및 R11은 R1에 대해 정의된 대로임);And R 11 is as defined for R 1 ; a 및 b는 각각 1, 2 또는 3임);a and b are 1, 2 or 3, respectively; Y는 -NH-, -NR5-이며(여기서, R5는 C1-6알킬이거나 Y는 -CH2- 또는 -O-임);Y is -NH-, -NR 5- , wherein R 5 is C 1-6 alkyl or Y is -CH 2 -or -O-; V는 산소 또는 황이고;V is oxygen or sulfur; D는 질소, 탄소 또는 CH기이며; W는 (CR16R17)t이거나(여기서, t는 2, 3 또는 4이고 R16및 R17은 각각 수소 또는 C1-6알킬임) W는 (CR16R17)u-J이며(여기서, u는 0, 1, 2 또는 3이고 J는 산소, 황, CR16=CR17, CR16=N, =CR16O, =CR16S 또는 =CR16-NR17임); X는 질소 또는 탄소이고;D is nitrogen, carbon or CH group; W is (CR 16 R 17 ) t (where t is 2, 3 or 4 and R 16 and R 17 are each hydrogen or C 1-6 alkyl) W is (CR 16 R 17 ) u -J ( Wherein u is 0, 1, 2 or 3 and J is oxygen, sulfur, CR 16 = CR 17 , CR 16 = N, = CR 16 O, = CR 16 S or = CR 16 -NR 17 ); X is nitrogen or carbon; Rb는 수소, 할로겐, 히드록시, C1-6알킬, 트리플루오로메틸, C1-6알콕시, C2-6알케닐, C1-4알킬에 의해 임의로 치환된 C3-7시클로알킬, 또는 아릴이며;R b is C 3-7 cycloalkyl optionally substituted by hydrogen, halogen, hydroxy, C 1-6 alkyl, trifluoromethyl, C 1-6 alkoxy, C 2-6 alkenyl, C 1-4 alkyl Or aryl; Rc는 수소 또는 C1-6알킬이고;R c is hydrogen or C 1-6 alkyl; 은 X가 질소일 때는 단일 결합이고 또는 X가 탄소일 때는 단일 또는 이중 결합이다. Is a single bond when X is nitrogen or a single or double bond when X is carbon. 제1항에 있어서, R1이 할로겐 원자인 화합물.The compound of claim 1, wherein R 1 is a halogen atom. 제1항 또는 제2항에 있어서, R2및(또는) R3가 각각 수소, 할로겐 또는 C1-6알킬기인 화합물.The compound of claim 1 or 2, wherein R 2 and / or R 3 are each hydrogen, halogen or a C 1-6 alkyl group. 제1항 내지 제3항 중 어느 한 항에 있어서, P1및 P2가 페닐, 나프틸 또는 퀴놀리닐인 화합물.The compound of any one of claims 1-3, wherein P 1 and P 2 are phenyl, naphthyl or quinolinyl. 제1항 내지 제4항 중 어느 한 항에 있어서, Y가 -NH-인 화합물.The compound of any one of claims 1-4 wherein Y is -NH-. 제1항 내지 제5항 중 어느 한 항에 있어서, D가 질소이고 W가 화학식6. The compound of claim 1, wherein D is nitrogen and W is of the formula -(CH2)2-를 갖는 기인 화합물.Compounds having a group of-(CH 2 ) 2- . 제1항 내지 제6항 중 어느 한 항에 있어서, Rb가 C1-6알킬기인 화합물.The compound of any one of claims 1-6 , wherein R b is a C 1-6 alkyl group. 제1항 내지 제7항 중 어느 한 항에 있어서, X가 질소인 화합물.8. A compound according to any one of claims 1 to 7, wherein X is nitrogen. 제1항에 있어서,The method of claim 1, 1-[(4-브로모-3-메틸페닐)아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1-[(4-bromo-3-methylphenyl) aminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole, 1-[(4-브로모-3-메틸페닐)아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1-[(4-bromo-3-methylphenyl) aminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole, 1-[(2,3-디클로로페닐)아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1-[(2,3-dichlorophenyl) aminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1H-indole, 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol, 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol, 1-[2,3-디클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,1- [2,3-dichloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl)- 1H-Indole, 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-(퀴놀린-5-일아미노카르보닐)-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- (quinolin-5-ylaminocarbonyl) -1H-indole, 2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) phenylaminocarbonyl] -1H-indole, 5-브로모-1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H- Indol, 2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol, 1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-메틸-6-(4-메틸피페라진-1-일)-1H-인돌,1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-methyl-6- (4-methylpiperazin-1-yl) -1H-indole , 2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-5-비닐-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -5-vinyl-1H- Indol, 2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol, 1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-5-에틸-6-(4-메틸피페라진-1-일)-1H-인돌,1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-ethyl-6- (4-methylpiperazin-1-yl) -1H-indole , 2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-5-트리플루오로메틸-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -5-trifluoromethyl -1H-indole, 1-[3-클로로-4-(피리딘-4-일)페닐아미노카르보닐]-2,3-디히드로-6-(4-메틸피페라진-1-일)-5-트리플루오로메틸-1H-인돌,1- [3-chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylpiperazin-1-yl) -5-trifluoromethyl- 1H-Indole, 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole , 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole , 2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1-인돌2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1-indole 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naph-1-ylacetyl] -1H-indole , 2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아세틸]-5-비닐-1H-인돌,2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylacetyl] -5-vinyl-1H-indole, 5-브로모-2,3-디히드로-6-(1-메틸피페리딘-4-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-Bromo-2,3-dihydro-6- (1-methylpiperidin-4-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl]- 1H-Indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H Indol, 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole, 2,3-디히드로-1-[4-(t-부톡시카르보닐아미노)페닐아미노카르보닐]-5-클로로-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-1- [4- (t-butoxycarbonylamino) phenylaminocarbonyl] -5-chloro-6- (4-methylpiperazin-1-yl) -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole, 6-브로모-7-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1,2,3,4-테트라히드로퀴놀린,6-bromo-7- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1,2,3,4- Tetrahydroquinoline, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(4-페녹시페닐아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (4-phenoxyphenylaminocarbonyl) -1H-indole, 5-클로로-2,3-디히드로-1-[4-(4-클로로페녹시)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (4-chlorophenoxy) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(퀴놀린-6-일아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (quinolin-6-ylaminocarbonyl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(3-페녹시페닐아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (3-phenoxyphenylaminocarbonyl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리미딘-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrimidin-2-yl) phenylaminocarbonyl] -1H-indole, 1-(3-벤조일페닐아미노카르보닐)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- (3-benzoylphenylaminocarbonyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole, 1-(4-벤조일페닐아미노카르보닐)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- (4-benzoylphenylaminocarbonyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(2-메틸퀴놀린-6-일아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (2-methylquinolin-6-ylaminocarbonyl) -1H-indole, 5-클로로-2,3-디히드로-1-[4-(퍼-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (per-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티엔-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thien-2-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-2-일)나프트-1-일아세틸]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-2-yl) naphth-1-ylacetyl] -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아세틸]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylacetyl] -1H-indole , 5-클로로-2,3-디히드로-1-[4-(1-메틸피페리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (1-methylpiperidin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole, 5-클로로-2,3-디히드로-1-[4-(2-메틸옥사졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2-methyloxazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole , 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(2-메틸피리딘-4-일)페닐아미노-카르보닐]-1H-인돌,5-Bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (2-methylpyridin-4-yl) phenylamino-carbonyl] -1 H- Indol, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(2-메틸피리딘-4-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (2-methylpyridin-4-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol, 5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol, 2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)페닐아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H Indol, 5-클로로-2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol, 5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol, 2,3-디히드로-1-[4-(2,6-디메틸피리딘-3-일)페닐아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-1- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1-yl) -1H Indol, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(5-메틸-1,2,4-옥사디아졸-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (5-methyl-1,2,4-oxadiazol-3-yl) phenyl Aminocarbonyl] -1 H-indole, 5-클로로-2,3-디히드로-1-[4-(3-메틸-1,2,4-옥사디아졸-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (3-methyl-1,2,4-oxadiazol-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin- 1-day) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[3-(피리미딘-2-일옥시)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [3- (pyrimidin-2-yloxy) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-{4-[N-메틸-N-(피리미딘-2-일)아미노]페닐아미노카르보닐}-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- {4- [N-methyl-N- (pyrimidin-2-yl) amino] phenylaminocar Carbonyl} -1H-indole, 5-브로모-2,3-디히드로-1-[4-(퍼-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (per-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티엔-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thien-3-yl) phenylaminocarbonyl] -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티아졸-2-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thiazol-2-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(티아졸-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (thiazol-2-yl) phenylaminocarbonyl] -1H-indole, 1-[4-(5-아세틸티엔-2-일)페닐아미노카르보닐]-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- [4- (5-acetylthien-2-yl) phenylaminocarbonyl] -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole, 1-(5-브로모나프트-1-일아세틸)-5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1H-인돌,1- (5-bromonaft-1-ylacetyl) -5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(8-페닐퀴놀린-5-일아미노카르보닐)-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (8-phenylquinolin-5-ylaminocarbonyl) -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-(8-페닐퀴놀린-5-일아미노카르보닐)-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- (8-phenylquinolin-5-ylaminocarbonyl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[2-(2-페닐에틸)퀴놀린-6-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [2- (2-phenylethyl) quinolin-6-ylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[5-(1-메틸피페리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [5- (1-methylpiperidin-4-yl) naphth-1-ylaminocarbox Carbonyl] -1H-indole, 5-브로모-2,3-디히드로-1-[4-(이소퀴놀린-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (isoquinolin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-1-[4-(이소퀴놀린-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (isoquinolin-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-3-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-3-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-3-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-메틸-1,2,3,4-테트라히드로이소퀴놀린-7-일)아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl) Aminocarbonyl] -1 H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-메틸-1,2,3,4-테트라히드로이소퀴놀린-7-일)아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl ) Aminocarbonyl] -1 H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-8-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-8-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(퀴놀린-8-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (quinolin-8-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-1-[4-(이미다졸-1-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (imidazol-1-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-4-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-4-yl) phenylaminocarbonyl] -1H-indole, 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-5-일)아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-5-yl) aminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole, 2,3-디히드로-5-메톡시-6-(4-메틸피페라진-1-일)-1-[(8-페닐퀴놀린-4-일)아미노카르보닐]-1H-인돌,2,3-dihydro-5-methoxy-6- (4-methylpiperazin-1-yl) -1-[(8-phenylquinolin-4-yl) aminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-1-[4-(2,6-디메틸-피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2,6-dimethyl-pyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole, 5-클로로-2,3-디히드로-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl)- 1H-Indole, 5-브로모-2,3-디히드로-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 2,3-디히드로-5-메톡시-1-[3-메틸-4-(6-메틸피리딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [3-methyl-4- (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-1-[5-(6-메틸피리딘-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (6-methylpyridin-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 2,3-디히드로-5-메톡시-1-[5-(6-메틸피리딘-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [5- (6-methylpyridin-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole, 5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-ethylpiperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol, 5-클로로-2,3-디히드로-6-(4-에틸피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-ethylpiperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H- Indol, 5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-[4-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌 히드로클로라이드,5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1- [4- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole hydrochloride , 5-클로로-2,3-디히드로-6-(피페라진-1-일)-1-[5-(피리딘-4-일)나프트-1-일아미노카르보닐]-1H-인돌 히드로클로라이드,5-chloro-2,3-dihydro-6- (piperazin-1-yl) -1- [5- (pyridin-4-yl) naphth-1-ylaminocarbonyl] -1H-indole hydrochloride , 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리다진-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridazin-3-yl) phenylaminocarbonyl] -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리다진-3-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridazin-3-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피라진-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrazin-2-yl) phenylaminocarbonyl] -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피라진-2-일)페닐아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyrazin-2-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-페닐피리딘-5-일)아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-phenylpyridin-5-yl) aminocarbonyl] -1H-indole, 5-브로모-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[(2-페닐피리딘-5-일)아미노카르보닐]-1H-인돌,5-bromo-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1-[(2-phenylpyridin-5-yl) aminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-1-[4-(6-메틸피리다진-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (6-methylpyridazin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole , 5-브로모-2,3-디히드로-1-[4-(6-메틸피리다진-3-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (6-methylpyridazin-3-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[4-(피리딘-3-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [4- (pyridin-3-yl) phenylaminocarbonyl] -1H-indole, 5-클로로-2,3-디히드로-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole , 2,3-디히드로-5-메톡시-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol, 5-브로모-2,3-디히드로-1-[4-(5-메틸옥사졸-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (5-methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol, 5-클로로-2,3-디히드로-1-[4-(1-메틸피라졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (1-methylpyrazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole , 5-브로모-2,3-1-[4-(1-메틸피라졸-4-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-1- [4- (1-methylpyrazol-4-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-1-[4′-시아노-3′-메틸바이페닐-4-아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4'-cyano-3'-methylbiphenyl-4-aminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol, 5-브로모-2,3-디히드로-1-[4′-시아노-3′-메틸바이페닐-4-아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-Bromo-2,3-dihydro-1- [4'-cyano-3'-methylbiphenyl-4-aminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol, 5-클로로-2,3-디히드로-1-[4-(2-메틸피리딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [4- (2-methylpyridin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole, 5-브로모-2,3-디히드로-1-[4-(2-메틸피리딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2-methylpyridin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H-indole , 5-클로로-2,3-디히드로-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- (4 -Methylpiperazin-1-yl) -1H-indole, 2,3-디히드로-5-메톡시-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- ( 4-methylpiperazin-1-yl) -1H-indole, 5-브로모-2,3-디히드로-1-[5-(3-메틸-1,2,4-옥사디아졸-5-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [5- (3-methyl-1,2,4-oxadiazol-5-yl) naphth-1-ylaminocarbonyl] -6- ( 4-methylpiperazin-1-yl) -1H-indole, 5-클로로-2,3-디히드로-1-[5-(5-메틸옥사졸-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (5-methyloxazol-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole, 2,3-디히드로-5-메톡시-1-[5-(5-메틸옥사졸-2-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [5- (5-methyloxazol-2-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole, 5-브로모-2,3-디히드로-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol, 2,3-디히드로-5-메톡시-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol, 5-클로로-2,3-디히드로-6-(4-메틸피페라진-1-일)-1-[3-메틸-4-(피리미딘-2-일)페닐아미노카르보닐]-1H-인돌,5-chloro-2,3-dihydro-6- (4-methylpiperazin-1-yl) -1- [3-methyl-4- (pyrimidin-2-yl) phenylaminocarbonyl] -1H- Indol, 5-브로모-2,3-디히드로-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol, 5-클로로-2,3-디히드로-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H- Indol, 2,3-디히드로-5-메톡시-1-[3-메틸-4-(피리미딘-5-일)페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [3-methyl-4- (pyrimidin-5-yl) phenylaminocarbonyl] -6- (4-methylpiperazin-1-yl) -1H Indol, 5-브로모-2,3-디히드로-1-[4-(2,6-디메틸피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole, 2,3-디히드로-5-메톡시-1-[4-(2,6-디메틸피리딘-4-일)-3-메틸페닐아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,2,3-dihydro-5-methoxy-1- [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylpiperazin-1-yl ) -1H-indole, 5-클로로-2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-chloro-2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1- 1) -1H-indole, 5-브로모-2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-6-(4-메틸피페라진-1-일)-1H-인돌,5-bromo-2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -6- (4-methylpiperazin-1 -Yl) -1H-indole, 2,3-디히드로-1-[5-(2,6-디메틸피리딘-4-일)나프트-1-일아미노카르보닐]-5-메톡시-6-(4-메틸피페라진-1-일)-1H-인돌인 화합물 또는 그의 약학적으로 수용가능한 염.2,3-dihydro-1- [5- (2,6-dimethylpyridin-4-yl) naphth-1-ylaminocarbonyl] -5-methoxy-6- (4-methylpiperazin-1 -Yl) -1H-indole compound or a pharmaceutically acceptable salt thereof. (a) 상기 화학식(I)에서 D가 질소이며 Y가 NH일 경우, 화학식(II)의 화합물(a) a compound of formula (II), in which D is nitrogen and Y is NH in formula (I) ＜화학식 II＞<Formula II> Ra-NC(=V) (여기서, Ra및 V는 화학식(I)에서 정의된 대로임)R a -NC (= V), where R a and V are as defined in formula (I) 또는 그의 보호 유도체와 화학식(III)의 화합물Or a protective derivative thereof and a compound of formula (III) ＜화학식 III＞<Formula III> (여기서, W, X, Rb및 Rc는 화학식(I)에서 정의된 대로임)Wherein W, X, R b and R c are as defined in formula (I) 또는 그의 보호 유도체를 결합하거나Or a protective derivative thereof (b) 상기 화학식(I)에서 D가 질소이며 Y가 NH 또는 NR5일 경우, 적절한 우레아 형성제와 함께 화학식(IV)의 화합물을(b) when D is nitrogen in formula (I) and Y is NH or NR 5 , a compound of formula (IV) with a suitable urea former ＜화학식 IV＞<Formula IV> Ra-NH2또는 Ra-NR5H (여기서, Ra및 R5는 화학식(I)에서 정의된 대로임)R a -NH 2 or R a -NR 5 H, wherein R a and R 5 are as defined in formula (I) 화학식(III)의 화합물과 반응시키며,Reacts with a compound of formula III (c) 상기 화학식(I)에서 D가 질소일 경우, 화학식(V)의 화합물을(c) when D in the formula (I) is nitrogen, the compound of formula (V) ＜화학식 V＞<Formula V> Ra-Y-(C=O)-L2(여기서, Ra는 화학식(I)에서 정의된 대로이고, Y는 -CH2- 또는R a -Y- (C = O) -L 2 , wherein R a is as defined in formula (I), and Y is -CH 2 -or -O-이며 L2는 적절한 이탈기임)-O- and L 2 is a suitable leaving group) 화학식(III)의 화합물과 반응시키고,Reacted with a compound of formula (III), (d) 상기 화학식(I)에서 D가 탄소 또는 CH일 경우, 화학식(VI)의 화합물을(d) when D in formula (I) is carbon or CH, a compound of formula (VI) ＜화학식 VI＞<Formula VI> Ra-NH2(여기서, Ra는 화학식(I)에서 정의된 대로임)R a -NH 2 , where R a is as defined in formula (I) 화학식(VII)의 화합물과 반응시키고,Reacted with a compound of formula (VII), ＜화학식 VII＞<Formula VII> (여기서, D는 탄소 또는 CH이며, W, X, Rb및 Rc는 화학식(I)에서 정의된Wherein D is carbon or CH and W, X, R b and R c are defined in Formula (I) 대로이고 L2는 적절한 이탈기임)L 2 is the appropriate leaving group) 이어서 임의로Then randomly ·임의의 보호기 제거,· Remove any protector, ·화학식(I)의 화합물을 화학식(I)의 또다른 화합물로 전환,Converting a compound of formula (I) to another compound of formula (I), ·약학적으로 수용가능한 염 형성Pharmaceutically acceptable salt formation 을 포함하는 제1항에 따른 화학식(I)의 화합물 및 그의 약학적으로 수용가능한 염의 제조 방법.A process for preparing a compound of formula (I) according to claim 1 and a pharmaceutically acceptable salt thereof. 치료에 사용하기 위한 제1항 내지 제9항 중 어느 한 항에 따른 화합물.10. A compound according to any one of claims 1 to 9 for use in therapy. 제1항 내지 제9항 중 어느 한 항에 따른 화합물 및 약학적으로 수용가능한 담체를 포함하는 약학 조성물.A pharmaceutical composition comprising a compound according to any one of claims 1 to 9 and a pharmaceutically acceptable carrier.
KR1019997009577A 1997-04-18 1998-04-14 Indole Derivatives Having Combined 5HT1A, 5HT1B and 5HT1D Receptor Antagonist Activity KR20010006487A (en)

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