KR20060099287A - Compounds inhibiting peptide deformylase, method for the preparation thereof and pharmaceutical composition containing same - Google Patents

Compounds inhibiting peptide deformylase, method for the preparation thereof and pharmaceutical composition containing same Download PDF

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KR20060099287A
KR20060099287A KR1020050020646A KR20050020646A KR20060099287A KR 20060099287 A KR20060099287 A KR 20060099287A KR 1020050020646 A KR1020050020646 A KR 1020050020646A KR 20050020646 A KR20050020646 A KR 20050020646A KR 20060099287 A KR20060099287 A KR 20060099287A
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sulfamoyl
butyl
pentyl
pyrrolidine
carboxylic acid
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이경주
이철순
신동규
현영란
허용석
윤정민
이재일
김철민
이윤석
이태규
노성구
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크리스탈지노믹스(주)
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    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F3/00—Input arrangements for transferring data to be processed into a form capable of being handled by the computer; Output arrangements for transferring data from processing unit to output unit, e.g. interface arrangements
    • G06F3/06—Digital input from, or digital output to, record carriers, e.g. RAID, emulated record carriers or networked record carriers
    • G06F3/0601—Interfaces specially adapted for storage systems
    • G06F3/0602—Interfaces specially adapted for storage systems specifically adapted to achieve a particular effect
    • G06F3/061—Improving I/O performance
    • G06F3/0613—Improving I/O performance in relation to throughput
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F1/00—Details not covered by groups G06F3/00 - G06F13/00 and G06F21/00
    • G06F1/26—Power supply means, e.g. regulation thereof
    • G06F1/263—Arrangements for using multiple switchable power supplies, e.g. battery and AC
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F13/00—Interconnection of, or transfer of information or other signals between, memories, input/output devices or central processing units
    • G06F13/14—Handling requests for interconnection or transfer
    • G06F13/16—Handling requests for interconnection or transfer for access to memory bus
    • G06F13/1668—Details of memory controller
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F13/00—Interconnection of, or transfer of information or other signals between, memories, input/output devices or central processing units
    • G06F13/14—Handling requests for interconnection or transfer
    • G06F13/20—Handling requests for interconnection or transfer for access to input/output bus
    • G06F13/28—Handling requests for interconnection or transfer for access to input/output bus using burst mode transfer, e.g. direct memory access DMA, cycle steal

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Abstract

본 발명은 펩타이드 디포밀라제(peptide deformylase, PDF)의 활성을 억제하는 하기 화학식 1의 화합물, 이의 제조방법 및 이를 함유하는 PDF 활성 억제용 조성물에 관한 것으로, 본 발명의 화합물은 박테리아 증식에 필요한 PDF의 활성을 억제하므로 다양한 박테리아에 의한 각종 감염증상의 치료제로서 유용하게 사용될 수 있다.The present invention relates to a compound of formula (1) which inhibits the activity of peptide deformylase (PDF), a preparation method thereof, and a composition for inhibiting PDF activity containing the same, wherein the compound of the present invention is required for bacterial growth Since it inhibits the activity of, it can be usefully used as a therapeutic agent for various infection symptoms caused by various bacteria.

화학식 1 Formula 1

Figure 112005013060010-PAT00001
Figure 112005013060010-PAT00001

상기 식에서, Where

n은 0 또는 1이며;n is 0 or 1;

X는 수소, 비치환되거나 치환된 C1-C6 알킬, 하이드록시, 또는 할로겐이며;X is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, hydroxy, or halogen;

R1은 수소, 비치환되거나 치환된 C1-C6 알킬, 비치환되거나 치환된 C1-C6 알케닐, 또는 헤테로알킬이며;R 1 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkenyl, or heteroalkyl;

m은 0 내지 5의 정수이며;m is an integer from 0 to 5;

Y는 -NR4, -S-, 또는 -CR2R3이며; Y is -NR 4 , -S-, or -CR 2 R 3 ;

R2 및 R3는 각각 독립적으로 H, R4, -OH, -OR4, -SH, -SR4, -NH2, -NHR4, -NR4R5, -C(=O)R4, -C(=O)OR4, -C(=O)SR4, -C(=O)NR4R5, -C(=O)OCHR4R5, -S(=O)2NR4R5, -N(R4)C(=O)R5, -N(R4)C(=O)OR5, -N(R4)S(=O)2R5 또는 -N(R4)S(=O)2OR5 이거나, 서로 결합하여 비치환되거나 치환된 사이클릭 알킬, 헤테로사이클릭 알킬, 방향족, 또는 헤테로방향족 고리를 형성한다. 여기에서, R4 및 R5는 각각 독립적으로 수소, 비치환되거나 치환된 C1-C6 알킬(치환기는 할로겐, 알콕시, 아미노, 모노 또는 다이알킬아미노, 하이드록실, 티올, 카르복시, 벤질, 시아노, 니트로 또는 비치환되거나 치환된 페닐-치환기는 할로겐, 알콕시, 아미노, 모노 또는 다이알킬아미노, 하이드록실, 티올, 카르복시, 페닐, 벤질, 시아노, 니트로, 카르복시알데하이드 또는 카르복시아미드-임), 헤테로알킬, 비치환되거나 치환된 C1-C6 알케닐, 헤테로알케닐, 비치환되거나 치환된 C1-C6 알카이닐, 알콕시, 비치환되거나 치환된 방향족(치환기는 알킬, 알케닐, 알카이닐, 할로겐, 알콕시, 아실옥시, -NH2, 다이알킬 아미노, -OH, -SH, 카복실, 벤질옥시, 페닐, 아릴옥시, 벤질, -CN, -NO2, -CHO 또는 -CONH2임), 또는 비치환되거나 치환된 헤테로방향족(치환기는 알킬, 알케닐, 알카이닐, 할로겐, 알콕시, 아실옥시, -NH2, 다이알킬 아미노, -OH, -SH, 카복실, 벤질옥시, 페닐, 아릴옥시, 벤질, -CN, -NO2, -CHO 또는 -CONH2)이다.R 2 and R 3 are each independently H, R 4 , -OH, -OR 4 , -SH, -SR 4 , -NH 2 , -NHR 4 , -NR 4 R 5 , -C (= O) R 4 , -C (= O) OR 4 , -C (= O) SR 4 , -C (= O) NR 4 R 5 , -C (= O) OCHR 4 R 5 , -S (= O) 2 NR 4 R 5 , -N (R 4 ) C (= O) R 5 , -N (R 4 ) C (= O) OR 5 , -N (R 4 ) S (= O) 2 R 5 or -N (R 4 ) S (= 0) 2 OR 5, or combine with each other to form an unsubstituted or substituted cyclic alkyl, heterocyclic alkyl, aromatic, or heteroaromatic ring. Wherein R 4 and R 5 are each independently hydrogen, unsubstituted or substituted C 1 -C 6 alkyl (substituents are halogen, alkoxy, amino, mono or dialkylamino, hydroxyl, thiol, carboxy, benzyl, cya No, nitro or unsubstituted or substituted phenyl-substituents are halogen, alkoxy, amino, mono or dialkylamino, hydroxyl, thiol, carboxy, phenyl, benzyl, cyano, nitro, carboxyaldehyde or carboxyamide-, Heteroalkyl, unsubstituted or substituted C 1 -C 6 alkenyl, heteroalkenyl, unsubstituted or substituted C 1 -C 6 alkynyl, alkoxy, unsubstituted or substituted aromatic (substituents are alkyl, alkenyl, alky Nil, halogen, alkoxy, acyloxy, -NH 2 , dialkyl amino, -OH, -SH, carboxyl, benzyloxy, phenyl, aryloxy, benzyl, -CN, -NO 2 , -CHO or -CONH 2 Or an unsubstituted or substituted heteroaromatic (substituent is al Kiel, alkenyl, alkynyl, halogen, alkoxy, acyloxy, -NH 2 , dialkyl amino, -OH, -SH, carboxyl, benzyloxy, phenyl, aryloxy, benzyl, -CN, -NO 2 , -CHO Or -CONH 2 ).

Description

펩타이드 디포밀라제 활성 억제 화합물, 이의 제조방법 및 이를 함유하는 약학 조성물 {COMPOUNDS INHIBITING PEPTIDE DEFORMYLASE, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION CONTAINING SAME}Peptide deformylase activity inhibiting compound, preparation method thereof and pharmaceutical composition containing same {COMPOUNDS INHIBITING PEPTIDE DEFORMYLASE, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION CONTAINING SAME}

본 발명은 펩타이드 디포밀라제 (peptide deformylase, PDF)의 활성을 억제하는 신규 화합물, 이의 제조방법 및 이를 유효성분으로 하는 약학 조성물에 관한 것이다.The present invention relates to a novel compound that inhibits the activity of peptide deformylase (PDF), a preparation method thereof, and a pharmaceutical composition using the same as an active ingredient.

항생제 사용에서 가장 큰 문제점은 내성균의 출현이 증가하는 것이다. 이를 해결하기 위해서는 기존 항생제들과는 전혀 다른 새 로운 표적의 선정, 및 사람을 비롯한 포유동물 및 박테리아 각각에 대해 다르게 작용하는 경로(pathway)의 선정이 필요하다. The biggest problem with antibiotic use is the increased appearance of resistant bacteria. To address this, it is necessary to select new targets that are completely different from existing antibiotics, and to select different pathways for different mammals and bacteria, including humans.

지금까지는 단백질 생합성에 관계된 유전자가 항생제의 주요 표적이었으며, 포유동물과 박테리아의 단백질 생합성 과정 중 박테리아에만 존재하는 합성경로를 차단할 수 있다면 보다 높은 선택적 항생효과를 얻을 수 있는데, 박테리아에만 존재하는 단백질 합성 효소로는 PDF를 예를 들 수 있다(Mazel et al., J. Mol. Biol. 1997, 266, 939; Mazel et al., EMBO J. 1994, 13, 914). Until now, genes related to protein biosynthesis have been the main targets of antibiotics, and if they can block synthetic pathways that exist only in bacteria during protein and biosynthesis in mammals, higher selective antibiotic effects can be obtained. Examples include PDF (Mazel et al., J. Mol. Biol. 1997, 266, 939; Mazel et al., EMBO J. 1994, 13, 914).

PDF가 대장균(E. coli) 등과 같은 미생물의 단백질 합성에 필수적이라는 사실은 1994년 처음 밝혀졌으며(Mazel et al., EMBO J. 1994, 13, 914), 최근에는 스타필로코커스 아우레우스(Staphylococcus aureus) 및 스트렙토코커스 뉴모니애(Streptococcus pneumoniae) 등과 같은 미생물의 생존을 위한 단백질 생합성에도 PDF가 반드시 필요하다는 사실이 밝혀졌다(Margolis et al., Antimicro. Agents Chemother. 2000, 44, 1825; Margolis et al., Antimicro. Agents Chemother. 2001, 45, 2432). 이후, PDF가 하등 진핵생물 등에도 존재함이 밝혀짐에 따라, PDF 억제제가 말라리아, 샤가스병(Chaga's disease) 등의 치료제로 사용될 수 있음이 제기되기도 하였다(Meinnel, Parasitol. Today, 2000, 16, 165). 한편, 현재까지 PDF는 사람에서는 아무런 기능도 하지 않는 것으로 밝혀져 있으므로 PDF 억제제는 사람을 비롯한 포유동물에 대한 독성도 낮을 것으로 예상된다. It was first discovered in 1994 that PDF was essential for protein synthesis in microorganisms such as E. coli (Mazel et al., EMBO J. 1994, 13, 914), and recently Staphylococcus PDF has also been found to be necessary for protein biosynthesis for the survival of microorganisms such as aureus ) and Streptococcus pneumoniae (Margolis et al., Antimicro.Agents Chemother . 2000, 44, 1825; Margolis et. al., Antimicro.Agents Chemother . 2001, 45, 2432). Later, as PDFs were found to be present in lower eukaryotes, it was also suggested that PDF inhibitors could be used as therapeutic agents for malaria and Chaga's disease (Meinnel, Parasitol. Today , 2000, 16 , 165). On the other hand, PDF has not been shown to function in humans so far, PDF inhibitors are expected to be low toxicity to mammals, including humans.

지난 몇 년간 다양한 종류의 PDF 억제제가 개발되었으나(Chen et al., Biochemistry, 2000, 39, 1256; Thomas et al., 40th Annual ICAAC Meeting, Abstract No. 2176; Hackbarth et al., 40th Annual ICAAC Meeting, Abstract No. 2173), 기존의 PDF 억제제들은 박테리아에 대한 억제활성 효과가 낮거나 박테리아의 세포벽을 투과하지 못함에 따라 항균 효과가 매우 미미하다는 단점이 있다. Over the past few years, a variety of PDF inhibitors have been developed (Chen et al., Biochemistry , 2000, 39, 1256; Thomas et al., 40th Annual ICAAC Meeting, Abstract No. 2176; Hackbarth et al., 40th Annual ICAAC Meeting, Abstract No. 2173), the conventional PDF inhibitors have a disadvantage that their antimicrobial effect is very low due to their low inhibitory activity against bacteria or their ability to penetrate the cell walls of bacteria.

이상에서 살펴본 바와 같이, PDF는 박테리아 생존에 필수적인 효소이며 대부분의 박테리아에 보존적으로 존재하여 훌륭한 항생제 표적 물질이 될 수 있으므로, 우수한 항균 효과를 갖는 새로운 PDF 억제제는 기존 항생제들의 여러 가지 단점들 을 극복할 수 있는 항생제로서 매우 유용할 것으로 기대된다.As discussed above, PDF is an essential enzyme for bacterial survival and is conservatively present in most bacteria, making it an excellent antibiotic target, so new PDF inhibitors with superior antimicrobial effects overcome many of the disadvantages of conventional antibiotics. It is expected to be very useful as an antibiotic.

본 발명의 목적은 펩타이드 디포밀라제의 활성을 억제하는 신규 화합물 및 이의 제조방법을 제공하는 것이다,It is an object of the present invention to provide novel compounds that inhibit the activity of peptide deformillase and methods for their preparation,

본 발명의 다른 목적은 상기 화합물을 포함하는 펩타이드 디포밀라제 활성 억제용 조성물을 제공하는 것이다.Another object of the present invention to provide a composition for inhibiting peptide deformillase activity comprising the compound.

상기 목적에 따라, 본 발명은 하기 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염을 제공한다:In accordance with this object, the present invention provides a compound of formula 1 or a pharmaceutically acceptable salt thereof:

Figure 112005013060010-PAT00002
Figure 112005013060010-PAT00002

상기 식에서, Where

n은 0 또는 1이며;n is 0 or 1;

X는 수소, 비치환되거나 치환된 C1-C6 알킬, 하이드록시, 또는 할로겐이며;X is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, hydroxy, or halogen;

R1은 수소, 비치환되거나 치환된 C1-C6 알킬, 비치환되거나 치환된 C1-C6 알케닐, 또는 헤테로알킬이며;R 1 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkenyl, or heteroalkyl;

m은 0 내지 5의 정수이며;m is an integer from 0 to 5;

Y는 -NR4, -S-, 또는 -CR2R3이며; Y is -NR 4 , -S-, or -CR 2 R 3 ;

R2 및 R3는 각각 독립적으로 H, R4, -OH, -OR4, -SH, -SR4, -NH2, -NHR4, -NR4R5, -C(=O)R4, -C(=O)OR4, -C(=O)SR4, -C(=O)NR4R5, -C(=O)OCHR4R5, -S(=O)2NR4R5, -N(R4)C(=O)R5, -N(R4)C(=O)OR5, -N(R4)S(=O)2R5 또는 -N(R4)S(=O)2OR5 이거나, 서로 결합하여 비치환되거나 치환된 사이클릭 알킬, 헤테로사이클릭 알킬, 방향족, 또는 헤테로방향족 고리를 형성한다(여기에서, R4 및 R5는 각각 독립적으로 수소, 비치환되거나 치환된 C1-C6 알킬(치환기는 할로겐, 알콕시, 아미노, 모노 또는 다이알킬아미노, 하이드록실, 티올, 카르복시, 벤질, 시아노, 니트로 또는 비치환되거나 치환된 페닐(치환기는 할로겐, 알콕시, 아미노, 모노 또는 다이알킬아미노, 하이드록실, 티올, 카르복시, 페닐, 벤질, 시아노, 니트로, 카르복시알데하이드 또는 카르복시아미드임)임), 헤테로알킬, 비치환되거나 치환된 C1-C6 알케닐, 헤테로알케닐, 비치환되거나 치환된 C1-C6 알카이닐, 알콕시, 비치환되거나 치환된 방향족(치환기는 알킬, 알케닐, 알카이닐, 할로겐, 알콕시, 아실옥시, -NH2, 다이알킬 아미노, -OH, -SH, 카복실, 벤질옥시, 페닐, 아릴옥시, 벤질, -CN, -NO2, -CHO 또는 -CONH2 임), 또는 비치환되거나 치환된 헤테로방향족(치환기는 알킬, 알케닐, 알카이닐, 할로겐, 알콕시, 아실옥시, -NH2, 다이알킬 아미노, -OH, -SH, 카복실, 벤질옥시, 페닐, 아릴옥시, 벤질, -CN, -NO2, -CHO 또는 -CONH2임)임).R 2 and R 3 are each independently H, R 4 , -OH, -OR 4 , -SH, -SR 4 , -NH 2 , -NHR 4 , -NR 4 R 5 , -C (= O) R 4 , -C (= O) OR 4 , -C (= O) SR 4 , -C (= O) NR 4 R 5 , -C (= O) OCHR 4 R 5 , -S (= O) 2 NR 4 R 5 , -N (R 4 ) C (= O) R 5 , -N (R 4 ) C (= O) OR 5 , -N (R 4 ) S (= O) 2 R 5 or -N (R 4 ) S (= 0) 2 OR 5, or combine with each other to form an unsubstituted or substituted cyclic alkyl, heterocyclic alkyl, aromatic, or heteroaromatic ring, wherein R 4 and R 5 are each independently Hydrogen, unsubstituted or substituted C 1 -C 6 alkyl (substituents are halogen, alkoxy, amino, mono or dialkylamino, hydroxyl, thiol, carboxy, benzyl, cyano, nitro or unsubstituted or substituted phenyl ( Substituents are halogen, alkoxy, amino, mono or dialkylamino, hydroxyl, thiol, carboxy, phenyl, benzyl, cyano, nitro, carboxyaldehyde or carboxyamide), heteroalkyl, Unsubstituted or substituted C 1 -C 6 alkenyl, heteroaryl-alkenyl, unsubstituted or substituted C 1 -C 6 alkynyl, alkoxy, unsubstituted or substituted aromatic (the substituent is alkyl, alkenyl, alkynyl, halogen, Alkoxy, acyloxy, -NH 2 , dialkyl amino, -OH, -SH, carboxyl, benzyloxy, phenyl, aryloxy, benzyl, -CN, -NO 2 , -CHO or -CONH 2 ), or unsubstituted Or substituted heteroaromatics (substituents are alkyl, alkenyl, alkynyl, halogen, alkoxy, acyloxy, -NH 2 , dialkyl amino, -OH, -SH, carboxyl, benzyloxy, phenyl, aryloxy, benzyl,- CN, -NO 2 , -CHO or -CONH 2 ).

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

본 발명에서, "방향족"이란 페닐 등과 같이 한 개의 고리를 갖거나 나프틸, 안트라실 등과 같이 여러 개의 고리를 갖는 구조를 의미하며, 헤테로 방향족이란 고리 중에 1-3개의 질소, 산소, 황 등과 같은 헤테로 원자를 함유하는 3 내지 9원 고리 화합물(예: 이미다졸, 피라졸, 피라진, 피리다진, 피리미딘, 피롤, 피리딜, 티오펜, 1,2,3-트라이아졸, 1,2,4-트라이아졸, 아이소옥사졸, 옥사졸, 아이소티아졸, 티아졸리딘, 티아졸, 1,2,5-옥사다이아졸, 1,2,3-옥사다이아졸, 1,2,5-티오다이아졸, 1,2,3-티오다이아졸, 1,3,4-옥사다이아졸, 1,3,4-티오다이아졸 등), 또는 이들 고리 화합물이 다른 방향족과 결합하여 여러 개의 고리를 갖는 화합물(예: 벤즈이미다졸, 벤즈옥사졸, 벤조티아졸, 인돌, 퀴놀린, 퀴나졸린, 벤조티에닐 등)을 의미한다. In the present invention, "aromatic" refers to a structure having one ring, such as phenyl, or a plurality of rings, such as naphthyl, anthracyl, etc., and heteroaromatic means 1-3 nitrogen, oxygen, sulfur, etc. 3- to 9-membered ring compounds containing heteroatoms, such as imidazole, pyrazole, pyrazine, pyridazine, pyrimidine, pyrrole, pyridyl, thiophene, 1,2,3-triazole, 1,2,4 -Triazole, isoxazole, oxazole, isothiazole, thiazolidine, thiazole, 1,2,5-oxadiazole, 1,2,3-oxadiazole, 1,2,5-thiodia Sol, 1,2,3-thiodiazole, 1,3,4-oxadiazole, 1,3,4-thiodiazole, etc.), or compounds in which these ring compounds combine with other aromatics to have several rings (E.g. benzimidazole, benzoxazole, benzothiazole, indole, quinoline, quinazoline, benzothienyl, etc.).

상기 화학식 1의 화합물 중 바람직한 것은,Among the compounds of the formula (1),

X가 수소, 하이드록시, 또는 할로겐이며;X is hydrogen, hydroxy, or halogen;

R1이 수소, 메틸, 에틸, 뷰틸, 3-메틸뷰틸, 펜틸, 2-사이클로헥실-1-에틸이 고,R 1 is hydrogen, methyl, ethyl, butyl, 3-methylbutyl, pentyl, 2-cyclohexyl-1-ethyl,

구조

Figure 112005013060010-PAT00003
이
Figure 112005013060010-PAT00004
또는
Figure 112005013060010-PAT00005
rescue
Figure 112005013060010-PAT00003
this
Figure 112005013060010-PAT00004
or
Figure 112005013060010-PAT00005

(여기에서, p는 1 또는 2이며, Where p is 1 or 2,

R6는 -NH2, -NHR4, -NR4R5, -C(=O)R4, -C(=O)OR4, -C(=O)NR4R5, -C(=O)OCHR4R5, 또는 -N(R4)C(=O)R5 이고(여기에서 R4 및 R5는 상기에서 정의된 바와 같음), 바람직하게는 -C(=O)NHR4 (여기에서 R4는 수소, 비치환되거나 치환된 C1-C6 알킬, 방향족, 또는 헤테로 방향족임) 또는 -C(=O)NR4R5 이며(여기에서 R4 및 R5는 각각 독립적으로 비치환되거나 치환된 C4-C10 헤테로사이클릭 알킬임), 더욱 바람직하게는 페닐아미노카보닐, 나프틸아미노카보닐, 4-페닐-페닐아미노카보닐, 4-페녹시-페닐아미노카보닐, 티아졸리디노-2-일-아미노카보닐, 4-메틸티아졸-2-일-아미노카보닐, 4,5-다이메틸티아졸-2-일-아미노카보닐, 4-페닐티아졸-2-일-아미노카보닐, 4-나프틸티아졸-2-일-아미노카보닐, 벤조티아졸-2-일-아미노카보닐, 6-메틸벤조티아졸-2-일-아미노카보닐, 5,6-다이메틸벤조티아졸-2-일-아미노카보닐, 6-플루오로벤조티아졸-2-일-아미노카보닐, 6-클로로벤조티아졸-2-일-아미노카보닐, 6-메톡시벤조티아졸-2-일-아미노카보닐, 4-메톡시벤조티아졸-2-일-아미노카보닐, 4-클로로벤조티아졸-2-일-아미노카보닐, 4-사이클로헥실벤조티아졸-2-일-아미노카보닐, 4-(1-피페리딘일) 벤조티아졸-2-일-아미노카보닐, 4-(1-모폴리닐)벤조티아졸-2-일-아미노카보닐, 2-머캅토에틸티오다이아졸-5-일, 4-페닐피페리딘-1-일-아미노카보닐, 3-(다이메틸아미노)피롤리딘-1-일-아미노카보닐, 4-메틸피페라진-1-일, 4-모폴리노에틸아미노카보닐, 4-벤질피페라진-1-일-아미노카보닐 또는 피페라진-1-일이며,R 6 is -NH 2 , -NHR 4 , -NR 4 R 5 , -C (= O) R 4 , -C (= O) OR 4 , -C (= O) NR 4 R 5 , -C (= O) OCHR 4 R 5 , or -N (R 4 ) C (= 0) R 5 , wherein R 4 and R 5 are as defined above, preferably -C (= 0) NHR 4 Where R 4 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, aromatic, or heteroaromatic; or —C (═O) NR 4 R 5 , wherein R 4 and R 5 are each independently C 4 -C 10 heterocyclic alkyl unsubstituted or substituted, more preferably phenylaminocarbonyl, naphthylaminocarbonyl, 4-phenyl-phenylaminocarbonyl, 4-phenoxy-phenylaminocarbon Nyl, thiazolidino-2-yl-aminocarbonyl, 4-methylthiazol-2-yl-aminocarbonyl, 4,5-dimethylthiazol-2-yl-aminocarbonyl, 4-phenylthiazole 2-yl-aminocarbonyl, 4-naphthylthiazol-2-yl-aminocarbonyl, benzothiazol-2-yl-aminocarbonyl, 6-methylbenzothiazol-2-yl-aminocarbonyl , 5,6-dimethylbenzo Thiazol-2-yl-aminocarbonyl, 6-fluorobenzothiazol-2-yl-aminocarbonyl, 6-chlorobenzothiazol-2-yl-aminocarbonyl, 6-methoxybenzothiazole- 2-yl-aminocarbonyl, 4-methoxybenzothiazol-2-yl-aminocarbonyl, 4-chlorobenzothiazol-2-yl-aminocarbonyl, 4-cyclohexylbenzothiazol-2-yl -Aminocarbonyl, 4- (1-piperidinyl) benzothiazol-2-yl-aminocarbonyl, 4- (1-morpholinyl) benzothiazol-2-yl-aminocarbonyl, 2-mer Captoethylthiodiazol-5-yl, 4-phenylpiperidin-1-yl-aminocarbonyl, 3- (dimethylamino) pyrrolidin-1-yl-aminocarbonyl, 4-methylpiperazin- 1-yl, 4-morpholinoethylaminocarbonyl, 4-benzylpiperazin-1-yl-aminocarbonyl or piperazin-1-yl,

R7은 -NH2, -NHR4, -NR4R5, -C(=O)R4, -C(=O)OR4, -C(=O)NR4R5, -C(=O)OCHR4R5, 또는 -N(R4)C(=O)R5 이고(여기에서 R4 및 R5는 상기에서 정의된 바와 같음), 바람직하게는 아미노 또는 -N(R4)C(=O)R5 이며(여기에서 R4, R5는 각각 수소, 비치환되거나 치환된 C1-C6 알킬, 방향족, 헤테로 방향족임), 더욱 바람직하게는 아미노, t-뷰틸카바모일, 4-바이페닐-1-카복사미딜, 4-플루오로페닐-1-카복사미딜, 4-t-뷰틸페닐-1-카복사미딜, 4-메톡시페닐-1-카복사미딜, 벤즈이미다졸-4-카복사미딜, 3-하이드록시페닐-1-카복사미딜, 나프토일-2-카복사미딜, 3-하이드록시페닐아세타미딜, 또는 4-페닐페닐아세타미딜이다.R 7 is -NH 2 , -NHR 4 , -NR 4 R 5 , -C (= O) R 4 , -C (= O) OR 4 , -C (= O) NR 4 R 5 , -C (= O) OCHR 4 R 5 , or -N (R 4 ) C (= 0) R 5 , wherein R 4 and R 5 are as defined above, preferably amino or -N (R 4 ) C (═O) R 5 , wherein R 4 , R 5 are each hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, aromatic, heteroaromatic, more preferably amino, t-butylcarbamoyl , 4-biphenyl-1-carboxamidyl, 4-fluorophenyl-1-carboxamidyl, 4-t-butylphenyl-1-carboxamidyl, 4-methoxyphenyl-1-carboxamidyl, benz Imidazole-4-carboxamidyl, 3-hydroxyphenyl-1-carboxamidyl, naphthoyl-2-carboxamidyl, 3-hydroxyphenylacetamidyl, or 4-phenylphenylacetamidyl.

본 발명의 화합물 중 가장 바람직한 화합물은 다음과 같다: The most preferred of the compounds of the present invention are as follows:

2-[뷰틸-(피페리딘-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (piperidine-1-sulfonyl) -amino] -N-hydroxy-acetamide;

2-[뷰틸-(모포린-4-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (morpholin-4-sulfonyl) -amino] -N-hydroxy-acetamide;

2-[뷰틸-(4-메틸-피페라진-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (4-methyl-piperazin-1-sulfonyl) -amino] -N-hydroxy-acetamide;

2-[(4-벤질-피페라진-1-설포닐)-뷰틸-아미노]-N-하이드록시-아세트아마이드;2-[(4-benzyl-piperazine-1-sulfonyl) -butyl-amino] -N-hydroxy-acetamide;

2-[뷰틸-(다이사이클로헥실 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (dicyclohexyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide;

2-[뷰틸-(다이벤질 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (dibenzyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide;

N-하이드록시-2-[(2-옥소-옥사졸리딘-3-설포닐)-펜틸-아미노]-아세트아마이드;N-hydroxy-2-[(2-oxo-oxazolidine-3-sulfonyl) -pentyl-amino] -acetamide;

2-[펜틸-(다이벤질 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [pentyl- (dibenzyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide;

3-[뷰틸-(2-옥소-옥사졸리딘-3-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (2-oxo-oxazolidine-3-sulfonyl) -amino] -N-hydroxy-propionamide;

3-[뷰틸-(피페리딘-1-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (piperidine-1-sulfonyl) -amino] -N-hydroxy-propionamide;

3-[뷰틸-(모포린-4-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (morpholin-4-sulfonyl) -amino] -N-hydroxy-propionamide;

3-[뷰틸-(4-메틸-피페라진-1-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (4-methyl-piperazin-1-sulfonyl) -amino] -N-hydroxy-propionamide;

3-[(4-벤질-피페라진-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(4-benzyl-piperazine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide;

3-[(다이사이클로헥실 아민-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(dicyclohexyl amine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide;

3-[(다이벤질 아민-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(dibenzyl amine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide;

[1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-카밤산 tert-뷰틸 에스터;[1- (Butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester;

2-[(3-아미노-피롤리딘-1-설포닐)-뷰틸-아미노]-N-하이드록시-아세트아마이드;2-[(3-amino-pyrrolidine-1-sulfonyl) -butyl-amino] -N-hydroxy-acetamide;

바이페닐-4-카복실산 [1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-아마이드;Biphenyl-4-carboxylic acid [1- (butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -amide;

N-[1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-4-플루오로-벤즈아마이드;N- [1- (Butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -4-fluoro-benzamide;

4-tert-뷰틸-N-[1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-벤즈아마이드;4-tert-Butyl-N- [1- (butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -benzamide;

바이페닐-4-카복실산 [1-(펜틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-아마이드;Biphenyl-4-carboxylic acid [1- (pentyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -amide;

N-[1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-4-메톡시-벤즈아마이드;N- [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -4-methoxy-benzamide;

1H-벤조이미다졸-5-카복실산 [1-(하이드록시카바모일 메틸-펜틸-설파모일)-피롤리딘-3-일]-아마이드;1H-benzoimidazole-5-carboxylic acid [1- (hydroxycarbamoyl methyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -amide;

3-하이드록시-N-[1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-벤즈아마이드;3-hydroxy-N- [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -benzamide;

나프탈렌-2-카복실산 [1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-아마이드;Naphthalene-2-carboxylic acid [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -amide;

N-하이드록시-2-({3-[2-(3-하이드록시-페닐)-아세틸아미노]-피롤리딘-1-설포닐}-펜틸-아미노)-아세트아마이드;N-hydroxy-2-({3- [2- (3-hydroxy-phenyl) -acetylamino] -pyrrolidine-1-sulfonyl} -pentyl-amino) -acetamide;

2-{[3-(2-바이페닐-4-일-아세틸아미노)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드;2-{[3- (2-biphenyl-4-yl-acetylamino) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide;

{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-카밤산 tert-뷰틸 에스터;{1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -carbamic acid tert-butyl ester;

3-[(3-아미노-피롤리딘-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(3-amino-pyrrolidine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide;

바이페닐-4-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드;Biphenyl-4-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide;

N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-4-플루오로-벤 즈아마이드;N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -4-fluoro-benzamide;

4-tert-뷰틸-N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-벤즈아마이드;4-tert-Butyl-N- {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -benzamide;

N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-4-메톡시-벤즈아마이드;N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -4-methoxy-benzamide;

1H-벤조이미다졸-5-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드;1 H-benzoimidazole-5-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide;

N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-3-하이드록시-벤즈아마이드;N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -3-hydroxy-benzamide;

나프탈렌-2-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드;Naphthalene-2-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 페닐아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid phenylamide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 나프탈렌-2-일아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid naphthalen-2-ylamide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 바이페닐-4-일아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid biphenyl-4-ylamide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-페녹시-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-phenoxy-phenyl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4,5-다이하이드로-티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4,5-dihydro-thiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-메틸-티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-methyl-thiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4,5-다이메틸-티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4,5-dimethyl-thiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-페닐-티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-phenyl-thiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-나프탈렌-2-일-티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-naphthalen-2-yl-thiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 벤조티아졸-2-일아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid benzothiazol-2-ylamide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-메틸-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-methyl-benzothiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (5,6-다이메틸-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (5,6-dimethyl-benzothiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-플루오로-벤조티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-fluoro-benzothiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-클로로-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-chloro-benzothiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-메톡시-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-methoxy-benzothiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-메톡시-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-methoxy-benzothiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-클로로-벤조티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-chloro-benzothiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-사이클로헥실-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-cyclohexyl-phenyl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-피페리딘-1-일-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-piperidin-1-yl-phenyl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-모포린-4-일-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-morpholin-4-yl-phenyl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (5-에틸설파닐-[1,3,4]티아다이아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (5-ethylsulfanyl- [1,3,4] thiadiazol-2-yl) -amide;

1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (2-모포린-4-일-에틸)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (2-morpholin-4-yl-ethyl) -amide;

2-{[2-(3-다이에틸아미노-피롤리딘-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드;2-{[2- (3-Diethylamino-pyrrolidine-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide;

N-하이드록시-2-{[2-(4-메틸-피페라진-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-아세트아마이드;N-hydroxy-2-{[2- (4-methyl-piperazin-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -acetamide;

N-하이드록시-2-{펜틸-[2-(4-페닐-피페라진-1-카보닐)-피롤리딘-1-설포닐]-아미노}-아세트아마이드;N-hydroxy-2- {pentyl- [2- (4-phenyl-piperazine-1-carbonyl) -pyrrolidine-1-sulfonyl] -amino} -acetamide;

2-{[2-(4-벤질-피페라진-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드;2-{[2- (4-benzyl-piperazine-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide;

N-하이드록시-2-{펜틸-[2-(피페라진-1-카보닐)-피롤리딘-1-설포닐]-아미노}-아세트아마이드;N-hydroxy-2- {pentyl- [2- (piperazin-1-carbonyl) -pyrrolidine-1-sulfonyl] -amino} -acetamide;

1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-메틸-티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-methyl-thiazol-2-yl) -amide;

1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4,5-다이메틸-티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4,5-dimethyl-thiazol-2-yl) -amide;

1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-페닐-티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-phenyl-thiazol-2-yl) -amide;

1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (6-플루오로-벤조티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (6-fluoro-benzothiazol-2-yl) -amide;

1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-사이클로헥실-페닐)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-cyclohexyl-phenyl) -amide;

1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 나프탈렌-2-일아마이드;1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid naphthalen-2-ylamide;

1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 바이페닐-4-일아마이드; 및1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid biphenyl-4-ylamide; And

1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 (4-페녹시-페닐)-아마이드.1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-phenoxy-phenyl) -amide.

본 발명의 화학식 1의 화합물은 그 구조 내에 비대칭 탄소를 1개 이상 가질 수 있으므로, 개개의 에난티오머 또는 부분입체이성체로 존재할 수 있고, 라세미체를 포함한 이들의 혼합물로도 존재할 수 있으며, 이러한 이성체 또는 이들의 혼합물 역시 본 발명의 범위에 포함된다.Since the compound of formula 1 of the present invention may have one or more asymmetric carbons in its structure, it may exist as individual enantiomers or diastereomers, and also as mixtures thereof including racemates, Isomers or mixtures thereof are also within the scope of the present invention.

본 발명에 따른 화합물은 또한 약제학적으로 허용되는 염을 형성할 수 있다. 이러한 약제학적으로 허용되는 염에는, 염산, 브롬화수소산, 황산, 질산, 인산 등과 같은 무기산; 및 아세트산, 글라이콜산, 락트산, 피루브산, 말론산, 말산, 말레인산, 푸마르산, 타르타르산, 시트르산, 메탄설폰산, 벤젠설폰산, 4-톨루엔설폰산 등과 같은 유기산의 염 등이 포함된다.The compounds according to the invention can also form pharmaceutically acceptable salts. Such pharmaceutically acceptable salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; And salts of organic acids such as acetic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, methanesulfonic acid, benzenesulfonic acid, 4-toluenesulfonic acid and the like.

상기 화학식 1의 화합물은 수화물, 용매화물 등의 형태로 제공될 수도 있으며, 특히 수화물은 상기 화합물을 제조하는 과정 중에 얻어질 수도 있고, 화합물의 흡습성으로 인해 시간이 경과함에 따라 얻어질 수도 있다. The compound of Formula 1 may be provided in the form of a hydrate, a solvate, and the like, in particular, a hydrate may be obtained during the preparation of the compound, or may be obtained over time due to the hygroscopicity of the compound.

본 발명의 상기 화학식 1의 화합물은 하기 반응식 1로 표시되는 합성경로에 따라 제조될 수 있다.The compound of Chemical Formula 1 of the present invention may be prepared according to the synthetic route represented by Scheme 1.

Figure 112005013060010-PAT00006
Figure 112005013060010-PAT00006

상기 반응식에서, X, n, R1, R2, R3, Y 및 m은 상기에서 정의한 바와 같다.In the above scheme, X, n, R 1 , R 2 , R 3 , Y and m are as defined above.

상기 반응식 1의 합성 경로는 다음과 같은 단계들을 포함한다:The synthetic route of Scheme 1 includes the following steps:

1) 클로로설포닐 아이소사이아네이트와 2-브로모에탄올을 반응시켜 2-옥소-옥사졸리딘-3-설포닐 클로라이드를 합성하고, 동일 용기내에서(in-situ) 아민 알킬 에스터를 반응시켜 화학식 2의 화합물을 얻는 단계;1) by reacting chlorosulfonyl isocyanate and 2-bromoethanol to synthesize 2-oxo-oxazolidine-3-sulfonyl chloride, and reacting the amine alkyl ester in the same vessel ( in-situ ) Obtaining a compound of Formula 2;

2) 화학식 2의 화합물을 아민 유도체와 반응시켜 화학식 3의 화합물을 합성하는 단계;2) reacting a compound of Formula 2 with an amine derivative to synthesize a compound of Formula 3;

3) 화학식 3의 화합물을 알킬 브로마이드와 반응시켜 화학식 4의 화합물을 합성하는 단계;3) synthesizing the compound of formula 4 by reacting the compound of formula 3 with alkyl bromide;

4) 화학식 4의 화합물을 수산화리튬으로 가수분해하여 화학식 5의 화합물을 합성하는 단계; 및4) synthesizing the compound of Formula 5 by hydrolyzing the compound of Formula 4 with lithium hydroxide; And

5) 화학식 5의 화합물에 O-벤질하이드록실아민을 결합시킨 후에 Pd/C와 수소를 이용하여 벤질기를 제거하여 화학식 1의 화합물을 합성하는 단계. 5) synthesizing the compound of Formula 1 by combining O-benzylhydroxylamine with the compound of Formula 5 and then removing the benzyl group using Pd / C and hydrogen.

상기 단계 1)의 반응은 염화메틸렌(MC) 중에서 트라이에틸아민(TEA) 존재 하에 -10 ℃ 내지 -20 ℃에서 2 내지 3시간 동안 수행하는 것이 바람직하다. 2-브로모에탄올 및 아민 알킬 에스터는 클로로설포닐 아이소사이아네이트의 양을 기준으로 각각 약 1 당량으로 사용한다.The reaction of step 1) is preferably carried out for 2 to 3 hours at -10 ℃ to -20 ℃ in the presence of triethylamine (TEA) in methylene chloride (MC). 2-bromoethanol and amine alkyl esters are each used in about 1 equivalent based on the amount of chlorosulfonyl isocyanate.

단계 2)의 반응은 아세토나이트릴(MeCN) 중에서 TEA 존재 하에 12 내지 15 시간 동안 수행하는 것이 바람직하다. 아민 유도체는 화합물 2의 양을 기준으로 약 1 당량으로 사용한다.The reaction of step 2) is preferably carried out in acetonitrile (MeCN) for 12-15 hours in the presence of TEA. The amine derivative is used in about 1 equivalent based on the amount of compound 2.

단계 3)의 반응은 다이메틸포름아미드(DMF) 중에서 탄산칼륨(K2CO3)의 존재 하에 50 내지 60 ℃에서 12 내지 15시간 동안 수행하는 것이 바람직하다. 알킬 브로마이드는 화합물 3의 양을 기준으로 약 1 내지 1.2 당량으로 사용한다.The reaction of step 3) is preferably carried out at 50 to 60 ° C. for 12 to 15 hours in the presence of potassium carbonate (K 2 CO 3 ) in dimethylformamide (DMF). Alkyl bromide is used in about 1 to 1.2 equivalents based on the amount of compound 3.

단계 4)에서, 반응용매로는 10 내지 20 부피비의 테트라하이드로퓨란(THF) 및 물의 혼합용매를 사용하고, 반응은 40 내지 50 ℃에서 2 내지 3시간 동안 수행하는 것이 바람직하다. 수산화리튬(LiOH·H2O)은 화합물 4의 양을 기준으로 약 4-5 당량으로 사용한다. In step 4), a mixed solvent of tetrahydrofuran (THF) and water in a volume ratio of 10 to 20 is used as the reaction solvent, and the reaction is preferably performed at 40 to 50 ° C. for 2 to 3 hours. Lithium hydroxide (LiOH.H 2 O) is used in about 4-5 equivalents based on the amount of compound 4.

또한, 단계 5)에서는 DMF 중에서 O-벤질하이드록실아민 1 내지 1.2 당량과 에틸렌다이클로라이드(EDC) 1 내지 1.2 당량, 하이드록시벤조트리아졸(HOBT) 1 내지 1.2 당량, 다이메틸아미노피리딘(DMAP) 1.5 내지 2.5 당량을 사용하여 상온에서 10 내지 15시간 반응시킨다.Further, in step 5), 1 to 1.2 equivalents of O-benzylhydroxylamine, 1 to 1.2 equivalents of ethylenedichloride (EDC), 1 to 1.2 equivalents of hydroxybenzotriazole (HOBT), and dimethylaminopyridine (DMAP) in DMF The reaction is performed at room temperature for 10 to 15 hours using 1.5 to 2.5 equivalents.

또 다른 방법으로, 화학식 5의 화합물을 옥살릴 클로라이드와 반응시켜 아실 클로라이드를 형성한 후에, 하이드록실 아민과 반응시켜 화학식 1의 화합물을 합성할 수도 있다. 이때, 반응용매로는 MC를 사용하며, 화학식 5의 화합물에 대해 옥살릴 클로라이드는 2 내지 3 당량, 하이드록실 아민은 2 내지 3 당량으로 사용한다.Alternatively, the compound of formula 5 may be reacted with oxalyl chloride to form acyl chloride, followed by hydroxyl amine to synthesize the compound of formula 1. In this case, MC is used as the reaction solvent, oxalyl chloride is used in the amount of 2 to 3 equivalents, and hydroxyl amine is used in the amount of 2 to 3 equivalents.

상기 화학식 3의 화합물에서 구조

Figure 112005013060010-PAT00007
이
Figure 112005013060010-PAT00008
(R6 = C(=O)NHR4)인 화합물("화합물 3-b")은 하기 반응식 2의 합성 과정에 따라 화학식 2-b의 화합물로부터 제조할 수 있다.Structure in the compound of Formula 3
Figure 112005013060010-PAT00007
this
Figure 112005013060010-PAT00008
Compounds (“Compound 3-b”) (R 6 = C (═O) NHR 4 ) may be prepared from compounds of Formula 2-b according to the synthesis procedures of Scheme 2 below.

Figure 112005013060010-PAT00009
Figure 112005013060010-PAT00009

상기 반응식에서, n 및 R4는 상기에서 정의한 바와 같다.In the above scheme, n and R 4 are as defined above.

상기 반응에서는, 화학식 2-b의 화합물에 프롤린 벤질 에스터를 결합시켜 화학식 6의 화합물을 제조한 후, Pd/C과 수소를 이용하여 벤질기를 제거하여 화학식 7의 화합물을 합성한다. 그리고 여기에 다양한 아민 유도체를 결합시켜 화합물 3-b를 합성한다.In the reaction, a compound of formula 7 is prepared by combining proline benzyl ester with a compound of formula 2-b, and then benzyl group is removed using Pd / C and hydrogen to synthesize a compound of formula 7. And compound 3-b is synthesize | combined here by combining various amine derivatives.

상기 화학식 3의 화합물에서 구조 이

Figure 112005013060010-PAT00011
(R7 = NHC(=O)R5)인 화합물(화합물 3-c)은 하기 반응식 3의 합성 과정에 따라 화학식 2-c의 화합물로부터 제조할 수 있다.Structure in the compound of Formula 3 this
Figure 112005013060010-PAT00011
Compound (Compound 3-c), wherein (R 7 = NHC (═O) R 5 ), may be prepared from the compound of Formula 2-c according to the synthesis procedure of Scheme 3 below.

Figure 112005013060010-PAT00012
Figure 112005013060010-PAT00012

상기 반응식에서, n 및 R5는 상기에서 정의한 바와 같다.In the above scheme, n and R 5 are as defined above.

상기 반응에서는, 화학식 2-c의 화합물에 일차 아민이 Boc로 보호된 3-아미노 피롤리딘을 결합시켜 화학식 8의 화합물을 제조한 후, 트라이플루오로 아세트산을 이용하여 Boc를 탈보호함으로써 화학식 9의 화합물을 합성한다. 여기에 다양한 카복실산 유도체를 결합시켜 화합물 3-c를 합성한다.In the above reaction, a compound of Formula 8 is prepared by combining 3-amino pyrrolidine in which a primary amine is protected by Boc to a compound of Formula 2-c, and then deprotecting Boc using trifluoro acetic acid. A compound of Compounds 3-c are synthesized by combining various carboxylic acid derivatives thereto.

상기 방법으로 얻어진 화학식 1의 화합물로부터 당분야에 공지된 방법들을 이용하여 약제학적으로 허용가능한 그의 염, 수화물, 용매화물, 이성체 등을 제조할 수 있다. Pharmaceutically acceptable salts, hydrates, solvates, isomers and the like thereof can be prepared from the compounds of formula 1 obtained by the above method using methods known in the art.

이와 같이 제조된 본 발명의 화학식 1의 화합물 또는 이의 약학적으로 허용되는 염, 수화물, 용매화물 또는 이성체는 박테리아의 증식에 반드시 필요한 PDF 효소의 활성을 효과적으로 억제하므로(IC50 값이 1 ~ 10,000 nM임), 다양한 종류의 박테리아, 예를 들면 그람 양성균; 그람 음성균; 호기성 또는 혐기성 박테리아; S. 아우레우스(aureus), S. 에피데르미디스(epidermidis) 등과 같은 스타필로코키(Staphylococci)균; E. 패칼리스(faecalis), E. 패시움(faecium) 등과 같은 엔테로코키(Enterococci)균; S. 뉴모니애(pneumoniae) 등과 같은 스트렙토코키(Streptococci)균; H. 인플루엔자(influenza) 등과 같은 해모필러스(Haemophilus)균; M. 카타르할리스(catarrhalis) 등과 같은 모락셀라(Moraxella)균; 대장균(E. coli) 등과 같은 에스케리키아(Escherichia)균; M. 튜베르큘로시스(tuberculosis) 등과 같은 마이코박테리아(Mycobacteria)균 등에 의한 감염증을 치료하는데 효과적으로 이용될 수 있다.The compound of formula 1 or a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof of the present invention prepared as described above effectively inhibits the activity of PDF enzymes necessary for the growth of bacteria (IC 50 value is 1 to 10,000 nM). ) Various kinds of bacteria, for example Gram-positive bacteria; Gram negative bacteria; Aerobic or anaerobic bacteria; S. aureus (aureus), Staphylococcus Corky (Staphylococci), such as S. epi-der US display (epidermidis) bacteria; Enterobacter Koki (Enterococci) bacteria, such as E. faecalis (faecalis), E. passive help (faecium); Corky streptomycin (Streptococci) microorganisms like S. pneumoniae (pneumoniae); To a brush Russ (Haemophilus) bacteria such as H. influenza (influenza); Moraxella bacteria, such as M. catarrhalis ; Escherichia (Escherichia) bacteria such as Escherichia coli (E. coli); In the treatment of infections caused by mycobacteria (Mycobacteria) bacteria such as M. tuberculosis tube suberic particulates (tuberculosis) it can be effectively utilized.

본 발명은 또한, 활성성분으로서 화학식 1의 화합물 또는 이의 약학적으로 허용가능한 염을 포함하는 PDF 활성 저해용 조성물을 제공한다. The present invention also provides a composition for inhibiting PDF activity comprising the compound of formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

본 발명의 약학 조성물은 다양한 경구 또는 비경구 투여형태로 제형화할 수 있다. 경구 투여용 제형으로는 예를 들면 정제, 캅셀제 등이 있는데, 이들 제형은 유효성분 이외에 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/또는 폴리에틸렌글리콜) 등을 함유할 수 있다. 상기 정제는 또한 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 트라가칸스, 메틸셀룰로즈, 소듐 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 이의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제, 및 감미제를 함유할 수 있다. 이러한 경구투여용 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있 다. 또한 비경구 투여용 제형의 대표적인 것은 주사용 제형으로 등장성 수용액 또는 현탁액이 바람직하다.The pharmaceutical compositions of the invention can be formulated in a variety of oral or parenteral dosage forms. Formulations for oral administration include, for example, tablets, capsules, and the like, which include, in addition to the active ingredient, diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine), glidants ( Such as silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols). The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, optionally starch, agar, alginic acid or Disintegrating or boiling mixtures such as sodium salts thereof and / or absorbents, colorants, flavoring agents, and sweetening agents. Such oral dosage forms can be prepared by conventional mixing, granulating or coating methods. Also representative of parenteral formulations are injectable formulations, preferably aqueous isotonic solutions or suspensions.

또한, 본 발명의 약학 조성물은 멸균되고/되거나 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 보조제 및 기타 치료적으로 유용한 물질을 함유할 수 있으며, 혼합, 과립화 또는 코팅 방법 등의 통상적인 방법에 따라 제제화할 수 있다.In addition, the pharmaceutical compositions of the present invention may contain adjuvant such as sterile and / or preservatives, stabilizers, hydrating or emulsifying accelerators, salts and / or buffers for the control of osmotic pressure and other therapeutically useful substances, mixing, granulating Formulation may be carried out in accordance with conventional methods such as a method of coating or coating.

본 발명에 따른 화학식 1의 화합물은 유효 성분으로서 사람을 포함하는 포유동물에 대해 하루에 0.01 내지 100 ㎎/㎏(체중), 바람직하게는 0.1 내지 50 ㎎/㎏(체중)의 양으로 1일 1회 또는 분할하여 경구, 또는 정맥내, 근육내 등의 비경구적 경로를 통해 투여할 수 있으며, 투여용량 수준은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법 및 배설률, 그리고 약제 혼합 및 질환의 중증도에 따라 변화시킬 수 있다. The compound of formula 1 according to the present invention is used in an amount of 0.01 to 100 mg / kg body weight per day, preferably 0.1 to 50 mg / kg body weight per day for mammals including humans as an active ingredient. It can be administered orally or by parenteral route such as intravenous or intramuscular, the dosage level is the weight, age, sex, health condition, diet, time of administration, method and excretion rate of the patient, and Depending on the drug mix and the severity of the disease.

이하, 하기 실시예에 의하여 본 발명을 더욱 상세하게 설명하고자 한다. 단, 하기 실시예는 본 발명을 예시하기 위한 것일 뿐 본 발명의 범위가 이들만으로 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

제조예 1: (2-옥소-옥사졸리딘-3-설포닐아미노)-알킬 에스터 (화합물 2)의 합성 (반응식 1의 방법)Preparation Example 1 Synthesis of (2-oxo-oxazolidine-3-sulfonylamino) -alkyl ester (Compound 2) (Method of Scheme 1)

Figure 112005013060010-PAT00013
Figure 112005013060010-PAT00013

클로로설포닐 아이소사이아네이트 (5ml, 57.45mmol)을 MC (50ml)에 녹이고 -10℃로 냉각한 후 2-브로모에탄올 (4.1ml, 57.45mmol)를 넣고 2시간 동안 -10℃에서 교반시켰다. 아민 알킬 에스터 (57.45mmol)와 TEA (24ml, 172.35mmol)를 넣은 후 상온에서 8시간동안 교반하였다. 반응이 완결되면 MC을 넣은 후 1N HCl 용액으로 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하여 화합물 2를 얻었다.Chlorosulfonyl isocyanate (5ml, 57.45mmol) was dissolved in MC (50ml), cooled to -10 ° C, 2-bromoethanol (4.1ml, 57.45mmol) was added thereto, and stirred at -10 ° C for 2 hours. . An amine alkyl ester (57.45 mmol) and TEA (24 ml, 172.35 mmol) were added thereto, followed by stirring at room temperature for 8 hours. After the reaction was completed, the MC was added and washed with 1N HCl solution. The organic layers were collected, dried over MgSO 4, and distilled under reduced pressure to obtain Compound 2.

제조예 2:(알킬/아릴 아민-1-설포닐아미노)-알킬 에스터 (화합물 3)의 합성 (반응식 1의 방법)Preparation Example 2 Synthesis of (alkyl / aryl amine-1-sulfonylamino) -alkyl ester (Compound 3) (method of Scheme 1)

Figure 112005013060010-PAT00014
Figure 112005013060010-PAT00014

화합물 2를 아세토나이트릴에 녹인 후, 아민 1.0당량과 TEA 3.0당량을 첨가하고 12시간동안 70℃에서 교반시켰다. 반응이 완결되면 에틸 아세테이트를 첨가하고 1N HCl 수용액으로 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하여 화합물 3을 얻었다.Compound 2 was dissolved in acetonitrile, and then 1.0 equivalent of amine and 3.0 equivalent of TEA were added and stirred at 70 ° C. for 12 hours. When the reaction was completed, ethyl acetate was added and washed with 1N HCl aqueous solution. The combined organic layers were dried over MgSO 4 and distilled under reduced pressure to obtain compound 3.

제조예 3: (2-알킬/아릴(R4)-카바모일-피롤리딘-1-설포닐아미노)-알킬 에스터 (화합물 3-b)의 합성 (반응식 2의 방법)Preparation Example 3 Synthesis of (2-Alkyl / aryl (R 4 ) -carbamoyl-pyrrolidine-1-sulfonylamino) -alkyl Ester (Compound 3-b) (Method of Scheme 2)

Figure 112005013060010-PAT00015
Figure 112005013060010-PAT00015

(단계 1)(Step 1)

화합물 2-b를 아세토나이트릴에 녹인 후, 프롤린 벤질 에스터 1.2당량과 TEA 3.0당량을 첨가하고 12시간동안 70℃에서 교반시켰다. 반응이 완결되면 에틸 아세테이트를 첨가하고 1N HCl 수용액으로 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하여 화합물 6을 얻었다.After dissolving compound 2-b in acetonitrile, 1.2 equivalents of proline benzyl ester and 3.0 equivalents of TEA were added and stirred at 70 ° C. for 12 hours. When the reaction was completed, ethyl acetate was added and washed with 1N HCl aqueous solution. The combined organic layers were dried over MgSO 4 and distilled under reduced pressure to obtain compound 6.

(단계 2)(Step 2)

화합물 6을 MeOH에 녹인 후, 5 wt% Pd/C (5 wt% Pd on activated carbon)를 촉매량 넣고, 수소풍선을 이용하여 5시간동안 교반하였다. 반응이 완결되면, 여과한 후 용매를 감압증류하여 화합물 7을 얻었다.After dissolving Compound 6 in MeOH, 5 wt% Pd / C (5 wt% Pd on activated carbon) was added in a catalytic amount, and stirred for 5 hours using a hydrogen balloon. When the reaction was completed, the solvent was distilled under reduced pressure after filtration to obtain Compound 7.

(단계 3)(Step 3)

화합물 7을 DMF에 녹인 후, EDC 1.2당량, HOBt 1.2당량, DMAP 2.0당량과 아민 1.2 당량을 넣고 상온에서 12시간동안 교반하였다. 반응이 완결되면 용매를 감압증류하여 제거한 후 에틸 아세테이트를 첨가하고, 물로 여러 번 씻어주었다. 유 기층을 모아서 MgSO4로 건조시킨 후 감압증류하였다. 플래시 컬럼 크로마토그래피로 분리 정제하여 화합물 3-b를 얻었다.After dissolving Compound 7 in DMF, 1.2 equivalents of EDC, 1.2 equivalents of HOBt, 2.0 equivalents of DMAP, and 1.2 equivalents of amine were added and stirred at room temperature for 12 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, ethyl acetate was added, and the mixture was washed several times with water. The organic layer was collected, dried over MgSO 4, and distilled under reduced pressure. Separation and purification by flash column chromatography gave Compound 3-b.

제조예 4: (3-알킬/아릴(R5)-카보닐아미노-피롤리딘-1-설포닐아미노)-알킬 에스터 (화합물 3-c)의 합성 (반응식 3의 방법)Preparation Example 4 Synthesis of (3-alkyl / aryl (R 5 ) -carbonylamino-pyrrolidine-1-sulfonylamino) -alkyl ester (Compound 3-c) (Method of Scheme 3)

Figure 112005013060010-PAT00016
Figure 112005013060010-PAT00016

(단계 1)(Step 1)

화합물 2-c를 아세토나이트릴에 녹인 후, 피롤리딘-3-일-카밤산 tert-뷰틸 에스터 1.2당량과 TEA 3.0당량을 첨가하고 12시간동안 70℃에서 교반시켰다. 반응이 완결되면 에틸 아세테이트를 첨가하고 1N HCl 수용액으로 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하여 화합물 8을 얻었다.Compound 2-c was dissolved in acetonitrile, and then 1.2 equivalents of pyrrolidin-3-yl-carbamic acid tert-butyl ester and 3.0 equivalents of TEA were added and stirred at 70 ° C. for 12 hours. When the reaction was completed, ethyl acetate was added and washed with 1N HCl aqueous solution. The combined organic layers were dried over MgSO 4 and distilled under reduced pressure to obtain compound 8.

(단계 2)(Step 2)

화합물 8을 MC에 녹인 후 트라이플루오로아세트산을 넣고 상온에서 12시간동안 교반하였다. 반응이 완결되면 용매를 감압증류하여 제거하고, 에틸 아세테이트를 첨가한 후 5% NaHCO3 용액으로 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 여과한 후 용매를 감압증류하여 화합물 9를 얻었다.Compound 8 was dissolved in MC and trifluoroacetic acid was added thereto, followed by stirring at room temperature for 12 hours. When the reaction was completed, the solvent was removed by distillation under reduced pressure, ethyl acetate was added and washed with 5% NaHCO 3 solution. The organic layer was collected, dried over MgSO 4 , filtered, and the solvent was distilled under reduced pressure to obtain Compound 9.

(단계 3)(Step 3)

화합물 9를 DMF에 녹인 후, EDC 1.2당량, HOBt 1.2당량, DMAP 2.0당량과 아민 1.2 당량을 넣고 상온에서 12시간동안 교반하였다. 반응이 완결되면 용매를 감압증류하여 제거한 후 에틸 아세테이트를 첨가하고, 물로 여러 번 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하였다. 플래시 컬럼 크로마토그래피로 분리 정제하여 화합물 3-c를 얻었다.After dissolving Compound 9 in DMF, 1.2 equivalents of EDC, 1.2 equivalents of HOBt, 2.0 equivalents of DMAP, and 1.2 equivalents of amine were added and stirred at room temperature for 12 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, ethyl acetate was added, and the mixture was washed several times with water. The combined organic layers were dried over MgSO 4 and distilled under reduced pressure. Separation and purification by flash column chromatography gave Compound 3-c.

제조예 5: [N-알킬(R1)-(알킬/아릴 아민-1-설포닐)-아미노]-알킬산 (화합물 5)의 합성 (반응식 1의 방법)Preparation Example 5 Synthesis of [N-alkyl (R 1 )-(alkyl / aryl amine-1-sulfonyl) -amino] -alkyl acid (Compound 5) (method of Scheme 1)

Figure 112005013060010-PAT00017
Figure 112005013060010-PAT00017

(단계 1)(Step 1)

화합물 3을 DMF에 녹인 후, K2CO3 3.0 당량과 알킬 브로마이드 (R1) 1.2 당량을 첨가하고 50℃에서 12시간동안 교반시켰다. 반응이 완결되면 DMF를 감압증류한 후에 에틸 아세테이트를 넣고 물로 여러 번 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하여 화합물 4를 얻었다.After dissolving compound 3 in DMF, 3.0 equivalents of K 2 CO 3 and 1.2 equivalents of alkyl bromide (R 1 ) were added and stirred at 50 ° C. for 12 hours. After completion of the reaction, DMF was distilled under reduced pressure, and ethyl acetate was added thereto and washed with water several times. The combined organic layers were dried over MgSO 4 and distilled under reduced pressure to obtain compound 4.

(단계 2)(Step 2)

화합물 4를 THF:H2O=1:1 용매에 녹인 후, LiOH.H2O 5.0당량을 첨가하고 3시 간동안 50℃에서 교반시켰다. 유기용매를 감압증류한 후 1N HCl 수용액을 첨가하여 산성화시키고 에틸 아세테이트로 추출하였다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하여 화합물 5를 얻었다.Compound 4 was dissolved in THF: H 2 O = 1: 1 solvent, then 5.0 equivalents of LiOH.H 2 O was added and stirred at 50 ° C. for 3 hours. The organic solvent was distilled under reduced pressure, acidified by adding 1N aqueous HCl solution, and extracted with ethyl acetate. The combined organic layers were dried over MgSO 4 and distilled under reduced pressure to obtain compound 5.

제조예 6: [N-알킬(R1)-(알킬/아릴 아민-1-설포닐)-아미노]-하이드록사민산 (화합물 1)의 합성 (반응식 1의 방법)Preparation Example 6 Synthesis of [N-alkyl (R 1 )-(alkyl / aryl amine-1-sulfonyl) -amino] -hydroxysanoic acid (Compound 1) (method of Scheme 1)

Figure 112005013060010-PAT00018
Figure 112005013060010-PAT00018

화합물 5를 MC에 녹인 후 DMF 촉매량과 옥살릴 클로라이드 3.0당량을 넣고 상온에서 2시간 동안 교반시켰다. 반응용액을 감압증류시키고 진공에서 감압건조한 후 THF에 녹인 용액을 3.0당량 H2NOH.HCl와 4.0당량 NaHCO3이 녹아있는 THF:H2O=1:1용매에 천천히 첨가하였다. 5분간 교반시킨 후 유기용매를 감압증류시켰다. 에틸 아세테이트로 묽힌 후 물로 세척하고, 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하여 화합물 1을 얻었다.Compound 5 was dissolved in MC, and then DMF catalyst amount and 3.0 equivalents of oxalyl chloride were added and stirred at room temperature for 2 hours. The reaction solution was distilled under reduced pressure and dried under reduced pressure in vacuo, and the solution dissolved in THF was slowly added to THF: H 2 O = 1: 1 solvent in which 3.0 equivalents of H 2 NOH.HCl and 4.0 equivalents of NaHCO 3 were dissolved. After stirring for 5 minutes, the organic solvent was distilled under reduced pressure. Diluted with ethyl acetate, washed with water, and the organic layer was collected, dried over MgSO 4, and distilled under reduced pressure to obtain Compound 1.

제조예 7: [N-알킬(R1)-(알킬/아릴 아민-1-설포닐)-아미노]-하이드록사민산 (화학식 1)의 합성 (반응식 1의 방법)Preparation Example 7 Synthesis of [N-alkyl (R 1 )-(alkyl / aryl amine-1-sulfonyl) -amino] -hydroxyxamic acid (Formula 1) (method of Scheme 1)

Figure 112005013060010-PAT00019
Figure 112005013060010-PAT00019

(단계 1)(Step 1)

화합물 5를 DMF에 녹인 후, EDC 1.2당량, HOBt 1.2당량, DMAP 2.0당량과 O-벤질 하이드록실 아민 HCl 염을 넣고 상온에서 12시간동안 교반하였다. 반응이 완결되면 용매를 감압증류하여 제거한 후 에틸 아세테이트를 첨가하고, 물로 여러 번 씻어주었다. 유기층을 모아서 MgSO4로 건조시킨 후 감압증류하였다. 플래시 컬럼 크로마토그래피로 분리 정제하여 중간 생성물을 얻었다.After dissolving Compound 5 in DMF, 1.2 equivalents of EDC, 1.2 equivalents of HOBt, 2.0 equivalents of DMAP, and O-benzyl hydroxyl amine HCl salt were added and stirred at room temperature for 12 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, ethyl acetate was added, and the mixture was washed several times with water. The combined organic layers were dried over MgSO 4 and distilled under reduced pressure. Separation and purification by flash column chromatography gave an intermediate product.

(단계 2)(Step 2)

단계 1에서 얻어진 생성물을 MeOH에 녹인 후, 5 wt% Pd/C을 촉매량 넣고, 수소풍선을 이용하여 5시간동안 교반하였다. 반응이 완결되면, 여과한 후 용매를 감압증류하였다. 필요한 경우 플래시 컬럼 크로마토그래피로 분리 정제하여 화합물 1을 얻었다.After dissolving the product obtained in step 1 in MeOH, 5 wt% Pd / C was added in a catalytic amount, and stirred for 5 hours using a hydrogen balloon. After the reaction was completed, the solvent was distilled under reduced pressure after filtration. If necessary, Compound 1 was obtained by separation and purification by flash column chromatography.

실시예 1 : 2-[뷰틸-(피페리딘-1-설포닐)-아미노]-N-하이드록시-아세트아마이드Example 1 2- [Butyl- (piperidine-1-sulfonyl) -amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00020
Figure 112005013060010-PAT00020

글라이신 메틸 에스터, 피페리딘 그리고 n-뷰틸 브로마이드를 사용하여 제조 예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5 and 6 using glycine methyl ester, piperidine and n-butyl bromide.

- Exact Mass : 293Exact Mass: 293

-1H-NMR (CDCl3, ppm) : 0.92 (3H, t), 1.28 (2H, m), 1.51~1.67 (8H, m), 3.15~3.28 (6H, m), 3.89 (2H, s) 1 H-NMR (CDCl 3 , ppm): 0.92 (3H, t), 1.28 (2H, m), 1.51-1.67 (8H, m), 3.15-3.28 (6H, m), 3.89 (2H, s)

실시예 2 : 2-[뷰틸-(모포린-4-설포닐)-아미노]-N-하이드록시-아세트아마이드Example 2 2- [Butyl- (morpholin-4-sulfonyl) -amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00021
Figure 112005013060010-PAT00021

글라이신 메틸 에스터, 모포린 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using glycine methyl ester, morpholine and n-butyl bromide.

- Exact Mass : 295Exact Mass: 295

- 1H-NMR(CDCl3, ppm) : 0.94(3H, t), 1.33(2H, m), 1.60(2H, m), 3.20(4H, m), 3.29(2H, t), 3.73(4H, m), 3.91(2H, s) 1 H-NMR (CDCl 3 , ppm): 0.94 (3H, t), 1.33 (2H, m), 1.60 (2H, m), 3.20 (4H, m), 3.29 (2H, t), 3.73 (4H , m), 3.91 (2H, s)

실시예 3 : 2-[뷰틸-(4-메틸-피페라진-1-설포닐)-아미노]-N-하이드록시-아세트아마이드Example 3: 2- [Butyl- (4-methyl-piperazin-1-sulfonyl) -amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00022
Figure 112005013060010-PAT00022

글라이신 메틸 에스터, 4-메틸 피페라진 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using glycine methyl ester, 4-methyl piperazine and n-butyl bromide.

- Exact Mass : 308Exact Mass: 308

- 1H-NMR(CDCl3, ppm) : 0.95(3H, t), 1.32(2H, m), 1.55(2H, m), 2.34(3H, s), 2.46(4H, m), 3.29(4H, m), 3.84(2H, s) 1 H-NMR (CDCl 3 , ppm): 0.95 (3H, t), 1.32 (2H, m), 1.55 (2H, m), 2.34 (3H, s), 2.46 (4H, m), 3.29 (4H , m), 3.84 (2H, s)

실시예 4 : 2-[(4-벤질-피페라진-1-설포닐)-뷰틸-아미노]-N-하이드록시-아세트아마이드Example 4: 2-[(4-benzyl-piperazin-1-sulfonyl) -butyl-amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00023
Figure 112005013060010-PAT00023

글라이신 메틸 에스터, 4-벤질 피페라진 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using glycine methyl ester, 4-benzyl piperazine and n-butyl bromide.

- Exact Mass : 384Exact Mass: 384

- 1H-NMR(CDCl3, ppm) : 0.93(3H, t), 1.30(2H, m), 1.54(2H, m), 2.72(4H, m), 3.24(2H, m), 3.38(4H, m), 3.76(2H, s), 3.89(2H, s), 7.30~7.37(5H, m) 1 H-NMR (CDCl 3 , ppm): 0.93 (3H, t), 1.30 (2H, m), 1.54 (2H, m), 2.72 (4H, m), 3.24 (2H, m), 3.38 (4H , m), 3.76 (2H, s), 3.89 (2H, s), 7.30-7.37 (5H, m)

실시예 5 : 2-[뷰틸-(다이사이클로헥실 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드Example 5 2- [Butyl- (dicyclohexyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00024
Figure 112005013060010-PAT00024

글라이신 메틸 에스터, 다이사이클로헥실 아민 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using glycine methyl ester, dicyclohexyl amine and n-butyl bromide.

- Exact Mass : 389Exact Mass: 389

- 1H-NMR (CDCl3, ppm) : 0.92 (3H, t), 1.12 (2H, m), 1.24~1.34 (6H, m), 1.54~1.61 (4H, m), 1.70~1.84 (12H, m), 3.05 (2H, m), 3.26 (2H, m), 3.89 (2H, s) -1 H-NMR (CDCl 3 , ppm): 0.92 (3H, t), 1.12 (2H, m), 1.24-1.34 (6H, m), 1.54-1.61 (4H, m), 1.70-1.84 (12H, m), 3.05 (2H, m), 3.26 (2H, m), 3.89 (2H, s)

실시예 6 : 2-[뷰틸-(다이벤질 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드Example 6 2- [Butyl- (dibenzyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00025
Figure 112005013060010-PAT00025

글라이신 메틸 에스터, 다이벤질 아민 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using glycine methyl ester, dibenzyl amine and n-butyl bromide.

- Exact Mass : 405Exact Mass: 405

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.26 (2H, m), 1.51 (2H, m), 3.22 (2H, dd), 4.02 (2H, s), 4.31 (4H, s), 7.24~7.35 (10H, m) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.26 (2H, m), 1.51 (2H, m), 3.22 (2H, dd), 4.02 (2H, s), 4.31 (4H , s), 7.24 ~ 7.35 (10H, m)

실시예 7 : N-하이드록시-2-[(2-옥소-옥사졸리딘-3-설포닐)-펜틸-아미노]-아세트아마이드Example 7 N-hydroxy-2-[(2-oxo-oxazolidine-3-sulfonyl) -pentyl-amino] -acetamide

Figure 112005013060010-PAT00026
Figure 112005013060010-PAT00026

글라이신 메틸 에스터와 n-펜틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using glycine methyl ester and n-pentyl bromide.

- Exact Mass : 309Exact Mass: 309

- 1H-NMR (CDCl3, ppm) : 0.91 (3H, t), 1.25 (4H, m), 1.58 (2H, m), 3.24 (4H, m), 3.72 (2H, m), 3.90 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.91 (3H, t), 1.25 (4H, m), 1.58 (2H, m), 3.24 (4H, m), 3.72 (2H, m), 3.90 (2H , m)

실시예 8 : 2-[펜틸-(다이벤질 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드Example 8 2- [pentyl- (dibenzyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00027
Figure 112005013060010-PAT00027

글라이신 메틸 에스터, 다이벤질 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using glycine methyl ester, dibenzyl amine and n-pentyl bromide.

- Exact Mass : 419Exact Mass: 419

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.27 (4H, m), 1.50 (2H, m), 3.24 (2H, dd), 4.02 (2H, s), 4.30 (4H, s), 7.24~7.35 (10H, m) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.27 (4H, m), 1.50 (2H, m), 3.24 (2H, dd), 4.02 (2H, s), 4.30 (4H , s), 7.24 ~ 7.35 (10H, m)

실시예 9 : 3-[뷰틸-(2-옥소-옥사졸리딘-3-설포닐)-아미노]-N-하이드록시-프로피온아마이드Example 9 3- [Butyl- (2-oxo-oxazolidine-3-sulfonyl) -amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00028
Figure 112005013060010-PAT00028

베타-알라닌 에틸 에스터와 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using beta-alanine ethyl ester and n-butyl bromide.

- Exact Mass : 309Exact Mass: 309

- 1H-NMR (CDCl3, ppm) : 0.94 (3H, t), 1.34 (4H, m), 1.56 (2H, m), 2.58 (2H, m), 3.19 (4H, m), 3.50 (2H, t), 3.74 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.94 (3H, t), 1.34 (4H, m), 1.56 (2H, m), 2.58 (2H, m), 3.19 (4H, m), 3.50 (2H , t), 3.74 (2H, m)

실시예 10 : 3-[뷰틸-(피페리딘-1-설포닐)-아미노]-N-하이드록시-프로피온아마이드Example 10 3- [Butyl- (piperidine-1-sulfonyl) -amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00029
Figure 112005013060010-PAT00029

베타-알라닌 에틸 에스터, 피페리딘 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using beta-alanine ethyl ester, piperidine and n-butyl bromide.

- Exact Mass : 307Exact Mass: 307

- 1H-NMR (CDCl3, ppm) : 0.92 (3H, t), 1.28 (2H, m), 1.49~1.62 (8H, m), 2.54 (2H, t), 3.08~3.16 (6H, m), 3.50 (2H, t) 1 H-NMR (CDCl 3 , ppm): 0.92 (3H, t), 1.28 (2H, m), 1.49-1.62 (8H, m), 2.54 (2H, t), 3.08-3.16 (6H, m) , 3.50 (2H, t)

실시예 11 : 3-[뷰틸-(모포린-4-설포닐)-아미노]-N-하이드록시-프로피온아마이드 Example 11 3- [Butyl- (morpholin-4-sulfonyl) -amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00030
Figure 112005013060010-PAT00030

베타-알라닌 에틸 에스터, 모포린 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using beta-alanine ethyl ester, morpholine and n-butyl bromide.

- Exact Mass : 309Exact Mass: 309

- 1H-NMR (CDCl3, ppm) : 0.93 (3H, t), 1.29 (2H, m), 1.55 (2H, m), 2.54 (2H, t), 3.15 (6H, m), 3.52 (2H, t), 3.73 (4H, m) 1 H-NMR (CDCl 3 , ppm): 0.93 (3H, t), 1.29 (2H, m), 1.55 (2H, m), 2.54 (2H, t), 3.15 (6H, m), 3.52 (2H , t), 3.73 (4H, m)

실시예 12 : 3-[뷰틸-(4-메틸-피페라진-1-설포닐)-아미노]-N-하이드록시-프로피온아마이드Example 12 3- [Butyl- (4-methyl-piperazin-1-sulfonyl) -amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00031
Figure 112005013060010-PAT00031

베타-알라닌 에틸 에스터, 4-메틸 피페라진 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using beta-alanine ethyl ester, 4-methyl piperazine and n-butyl bromide.

- Exact Mass : 322Exact Mass: 322

- 1H-NMR (CDCl3, ppm) : 0.92 (3H, t), 1.35 (2H, m), 1.53 (2H, m), 2.38 (3H, s), 2.58 (4H, m), 3.05 (4H, q), 3.32 (4H, m), 4.16 (1H, t) 1 H-NMR (CDCl 3 , ppm): 0.92 (3H, t), 1.35 (2H, m), 1.53 (2H, m), 2.38 (3H, s), 2.58 (4H, m), 3.05 (4H , q), 3.32 (4H, m), 4.16 (1H, t)

실시예 13 : 3-[(4-벤질-피페라진-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드Example 13: 3-[(4-benzyl-piperazine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00032
Figure 112005013060010-PAT00032

베타-알라닌 에틸 에스터, 4-벤질 피페라진 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using beta-alanine ethyl ester, 4-benzyl piperazine and n-butyl bromide.

- Exact Mass : 398Exact Mass: 398

- 1H-NMR (CDCl3, ppm) : 0.92 (3H, t), 1.35 (2H, m), 1.53 (2H, m), 2.50 (2H, t), 2.62 (4H, m), 3.14 (2H, t), 3.24 (4H, q), 3.50 (2H, m), 3.65 (2H, s), 7.29~7.34 (5H, m) 1 H-NMR (CDCl 3 , ppm): 0.92 (3H, t), 1.35 (2H, m), 1.53 (2H, m), 2.50 (2H, t), 2.62 (4H, m), 3.14 (2H , t), 3.24 (4H, q), 3.50 (2H, m), 3.65 (2H, s), 7.29-7.34 (5H, m)

실시예 14 : 3-[(다이사이클로헥실 아민-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드Example 14 3-[(dicyclohexyl amine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00033
Figure 112005013060010-PAT00033

베타-알라닌 에틸 에스터, 다이사이클로헥실 아민 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using beta-alanine ethyl ester, dicyclohexyl amine and n-butyl bromide.

- Exact Mass : 403Exact Mass: 403

- 1H-NMR (CDCl3, ppm) : 0.92 (3H, t), 1.12 (2H, m), 1.24~1.34 (6H, m), 1.54~1.61 (4H, m), 1.70~1.84 (12H, m), 2.58 (2H, t), 3.05 (2H, m), 3.15 (2H, m), 3.54 (2H, m) -1 H-NMR (CDCl 3 , ppm): 0.92 (3H, t), 1.12 (2H, m), 1.24-1.34 (6H, m), 1.54-1.61 (4H, m), 1.70-1.84 (12H, m), 2.58 (2H, t), 3.05 (2H, m), 3.15 (2H, m), 3.54 (2H, m)

실시예 15 : 3-[(다이벤질 아민-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드Example 15 3-[(dibenzyl amine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00034
Figure 112005013060010-PAT00034

베타-알라닌 에틸 에스터, 다이벤질 아민 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 2, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 2, 5, 6 using beta-alanine ethyl ester, dibenzyl amine and n-butyl bromide.

- Exact Mass : 419Exact Mass: 419

- 1H-NMR (CDCl3, ppm) : 0.92 (3H, t), 1.28 (2H, m), 1.56 (2H, m), 2.69 (2H, t), 3.12 (2H, t), 3.47 (2H, t), 4.27 (4H, s), 7.26~7.33 (10H, m) 1 H-NMR (CDCl 3 , ppm): 0.92 (3H, t), 1.28 (2H, m), 1.56 (2H, m), 2.69 (2H, t), 3.12 (2H, t), 3.47 (2H , t), 4.27 (4H, s), 7.26 ~ 7.33 (10H, m)

실시예 16 : [1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-카밤산 tert-뷰틸 에스터Example 16 [1- (Butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester

Figure 112005013060010-PAT00035
Figure 112005013060010-PAT00035

글라이신 메틸 에스터와 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, and 7 using glycine methyl ester and n-butyl bromide.

- Exact Mass : 394Exact Mass: 394

- 1H-NMR (CDCl3, ppm) : 0.91 (3H, t), 1.30 (2H, m), 1.45 (9H, s), 1.58 (2H, m), 1.90 (1H, m), 2.13 (1H, m), 3.28~3.49 (6H, m), 3.86 (2H, s), 4.13 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.91 (3H, t), 1.30 (2H, m), 1.45 (9H, s), 1.58 (2H, m), 1.90 (1H, m), 2.13 (1H , m), 3.28-3.49 (6H, m), 3.86 (2H, s), 4.13 (1H, br)

실시예 17 : 2-[(3-아미노-피롤리딘-1-설포닐)-뷰틸-아미노]-N-하이드록시-아세트아마이드Example 17 2-[(3-amino-pyrrolidine-1-sulfonyl) -butyl-amino] -N-hydroxy-acetamide

Figure 112005013060010-PAT00036
Figure 112005013060010-PAT00036

실시예 9 에서 얻은 화합물을 TFA / MC 조건에서 탈보호하여 표제화합물을 합성하였다.The compound obtained in Example 9 was deprotected under TFA / MC conditions to synthesize the title compound.

- Exact Mass : 294Exact Mass: 294

- 1H-NMR (MeOH-d4, ppm) : 0.95 (3H, t), 1.32 (2H, m), 1.58 (2H, m), 1.92 (1H, m), 2.13 (2H, m), 3.35 (2H, m), 3.56 (2H, m), 3.82 (2H, d) 1 H-NMR (MeOH-d4, ppm): 0.95 (3H, t), 1.32 (2H, m), 1.58 (2H, m), 1.92 (1H, m), 2.13 (2H, m), 3.35 ( 2H, m), 3.56 (2H, m), 3.82 (2H, d)

실시예 18 : 바이페닐-4-카복실산 [1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-아마이드Example 18 Biphenyl-4-carboxylic acid [1- (butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -amide

Figure 112005013060010-PAT00037
Figure 112005013060010-PAT00037

글라이신 메틸 에스터, 바이페닐 카복실산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using glycine methyl ester, biphenyl carboxylic acid and n-butyl bromide.

- Exact Mass : 474Exact Mass: 474

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.24 (2H, m), 1.35 (2H, m), 2.09 (1H, m), 2.26 (1H, m), 2.58~2.74 (3H, m), 3.27~3.62 (6H, m), 3.85 (2H, d), 4.68 (1H, br), 7.34~7.52 (3H, m), 7.52~7.69 (4H, m), 7.93 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.24 (2H, m), 1.35 (2H, m), 2.09 (1H, m), 2.26 (1H, m), 2.58-2.74 (3H, m), 3.27-3.62 (6H, m), 3.85 (2H, d), 4.68 (1H, br), 7.34-7.52 (3H, m), 7.52-7.69 (4H, m), 7.93 (2H , m)

실시예 19 : N-[1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-4-플루오로-벤즈아마이드Example 19 N- [1- (Butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -4-fluoro-benzamide

Figure 112005013060010-PAT00038
Figure 112005013060010-PAT00038

글라이신 메틸 에스터, 4-플루오로 벤조산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using glycine methyl ester, 4-fluoro benzoic acid and n-butyl bromide.

- Exact Mass : 416Exact Mass: 416

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.27 (2H, m), 1.56 (2H, m), 2.08 (1H, m), 2.23 (1H, m), 2.64 (3H, m), 3.25~3.60 (6H, m), 3.83 (2H, d), 4.66 (1H, br), 7.08 (2H, d), 7.89 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.27 (2H, m), 1.56 (2H, m), 2.08 (1H, m), 2.23 (1H, m), 2.64 (3H , m), 3.25-3.60 (6H, m), 3.83 (2H, d), 4.66 (1H, br), 7.08 (2H, d), 7.89 (2H, d)

실시예 20 : 4-tert-뷰틸-N-[1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-벤즈아마이드Example 20 4-tert-Butyl-N- [1- (butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -benzamide

Figure 112005013060010-PAT00039
Figure 112005013060010-PAT00039

글라이신 메틸 에스터, 4-tert-뷰틸 벤조산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using glycine methyl ester, 4-tert-butyl benzoic acid and n-butyl bromide.

- Exact Mass : 454Exact Mass: 454

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.24 (2H, m), 1.30 (9H, s), 1.53 (2H, s), 2.04 (1H, m), 2.21 (1H, m), 2.43 (1H, m), 3.31-3.61 (6H, m), 3.85 (2H, d), 4.60 (1H, br), 7.41 (2H, d), 7.77 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.24 (2H, m), 1.30 (9H, s), 1.53 (2H, s), 2.04 (1H, m), 2.21 (1H , m), 2.43 (1H, m), 3.31-3.61 (6H, m), 3.85 (2H, d), 4.60 (1H, br), 7.41 (2H, d), 7.77 (2H, d)

실시예 21 : 바이페닐-4-카복실산 [1-(펜틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-아마이드Example 21 biphenyl-4-carboxylic acid [1- (pentyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -amide

Figure 112005013060010-PAT00040
Figure 112005013060010-PAT00040

글라이신 메틸 에스터, 바이페닐 카복실산 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using glycine methyl ester, biphenyl carboxylic acid and n-pentyl bromide.

- Exact Mass : 488Exact Mass: 488

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.20~1.38 (4H, m), 1.56 (2H, m), 2.05 (1H, m), 2.33 (1H, m), 2.64 (1H, m), 3.25~3.49 (6H, m), 4.05 (2H, d), 4.71 (1H, br), 7.30~7.48 (3H, m), 7.74~7.70 (4H, m), 7.89 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.20-1.38 (4H, m), 1.56 (2H, m), 2.05 (1H, m), 2.33 (1H, m), 2.64 (1H, m), 3.25-3.49 (6H, m), 4.05 (2H, d), 4.71 (1H, br), 7.30-7.48 (3H, m), 7.74-7.70 (4H, m), 7.89 (2H , d)

실시예 22 : N-[1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-4-메톡시-벤즈아마이드Example 22 N- [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -4-methoxy-benzamide

Figure 112005013060010-PAT00041
Figure 112005013060010-PAT00041

글라이신 메틸 에스터, 4-메톡시 벤조산 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the procedure of Preparation Examples 1, 3, 5, 7 using glycine methyl ester, 4-methoxy benzoic acid and n-pentyl bromide.

- Exact Mass : 442Exact Mass: 442

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.21~1.39 (4H, m), 1.54 (2H, m), 2.04 (1H, m), 2.22 (1H, m), 2.42 (1H, m), 3.30~3.62 (6H, m), 3.80 (3H, s), 3.95 (2H, d), 4.62 (1H, br), 6.88 (2H, d), 7.81 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.21-1.39 (4H, m), 1.54 (2H, m), 2.04 (1H, m), 2.22 (1H, m), 2.42 (1H, m), 3.30-3.62 (6H, m), 3.80 (3H, s), 3.95 (2H, d), 4.62 (1H, br), 6.88 (2H, d), 7.81 (2H, d)

실시예 23 : 1H-벤조이미다졸-5-카복실산 [1-(하이드록시카바모일 메틸-펜틸-설파모일)-피롤리딘-3-일]-아마이드Example 23 1H-benzoimidazole-5-carboxylic acid [1- (hydroxycarbamoyl methyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -amide

Figure 112005013060010-PAT00042
Figure 112005013060010-PAT00042

글라이신 메틸 에스터, 1H-벤조이미다졸 카복실산 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 3, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 6 using glycine methyl ester, 1H-benzoimidazole carboxylic acid and n-pentyl bromide.

- Exact Mass : 452Exact Mass: 452

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.19~1.38 (4H, m), 1.50 (2H, m), 2.05 (1H, m), 2.32 (1H, m), 2.65 (1H, m), 3.31~3.63 (6H, m), 3.95 (2H, d), 4.60 (1H, br), 7.41 (1H, d), 7.76 (1H, d), 8.33 (1H, d), 9.13 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.19-1.38 (4H, m), 1.50 (2H, m), 2.05 (1H, m), 2.32 (1H, m), 2.65 (1H, m), 3.31-3.63 (6H, m), 3.95 (2H, d), 4.60 (1H, br), 7.41 (1H, d), 7.76 (1H, d), 8.33 (1H, d), 9.13 (1 H, s)

실시예 24 : 3-하이드록시-N-[1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-벤즈아마이드Example 24 3-hydroxy-N- [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -benzamide

Figure 112005013060010-PAT00043
Figure 112005013060010-PAT00043

글라이신 메틸 에스터, 3-하이드록시 벤조산 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 3, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 6 using glycine methyl ester, 3-hydroxy benzoic acid and n-pentyl bromide.

- Exact Mass : 428Exact Mass: 428

- 1H-NMR (CDCl3, ppm) : 0.85 (3H, t), 1.23 (4H, m), 1.54 (2H, m), 2.02 (1H, m), 2.20 (1H, m), 2.65 (1H, m), 3.24~3.58 (6H, m), 3.95 (2H, d), 4.62 (1H, br), 6.93 (1H, d), 7.22~7.34 (3H, m) 1 H-NMR (CDCl 3 , ppm): 0.85 (3H, t), 1.23 (4H, m), 1.54 (2H, m), 2.02 (1H, m), 2.20 (1H, m), 2.65 (1H , m), 3.24-3.58 (6H, m), 3.95 (2H, d), 4.62 (1H, br), 6.93 (1H, d), 7.22-7.34 (3H, m)

실시예 25 : 나프탈렌-2-카복실산 [1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-아마이드Example 25 Naphthalene-2-carboxylic Acid [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -amide

Figure 112005013060010-PAT00044
Figure 112005013060010-PAT00044

글라이신 메틸 에스터, 2-나프탈렌 카복실산 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the procedure of Preparation Examples 1, 3, 5, 7 using glycine methyl ester, 2-naphthalene carboxylic acid and n-pentyl bromide.

- Exact Mass : 462Exact Mass: 462

- 1H-NMR (CDCl3, ppm) : 0.84 (3H, t), 1.25 (4H, m), 1.56 (2H, m), 2.02 (1H, m), 2.25 (1H, m), 2.77 (1H, m), 3.30~3.59 (6H, m), 3.79 (2H, d), 4.70 (1H, br), 7.52 (1H, m), 7.80~7.95 (4H, m), 8.42 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.84 (3H, t), 1.25 (4H, m), 1.56 (2H, m), 2.02 (1H, m), 2.25 (1H, m), 2.77 (1H , m), 3.30-3.59 (6H, m), 3.79 (2H, d), 4.70 (1H, br), 7.52 (1H, m), 7.80-7.95 (4H, m), 8.42 (1H, s)

실시예 26 : N-하이드록시-2-({3-[2-(3-하이드록시-페닐)-아세틸아미노]-피롤리딘-1-설포닐}-펜틸-아미노)-아세트아마이드Example 26 N-hydroxy-2-({3- [2- (3-hydroxy-phenyl) -acetylamino] -pyrrolidine-1-sulfonyl} -pentyl-amino) -acetamide

Figure 112005013060010-PAT00045
Figure 112005013060010-PAT00045

글라이신 메틸 에스터, 3-하이드록시 페닐 아세트산 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 3, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 6 using glycine methyl ester, 3-hydroxy phenyl acetic acid and n-pentyl bromide.

- Exact Mass : 442Exact Mass: 442

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.23 (4H, m), 1.53 (2H, m), 2.04 (1H, m), 2.10 (1H, m), 2.48 (1H, m), 3.10~3.61 (6H, m), 3.69 (2H, s), 3.98 (2H, s), 4.39 (1H, br), 6.64~6.79 (3H, m), 7.13 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.23 (4H, m), 1.53 (2H, m), 2.04 (1H, m), 2.10 (1H, m), 2.48 (1H , m), 3.10-3.61 (6H, m), 3.69 (2H, s), 3.98 (2H, s), 4.39 (1H, br), 6.64-6.69 (3H, m), 7.13 (1H, s)

실시예 27 : 2-{[3-(2-바이페닐-4-일-아세틸아미노)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드Example 27 2-{[3- (2-Biphenyl-4-yl-acetylamino) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide

Figure 112005013060010-PAT00046
Figure 112005013060010-PAT00046

글라이신 메틸 에스터, 바이페닐-4-일 아세트산 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using glycine methyl ester, biphenyl-4-yl acetic acid and n-pentyl bromide.

- Exact Mass : 502-Exact Mass: 502

- 1H-NMR (CDCl3, ppm) : 0.85 (3H, t), 1.25 (4H, m), 1.51 (2H, m), 2.02 (1H, m), 2.11 (1H, m), 2.47 (1H, m), 3.12~3.51 (6H, m), 3.55 (2H, s), 3.98 (2H, d), 4.71 (1H, br), 7.27~7.49 (5H, m), 7.54 (4H, m) 1 H-NMR (CDCl 3 , ppm): 0.85 (3H, t), 1.25 (4H, m), 1.51 (2H, m), 2.02 (1H, m), 2.11 (1H, m), 2.47 (1H , m), 3.12-3.51 (6H, m), 3.55 (2H, s), 3.98 (2H, d), 4.71 (1H, br), 7.27-7.49 (5H, m), 7.54 (4H, m)

실시예 28 : {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-카밤산 tert-뷰틸 에스터Example 28 {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -carbamic acid tert-butyl ester

Figure 112005013060010-PAT00047
Figure 112005013060010-PAT00047

베타-알라닌 에틸 에스터를 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 6 using beta-alanine ethyl ester using n-butyl bromide.

- Exact Mass : 408-Exact Mass: 408

- 1H-NMR (CDCl3, ppm) : 0.93 (3H, t), 1.31 (2H, m), 1.45 (9H, s), 1.55 (2H, m), 1.90 (1H, m), 2.18 (1H, m), 2.50 (2H, m), 3.16 (4H, m), 3.33~3.55 (6H, m), 4.19 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.93 (3H, t), 1.31 (2H, m), 1.45 (9H, s), 1.55 (2H, m), 1.90 (1H, m), 2.18 (1H , m), 2.50 (2H, m), 3.16 (4H, m), 3.33-3.55 (6H, m), 4.19 (1H, br)

실시예 29 : 3-[(3-아미노-피롤리딘-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드Example 29 3-[(3-amino-pyrrolidine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide

Figure 112005013060010-PAT00048
Figure 112005013060010-PAT00048

실시예 28에서 얻은 화합물을 TFA / MC 조건에서 탈보호를 하여 표제화합물을 합성하였다.The compound obtained in Example 28 was deprotected under TFA / MC conditions to synthesize the title compound.

- Exact Mass : 308Exact Mass: 308

- 1H-NMR (CDCl3, ppm) : 0.95 (3H, t), 1.21~1.34 (3H, m), 1.60 (2H, m), 2.01 (2H, m), 2.37 (2H, m), 3.23~3.31 (6H, m), 3.45~3.53 (4H, m), 3.92 (1H, br), 4.10 (1H, m) 1 H-NMR (CDCl 3 , ppm): 0.95 (3H, t), 1.21-1.34 (3H, m), 1.60 (2H, m), 2.01 (2H, m), 2.37 (2H, m), 3.23 ~ 3.31 (6H, m), 3.45-3.53 (4H, m), 3.92 (1H, br), 4.10 (1H, m)

실시예 30 : 바이페닐-4-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드Example 30 Biphenyl-4-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide

Figure 112005013060010-PAT00049
Figure 112005013060010-PAT00049

베타-알라닌 에틸 에스터, 바이페닐 카복실산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using beta-alanine ethyl ester, biphenyl carboxylic acid and n-butyl bromide.

- Exact Mass : 488Exact Mass: 488

- 1H-NMR(CDCl3, ppm) : 0.93 (3H, t), 1.26 (2H, m), 1.57 (2H, m), 2.18 (1H, m), 2.29 (1H, m), 2.49~2.75 (3H, m), 3.20 (2H, m), 3.40 (2H, m), 3.49~3.60 (4H, m), 4.68 (1H, br), 7.34~7.51 (3H, m), 7.53~7.70 (4H, m), 7.91 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.93 (3H, t), 1.26 (2H, m), 1.57 (2H, m), 2.18 (1H, m), 2.29 (1H, m), 2.49-2.75 (3H, m), 3.20 (2H, m), 3.40 (2H, m), 3.49-3.60 (4H, m), 4.68 (1H, br), 7.34-7.51 (3H, m), 7.53-7.70 (4H , m), 7.91 (2H, m)

실시예 31 : N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-4-플루오로-벤즈아마이드Example 31 N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -4-fluoro-benzamide

Figure 112005013060010-PAT00050
Figure 112005013060010-PAT00050

베타-알라닌 에틸 에스터, 4-플루오로 벤조산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using beta-alanine ethyl ester, 4-fluoro benzoic acid and n-butyl bromide.

- Exact Mass : 430Exact Mass: 430

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.26 (2H, m), 1.56 (2H, m), 2.04 (1H, m), 2.25 (1H, m), 2.57 (1H, m), 3.19 (2H, m), 3.35 (2H, m), 3.40~3.61 (4H, m), 4.65 (1H, br), 7.08 (2H, d), 7.82 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.26 (2H, m), 1.56 (2H, m), 2.04 (1H, m), 2.25 (1H, m), 2.57 (1H , m), 3.19 (2H, m), 3.35 (2H, m), 3.40-3.61 (4H, m), 4.65 (1H, br), 7.08 (2H, d), 7.82 (2H, d)

실시예 32 : 4-tert-뷰틸-N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-벤즈아마이드Example 32 4-tert-Butyl-N- {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -benzamide

Figure 112005013060010-PAT00051
Figure 112005013060010-PAT00051

베타-알라닌 에틸 에스터, 4-tert-뷰틸 벤조산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using beta-alanine ethyl ester, 4-tert-butyl benzoic acid and n-butyl bromide.

- Exact Mass : 468Exact Mass: 468

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.24 (2H, m), 1.30 (9H, s), 1.55 (2H, m), 2.04 (1H, m), 2.25 (1H, m), 2.51 (2H, m), 2.88 (1H, m), 3.16 (2H, m), 3.32 (2H, m), 3.42~3.58 (4H, m), 4.64 (1H, br), 7.40 (2H, d), 7.73 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.24 (2H, m), 1.30 (9H, s), 1.55 (2H, m), 2.04 (1H, m), 2.25 (1H , m), 2.51 (2H, m), 2.88 (1H, m), 3.16 (2H, m), 3.32 (2H, m), 3.42-3.58 (4H, m), 4.64 (1H, br), 7.40 ( 2H, d), 7.73 (2H, d)

실시예 33 : N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-4-메톡시-벤즈아마이드Example 33 N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -4-methoxy-benzamide

Figure 112005013060010-PAT00052
Figure 112005013060010-PAT00052

베타-알라닌 에틸 에스터, 4-메톡시 벤조산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using beta-alanine ethyl ester, 4-methoxy benzoic acid and n-butyl bromide.

- Exact Mass : 442Exact Mass: 442

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.25 (2H, m), 1.51 (2H, m), 2.04 (1H, m), 2.23 (1H, m), 2.25 (1H, m), 3.13 (2H, m), 3.23 (2H, m), 3.38-3.56 (4H, m), 3.82 (2H, t), 4.60 (1H, br), 6.85 (2H, d), 7.73 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.25 (2H, m), 1.51 (2H, m), 2.04 (1H, m), 2.23 (1H, m), 2.25 (1H , m), 3.13 (2H, m), 3.23 (2H, m), 3.38-3.56 (4H, m), 3.82 (2H, t), 4.60 (1H, br), 6.85 (2H, d), 7.73 ( 2H, d)

실시예 34 : 1H-벤조이미다졸-5-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드Example 34 1H-Benzoimidazole-5-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide

Figure 112005013060010-PAT00053
Figure 112005013060010-PAT00053

베타-알라닌 에틸 에스터, 1H-벤조이미다졸-5-카복실산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 6 using beta-alanine ethyl ester, 1H-benzoimidazole-5-carboxylic acid and n-butyl bromide.

- Exact Mass : 452Exact Mass: 452

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.25 (2H, m), 1.48 (2H, m), 2.06 (1H, m), 2.31 (1H, m), 2.66 (1H, m), 3.10 (2H, m), 3.25 (2H, m), 3.32-3.59 (4H, m), 3.68 (2H, t), 4.54 (1H, br), 7.40 (1H, d), 7.74 (1H, d), 8.16 (1H, d), 8.55 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.25 (2H, m), 1.48 (2H, m), 2.06 (1H, m), 2.31 (1H, m), 2.66 (1H , m), 3.10 (2H, m), 3.25 (2H, m), 3.32-3.59 (4H, m), 3.68 (2H, t), 4.54 (1H, br), 7.40 (1H, d), 7.74 ( 1H, d), 8.16 (1H, d), 8.55 (1H, s)

실시예 35 : N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-3-하이드록시-벤즈아마이드Example 35 N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -3-hydroxy-benzamide

Figure 112005013060010-PAT00054
Figure 112005013060010-PAT00054

베타-알라닌 에틸 에스터, 3-하이드록시 벤조산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 6 using beta-alanine ethyl ester, 3-hydroxy benzoic acid and n-butyl bromide.

- Exact Mass : 428Exact Mass: 428

- 1H-NMR (CDCl3, ppm) : 0.91 (3H, t), 1.26 (2H, m), 1.55 (2H, m), 2.05 (1H, m), 2.30 (1H, m), 2.64 (1H, m), 3.15 (2H, m), 3.32 (2H, m), 3.34-3.55 (4H, m), 3.60 (2H, m), 4.60 (1H, br), 6.97 (1H, d), 7.18~7.28 (3H, m) 1 H-NMR (CDCl 3 , ppm): 0.91 (3H, t), 1.26 (2H, m), 1.55 (2H, m), 2.05 (1H, m), 2.30 (1H, m), 2.64 (1H , m), 3.15 (2H, m), 3.32 (2H, m), 3.34-3.55 (4H, m), 3.60 (2H, m), 4.60 (1H, br), 6.97 (1H, d), 7.18- 7.28 (3H, m)

실시예 36 : 나프탈렌-2-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드Example 36 naphthalene-2-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide

Figure 112005013060010-PAT00055
Figure 112005013060010-PAT00055

베타-알라닌 에틸 에스터, 2-나프탈렌 벤조산 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 3, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 3, 5, 7 using beta-alanine ethyl ester, 2-naphthalene benzoic acid and n-butyl bromide.

- Exact Mass : 462Exact Mass: 462

- 1H-NMR (CDCl3, ppm) : 0.91 (3H, t), 1.24 (2H, m), 1.56 (2H, m), 2.06 (1H, m), 2.31 (1H, m), 2.63 (1H, m), 3.17 (2H, m), 3.37 (2H, m), 3.41-3.58 (4H, m), 3.61 (2H, m), 4.72 (1H, br), 7.53 (2H, m), 7.86 (4H, m), 8.34 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.91 (3H, t), 1.24 (2H, m), 1.56 (2H, m), 2.06 (1H, m), 2.31 (1H, m), 2.63 (1H , m), 3.17 (2H, m), 3.37 (2H, m), 3.41-3.58 (4H, m), 3.61 (2H, m), 4.72 (1H, br), 7.53 (2H, m), 7.86 ( 4H, m), 8.34 (1H, s)

실시예 37 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 페닐 아마이드Example 37 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid phenylamide

Figure 112005013060010-PAT00056
Figure 112005013060010-PAT00056

글라이신 메틸 에스터, 아닐린 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, aniline and n-pentyl bromide.

- Exact Mass : 412Exact Mass: 412

- 1H-NMR (CDCl3, ppm) : 0.84 (3H, t), 1.26 (4H, m), 1.58 (2H, m), 2.04 (2H, m), 2.22 (1H, m), 2.46 (1H, m), 3.39 (4H, m), 3.67~3.91 (2H, dd), 4.39 (1H, m), 7.14 (1H, t), 7.32 (2H, m), 7.54 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.84 (3H, t), 1.26 (4H, m), 1.58 (2H, m), 2.04 (2H, m), 2.22 (1H, m), 2.46 (1H , m), 3.39 (4H, m), 3.67-3.91 (2H, dd), 4.39 (1H, m), 7.14 (1H, t), 7.32 (2H, m), 7.54 (2H, d)

실시예 38 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 나프탈렌-2-일아마이드Example 38 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid naphthalen-2-ylamide

Figure 112005013060010-PAT00057
Figure 112005013060010-PAT00057

글라이신 메틸 에스터, 2-나프틸 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 2-naphthyl amine and n-pentyl bromide.

- Exact Mass : 462Exact Mass: 462

- 1H-NMR (CDCl3, ppm) : 0.82 (3H, t), 1.25 (4H, m), 1.55 (2H, m), 2.04 (2H, m), 2.20 (1H, m), 2.45 (1H, m), 3.40 (4H, m), 3.67~3.91 (2H, dd), 4.39 (1H, m), 7.42 (2H, m), 7.52 (1H, dd), 7.77 (3H, m), 8.26 (1H, d) 1 H-NMR (CDCl 3 , ppm): 0.82 (3H, t), 1.25 (4H, m), 1.55 (2H, m), 2.04 (2H, m), 2.20 (1H, m), 2.45 (1H , m), 3.40 (4H, m), 3.67-3.91 (2H, dd), 4.39 (1H, m), 7.42 (2H, m), 7.52 (1H, dd), 7.77 (3H, m), 8.26 ( 1H, d)

실시예 39 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 바이페닐-4-일아마이드Example 39 1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid biphenyl-4-ylamide

Figure 112005013060010-PAT00058
Figure 112005013060010-PAT00058

글라이신 메틸 에스터, 4-바이페닐 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-biphenyl amine and n-pentyl bromide.

- Exact Mass : 488Exact Mass: 488

- 1H-NMR (CDCl3, ppm) : 0.84 (3H, t), 1.24 (4H, m), 1.57 (2H, m), 2.04 (2H, m), 2.20 (1H, m), 2.45 (1H, m), 3.40 (4H, m), 3.76~3.92 (2H, dd), 4.40 (1H, m), 7.32 (1H, d), 7.43 (2H, t), 7.56 (4H, m), 7.65 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.84 (3H, t), 1.24 (4H, m), 1.57 (2H, m), 2.04 (2H, m), 2.20 (1H, m), 2.45 (1H , m), 3.40 (4H, m), 3.76-3.92 (2H, dd), 4.40 (1H, m), 7.32 (1H, d), 7.43 (2H, t), 7.56 (4H, m), 7.65 ( 2H, d)

실시예 40 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-페녹시-페닐)-아마이드Example 40 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-phenoxy-phenyl) -amide

Figure 112005013060010-PAT00059
Figure 112005013060010-PAT00059

글라이신 메틸 에스터, 4-페녹시 페닐 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-phenoxy phenyl amine and n-pentyl bromide.

- Exact Mass : 504-Exact Mass: 504

- 1H-NMR (CDCl3, ppm) : 0.86 (3H, t), 1.24 (4H, m), 1.56 (2H, m), 2.01 (2H, m), 2.20 (1H, m), 2.45 (1H, m), 3.29~3.43 (4H, m), 3.73~3.89 (2H, dd), 4.35 (1H, m), 6.96 (4H, t), 7.07 (1H, t), 7.31 (2H, t), 7.54 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.86 (3H, t), 1.24 (4H, m), 1.56 (2H, m), 2.01 (2H, m), 2.20 (1H, m), 2.45 (1H , m), 3.29-3.43 (4H, m), 3.73-3.89 (2H, dd), 4.35 (1H, m), 6.96 (4H, t), 7.07 (1H, t), 7.31 (2H, t), 7.54 (2H, d)

실시예 41 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4,5-다이하이드로-티아졸-2-일)-아마이드Example 41 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4,5-dihydro-thiazol-2-yl) -amide

Figure 112005013060010-PAT00060
Figure 112005013060010-PAT00060

글라이신 메틸 에스터, 4,5-다이하이드로 티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4,5-dihydro thiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 421Exact Mass: 421

- 1H-NMR (CDCl3, ppm) : 0.86 (3H, t), 1.26~1.35 (6H, m), 1.60 (2H, m), 1.84 (2H, m), 2.00 (4H, m), 2.20 (2H, m), 3.15 (2H, m), 3.37 (2H, m), 3.68~3.90 (2H, dd), 4.17 (1H, m), 1 H-NMR (CDCl 3 , ppm): 0.86 (3H, t), 1.26-1.35 (6H, m), 1.60 (2H, m), 1.84 (2H, m), 2.00 (4H, m), 2.20 (2H, m), 3.15 (2H, m), 3.37 (2H, m), 3.68-3.90 (2H, dd), 4.17 (1H, m),

실시예 42 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-메틸-티아졸-2-일)-아마이드Example 42 1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-methyl-thiazol-2-yl) -amide

Figure 112005013060010-PAT00061
Figure 112005013060010-PAT00061

글라이신 메틸 에스터, 4-메틸 티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-methyl thiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 433Exact Mass: 433

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.25~1.32 (4H, m), 1.62 (2H, m), 1.93 (2H, m), 2.00 (2H, m), 2.23 (2H, m), 2.30 (3H, t), 3.42 (2H, m), 3.54 (2H, m), 3.77~4.09 (2H, dd), 4.58 (1H, m), 6.40 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.25-1.32 (4H, m), 1.62 (2H, m), 1.93 (2H, m), 2.00 (2H, m), 2.23 (2H, m), 2.30 (3H, t), 3.42 (2H, m), 3.54 (2H, m), 3.77-4.09 (2H, dd), 4.58 (1H, m), 6.40 (1H, s)

실시예 43 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4,5-다이메틸-티아졸-2-일)-아마이드Example 43 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4,5-dimethyl-thiazol-2-yl) -amide

Figure 112005013060010-PAT00062
Figure 112005013060010-PAT00062

글라이신 메틸 에스터, 4,5-다이메틸 티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4,5-dimethyl thiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 447Exact Mass: 447

- 1H-NMR (CDCl3, ppm) : 0.88 (3H, t), 1.18~1.35 (4H, m), 1.59 (2H, m), 1.95 (2H, m), 2.08 (2H, m), 2.17 (3H, s), 2.19 (1H, m), 2.24 (3H, s), 3.41 (2H, m), 3.51 (1H, m), 3.67 (1H, m), 3.79~4.22 (2H, dd) 1 H-NMR (CDCl 3 , ppm): 0.88 (3H, t), 1.18-1.35 (4H, m), 1.59 (2H, m), 1.95 (2H, m), 2.08 (2H, m), 2.17 (3H, s), 2.19 (1H, m), 2.24 (3H, s), 3.41 (2H, m), 3.51 (1H, m), 3.67 (1H, m), 3.79-4.22 (2H, dd)

실시예 44 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-페닐-티아졸-2-일)-아마이드Example 44 1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-phenyl-thiazol-2-yl) -amide

Figure 112005013060010-PAT00063
Figure 112005013060010-PAT00063

글라이신 메틸 에스터, 4-페닐 티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-phenyl thiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 495Exact Mass: 495

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.25~1.32 (4H, m), 1.62 (2H, m), 1.93 (2H, m), 2.00 (2H, m), 2.23 (2H, m), 3.42 (2H, m), 3.54 (2H, m), 3.77~4.09 (2H, dd), 4.58 (1H, m), 7.10 (1H, s), 7.39 (3H, m), 7.68 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.25-1.32 (4H, m), 1.62 (2H, m), 1.93 (2H, m), 2.00 (2H, m), 2.23 (2H, m), 3.42 (2H, m), 3.54 (2H, m), 3.77-4.09 (2H, dd), 4.58 (1H, m), 7.10 (1H, s), 7.39 (3H, m), 7.68 (2H, m)

실시예 45 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-나프탈렌-2-일-티아졸-2-일)-아마이드Example 45 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-naphthalen-2-yl-thiazol-2-yl) -amide

Figure 112005013060010-PAT00064
Figure 112005013060010-PAT00064

글라이신 메틸 에스터, 4-나프탈렌-2-일 티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-naphthalen-2-yl thiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 545Exact Mass: 545

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.25~1.32 (4H, m), 1.62 (2H, m), 1.93 (2H, m), 2.00 (2H, m), 2.23 (2H, m), 3.42 (2H, m), 3.54 (2H, m), 3.77~4.09 (2H, dd), 4.58 (1H, m), 7.20 (1H, s), 7.50 (2H, m), 7.75~8.10 (4H, m), 8.16 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.25-1.32 (4H, m), 1.62 (2H, m), 1.93 (2H, m), 2.00 (2H, m), 2.23 (2H, m), 3.42 (2H, m), 3.54 (2H, m), 3.77-4.09 (2H, dd), 4.58 (1H, m), 7.20 (1H, s), 7.50 (2H, m), 7.75-8.10 (4H, m), 8.16 (1H, s)

실시예 46 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 벤조 티아졸-2-일아마이드Example 46 1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid benzothiazol-2-ylamide

Figure 112005013060010-PAT00065
Figure 112005013060010-PAT00065

글라이신 메틸 에스터, 벤조티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5 and 6 using glycine methyl ester, benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 469Exact Mass: 469

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 3.31~3.37 (2H, m), 3.77~3.85 (2H, dd), 3.86~4.15 (2H, dd) 4.58 (1H, m), 7.31 (1H, t), 7.45 (1H, t), 7.70 (1H, d), 7.80 (1H, d) -1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 3.31 ~ 3.37 (2H, m), 3.77-3.85 (2H, dd), 3.86-4.15 (2H, dd) 4.58 (1H, m), 7.31 (1H, t), 7.45 (1H, t), 7.70 (1H, d), 7.80 (1 H, d)

실시예 47 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-메틸-벤조티아졸-2-일)-아마이드Example 47 1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-methyl-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00066
Figure 112005013060010-PAT00066

글라이신 메틸 에스터, 6-메틸 벤조티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 6-methyl benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 483Exact Mass: 483

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.46 (3H, s), 3.31~3.37 (2H, m), 3.77~3.85 (2H, dd), 3.86~4.07 (2H, dd), 4.58 (1H, m), 6.07 (1H, br), 6.57 (1H, br), 7.24 (1H, d), 7.64 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.46 (3H, s), 3.31-3.37 (2H, m), 3.77-3.85 (2H, dd), 3.86-4.07 (2H, dd), 4.58 (1H, m), 6.07 (1H, br), 6.57 (1H , br), 7.24 (1H, d), 7.64 (2H, m)

실시예 48 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (5,6-다이메틸-벤조티아졸-2-일)-아마이드Example 48 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (5,6-dimethyl-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00067
Figure 112005013060010-PAT00067

글라이신 메틸 에스터, 5,6-다이메틸 벤조티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 5,6-dimethyl benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 497Exact Mass: 497

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31~3.37 (2H, m), 3.77~3.85 (2H, dd), 3.86~4.06 (2H, dd), 4.58 (1H, m), 5.95 (1H, br), 6.54 (1H, br), 7.53 (1H, s), 7.55 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31-3.37 (2H, m), 3.77-3.85 (2H, dd), 3.86-4.06 (2H, dd), 4.58 (1H, m), 5.95 (1H, br), 6.54 (1H , br), 7.53 (1H, s), 7.55 (1H, s)

실시예 49 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-플루오로-벤조티아졸-2-일)-아마이드Example 49 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-fluoro-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00068
Figure 112005013060010-PAT00068

글라이신 메틸 에스터, 6-플루오로 벤조티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 6-fluoro benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 487Exact Mass: 487

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31~3.37 (2H, m), 3.77~3.85 (2H, dd), 4.00~4.20 (2H, dd), 4.54 (1H, m), 7.15 (1H, dt), 7.49 (1H, dd), 7.69 (1H, dd) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31-3.37 (2H, m), 3.77-3.85 (2H, dd), 4.00-4.20 (2H, dd), 4.54 (1H, m), 7.15 (1H, dt), 7.49 (1H , dd), 7.69 (1H, dd)

실시예 50 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-클로로-벤조티아졸-2-일)-아마이드Example 50 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-chloro-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00069
Figure 112005013060010-PAT00069

글라이신 메틸 에스터, 6-클로로 벤조티아졸-2-일 아민 그리고 n-펜틸 브로 마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 6-chloro benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 503Exact Mass: 503

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31~3.37 (2H, m), 3.77~3.85 (2H, dd), 4.00~4.20 (2H, dd), 4.54 (1H, m), 7.15 (1H, m), 7.49 (1H, m), 7.69 (1H, m) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31-3.37 (2H, m), 3.77-3.85 (2H, dd), 4.00-4.20 (2H, dd), 4.54 (1H, m), 7.15 (1H, m), 7.49 (1H , m), 7.69 (1H, m)

실시예 51 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-메톡시-벤조티아졸-2-일)-아마이드Example 51 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-methoxy-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00070
Figure 112005013060010-PAT00070

글라이신 메틸 에스터, 6-메톡시 벤조티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 6-methoxy benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 499Exact Mass: 499

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.35 (2H, m), 3.77~3.83 (2H, dd), 3.85 (3H, s), 4.10~4.20 (2H, m), 4.54 (1H, m), 6.98 (1H, d), 7.23 (1H, m), 7.62 (1H, d) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.35 (2H, m), 3.77-3.83 (2H, dd), 3.85 (3H, s), 4.10-4.20 (2H, m), 4.54 (1H, m), 6.98 (1H, d ), 7.23 (1H, m), 7.62 (1H, d)

실시예 52 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-메톡시-벤조티아졸-2-일)-아마이드Example 52 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-methoxy-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00071
Figure 112005013060010-PAT00071

글라이신 메틸 에스터, 4-메톡시 벤조티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-methoxy benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 499Exact Mass: 499

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.35 (2H, m), 3.77~3.85 (2H, dd), 4.11 (3H, s), 4.10~4.20 (2H, m), 4.54 (1H, m), 6.94 (1H, m), 7.38 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.35 (2H, m), 3.77-3.85 (2H, dd), 4.11 (3H, s), 4.10-4.20 (2H, m), 4.54 (1H, m), 6.94 (1H, m ), 7.38 (2H, m)

실시예 53 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-클로로-벤조티아졸-2-일)-아마이드Example 53 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-chloro-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00072
Figure 112005013060010-PAT00072

글라이신 메틸 에스터, 4-클로로 벤조티아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-chloro benzothiazol-2-yl amine and n-pentyl bromide.

- Exact Mass : 503Exact Mass: 503

- 1H-NMR (CDCl3, ppm) : 0.83 (3H, t), 1.23~1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31~3.37 (2H, m), 3.77~3.85 (2H, dd), 4.00~4.20 (2H, dd), 4.54 (1H, m), 7.26 (1H, br), 7.45 (1H, br), 7.70 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.83 (3H, t), 1.23-1.29 (4H, m), 1.56 (2H, m), 2.03 (2H, m), 2.33 (2H, m), 2.36 (3H, s), 3.31-3.37 (2H, m), 3.77-3.85 (2H, dd), 4.00-4.20 (2H, dd), 4.54 (1H, m), 7.26 (1H, br), 7.45 (1H , 7.70 (1H, br)

실시예 54 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-사이클로헥실-페닐)-아마이드Example 54 1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-cyclohexyl-phenyl) -amide

Figure 112005013060010-PAT00073
Figure 112005013060010-PAT00073

글라이신 메틸 에스터, 4-사이클로헥실 페닐 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-cyclohexyl phenyl amine and n-pentyl bromide.

- Exact Mass : 494Exact Mass: 494

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.26 (4H, m), 1.40 (4H, m), 1.61 (2H, m), 1.76 (2H, m), 1.83 (4H, m), 1.97~2.15 (2H, m), 2.26~2.48 (2H, m), 3.25~3.43 (4H, m), 3.70~3.90 (1H, br, d), 4.65 (1H, m), 7.17 (2H, d), 7.40 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.26 (4H, m), 1.40 (4H, m), 1.61 (2H, m), 1.76 (2H, m), 1.83 (4H , m), 1.97-2.15 (2H, m), 2.26-2.48 (2H, m), 3.25-3.43 (4H, m), 3.70-3.90 (1H, br, d), 4.65 (1H, m), 7.17 (2H, d), 7.40 (2H, d)

실시예 55 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-피페리딘-1-일-페닐)-아마이드Example 55 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-piperidin-1-yl-phenyl) -amide

Figure 112005013060010-PAT00074
Figure 112005013060010-PAT00074

글라이신 메틸 에스터, 4-피페리딘-1-일 페닐 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the procedure of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-piperidin-1-yl phenyl amine and n-pentyl bromide.

- Exact Mass : 495Exact Mass: 495

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.25~1.32 (4H, m), 1.58 (4H, m), 1.70 (4H, m), 1.98 (2H, m), 2.12~2.29 (2H, m), 3.11 (2H, m), 3.28~3.71 (4H, m), 3.65~3.90 (1H, dd), 4.31 (1H, br), 7.12 (2H, d), 7.38 (2H, d), 7.88 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.25-1.32 (4H, m), 1.58 (4H, m), 1.70 (4H, m), 1.98 (2H, m), 2.12 ~ 2.29 (2H, m), 3.11 (2H, m), 3.28-3.71 (4H, m), 3.65-3.90 (1H, dd), 4.31 (1H, br), 7.12 (2H, d), 7.38 (2H , d), 7.88 (1 H, br)

실시예 56 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-모포린-4-일-페닐)-아마이드Example 56 1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-morpholin-4-yl-phenyl) -amide

Figure 112005013060010-PAT00075
Figure 112005013060010-PAT00075

글라이신 메틸 에스터, 4-모포린-4-일 페닐 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-morpholin-4-yl phenyl amine and n-pentyl bromide.

- Exact Mass : 497Exact Mass: 497

- 1H-NMR (CDCl3, ppm) : 0.86 (3H, t), 1.25 (4H, m), 1.50~1.57 (2H, m), 1.81 (2H, m), 1.92 (2H, m), 2.19 (2H, m), 2.60 (2H, m), 3.08~3.18 (4H, m), 3.40 (2H, m), 3.84 (4H, m), 4.39 (1H, m), 6.85 (2H, m), 7.46 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.86 (3H, t), 1.25 (4H, m), 1.50-1.57 (2H, m), 1.81 (2H, m), 1.92 (2H, m), 2.19 (2H, m), 2.60 (2H, m), 3.08-3.18 (4H, m), 3.40 (2H, m), 3.84 (4H, m), 4.39 (1H, m), 6.85 (2H, m), 7.46 (2H, d)

실시예 57 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (5-에틸설파닐-[1,3,4]티아다이아졸-2-일)-아마이드Example 57 1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (5-ethylsulfanyl- [1,3,4] thiadiazol-2-yl) -amide

Figure 112005013060010-PAT00076
Figure 112005013060010-PAT00076

글라이신 메틸 에스터, 5-에틸설파닐-[1,3,4]티아다이아졸-2-일 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.Synthesis of the title compound according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 5-ethylsulfanyl- [1,3,4] thiadiazol-2-yl amine and n-pentyl bromide It was.

- Exact Mass : 480-Exact Mass: 480

- 1H-NMR (CDCl3, ppm) : 0.90 (3H, t), 1.24 (4H, m), 1.47 (3H, t), 1.63 (2H, m), 2.09 (2H, m), 2.17 (1H, m), 2.37 (1H, m), 3.25~3.65 (4H, m), 3.89~4.24 (2H, dd), 4.68 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.90 (3H, t), 1.24 (4H, m), 1.47 (3H, t), 1.63 (2H, m), 2.09 (2H, m), 2.17 (1H , m), 2.37 (1H, m), 3.25-3.65 (4H, m), 3.89-4.24 (2H, dd), 4.68 (1H, br)

실시예 58 : 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (2-모포린-4-일-에틸)-아마이드Example 58 l- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (2-morpholin-4-yl-ethyl) -amide

Figure 112005013060010-PAT00077
Figure 112005013060010-PAT00077

글라이신 메틸 에스터, 2-모포린-4-일 에틸 아민 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 2-morpholin-4-yl ethyl amine and n-pentyl bromide.

- Exact Mass : 449Exact Mass: 449

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.26 (4H, m), 1.64 (2H, m), 1.82~2.11 (3H, m), 2.24 (1H, m), 2.45~2.65 (6H, m), 3.34 (2H, m), 3.38~3.50 (4H, m), 3.68~3.75 (4H, m), 3.82 (1H, d), 4.21 (1H, m), 6.93 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.26 (4H, m), 1.64 (2H, m), 1.82-2.11 (3H, m), 2.24 (1H, m), 2.45 ~ 2.65 (6H, m), 3.34 (2H, m), 3.38-3.50 (4H, m), 3.68-3.75 (4H, m), 3.82 (1H, d), 4.21 (1H, m), 6.93 (1H , br)

실시예 59 : 2-{[2-(3-다이에틸아미노-피롤리딘-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드Example 59 2-{[2- (3-Diethylamino-pyrrolidine-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide

Figure 112005013060010-PAT00078
Figure 112005013060010-PAT00078

글라이신 메틸 에스터, 3-다이에틸아미노-피롤리딘 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the procedure of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 3-diethylamino-pyrrolidine and n-pentyl bromide.

- Exact Mass : 461Exact Mass: 461

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.02 (6H, t), 1.27 (4H, m), 1.63 (2H, m), 1.88~1.94 (3H, m), 2.06 (1H, m), 2.24 (2H, m), 2.64 (4H, q), 3.23 (2H, m), 3.34 (2H, m), 3.46 (2H, m), 3.51~3.68 (2H, m), 3.83 (1H, m), 3.90 (2H, d), 4.47 (1H, m) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.02 (6H, t), 1.27 (4H, m), 1.63 (2H, m), 1.88-1.94 (3H, m), 2.06 (1H, m), 2.24 (2H, m), 2.64 (4H, q), 3.23 (2H, m), 3.34 (2H, m), 3.46 (2H, m), 3.51-3.68 (2H, m), 3.83 (1H, m), 3.90 (2H, d), 4.47 (1H, m)

실시예 60 : N-하이드록시-2-{[2-(4-메틸-피페라진-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-아세트아마이드Example 60 N-hydroxy-2-{[2- (4-methyl-piperazine-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -acetamide

Figure 112005013060010-PAT00079
Figure 112005013060010-PAT00079

글라이신 메틸 에스터, 4-메틸 피페라진 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-methyl piperazine and n-pentyl bromide.

- Exact Mass : 419Exact Mass: 419

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.27 (4H, m), 1.62 (2H, m), 1.83 (1H, m), 1.89~2.10 (2H, m), 2.24 (1H, m), 2.31 (3H, s), 2.33~2.54 (4H, m), 3.19 (1H, m), 3.32 (1H, m), 3.39~3.52 (3H, m), 3.53~3.69 (2H, m), 3.58 (1H, d), 3.76 (1H, m), 3.89 (1H, d), 4.70 (1H, m) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.27 (4H, m), 1.62 (2H, m), 1.83 (1H, m), 1.89-2.10 (2H, m), 2.24 (1H, m), 2.31 (3H, s), 2.33-2.54 (4H, m), 3.19 (1H, m), 3.32 (1H, m), 3.39-3.52 (3H, m), 3.53-3.69 (2H , m), 3.58 (1H, d), 3.76 (1H, m), 3.89 (1H, d), 4.70 (1H, m)

실시예 61 : N-하이드록시-2-{펜틸-[2-(4-페닐-피페라진-1-카보닐)-피롤리딘-1-설포닐]-아미노}-아세트아마이드Example 61 N-hydroxy-2- {pentyl- [2- (4-phenyl-piperazine-1-carbonyl) -pyrrolidine-1-sulfonyl] -amino} -acetamide

Figure 112005013060010-PAT00080
Figure 112005013060010-PAT00080

글라이신 메틸 에스터, 4-페닐 피페라진 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-phenyl piperazine and n-pentyl bromide.

- Exact Mass : 481Exact Mass: 481

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.23~1.30 (4H, m), 1.62 (2H, m), 1.80~2.02 (4H, m), 2.25 (1H, m), 2.60 (1H, m), 3.19 (2H, m), 3.45 (2H, m), 3.60 (2H, d), 3.90 (2H, m), 3.94 (2H, m), 4.76 (1H, m), 6.92 (2H, d), 7.28 (3H, m), 12.3 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.23-1.30 (4H, m), 1.62 (2H, m), 1.80-2.02 (4H, m), 2.25 (1H, m) , 2.60 (1H, m), 3.19 (2H, m), 3.45 (2H, m), 3.60 (2H, d), 3.90 (2H, m), 3.94 (2H, m), 4.76 (1H, m), 6.92 (2H, d), 7.28 (3H, m), 12.3 (1H, br)

실시예 62 : 2-{[2-(4-벤질-피페라진-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드Example 62 2-{[2- (4-benzyl-piperazin-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide

Figure 112005013060010-PAT00081
Figure 112005013060010-PAT00081

글라이신 메틸 에스터, 4-벤질 피페라진 그리고 n-펜틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-benzyl piperazine and n-pentyl bromide.

- Exact Mass : 495Exact Mass: 495

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.28 (4H, m), 1.62 (2H, m), 1.83 (1H, m), 1.99 (2H, m), 2.24 (1H, m), 2.34~2.54 (4H, m), 3.18 (1H, m), 3.32 (1H, m), 3.40~3.51 (3H, m), 3.52 (2H, s), 3.61 (1H, m), 3.57 (1H, d), 3.76 (1H, m), 3.92 (1H, d), 4.70 (1H, m), 7.27~7.38 (5H, m) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.28 (4H, m), 1.62 (2H, m), 1.83 (1H, m), 1.99 (2H, m), 2.24 (1H , m), 2.34 to 2.54 (4H, m), 3.18 (1H, m), 3.32 (1H, m), 3.40 to 3.51 (3H, m), 3.52 (2H, s), 3.61 (1H, m), 3.57 (1H, d), 3.76 (1H, m), 3.92 (1H, d), 4.70 (1H, m), 7.27-7.38 (5H, m)

실시예 63 : N-하이드록시-2-{펜틸-[2-(피페라진-1-카보닐)-피롤리딘-1-설포닐]-아미노}-아세트아마이드Example 63 N-hydroxy-2- {pentyl- [2- (piperazin-1-carbonyl) -pyrrolidine-1-sulfonyl] -amino} -acetamide

Figure 112005013060010-PAT00082
Figure 112005013060010-PAT00082

실시예 62를 MeOH에 녹인 후, Pd(OH)2 / 50psi 수소 조건에서 벤질기를 제 거하여 표제화합물을 합성하였다. After dissolving Example 62 in MeOH, the title compound was synthesized by removing the benzyl group under Pd (OH) 2/50 psi hydrogen conditions.

- Exact Mass : 405Exact Mass: 405

- 1H-NMR (CDCl3, ppm) : 0.87 (3H, t), 1.27 (4H, m), 1.62 (2H, m), 1.83 (1H, m), 1.99 (2H, m), 2.24 (1H, m), 2.91~3.17 (4H, m), 3.19 (1H, m), 3.32~3.51 (3H, m), 3.61 (2H, m), 3.72 (1H, d), 3.88 (1H, m), 3.86 (1H, d), 4.74 (1H, m) 1 H-NMR (CDCl 3 , ppm): 0.87 (3H, t), 1.27 (4H, m), 1.62 (2H, m), 1.83 (1H, m), 1.99 (2H, m), 2.24 (1H , m), 2.91-3.17 (4H, m), 3.19 (1H, m), 3.32-3.51 (3H, m), 3.61 (2H, m), 3.72 (1H, d), 3.88 (1H, m), 3.86 (1 H, d), 4.74 (1 H, m)

실시예 64 : 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-메틸-티아졸-2-일)-아마이드Example 64 1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-methyl-thiazol-2-yl) -amide

Figure 112005013060010-PAT00083
Figure 112005013060010-PAT00083

글라이신 메틸 에스터, 4-메틸 티아졸-2-일 아민 그리고 3-메틸 뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-methyl thiazol-2-yl amine and 3-methyl butyl bromide.

- Exact Mass : 433Exact Mass: 433

- 1H-NMR (CDCl3, ppm) : 0.93 (6H, d), 1.52 (2H, m), 1.57 (1H, m), 2.00 (2H, m), 2.25 (2H, m), 2.30 (3H, s), 3.44 (2H, m), 3.62 (1H, m), 3.77 (2H, m), 4.06 (1H, m), 4.59 (1H, br), 6.53 (1H, s) 1 H-NMR (CDCl 3 , ppm): 0.93 (6H, d), 1.52 (2H, m), 1.57 (1H, m), 2.00 (2H, m), 2.25 (2H, m), 2.30 (3H , s), 3.44 (2H, m), 3.62 (1H, m), 3.77 (2H, m), 4.06 (1H, m), 4.59 (1H, br), 6.53 (1H, s)

실시예 65 : 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4,5-다이메틸-티아졸-2-일)-아마이드Example 65 1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4,5-dimethyl-thiazol-2-yl) -amide

Figure 112005013060010-PAT00084
Figure 112005013060010-PAT00084

글라이신 메틸 에스터, 45,-다이메틸 티아졸-2-일 아민 그리고 3-메틸 뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 45, -dimethyl thiazol-2-yl amine and 3-methyl butyl bromide.

- Exact Mass : 447Exact Mass: 447

- 1H-NMR (CDCl3, ppm) : 0.92 (6H, d), 1.45~1.60 (4H, m), 1.90 (1H, m), 2.00 (2H, m), 2.18 (3H, s), 2.27 (3H, s), 3.44 (2H, m), 3.62 (1H, m), 3.80 (2H, m), 4.05 (1H, d), 4.57 (1H, br) 1 H-NMR (CDCl 3 , ppm): 0.92 (6H, d), 1.45-1.60 (4H, m), 1.90 (1H, m), 2.00 (2H, m), 2.18 (3H, s), 2.27 (3H, s), 3.44 (2H, m), 3.62 (1H, m), 3.80 (2H, m), 4.05 (1H, d), 4.57 (1H, br)

실시예 66 : 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-페닐-티아졸-2-일)-아마이드Example 66 l- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-phenyl-thiazol-2-yl) -amide

Figure 112005013060010-PAT00085
Figure 112005013060010-PAT00085

글라이신 메틸 에스터, 4-페닐 티아졸-2-일 아민 그리고 3-메틸 뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 4-phenyl thiazol-2-yl amine and 3-methyl butyl bromide.

- Exact Mass : 495Exact Mass: 495

- 1H-NMR (CDCl3, ppm) : 0.92 (6H, d), 1.53 (1H, m), 1.61 (2H, m), 2.02 (2H, m), 2.26 (2H, m), 3.46 (2H, m), 3.58~3.80 (3H, m), 3.98 (1H, m), 4.62 (1H, br), 7.10 (1H, s), 7.39 (3H, m), 7.68 (2H, m) 1 H-NMR (CDCl 3 , ppm): 0.92 (6H, d), 1.53 (1H, m), 1.61 (2H, m), 2.02 (2H, m), 2.26 (2H, m), 3.46 (2H , m), 3.58-3.80 (3H, m), 3.98 (1H, m), 4.62 (1H, br), 7.10 (1H, s), 7.39 (3H, m), 7.68 (2H, m)

실시예 67 : 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (6-플루오로-벤조티아졸-2-일)-아마이드Example 67 1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (6-fluoro-benzothiazol-2-yl) -amide

Figure 112005013060010-PAT00086
Figure 112005013060010-PAT00086

글라이신 메틸 에스터, 6-플루오로 벤조티아졸-2-일 아민 그리고 3-메틸 뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 6의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 6 using glycine methyl ester, 6-fluoro benzothiazol-2-yl amine and 3-methyl butyl bromide.

- Exact Mass : 487Exact Mass: 487

- 1H-NMR (CDCl3, ppm) : 0.92 (6H, d), 1.53 (1H, m), 1.61 (2H, m), 2.05 (2H, m), 2.29 (2H, m), 3.45 (2H, m), 3.64 (1H, m), 3.80 (2H, m), 4.11 (1H, m), 4.65 (1H, br), 7.17 (1H, m), 7.39 (1H, s), 7.48 (1H, d), 7.64 (1H, m) 1 H-NMR (CDCl 3 , ppm): 0.92 (6H, d), 1.53 (1H, m), 1.61 (2H, m), 2.05 (2H, m), 2.29 (2H, m), 3.45 (2H , m), 3.64 (1H, m), 3.80 (2H, m), 4.11 (1H, m), 4.65 (1H, br), 7.17 (1H, m), 7.39 (1H, s), 7.48 (1H, d), 7.64 (1 H, m)

실시예 68 : 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복 실산 (4-사이클로헥실-페닐)-아마이드Example 68 1- [Hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxyl acid (4-cyclohexyl-phenyl) -amide

Figure 112005013060010-PAT00087
Figure 112005013060010-PAT00087

글라이신 메틸 에스터, 4-사이클로헥실 페닐 아민 그리고 3-메틸 뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using glycine methyl ester, 4-cyclohexyl phenyl amine and 3-methyl butyl bromide.

- Exact Mass : 494Exact Mass: 494

- 1H-NMR (CDCl3, ppm) : 0.89 (6H, d), 1.38 (4H, m), 1.52 (3H, m), 1.73 (2H, m), 1.77 (4H, m), 2.05 (2H, m), 2.29 (1H, m), 2.46 (1H, m), 3.49 (4H, m), 3.89 (1H, m), 4.38 (1H, br), 7.15 (2H, d), 7.45 (2H, d) 1 H-NMR (CDCl 3 , ppm): 0.89 (6H, d), 1.38 (4H, m), 1.52 (3H, m), 1.73 (2H, m), 1.77 (4H, m), 2.05 (2H , m), 2.29 (1H, m), 2.46 (1H, m), 3.49 (4H, m), 3.89 (1H, m), 4.38 (1H, br), 7.15 (2H, d), 7.45 (2H, d)

실시예 69 : 1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 나프탈렌-2-일아마이드Example 69 1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid naphthalen-2-ylamide

Figure 112005013060010-PAT00088
Figure 112005013060010-PAT00088

베타-알라닌 에틸 에스터, 2-나프틸 아민 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using beta-alanine ethyl ester, 2-naphthyl amine and n-butyl bromide.

- Exact Mass : 462Exact Mass: 462

- 1H-NMR (CDCl3, ppm) : 0.89 (3H, t), 1.25 (2H, m), 1.58 (2H, m), 2.02 (2H, m), 2.30 (2H, m), 2.49 (2H, m), 3.25 (2H, m), 3.38 (2H, m), 3.63 (2H, m), 4.38 (1H, m), 7.43 (2H, m), 7.53 (1H, dd), 7.77 (3H, m), 8.01 (1H,s) 1 H-NMR (CDCl 3 , ppm): 0.89 (3H, t), 1.25 (2H, m), 1.58 (2H, m), 2.02 (2H, m), 2.30 (2H, m), 2.49 (2H , m), 3.25 (2H, m), 3.38 (2H, m), 3.63 (2H, m), 4.38 (1H, m), 7.43 (2H, m), 7.53 (1H, dd), 7.77 (3H, m), 8.01 (1H, s)

실시예 70 : 1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 바이페닐-4-일아마이드Example 70 1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid biphenyl-4-ylamide

Figure 112005013060010-PAT00089
Figure 112005013060010-PAT00089

베타-알라닌 에틸 에스터, 4-바이페닐 아민 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using beta-alanine ethyl ester, 4-biphenyl amine and n-butyl bromide.

- Exact Mass : 488Exact Mass: 488

- 1H-NMR (CDCl3, ppm) : 0.93 (3H, t), 1.32 (2H, m), 1.59 (2H, m), 1.99 (2H, m), 2.17 (2H, m), 2.65 (2H, m), 3.30~3.49 (3H, m), 3.60 (1H, m), 4.33 (1H, m), 7.32 (1H, d), 7.43 (2H, t), 7.55~7.60 (6H, m) 1 H-NMR (CDCl 3 , ppm): 0.93 (3H, t), 1.32 (2H, m), 1.59 (2H, m), 1.99 (2H, m), 2.17 (2H, m), 2.65 (2H , m), 3.30-3.49 (3H, m), 3.60 (1H, m), 4.33 (1H, m), 7.32 (1H, d), 7.43 (2H, t), 7.55-7.60 (6H, m)

실시예 71 : 1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 (4-페녹시-페닐)-아마이드Example 71 1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-phenoxy-phenyl) -amide

Figure 112005013060010-PAT00090
Figure 112005013060010-PAT00090

베타-알라닌 에틸 에스터, 4-페녹시 페닐 아민 그리고 n-뷰틸 브로마이드를 사용하여 제조예 1, 4, 5, 7의 방법에 따라 표제화합물을 합성하였다.The title compound was synthesized according to the method of Preparation Examples 1, 4, 5, 7 using beta-alanine ethyl ester, 4-phenoxy phenyl amine and n-butyl bromide.

- Exact Mass : 504-Exact Mass: 504

- 1H-NMR (CDCl3, ppm) : 0.93 (3H, t), 1.26 (2H, m), 1.57 (2H, m), 2.01 (2H, m), 2.25 (2H, m), 2.50 (2H, m), 3.10~3.49 (5H, m), 3.59 (1H, m), 4.31 (1H, m), 6.97~7.02 (4H, m), 7.09 (1H, t), 7.30 (2H, m), 7.52 (2H, m), 8.24 (1H, m) 1 H-NMR (CDCl 3 , ppm): 0.93 (3H, t), 1.26 (2H, m), 1.57 (2H, m), 2.01 (2H, m), 2.25 (2H, m), 2.50 (2H , m), 3.10-3.49 (5H, m), 3.59 (1H, m), 4.31 (1H, m), 6.97-7.02 (4H, m), 7.09 (1H, t), 7.30 (2H, m), 7.52 (2H, m), 8.24 (1H, m)

시험예: PDF 효소 저해 활성 분석Test Example: Analysis of PDF Enzyme Inhibitory Activity

실시예에서 제조한 화합물들의 PDF 효소 활성 저해능을 다음과 같이 측정하였다. PDF enzyme activity inhibitory activity of the compounds prepared in Example was measured as follows.

우선, 실험에 사용된 PDF를 다음과 같이 유전자 재조합 방법에 의해 대장균으로부터 제조하였다. First, the PDF used in the experiment was prepared from E. coli by the genetic recombination method as follows.

대장균(E. coli)의 디포밀라제 유전자를 대장균에서 클로닝하여 pET21b (Invitrogen)에 삽입한 후, 대장균 BL21 (DE3) 균주에 형질전환하였다. 형질전환된 대장균 균주를 100 ㎍/ml의 암피실린이 함유된 루리아 배지(LB, 1% 박토트립톤, 0.5% 효모 추출물, 1% 염화나트륨)에서 37 ℃로 박테리아의 흡광도가 600 nm의 파장에서 약 0.5 정도가 될 때까지 키운 다음, IPTG를 최종 농도가 1 mM이 되도록 첨가하였다. IPTG를 첨가한 후 4시간이 지나면 10분간 원심분리(10,000 g)하여 세포 침전물을 수거하였다. 수거한 세포 침전물을 완충용액(20 mM MES, 10 mM NaCl, 1 mM EDTA, 1 mM 1,10-페난트롤린, 10 mM b-머캡토에탄올, 1% 트라이톤 X-100Ｒ(Sigma사), 0.5% 프로타민설페이트(Sigma사), pH 6.0)에 현탁시킨 다음, 얼음중탕에서 초음파 분쇄기를 이용하여 세포를 파쇄하였다. 얻어진 용액을 원심분리기로 16,000 rpm에서 30분간 원심분리한 후, 상층액을 완충용액(20 mM MES, 10 mM NaCl, pH 6.0)으로 SP-세파로스 컬럼(Amersham Bioscience)에 결합시킨 후, 0 내지 1 M NaCl 농도구배를 이용하여 용출한 후 SDS-PAGE 젤에 전기영동하여 디포밀라제 단백질을 얻었다. 이어서, 얻어진 디포밀라제 단백질을 농축한 후, 다시 완충용액 (20 mM Tris, 10 mM NaCl, pH 8.5)으로 10배 희석하고, Q-세파로스 컬럼 (Amersham Bioscience) 에 결합시킨 후, 0 내지 1 M NaCl 농도 구배를 이용하여 디포밀라제 단백질을 용출하였다. 용출된 디포밀라제 단백질을 완충용액(20 mM 트라이스, 0.5 M NaCl, 5 mM 이미다졸, pH 8.0)으로 투석하여 탈론 코발트 어피니티 컬럼(Talon cobalt affinity column, Pharmacia)에 주입하였다. 컬럼을 완충용액(20 mM Tris, 10 mM NaCl, pH 8.5)으로 충분히 세척한 후 0 내지 0.5 M 이미다졸 농도 구배를 이용하여 용출한 후 SDS-PAGE 젤에 전기영동하여 디포밀라제 단백질을 얻었다. 이어서, 포름산 탈수소효소(FDH)와의 결합 분석방법(Lazennec et al., Anal. Biochem. 244, 1808 (1997))에 의해 PDF 효소 저해 활성을 측정하였다.The E. coli deformillase gene was cloned from E. coli, inserted into pET21b (Invitrogen), and transformed into E. coli BL21 (DE3) strain. The transformed E. coli strains were absorbed at 37 ° C. in Luria medium (LB, 1% bactotrypton, 0.5% yeast extract, 1% sodium chloride) containing 100 μg / ml of ampicillin at about 0.5 nm at a wavelength of 600 nm. After raising to a degree, IPTG was added to a final concentration of 1 mM. After 4 hours after the addition of IPTG, the cell precipitate was collected by centrifugation (10,000 g) for 10 minutes. The collected cell precipitate was buffered (20 mM MES, 10 mM NaCl, 1 mM EDTA, 1 mM 1,10-phenanthroline, 10 mM b-mercaptoethanol, 1% Triton X-100 R (Sigma), After suspension in 0.5% protamine sulfate (Sigma), pH 6.0), the cells were disrupted using an ultrasonic grinder in an ice bath. The obtained solution was centrifuged at 16,000 rpm for 30 minutes by centrifugation, and then the supernatant was bound to SP-Sepharose column (Amersham Bioscience) with buffer (20 mM MES, 10 mM NaCl, pH 6.0), and then 0 to Elution was carried out using a 1 M NaCl gradient, followed by electrophoresis on SDS-PAGE gel to obtain a deformylase protein. Subsequently, the obtained deformillase protein was concentrated, then diluted 10-fold again with a buffer solution (20 mM Tris, 10 mM NaCl, pH 8.5), bound to a Q-Sepharose column (Amersham Bioscience), and then 0 to 1 Deformillase protein was eluted using the M NaCl concentration gradient. The eluted deformillase protein was dialyzed with buffer (20 mM Tris, 0.5 M NaCl, 5 mM imidazole, pH 8.0) and injected into a Talon cobalt affinity column (Pharmacia). The column was sufficiently washed with buffer (20 mM Tris, 10 mM NaCl, pH 8.5), eluted using a 0 to 0.5 M imidazole concentration gradient, and electrophoresed on an SDS-PAGE gel to obtain a deformylase protein. Subsequently, PDF enzyme inhibitory activity was measured by a binding assay with formic acid dehydrogenase (FDH) (Lazennec et al., Anal. Biochem. 244, 1808 (1997)).

구체적으로는, 완충용액(50 mM HEPES, pH 7.2), 10 mM NaCl 및 0.2 mg/ml BSA를 혼합한 용액에 기질로서 1 mM 포밀메티오닐루이실-p-니트로아닐라이드, 1 mM NAD 및 FDH 0.2 단위/ml를 첨가하였다. 여기에, 상기에서 얻어진 디포밀라제 단백질을 10 nM 첨가하고 상온에서 반응시킨 후 UV-분광광도계를 이용하여 340 nm의 파장에서 NADH의 흡광도를 측정하였다. 이어서, 효소저해제로서 상기 실시예에서 제조된 화합물들을 12.5 mM 농도로 DMSO에 용해시켜 전체 반응액의 5% 이내로 첨가하고, 효소 저해 활성을 측정하였다. 이 때, 효소 저해 활성은 시험 화합물이 없는 상태에서의 NADH 증가 정도에 대한, 시험 화합물에 의한 NADH 증가 정도를 백분율로 표시하고 50%의 효소 활성을 저해하는 시험 화합물의 농도를 IC50으로 결정하였다. 비교군으로서 대표적인 PDF 저해제인 액티노닌(actinonin)을 이용하여 동일한 시험을 반복하였으며, 상기 시험 결과는 하기 표 1에 나타내었다. Specifically, 1 mM formylmethionyl ylsilyl-p-nitroanilide, 1 mM NAD and FDH as a substrate in a solution mixed with a buffer solution (50 mM HEPES, pH 7.2), 10 mM NaCl and 0.2 mg / ml BSA. 0.2 units / ml was added. Here, 10 nM of the obtained deformillase protein was added thereto and reacted at room temperature, and then the absorbance of NADH was measured at a wavelength of 340 nm using a UV-spectrophotometer. Subsequently, the compounds prepared in the above examples as enzyme inhibitors were dissolved in DMSO at a concentration of 12.5 mM, added within 5% of the total reaction solution, and enzyme inhibitory activity was measured. At this time, the enzyme inhibitory activity was expressed as a percentage of the NADH increase by the test compound with respect to the NADH increase in the absence of the test compound, and the concentration of the test compound that inhibited the enzyme activity of 50% was determined as IC 50 . . As a comparison group, the same test was repeated using a typical PDF inhibitor, actinonin, and the test results are shown in Table 1 below.

Figure 112005013060010-PAT00091
Figure 112005013060010-PAT00091

상기 표 1로부터, 본 발명에 따른 화학식 1의 화합물들이 매우 우수한 PDF 저해활성을 나타냄을 알 수 있다.From Table 1, it can be seen that the compounds of the formula 1 according to the present invention shows very good PDF inhibitory activity.

상기에서 살펴본 바와 같이, 본 발명의 화학식 1의 화합물들은 박테리아의 증식에 반드시 필요한 효소인 펩타이드 디포밀라제의 활성을 효과적으로 억제하므로 다양한 박테리아에 의한 여러 가지 감염증상 치료에 유용하게 사용될 수 있다.As described above, the compounds of Formula 1 of the present invention effectively inhibit the activity of peptide deformillase, an enzyme necessary for the growth of bacteria, and thus may be useful for treating various infections caused by various bacteria.

Claims (12)

하기 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염: A compound of Formula 1 or a pharmaceutically acceptable salt thereof: 화학식 1 Formula 1
Figure 112005013060010-PAT00092
Figure 112005013060010-PAT00092
 상기 식에서, Where n은 0 또는 1이며;n is 0 or 1; X는 수소, 비치환되거나 치환된 C1-C6 알킬, 하이드록시, 또는 할로겐이며;X is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, hydroxy, or halogen; R1은 수소, 비치환되거나 치환된 C1-C6 알킬, 비치환되거나 치환된 C1-C6 알케닐, 또는 헤테로알킬이며;R 1 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkenyl, or heteroalkyl; m은 0 내지 5의 정수이며;m is an integer from 0 to 5; Y는 -NR4, -S-, 또는 -CR2R3이며; Y is -NR 4 , -S-, or -CR 2 R 3 ; R2 및 R3는 각각 독립적으로 H, R4, -OH, -OR4, -SH, -SR4, -NH2, -NHR4, -NR4R5, -C(=O)R4, -C(=O)OR4, -C(=O)SR4, -C(=O)NR4R5, -C(=O)OCHR4R5, -S(=O)2NR4R5, -N(R4)C(=O)R5, -N(R4)C(=O)OR5, -N(R4)S(=O)2R5 또는 -N(R4)S(=O)2OR5 이거나, 서로 결합하여 비치환되거나 치환된 사이클릭 알킬, 헤테로사이클릭 알킬, 방향족, 또는 헤테로방향족 고리를 형성한다(여기에서, R4 및 R5는 각각 독립적으로 수소, 비치환되거나 치환된 C1-C6 알킬(치환기는 할로겐, 알콕시, 아미노, 모노 또는 다이알킬아미노, 하이드록실, 티올, 카르복시, 벤질, 시아노, 니트로 또는 비치환되거나 치환된 페닐(치환기는 할로겐, 알콕시, 아미노, 모노 또는 다이알킬아미노, 하이드록실, 티올, 카르복시, 페닐, 벤질, 시아노, 니트로, 카르복시알데하이드 또는 카르복시아미드임)임), 헤테로알킬, 비치환되거나 치환된 C1-C6 알케닐, 헤테로알케닐, 비치환되거나 치환된 C1-C6 알카이닐, 알콕시, 비치환되거나 치환된 방향족(치환기는 알킬, 알케닐, 알카이닐, 할로겐, 알콕시, 아실옥시, -NH2, 다이알킬 아미노, -OH, -SH, 카복실, 벤질옥시, 페닐, 아릴옥시, 벤질, -CN, -NO2, -CHO 또는 -CONH2임), 또는 비치환되거나 치환된 헤테로방향족(치환기는 알킬, 알케닐, 알카이닐, 할로겐, 알콕시, 아실옥시, -NH2, 다이알킬 아미노, -OH, -SH, 카복실, 벤질옥시, 페닐, 아릴옥시, 벤질, -CN, -NO2, -CHO 또는 -CONH2임)임).R 2 and R 3 are each independently H, R 4 , -OH, -OR 4 , -SH, -SR 4 , -NH 2 , -NHR 4 , -NR 4 R 5 , -C (= O) R 4 , -C (= O) OR 4 , -C (= O) SR 4 , -C (= O) NR 4 R 5 , -C (= O) OCHR 4 R 5 , -S (= O) 2 NR 4 R 5 , -N (R 4 ) C (= O) R 5 , -N (R 4 ) C (= O) OR 5 , -N (R 4 ) S (= O) 2 R 5 or -N (R 4 ) S (= 0) 2 OR 5, or combine with each other to form an unsubstituted or substituted cyclic alkyl, heterocyclic alkyl, aromatic, or heteroaromatic ring, wherein R 4 and R 5 are each independently Hydrogen, unsubstituted or substituted C 1 -C 6 alkyl (substituents are halogen, alkoxy, amino, mono or dialkylamino, hydroxyl, thiol, carboxy, benzyl, cyano, nitro or unsubstituted or substituted phenyl ( Substituents are halogen, alkoxy, amino, mono or dialkylamino, hydroxyl, thiol, carboxy, phenyl, benzyl, cyano, nitro, carboxyaldehyde or carboxyamide), heteroalkyl, Unsubstituted or substituted C 1 -C 6 alkenyl, heteroaryl-alkenyl, unsubstituted or substituted C 1 -C 6 alkynyl, alkoxy, unsubstituted or substituted aromatic (the substituent is alkyl, alkenyl, alkynyl, halogen, Alkoxy, acyloxy, -NH 2 , dialkyl amino, -OH, -SH, carboxyl, benzyloxy, phenyl, aryloxy, benzyl, -CN, -NO 2 , -CHO or -CONH 2 ), or unsubstituted Or substituted heteroaromatics (substituents are alkyl, alkenyl, alkynyl, halogen, alkoxy, acyloxy, -NH 2 , dialkyl amino, -OH, -SH, carboxyl, benzyloxy, phenyl, aryloxy, benzyl,- CN, -NO 2 , -CHO or -CONH 2 ). 제1항에 있어서,The method of claim 1, X가 수소, 하이드록시, 또는 할로겐이며;X is hydrogen, hydroxy, or halogen; R1이 수소, 메틸, 에틸, 뷰틸, 3-메틸뷰틸, 펜틸, 2-사이클로헥실-1-에틸이고;R 1 is hydrogen, methyl, ethyl, butyl, 3-methylbutyl, pentyl, 2-cyclohexyl-1-ethyl; 구조
Figure 112005013060010-PAT00093
이
Figure 112005013060010-PAT00094
(여기에서, p는 1 또는 2이며, R6는 -NH2, -NHR4, -NR4R5, -C(=O)R4, -C(=O)OR4, -C(=O)NR4R5, -C(=O)OCHR4R5, 또는 -N(R4)C(=O)R5 임(여기에서 R4 및 R5는 제1항에서 정의된 바와 같음))인rescue
Figure 112005013060010-PAT00093
this
Figure 112005013060010-PAT00094
Wherein p is 1 or 2, and R 6 is -NH 2 , -NHR 4 , -NR 4 R 5 , -C (= 0) R 4 , -C (= 0) OR 4 , -C (= O) NR 4 R 5 , -C (= 0) OCHR 4 R 5 , or -N (R 4 ) C (= 0) R 5 , wherein R 4 and R 5 are as defined in claim 1 ))sign 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염.A compound of formula 1 or a pharmaceutically acceptable salt thereof. 제2항에 있어서,The method of claim 2, R6가 -C(=O)NHR4 (여기에서 R4는 수소, 비치환되거나 치환된 C1-C6 알킬, 방향족, 또는 헤테로 방향족임) 또는 -C(=O)NR4R5 (여기에서 R4 및 R5는 각각 독립적으로 비치환되거나 치환된 C4-C10 헤테로사이클릭 알킬임)인 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염.R 6 is —C (═O) NHR 4 , wherein R 4 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, aromatic, or heteroaromatic; or —C (═O) NR 4 R 5 ( Wherein R 4 and R 5 are each independently unsubstituted or substituted C 4 -C 10 heterocyclic alkyl) or a pharmaceutically acceptable salt thereof. 제2항에 있어서,The method of claim 2, R6가 페닐아미노카보닐, 나프틸아미노카보닐, 4-페닐-페닐아미노카보닐, 4-페녹시-페닐아미노카보닐, 티아졸리디노-2-일-아미노카보닐, 4-메틸티아졸-2-일-아미노카보닐, 4,5-다이메틸티아졸-2-일-아미노카보닐, 4-페닐티아졸-2-일-아미노카보닐, 4-나프틸티아졸-2-일-아미노카보닐, 벤조티아졸-2-일-아미노카보닐, 6-메틸벤조티 아졸-2-일-아미노카보닐, 5,6-다이메틸벤조티아졸-2-일-아미노카보닐, 6-플루오로벤조티아졸-2-일-아미노카보닐, 6-클로로벤조티아졸-2-일-아미노카보닐, 6-메톡시벤조티아졸-2-일-아미노카보닐, 4-메톡시벤조티아졸-2-일-아미노카보닐, 4-클로로벤조티아졸-2-일-아미노카보닐, 4-사이클로헥실벤조티아졸-2-일-아미노카보닐, 4-(1-피페리딘일)벤조티아졸-2-일-아미노카보닐, 4-(1-모폴리닐)벤조티아졸-2-일-아미노카보닐, 2-머캅토에틸티오다이아졸-5-일, 4-페닐피페리딘-1-일-아미노카보닐, 3-(다이메틸아미노)피롤리딘-1-일-아미노카보닐, 4-메틸피페라진-1-일, 4-모폴리노에틸아미노카보닐, 4-벤질피페라진-1-일-아미노카보닐 또는 피페라진-1-일인 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염.R 6 is phenylaminocarbonyl, naphthylaminocarbonyl, 4-phenyl-phenylaminocarbonyl, 4-phenoxy-phenylaminocarbonyl, thiazolidino-2-yl-aminocarbonyl, 4-methylthiazole 2-yl-aminocarbonyl, 4,5-dimethylthiazol-2-yl-aminocarbonyl, 4-phenylthiazol-2-yl-aminocarbonyl, 4-naphthylthiazol-2-yl -Aminocarbonyl, benzothiazol-2-yl-aminocarbonyl, 6-methylbenzothiazol-2-yl-aminocarbonyl, 5,6-dimethylbenzothiazol-2-yl-aminocarbonyl, 6-fluorobenzothiazol-2-yl-aminocarbonyl, 6-chlorobenzothiazol-2-yl-aminocarbonyl, 6-methoxybenzothiazol-2-yl-aminocarbonyl, 4-meth Methoxybenzothiazol-2-yl-aminocarbonyl, 4-chlorobenzothiazol-2-yl-aminocarbonyl, 4-cyclohexylbenzothiazol-2-yl-aminocarbonyl, 4- (1-py Ferridinyl) benzothiazol-2-yl-aminocarbonyl, 4- (1-morpholinyl) benzothiazol-2-yl-aminocarbonyl, 2-mercaptoethylthioda Azol-5-yl, 4-phenylpiperidin-1-yl-aminocarbonyl, 3- (dimethylamino) pyrrolidin-1-yl-aminocarbonyl, 4-methylpiperazin-1-yl, A compound of formula 1 or a pharmaceutically acceptable salt thereof, which is 4-morpholinoethylaminocarbonyl, 4-benzylpiperazin-1-yl-aminocarbonyl or piperazin-1-yl. 제1항에 있어서,The method of claim 1, X가 수소, 하이드록시, 또는 할로겐이며;X is hydrogen, hydroxy, or halogen; R1이 수소, 메틸, 에틸, 뷰틸, 3-메틸뷰틸, 펜틸, 2-사이클로헥실-1-에틸이고;R 1 is hydrogen, methyl, ethyl, butyl, 3-methylbutyl, pentyl, 2-cyclohexyl-1-ethyl; 구조
Figure 112005013060010-PAT00095
이
Figure 112005013060010-PAT00096
(여기에서, p는 1 또는 2이며, R7은 -NH2, -NHR4, -NR4R5, -C(=O)R4, -C(=O)OR4, -C(=O)NR4R5, -C(=O)OCHR4R5, 또는 -N(R4)C(=O)R5 임(여기에서 R4 및 R5는 상기에서 정의된 바와 같음))인rescue
Figure 112005013060010-PAT00095
this
Figure 112005013060010-PAT00096
Wherein p is 1 or 2, and R 7 is -NH 2 , -NHR 4 , -NR 4 R 5 , -C (= 0) R 4 , -C (= 0) OR 4 , -C (= O) NR 4 R 5 , -C (= 0) OCHR 4 R 5 , or -N (R 4 ) C (= 0) R 5 , wherein R 4 and R 5 are as defined above sign 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염. A compound of formula 1 or a pharmaceutically acceptable salt thereof. 제5항에 있어서,The method of claim 5, R7이 아미노 또는 -N(R4)C(=O)R5 (여기에서 R4, R5는 각각 수소, 비치환되거나 치환된 C1-C6 알킬, 방향족, 헤테로 방향족임)인 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염. R 7 is amino or —N (R 4 ) C (═O) R 5 , wherein R 4 , R 5 are each hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, aromatic, heteroaromatic 1 or a pharmaceutically acceptable salt thereof. 제5항에 있어서,The method of claim 5, R7이 아미노, t-뷰틸카바모일, 4-바이페닐-1-카복사미딜, 4-플루오로페닐-1-카복사미딜, 4-t-뷰틸페닐-1-카복사미딜, 4-메톡시페닐-1-카복사미딜, 벤즈이미다졸-4-카복사미딜, 3-하이드록시페닐-1-카복사미딜, 나프토일-2-카복사미딜, 3-하이드록시페닐아세타미딜, 또는 4-페닐페닐아세타미딜인 화학식 1의 화합물 또는 약학적으로 허용되는 그의 염. R 7 is amino, t-butylcarbamoyl, 4-biphenyl-1-carboxamidyl, 4-fluorophenyl-1-carboxamidyl, 4-t-butylphenyl-1-carboxamidyl, 4-meth Oxyphenyl-1-carboxamidyl, benzimidazole-4-carboxamidyl, 3-hydroxyphenyl-1-carboxamidyl, naphthoyl-2-carboxamidyl, 3-hydroxyphenylacetamidyl, or A compound of formula (I) or a pharmaceutically acceptable salt thereof, which is 4-phenylphenylacetamyl. 제 1 항에 있어서,The method of claim 1, 하기 화합물들로 구성된 군으로부터 선택되는 것을 특징으로 하는 화합물 또는 이의 약학적으로 허용되는 염:A compound or a pharmaceutically acceptable salt thereof, characterized in that it is selected from the group consisting of: 2-[뷰틸-(피페리딘-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (piperidine-1-sulfonyl) -amino] -N-hydroxy-acetamide; 2-[뷰틸-(모포린-4-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (morpholin-4-sulfonyl) -amino] -N-hydroxy-acetamide; 2-[뷰틸-(4-메틸-피페라진-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (4-methyl-piperazin-1-sulfonyl) -amino] -N-hydroxy-acetamide; 2-[(4-벤질-피페라진-1-설포닐)-뷰틸-아미노]-N-하이드록시-아세트아마이드;2-[(4-benzyl-piperazine-1-sulfonyl) -butyl-amino] -N-hydroxy-acetamide; 2-[뷰틸-(다이사이클로헥실 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (dicyclohexyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide; 2-[뷰틸-(다이벤질 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [butyl- (dibenzyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide; N-하이드록시-2-[(2-옥소-옥사졸리딘-3-설포닐)-펜틸-아미노]-아세트아마이드;N-hydroxy-2-[(2-oxo-oxazolidine-3-sulfonyl) -pentyl-amino] -acetamide; 2-[펜틸-(다이벤질 아민-1-설포닐)-아미노]-N-하이드록시-아세트아마이드;2- [pentyl- (dibenzyl amine-1-sulfonyl) -amino] -N-hydroxy-acetamide; 3-[뷰틸-(2-옥소-옥사졸리딘-3-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (2-oxo-oxazolidine-3-sulfonyl) -amino] -N-hydroxy-propionamide; 3-[뷰틸-(피페리딘-1-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (piperidine-1-sulfonyl) -amino] -N-hydroxy-propionamide; 3-[뷰틸-(모포린-4-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (morpholin-4-sulfonyl) -amino] -N-hydroxy-propionamide; 3-[뷰틸-(4-메틸-피페라진-1-설포닐)-아미노]-N-하이드록시-프로피온아마이드;3- [butyl- (4-methyl-piperazin-1-sulfonyl) -amino] -N-hydroxy-propionamide; 3-[(4-벤질-피페라진-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(4-benzyl-piperazine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide; 3-[(다이사이클로헥실 아민-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(dicyclohexyl amine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide; 3-[(다이벤질 아민-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(dibenzyl amine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide; [1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-카밤산 tert-뷰틸 에스터;[1- (Butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester; 2-[(3-아미노-피롤리딘-1-설포닐)-뷰틸-아미노]-N-하이드록시-아세트아마이드;2-[(3-amino-pyrrolidine-1-sulfonyl) -butyl-amino] -N-hydroxy-acetamide; 바이페닐-4-카복실산 [1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-아마이드;Biphenyl-4-carboxylic acid [1- (butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -amide; N-[1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-4-플루오로-벤즈아마이드;N- [1- (Butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -4-fluoro-benzamide; 4-tert-뷰틸-N-[1-(뷰틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-벤즈아마이드;4-tert-Butyl-N- [1- (butyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -benzamide; 바이페닐-4-카복실산 [1-(펜틸-하이드록시카바모일메틸-설파모일)-피롤리딘-3-일]-아마이드;Biphenyl-4-carboxylic acid [1- (pentyl-hydroxycarbamoylmethyl-sulfamoyl) -pyrrolidin-3-yl] -amide; N-[1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-4-메톡시-벤즈아마이드;N- [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -4-methoxy-benzamide; 1H-벤조이미다졸-5-카복실산 [1-(하이드록시카바모일 메틸-펜틸-설파모일)-피롤리딘-3-일]-아마이드;1H-benzoimidazole-5-carboxylic acid [1- (hydroxycarbamoyl methyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -amide; 3-하이드록시-N-[1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-벤즈아마이드;3-hydroxy-N- [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -benzamide; 나프탈렌-2-카복실산 [1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-3-일]-아마이드;Naphthalene-2-carboxylic acid [1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidin-3-yl] -amide; N-하이드록시-2-({3-[2-(3-하이드록시-페닐)-아세틸아미노]-피롤리딘-1-설포닐}-펜틸-아미노)-아세트아마이드;N-hydroxy-2-({3- [2- (3-hydroxy-phenyl) -acetylamino] -pyrrolidine-1-sulfonyl} -pentyl-amino) -acetamide; 2-{[3-(2-바이페닐-4-일-아세틸아미노)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드;2-{[3- (2-biphenyl-4-yl-acetylamino) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide; {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-카밤산 tert-뷰틸 에스터;{1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -carbamic acid tert-butyl ester; 3-[(3-아미노-피롤리딘-1-설포닐)-뷰틸-아미노]-N-하이드록시-프로피온아마이드;3-[(3-amino-pyrrolidine-1-sulfonyl) -butyl-amino] -N-hydroxy-propionamide; 바이페닐-4-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘- 3-일}-아마이드;Biphenyl-4-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin- 3-yl} -amide; N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-4-플루오로-벤즈아마이드;N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -4-fluoro-benzamide; 4-tert-뷰틸-N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-벤즈아마이드;4-tert-Butyl-N- {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -benzamide; N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-4-메톡시-벤즈아마이드;N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -4-methoxy-benzamide; 1H-벤조이미다졸-5-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드;1 H-benzoimidazole-5-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide; N-{1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-3-하이드록시-벤즈아마이드;N- {1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -3-hydroxy-benzamide; 나프탈렌-2-카복실산 {1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-3-일}-아마이드;Naphthalene-2-carboxylic acid {1- [butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidin-3-yl} -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 페닐아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid phenylamide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 나프탈렌-2-일아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid naphthalen-2-ylamide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 바이페닐-4-일아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid biphenyl-4-ylamide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-페녹시-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-phenoxy-phenyl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4,5-다이하이드로-티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4,5-dihydro-thiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-메틸-티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-methyl-thiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4,5-다이메틸-티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4,5-dimethyl-thiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-페닐-티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-phenyl-thiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-나프탈렌-2-일-티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-naphthalen-2-yl-thiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 벤조티아졸-2-일아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid benzothiazol-2-ylamide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-메틸-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-methyl-benzothiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (5,6-다이메틸-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (5,6-dimethyl-benzothiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-플루오로-벤조티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-fluoro-benzothiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-클로로-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-chloro-benzothiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (6-메톡시-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (6-methoxy-benzothiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-메톡시-벤조티아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-methoxy-benzothiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-클로로-벤조티아졸-2-일)-아마이드;1- (hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-chloro-benzothiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-사이클로헥실-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-cyclohexyl-phenyl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-피페리딘-1-일-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-piperidin-1-yl-phenyl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (4-모포린-4-일-페닐)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (4-morpholin-4-yl-phenyl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (5-에틸설파닐-[1,3,4]티아다이아졸-2-일)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (5-ethylsulfanyl- [1,3,4] thiadiazol-2-yl) -amide; 1-(하이드록시카바모일메틸-펜틸-설파모일)-피롤리딘-2-카복실산 (2-모포린-4-일-에틸)-아마이드;1- (Hydroxycarbamoylmethyl-pentyl-sulfamoyl) -pyrrolidine-2-carboxylic acid (2-morpholin-4-yl-ethyl) -amide; 2-{[2-(3-다이에틸아미노-피롤리딘-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드;2-{[2- (3-Diethylamino-pyrrolidine-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide; N-하이드록시-2-{[2-(4-메틸-피페라진-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-아세트아마이드;N-hydroxy-2-{[2- (4-methyl-piperazin-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -acetamide; N-하이드록시-2-{펜틸-[2-(4-페닐-피페라진-1-카보닐)-피롤리딘-1-설포닐]-아미노}-아세트아마이드;N-hydroxy-2- {pentyl- [2- (4-phenyl-piperazine-1-carbonyl) -pyrrolidine-1-sulfonyl] -amino} -acetamide; 2-{[2-(4-벤질-피페라진-1-카보닐)-피롤리딘-1-설포닐]-펜틸-아미노}-N-하이드록시-아세트아마이드;2-{[2- (4-benzyl-piperazine-1-carbonyl) -pyrrolidine-1-sulfonyl] -pentyl-amino} -N-hydroxy-acetamide; N-하이드록시-2-{펜틸-[2-(피페라진-1-카보닐)-피롤리딘-1-설포닐]-아미노}-아세트아마이드;N-hydroxy-2- {pentyl- [2- (piperazin-1-carbonyl) -pyrrolidine-1-sulfonyl] -amino} -acetamide; 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-메틸-티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-methyl-thiazol-2-yl) -amide; 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4,5-다이메틸-티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4,5-dimethyl-thiazol-2-yl) -amide; 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-페닐-티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-phenyl-thiazol-2-yl) -amide; 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (6-플루오로-벤조티아졸-2-일)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (6-fluoro-benzothiazol-2-yl) -amide; 1-[하이드록시카바모일메틸-(3-메틸-뷰틸)-설파모일]-피롤리딘-2-카복실산 (4-사이클로헥실-페닐)-아마이드;1- [hydroxycarbamoylmethyl- (3-methyl-butyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-cyclohexyl-phenyl) -amide; 1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 나프탈렌-2-일아마이드;1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid naphthalen-2-ylamide; 1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 바이페닐-4-일아마이드; 및1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid biphenyl-4-ylamide; And 1-[뷰틸-(2-하이드록시카바모일-에틸)-설파모일]-피롤리딘-2-카복실산 (4-페녹시-페닐)-아마이드.1- [Butyl- (2-hydroxycarbamoyl-ethyl) -sulfamoyl] -pyrrolidine-2-carboxylic acid (4-phenoxy-phenyl) -amide. 하기 단계들을 포함하는, 제1항의 화학식 1의 화합물의 제조 방법:A process for preparing the compound of formula 1 of claim 1 comprising the following steps: 1) 클로로설포닐 아이소사이아네이트와 2-브로모에탄올을 반응시켜 2-옥소-옥사졸리딘-3-설포닐 클로라이드를 합성하고, 동일 용기내에서(in-situ) 아민 알킬 에스터를 반응시켜 화학식 2의 화합물을 얻는 단계;1) by reacting chlorosulfonyl isocyanate and 2-bromoethanol to synthesize 2-oxo-oxazolidine-3-sulfonyl chloride, and reacting the amine alkyl ester in the same vessel ( in-situ ) Obtaining a compound of Formula 2; 2) 화학식 2의 화합물을 아민 유도체와 반응시켜 화학식 3의 화합물을 합성하는 단계;2) reacting a compound of Formula 2 with an amine derivative to synthesize a compound of Formula 3; 3) 화학식 3의 화합물을 알킬 브로마이드와 반응시켜 화학식 4의 화합물을 합성하는 단계;3) synthesizing the compound of formula 4 by reacting the compound of formula 3 with alkyl bromide; 4) 화학식 4의 화합물을 수산화리튬으로 가수분해하여 화학식 5의 화합물을 합성하는 단계; 및4) synthesizing the compound of Formula 5 by hydrolyzing the compound of Formula 4 with lithium hydroxide; And 5) 화학식 5의 화합물에 O-벤질하이드록실아민을 결합시킨 후에 Pd/C와 수소를 이용하여 벤질기를 제거하여 화학식 1의 화합물을 합성하는 단계. 5) synthesizing the compound of Formula 1 by combining O-benzylhydroxylamine with the compound of Formula 5 and then removing the benzyl group using Pd / C and hydrogen. 화학식 1Formula 1
Figure 112005013060010-PAT00097
Figure 112005013060010-PAT00097
 화학식 2Formula 2
Figure 112005013060010-PAT00098
Figure 112005013060010-PAT00098
 화학식 3Formula 3
Figure 112005013060010-PAT00099
Figure 112005013060010-PAT00099
 화학식 4Formula 4
Figure 112005013060010-PAT00100
Figure 112005013060010-PAT00100
 화학식 5Formula 5
Figure 112005013060010-PAT00101
Figure 112005013060010-PAT00101
 활성성분으로서 제1항의 화학식 1의 화합물 또는 이의 약학적으로 허용가능한 염을 포함하는, 펩타이드 디포밀라제 활성 저해용 조성물.A composition for inhibiting peptide deformillase activity, comprising the compound of formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. 제10항에 있어서,The method of claim 10, 박테리아에 의한 감염증 치료에 사용되는 것을 특징으로 하는 약학 조성물.A pharmaceutical composition, which is used for the treatment of infection by bacteria. 제11항에 있어서,The method of claim 11, 박테리아가 그람 양성균, 그람 음성균, 호기성 또는 혐기성 박테리아, 스타필로코키(Staphylococci)균, 엔테로코키(Enterococci)균, 스트렙토코키(Streptococci)균, 하에모필러스(Haemophilus)균, 모락셀라(Moraxella)균, 에스케리키아(Escherichia)균, 및 마이코박테리아(Mycobacteria) 균 중에서 선택된 1종 이상임을 특징으로 하는 조성물.-Positive bacteria to Gram, gram-negative, aerobic or anaerobic bacteria, Staphylococcus Koki (Staphylococci) bacteria, Enterobacter Koki (Enterococci) bacteria, Streptococcus Koki (Streptococci) microorganisms, under a brush Russ (Haemophilus) bacteria, morak Cellar (Moraxella) bacteria, the composition as claimed Escherichia (Escherichia) bacteria and mycobacteria (mycobacteria) at least one selected from bacteria.
KR1020050020646A 2005-03-11 2005-03-11 Compounds inhibiting peptide deformylase, method for the preparation thereof and pharmaceutical composition containing same KR20060099287A (en)

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