公开(公告)号：KR1020110048337A

公开(公告)日：2011-05-11

申请号：KR1020090105097

申请日：2009-11-02

Applicant: 한국화학연구원

Inventor： 정희정 ,  이철해 ,  김재학 ,  정원장 ,  김비치 ,  박선필

IPC: C07C239/14 ,  C07C231/14 ,  A61K31/165 ,  A61P35/00

Abstract: PURPOSE: A 6-amino-N-hydroxyhexanamide compound is provided to ensure strong cell proliferation inhibitory power by inhibiting enzyme activity of histone deacetylase, thereby enabling use as anti-cancer drug or enzyme activity inhibitory agent of histone deacetylase. CONSTITUTION: A compound is selected from a 6-amido-N-hydroxyhexanamide compound represented by chemical formula 1 and pharmaceutically acceptable salts thereof. In chemical formula 1, X is a single bond or selected from the group of C1-6 alkylenyl; and R is hydroxy, C3-8 cycloalkyl, C3-8 cycloalkenyl, C1-6 alkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, 5-7-membered aryl, 5-7-membered heteroaryl including 1-3 hetero atoms selected from N and O, and 5-7-membered heterocycloalkyl including 1-3 hetero atoms selected from N and O.

Abstract translation: 目的：提供6-氨基-N-羟基己酰胺化合物，以通过抑制组蛋白脱乙酰酶的酶活性来确保强的细胞增殖抑制能力，从而可用作组蛋白脱乙酰酶的抗癌药物或酶活性抑制剂。 构成：化合物选自由化学式1表示的6-氨基-N-羟基己酰胺化合物及其药学上可接受的盐。 在化学式1中，X是单键或选自C 1-6亚烷基; 和R为羟基，C 3-8环烷基，C 3-8环烯基，C 1-6烷氧基，氨基，C 1-6烷基氨基，二（C 1-6烷基）氨基，5-7元芳基，5-7元杂芳基，包括 1-3个选自N和O的杂原子和包含1-3个选自N和O的杂原子的5-7元杂环烷基。

公开(公告)号：KR100820039B1

公开(公告)日：2008-04-07

申请号：KR1020060109436

申请日：2006-11-07

Applicant: 한국화학연구원 ,  크리스탈지노믹스(주)

Inventor： 이철해 ,  정희정 ,  김재학 ,  정원장 ,  조중명 ,  노성구 ,  현영란 ,  이철순

IPC: C07C233/22 ,  C07C233/21 ,  C07C217/16

Abstract: An alkylamino naphthalenyloxymethyl propenyl hydroxybenzamide derivative is provided to obtain a pharmaceutical composition having an anti-cancer effect by inhibiting activity of histone deacetylase, inducing differentiation of tumor cells and inhibiting growth of tumor cells. An alkylamino naphthalenyloxymethyl propenyl hydroxybenzamide derivative is represented by the following formula 1. In formula 1, R1 is H or a C1-C3 alkyl; R2 is a C1-C6 alkyl non-substituted or substituted with a substituent selected from the group consisting of di-C1-C3 alkylamino, C1-C4 alkylpyrrolidinyl, morpholinyl, imidazolyl, methoxy and thiophenyl, a C1-C6 alkyl substituted with hydroxyphenyl, di-C1-C3 alkylaminophenyl, methoxyphenyl or trifluoromethoxyphenyl, pyrrolidine non-substituted or substituted with C1-C3 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl C1-C3 alkyl, benzyl or C3-C8 cycloalkylcarbonyl, piperidine substituted with a C3-C8 cycloalkyl or C1-C6 alkyl, or a C3-C8 cycloalkyl, with the proviso that when R1 is H or CH3, R2 is not non-substituted C1-C2 alkyl and morpholinyl-substituted C1-C2 alkyl.

Abstract translation: 提供烷基氨基萘氧基甲基丙烯基羟基苯甲酰胺衍生物，通过抑制组蛋白脱乙酰酶的活性，诱导肿瘤细胞的分化和抑制肿瘤细胞的生长来获得具有抗癌作用的药物组合物。 烷基氨基萘氧基甲基丙烯基羟基苯甲酰胺衍生物由下式1表示。在式1中，R 1为H或C 1 -C 3烷基; R2是未取代或被选自二C1-C3烷基氨基，C1-C4烷基吡咯烷基，吗啉基，咪唑基，甲氧基和噻吩基的取代基取代的C1-C6烷基，被羟基苯基取代的C1-C6烷基， 二-C 1 -C 3烷基氨基苯基，甲氧基苯基或三氟甲氧基苯基，未被取代或被C 1 -C 3烷基，C 3 -C 8环烷基，C 3 -C 8环烷基C 1 -C 3烷基，苄基或C 3 -C 8环烷基羰基取代的吡咯烷， C8环烷基或C1-C6烷基，或C3-C8环烷基，条件是当R 1为H或CH 3时，R 2不是未取代的C 1 -C 2烷基和吗啉基取代的C 1 -C 2烷基。

公开(公告)号：KR100814092B1

公开(公告)日：2008-03-14

申请号：KR1020060108230

申请日：2006-11-03

Applicant: 한국화학연구원 ,  크리스탈지노믹스(주)

Inventor： 이철해 ,  정희정 ,  김재학 ,  정원장 ,  조중명 ,  노성구 ,  현영란 ,  이철순

IPC: C07C235/18 ,  C07C235/10 ,  C07C233/05

Abstract: An alkylcarbamoyl naphthalenyloxy octenoyl hydroxyamide derivative, its pharmaceutically acceptable salt, a method for preparing the derivative, and an anticancer pharmaceutical composition containing the derivative or the salt are provided to inhibit the enzymatic activity of histone deacetylase effectively and to suppress the proliferation of tumor cells. An alkylcarbamoyl naphthalenyloxy octenoyl hydroxyamide derivative is represented by the formula 1, wherein R1 is a C1-C3 alkyl group substituted or unsubstituted with at least one substituent selected from the group consisting of a halophenyl group, a C1-C3 alkoxy C1-C3 alkyl group, a cyclohexanyl group, a furanyl group, a thiophenyl group, an imidazole group, an imidazolidyl C1-C3 alkyl group, a C1-C3 alkylamino group, a di-C1-C3 alkylamino group, a hydroxyphenyl group, a tetrahydrofuranyl group, a cyclohexyl group, a cyclohexenyl group, an oxopyrrolidinyl group, an alkoxyphenyl group, a di-C1-C3 alkylaminophenyl group, a C1-C3 alkylpyrrolidinyl group and a trifluoromethoxyphenyl group; a pyrrolidine group substituted or unsubstituted with at least one substituent selected from the group consisting of a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl C1-C3 alkyl group, a benzyl group, a C1-C3 alkyl group or a C3-C8 cycloalkylcarbonyl group; a piperidine group substituted with a C1-C3 alkyl group or a C3-C8 cycloalkyl group; a furan group; or a C3-C8 cycloalkyl group.

Abstract translation: 提供烷基氨基甲酰基萘氧基辛烯酰羟基酰胺衍生物，其药学上可接受的盐，制备该衍生物的方法和含有该衍生物或其盐的抗癌药物组合物，以有效抑制组蛋白脱乙酰酶的酶活性并抑制肿瘤细胞的增殖。 烷基氨基甲酰基萘氧基辛烯酰羟基酰胺衍生物由式1表示，其中R1是被至少一个选自卤代苯基，C1-C3烷氧基C1-C3烷基的取代基取代或未取代的C1-C3烷基 环己烷基，呋喃基，噻吩基，咪唑基，咪唑烷基C1-C3烷基，C1-C3烷基氨基，二C1-C3烷基氨基，羟基苯基，四氢呋喃基， 环己基，环己烯基，氧代吡咯烷基，烷氧基苯基，二-C1-C3烷基氨基苯基，C1-C3烷基吡咯烷基和三氟甲氧基苯基; 用至少一个选自C 3 -C 8环烷基，C 3 -C 8环烷基C 1 -C 3烷基，苄基，C 1 -C 3烷基或C 3 -C 8的取代基取代或未取代的吡咯烷基 环烷基羰基; 被C1-C3烷基或C3-C8环烷基取代的哌啶基; 一个呋喃组; 或C 3 -C 8环烷基。

公开(公告)号：KR100446432B1

公开(公告)日：2004-08-30

申请号：KR1020010048742

申请日：2001-08-13

Applicant: 한국화학연구원

Inventor： 김봉진 ,  이철해 ,  정원장 ,  정희정 ,  김재학 ,  편도규

IPC: C07D417/14

CPC classification number: Y02P20/55

Abstract: PURPOSE: Provided are 2-benzothiazole carbapenem derivatives represented by the formula 1, a preparation method thereof and the composition containing the same. The composition has an excellent antibiotic property and is effective against resistant bacteria such as methicillin resistant Staphylococcus Aureus, MRSA and ofloxacin resistant Staphylococcus Aureus(QRSA). CONSTITUTION: In the carbapenem derivatives represented by the formula 1, M is hydrogen or a pair ion forming pharmaceutically allowed salts. The synthetic rout comprises reacting a compound of the formula 2 with a compound of the formula 3 to make a compound of the formula 4, and eliminating the carboxy protecting group from it. In the formula 4, R1 is a hydroxy protecting group such as tert-butyl silyl or triethylsilyl group; R2 is a carboxy protecting group such as p-nitrobenzyl, aryl or p-methoxybenzyl; R3 is an amine protecting group such as aryloxy carbonyl or p-nitrobenzyloxy carbonyl.

Abstract translation: 目的：提供由式1表示的2-苯并噻唑碳青霉烯衍生物，其制备方法和含有其的组合物。 该组合物具有优异的抗生素性质，并且对抵抗性细菌例如耐甲氧西林金黄色葡萄球菌，MRSA和耐氧氟沙星金黄色葡萄球菌（QRSA）是有效的。 构成：在由式1表示的碳代青霉烯衍生物中，M为氢或形成药学允许盐的一对离子。 合成路线包括将式2的化合物与式3的化合物反应以制备式4的化合物，并从其中除去羧基保护基。 式4中，R 1为羟基保护基，例如叔丁基甲硅烷基或三乙基甲硅烷基; R2是羧基保护基，如对硝基苄基，芳基或对甲氧基苄基; R3是胺保护基团，如芳氧基羰基或对硝基苄氧基羰基。

公开(公告)号：KR100385364B1

公开(公告)日：2003-05-27

申请号：KR1020020052421

申请日：2002-09-02

Applicant: 동화약품주식회사 ,  한국화학연구원

Inventor： 이철해 ,  김봉진 ,  정원장 ,  김재학 ,  정희정 ,  김은정 ,  송신섭 ,  정용호 ,  곽현정 ,  이진수 ,  편도규

IPC: C07D265/22

Abstract: PURPOSE: Provided are azetidinone compound of the formula(I) as an intermediate useful for the manufacture of carbapenem antibiotics and a process for the preparation thereof. CONSTITUTION: The azetidine compound is represented by the formula(I). It is useful as an intermediate for the manufacture of beta-methylcarbapenem antibiotics and manufactured by reacting 4-acetoxy-azetidine compound of the formula(II) and alpha-halo propionic acid amide compound of the formula(III).

Abstract translation: 目的：提供式（I）的氮杂环丁酮化合物作为可用于制备碳青霉烯类抗生素的中间体及其制备方法。 构成：氮杂环丁烷化合物由式（I）表示。 它可用作制备β-甲基碳青霉烯类抗生素的中间体，并通过使式（II）的4-乙酰氧基 - 氮杂环丁烷化合物与式（III）的α-卤代丙酰胺化合物反应制备。

公开(公告)号：KR100814100B1

公开(公告)日：2008-03-14

申请号：KR1020060108182

申请日：2006-11-03

Applicant: 한국화학연구원 ,  크리스탈지노믹스(주)

Inventor： 이철해 ,  정희정 ,  김재학 ,  정원장 ,  조중명 ,  노성구 ,  현영란 ,  이철순

IPC: C07C237/30 ,  C07C235/10 ,  C07C235/18

Abstract: An alkylcarbamoyl naphthaleneoxypropenyl hydroxybenzamide derivative, its pharmaceutically acceptable salt, a method for preparing the derivative, and an anticancer pharmaceutical composition containing the derivative are provided to inhibit effectively the enzymatic activity of histone deacetylase and to suppress the proliferation of tumor cells. An alkylcarbamoyl naphthaleneoxypropenyl hydroxybenzamide derivative is represented by the formula 1, wherein R1 is H; and R2 is a C1-C6 alkyl group substituted or unsubstituted with at least one substituent selected from the group consisting of a di-C1-C3 alkylamino group, a pyrrolidinyl group, an oxopyrrolidinyl group, a methoxypyrrolidinyl group, a C1-C3 alkylpiperidinyl group, a morpholinyl group, an imidazolyl group, a methoxy group, an ethoxy group, a tetrahydroxyfuran group, a C3-C8 cycloalkenyl group, a furanyl group and a thiophenyl group, a C1-C6 alkyl group substituted with a fluorophenyl group, a di-C1-C3 alkylaminophenyl group or a methoxyphenyl group, a piperidine group substituted with a C1-C6 alkyl group, or a C3-C8 cycloalkyl group.

Abstract translation: 提供烷基氨基甲酰基萘氧基丙烯基羟基苯甲酰胺衍生物，其药学上可接受的盐，制备该衍生物的方法和含有该衍生物的抗癌药物组合物，以有效地抑制组蛋白脱乙酰酶的酶活性并抑制肿瘤细胞的增殖。 烷基氨基甲酰基萘氧基丙烯基羟基苯甲酰胺衍生物由式1表示，其中R 1是H; 并且R 2是被至少一个选自二-C 1 -C 3烷基氨基，吡咯烷基，氧代吡咯烷基，甲氧基吡咯烷基，C 1 -C 3烷基哌啶基的取代基取代或未取代的C 1 -C 6烷基 ，吗啉基，咪唑基，甲氧基，乙氧基，四羟基呋喃基，C3-C8环烯基，呋喃基和噻吩基，被氟苯基取代的C1-C6烷基，二 -C 1 -C 3烷基氨基苯基或甲氧基苯基，被C 1 -C 6烷基取代的哌啶基或C 3 -C 8环烷基。

公开(公告)号：KR1020020006889A

公开(公告)日：2002-01-26

申请号：KR1020000040396

申请日：2000-07-14

Applicant: 한국화학연구원

Inventor： 이철해 ,  김재학 ,  정희정 ,  편도규 ,  곽현정 ,  송신섭 ,  김은정 ,  김봉진 ,  정원장

IPC: C07D205/08

Abstract: PURPOSE: Provided are 2-arylethenyl carbapenem derivative of the formula(1) and its pharmaceutically acceptable salt which have therapeutic effect in methicillin resistant staphylococcus aureus(MRSA) infection. And its manufacturing method and an antibacterial composition containing it as an active ingredient are also provided. CONSTITUTION: 2-arylethenyl carbapenem derivative is represented by the formula(1), wherein R is halogen, nitro, hydroxy or cyano substituted phenyl or fused aryl group; or halogen or C1-3 alkyl group substituted monocyclic, bicyclic or tricyclic 5 or 6 membered hetero aryl group containing at least one of O, S or N atom; and M is hydrogen or zwitterion forming pharmaceutically acceptable salts.

Abstract translation: 目的：提供式（1）的2-亚乙烯基碳青霉烯衍生物及其药用盐，其在耐甲氧西林金黄色葡萄球菌（MRSA）感染中具有治疗作用。 还提供其制造方法和含有它作为活性成分的抗菌组合物。 构成：2-亚乙烯基碳代青霉烯衍生物由式（1）表示，其中R是卤素，硝基，羟基或氰基取代的苯基或稠合芳基; 或含有O，S或N原子中的至少一个的卤素或C 1-3烷基取代的单环，双环或三环5或6元杂芳基; M是氢或两性离子形成药学上可接受的盐。

公开(公告)号：KR101109122B1

公开(公告)日：2012-06-12

申请号：KR1020090105096

申请日：2009-11-02

Applicant: 한국화학연구원

Inventor： 정희정 ,  이철해 ,  김재학 ,  정원장 ,  김비치 ,  박선필

IPC: C07C239/14 ,  C07C231/14 ,  A61K31/165 ,  A61P35/00

Abstract: PURPOSE: A 6-amido-n-hydroxyhexanamide compound is provided to selectively induce the terminal differentiation of tumor cell by effectively inhibiting enzyme activity of histone deacetylase, and to inhibit the proliferation of tumor cell. CONSTITUTION: A compound is selected from a 6-amido-n-hydroxyhexanamide compound represented by chemical formula 1 and pharmaceutically acceptable salts thereof. In chemical formula 1, X is selected from a single bond or the group of C1-6 alkylenyl; R is amino, C1-6 alkylamino, di(C1-6 alkyl)amino, 5-9-membered aryl, 5-9-membered aryl C1-6 alkyl, 5-9-membered aryl C1-6 alkyloxy, 5-9-membered heteroaryl including 1-3 hetero atoms selected from N and O, and 5-7-membered heterocycloalkyl including 1-3 hetero atoms selected from N and O.

公开(公告)号：KR100814098B1

公开(公告)日：2008-03-14

申请号：KR1020060108228

申请日：2006-11-03

Applicant: 한국화학연구원 ,  크리스탈지노믹스(주)

Inventor： 이철해 ,  정희정 ,  김재학 ,  정원장 ,  조중명 ,  노성구 ,  현영란 ,  이철순

IPC: C07C237/16 ,  C07C237/14 ,  C07C233/19

Abstract: An alkylcarbamoyl naphthalenyloxy methyloct N-hydroxyenamide derivative, its pharmaceutically acceptable salt, a method for preparing the derivative, and an anticancer pharmaceutical composition containing the derivative are provided to inhibit the enzymatic activity of histone deacetylase effectively and the proliferation of tumor cells. An alkylcarbamoyl naphthalenyloxy methyloct N-hydroxyenamide derivative is represented by the formula 1, wherein R1 is a C1-C3 alkyl group substituted or unsubstituted with at least one substituent selected from the group consisting of a C1-C3 alkyl group, a C1-C3 alkoxy group, a hydroxy C1-C3 alkyl group, a halophenyl group, a piperidinyl group, a morpholinyl group, a cyanomethyl group, a piperazinyl group, a di-C1-C3 alkylamino group, a di-C1-C3 alkylamino C1-C3 alkyl group, a piperidinyl C1-C3 alkyl group, a C1-C3 alkoxy C1-C3 alkyl group, a morpholino C1-C3 alkyl group, a piperazino C1-C3 alkyl group, a pyrrolidinyl group, an oxopyrrolidinyl group, a C1-C3 alkylpyrrolidinyl group, an imidazole group, an imidazolyl C1-C3 alkyl group and a thiophenyl group.

Abstract translation: 提供烷基氨基甲酰基萘氧基甲基N-羟基酰胺衍生物，其药学上可接受的盐，制备该衍生物的方法和含有该衍生物的抗癌药物组合物，以有效抑制组蛋白脱乙酰酶的酶活性和肿瘤细胞的增殖。 烷基氨基甲酰基萘氧基甲基N-羟基酰胺衍生物由式1表示，其中R 1是被至少一个选自C 1 -C 3烷基，C 1 -C 3烷氧基的取代基取代或未取代的C 1 -C 3烷基 基团，羟基C 1 -C 3烷基，卤代苯基，哌啶基，吗啉基，氰基甲基，哌嗪基，二-C 1 -C 3烷基氨基，二-C 1 -C 3烷基氨基C 1 -C 3烷基 基团，哌啶基C1-C3烷基，C1-C3烷氧基C1-C3烷基，吗啉代C1-C3烷基，哌嗪基C1-C3烷基，吡咯烷基，氧代吡咯烷基，C1-C3烷基吡咯烷基 基团，咪唑基，咪唑基C1-C3烷基和噻吩基。

公开(公告)号：KR100718493B1

公开(公告)日：2007-05-16

申请号：KR1020050103689

申请日：2005-11-01

Applicant: 한국화학연구원 ,  크리스탈지노믹스(주)

Inventor： 이철해 ,  정희정 ,  김재학 ,  정원장 ,  조중명 ,  노성구 ,  이태규 ,  현영란

IPC: C07D295/155 ,  C07D295/112 ,  A61P35/00

Abstract: 본 발명은 하기
화학식 1 의 알킬아미노 나프탈렌일옥시메틸 프로페닐 하이드록시벤즈아마이드 유도체(alkylamino naphthalenyloxymethyl propenyl hydroxybenzamide derivatives), 이의 제조방법 및 이를 유효성분으로 하는 항암제용 약학 조성물에 관한 것으로, 본 발명의 알킬아미노 나프탈렌일옥시메틸 프로페닐 하이드록시벤즈아마이드 유도체는 히스톤 디아세틸라제(histone deacetylase)의 효소활성을 효과적으로 저해하여 종양세포의 증식을 억제하는데 유용하게 사용될 수 있다.


상기 식에서,
R
1 은 수소 또는 메틸이고;
R
2 는 각각 독립적으로 C
1-2 알킬, 하이드록시C
1-2 알킬, 할로C
1-2 알킬, 피페리디닐, 몰포리닐, 사이아노메틸, 피페라지닐, 다이C
1-2 알킬아미노C
1-3 알킬, 피페리디닐C
1-2 알킬, 몰포리노C
1-2 알킬 및 피페라지노C
1-2 알킬로 구성된 군으로부터 선택된 하나 이상의 치환체로 치환되거나 치환되지 않은 C
1
-
2 알킬이거나;
R
1 및 R
2 는 서로 연결되어 그들이 부착된 질소 원자와 함께 몰포리닐, 피페리디닐 또는 피페라지닐 고리를 형성한다.