公开(公告)号：KR1020090124229A

公开(公告)日：2009-12-03

申请号：KR1020080050305

申请日：2008-05-29

Applicant: 한국화학연구원

Inventor： 공영대 ,  민경훈 ,  이태호 ,  전문국 ,  황순희

IPC: C07D311/74 ,  C07D311/02

Abstract: PURPOSE: A novel 2-alkoxymethyl-2-methyl-6-ureido benzopyran derivative is provided to enhance anticancer activity and reduce side effect to normal cells. CONSTITUTION: A 2-alkoxymethyl-2-methyl-6-ureido benzopyran derivative is denoted by chemical formula 1. A method for preparing the 2-alkoxymethyl-2-methyl-6-ureido benzopyran derivative comprises: a step of reacting benzopyran derivative of chemical formula 2 with isocyanate of chemical formula 3 substituted with R^2; and a step of introducing ureido group substituted with R^2 to produce 2-alkoxy methyl-2-methyl-6-ureido benzopyran derivative.

Abstract translation: 目的：提供新的2-烷氧基甲基-2-甲基-6-脲基苯并吡喃衍生物，以增强抗癌活性，降低对正常细胞的副作用。 构成：2-烷氧基甲基-2-甲基-6-脲基苯并吡喃衍生物由化学式1表示。制备2-烷氧基甲基-2-甲基-6-脲基苯并吡喃衍生物的方法包括：使苯并吡喃衍生物 化学式2与化学式3的异氰酸酯取代为R ^ 2; 和引入被R ^ 2取代的脲基的步骤，得到2-烷氧基甲基-2-甲基-6-脲基苯并吡喃衍生物。

公开(公告)号：KR1020090090791A

公开(公告)日：2009-08-26

申请号：KR1020080016256

申请日：2008-02-22

Applicant: 한국화학연구원

Inventor： 공영대 ,  전문국 ,  이태호 ,  황순희 ,  이병호 ,  오광석 ,  유성은

IPC: C07D401/12 ,  C07D405/14 ,  A61K31/496

Abstract: A 1-(3-alkoxyqunoxaline-2-yl)-3-[1-(arylmethyl)piperidin-4-yl] urea derivative is procieed to treat obesity diseases which causes MCH activity by suppressing MCH1R. A 1-(3-alkoxyqunoxaline-2-yl)-3-[1-(arylmethyl)piperidin-4-yl] urea derivative is denoted by the chemical formula 1. In the chemical formula 1, R1, R2, R3 and R4 is hydrogen atom, halogen atom, alkyl group of C1-C3, alkoxy group of C1-C3, R5 is alkyl group of C1-C3 or haloalkyl group of C1-C3, R6, R7, R8, R9 and R10 is hydrogen atom, halogen atom, hydroxyl group, nitro group, cyano group, acetoxy group, alkyl group of C1-C3, alkoxy group of C1-C3.

Abstract translation: 1-（3-烷氧基喹喔啉-2-基）-3- [1-（芳基甲基）哌啶-4-基]脲衍生物用于治疗通过抑制MCH1R而引起MCH活性的肥胖症。 化学式1表示1-（3-烷氧基喹喔啉-2-基）-3- [1-（芳基甲基）哌啶-4-基]脲衍生物。在化学式1中，R1，R2，R3和R4 是氢原子，卤素原子，C1-C3的烷基，C1-C3的烷氧基，R5是C1-C3的烷基或C1-C3的卤代烷基，R6，R7，R8，R9和R10是氢原子， 卤素原子，羟基，硝基，氰基，乙酰氧基，C1-C3的烷基，C1-C3的烷氧基。

公开(公告)号：KR100874209B1

公开(公告)日：2008-12-15

申请号：KR1020070083038

申请日：2007-08-17

Applicant: 한국화학연구원

Inventor： 이종철 ,  이기인 ,  공영대 ,  김광록 ,  천혜경

IPC: C07D487/04 ,  A61K31/5517 ,  A61P35/00

CPC classification number: Y02P20/55 ,  C07D487/04 ,  A61K31/5517

Abstract: A 3,10-dihydro-1H-[1,4]diazepino[5,6-b]indole-2-one derivative, a method for preparing the derivative, and an anticancer medicine containing the derivative are provided to improve the activity for the cancer derived from the overexpression of CDC25B. A 3,10-dihydro-1H-[1,4]diazepino[5,6-b]indole-2-one derivative is represented by the formula 1, wherein R is H, a halogen atom, a C1-C4 alkyl group, a ORa or -OSO2Rb; Ra is a C1-C4 alkyl group, a benzyl group substituted or unsubstituted with a halogen atom, an unsubstituted phenyl group, or a trityl group; Rb is a C1-C4 alkyl group, a C1-C4 haloalkyl group, or an unsubstituted phenyl group; R1 is H, a C1-C4 alkyl group, -CH2CO2Rb, or a benzyl group substituted or unsubstituted with a halogen atom; Rb is a C1-C4 alkyl group; R2 and R3 are independently H, a C1-C6 alkyl group, -CH2ORa, -(CH2)nCO2Rb, -(CH2)nCONH2, a phenyl group, a benzyl group substituted or unsubstituted with a protection group, or a pyridyl group; Ra and Rb is H or a C1-C4 alkyl group; and n is an integer of 1-5.

Abstract translation: 提供3,10-二氢-1H- [1,4]二氮杂基[5,6-b]吲哚-2-酮衍生物，制备该衍生物的方法和含有该衍生物的抗癌药物以提高其活性 癌症来源于CDC25B的过表达。 3,10-二氢-1H- [1,4]二氮杂基[5,6-b]吲哚-2-酮衍生物由式1表示，其中R是H，卤素原子，C 1 -C 4烷基 ，ORa或-OSO2Rb; Ra是C1-C4烷基，被卤原子取代或未取代的苄基，未取代的苯基或三苯甲基; Rb是C1-C4烷基，C1-C4卤代烷基或未取代的苯基; R1是H，C1-C4烷基，-CH2CO2Rb或被卤素原子取代或未取代的苄基; Rb是C1-C4烷基; R2和R3独立地是H，C1-C6烷基，-CH2ORa， - （CH2）nCO2Rb， - （CH2）nCONH2，苯基，被保护基取代或未取代的苄基或吡啶基; R a和R b为H或C 1 -C 4烷基; n为1-5的整数。

公开(公告)号：KR1020080004646A

公开(公告)日：2008-01-10

申请号：KR1020060063214

申请日：2006-07-06

Applicant: 제이더블유중외제약 주식회사 ,  한국화학연구원

Inventor： 이수진 ,  공영대 ,  전문국 ,  문성환 ,  전기호 ,  김종민 ,  이상휘 ,  이상학 ,  강명주

IPC: C07D471/04

CPC classification number: Y02P20/55 ,  C07D471/04

Abstract: A 2-alkylenyloxy-3-ethynylpyrido[2,3-b]pyrazine derivative is provided to be usefully used as an anticancer agent by using excellent HIF-1alpha gene expression inhibitory activity thereof. A 2-alkylenyloxy-3-ethynylpyrido[2,3-b]pyrazine derivative is represented by the formula(1), where A is selected from the group consisting of alkyl, aryl, and heteroaryl; Y is a single bond, or an alkylene which may be substituted by one to five substituents selected from the group consisting of hydroxy, alkyl-OH, O-alkyl and phenyl; Z is selected from the group consisting of H, halogen, hydroxy, alkyl, alkyl-OH, alkenyl, haloalkyl, O-alkyl, O-haloalkyl, O-aryl, O-heteroaryl, O-heterocycle, O-alkyl-aryl, O-alkyl-heteroaryl, O-alkyl-heterocycle, O-alkyl-NH2, O-alkyl-NH(alkyl), O-alkyl-N(alkyl)2, C(O)alkyl, alkyl-C(O)alkoxy, C(O)NH2, C(O)NH(alkyl), C(O)N(alkyl)2, C(O)NH(aryl), C(O)N(aryl)2, C(O)NH(heteroaryl), C(O)N(heteroaryl)2, C(O)O-alkyl, C(O)O-aryl, C(O)O-heteroaryl, OC(O)-alkyl, OC(O)-aryl, OC(O)heteroaryl, OC(O)NH2, OC(O)NH(alkyl), OC(O)N(alkyl)2, OC(O)N(alkyl)N(alkyl)2, OC(O)NH(aryl), OC(O)NH(heteroaryl), NH2, NH(alkyl), N(alkyl)2, NH(aryl), N(alkyl)(aryl), N(aryl)2, NH(heteroaryl), etc., provided that a compound that the A is methyl, and Y-Z is H is excluded. A pharmaceutical composition for treating and preventing cancer comprises the 2-alkylenyloxy-3-ethynylpyrido[2,3-b]pyrazine derivative or a pharmaceutically acceptable salt thereof.

Abstract translation: 提供2-亚烷基氧基-3-乙炔基吡啶并[2,3-b]吡嗪衍生物通过使用优异的HIF-1α基因表达抑制活性可用作抗癌剂。 2-烷基氧基-3-乙炔基吡啶并[2,3-b]吡嗪衍生物由式（1）表示，其中A选自烷基，芳基和杂芳基; Y是单键，或可以被一至五个选自羟基，烷基-OH，O-烷基和苯基的取代基取代的亚烷基; Z选自H，卤素，羟基，烷基，烷基-OH，烯基，卤代烷基，O-烷基，O-卤代烷基，O-芳基，O-杂芳基，O-杂环，O-烷基 - 芳基， O-烷基 - 杂芳基，O-烷基 - 杂环，O-烷基-NH 2，O-烷基-NH（烷基），O-烷基-N（烷基）2，C（O）烷基，烷基-C（O） ，C（O）NH 2，C（O）NH（烷基），C（O）N（烷基）2，C（O）NH（芳基），C（O）N（芳基）2，C（O） （O）O-杂芳基，C（O） - 烷基，OC（O） - 烷基，C（O） 芳基，OC（O）杂芳基，OC（O）NH 2，OC（O）NH（烷基），OC（O）N（烷基）2，OC（O） ）NH（芳基），OC（O）NH（杂芳基），NH 2，NH（烷基），N（烷基）2，NH（芳基），N（烷基）（芳基），N（芳基）2，NH ）等，条件是排除A为甲基，YZ为H的化合物。 用于治疗和预防癌症的药物组合物包括2-亚烷基氧基-3-乙炔基吡啶并[2,3-b]吡嗪衍生物或其药学上可接受的盐。

公开(公告)号：KR100769732B1

公开(公告)日：2007-10-23

申请号：KR1020060068562

申请日：2006-07-21

Applicant: 한국화학연구원 ,  한국생명공학연구원

Inventor： 공영대 ,  권기선 ,  서해영 ,  전문국 ,  유성은 ,  박성섭 ,  서현우 ,  유승완

IPC: A61K31/352 ,  A61P25/28

Abstract: A 2,2'-alkylsubstitued-3,4-dehydro-6-alkylamino benzopyran derivative is provided to secure the activity of controlling neuronal death by controlling the activity of a glutamate receptor, thereby being useful as a prophylactic and therapeutic agent of stroke, epilepsy, amyotrophic lateral sclerosis, Parkinson's diseases, Huntington's disease and Alzheimer's disease. A pharmaceutical composition comprises a 2,2'-double substituted-7,8-double substituted-6-alkylamino benzopyran derivative represented by the formula(1) or a pharmaceutically acceptable salt thereof. In the formula(1), R^1 is C1-10 alkyl, benzyl, or substituted benzyl, phenethyl, 2-pyrimidylmethyl, thiophene, 2-methylthiophenemethyl, 5-methyl-2-thiophenemethyl, 3-thiophenemethyl, indolylmethyl, benzo dioxiranylmethyl, naphthalenylmethyl, or furanylmethyl, each R^2 and R^3 is H, C1-6 alkyl, halogen, or phenyl and substituted phenyl, R^4 is C1-10 alkyl, phenyl or substituted phenyl, or a hetero-cyclic group selected from the group consisting of thiophene and furan(wherein the benzyl, phenyl or the heterocyclic group is able to be substituted by 1-4 substituents selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, nitro, cyano and C1-6 alkoxy), and n is an integer from 1 to 5.

Abstract translation: 提供了一种2,2'-烷基苯基-3,4-脱氢-6-烷基氨基苯并吡喃衍生物，以通过控制谷氨酸受体的活性来确保控制神经元死亡的活性，从而可用作中风的预防和治疗剂， 癫痫，肌萎缩性侧索硬化，帕金森病，亨廷顿病和阿尔茨海默病。 药物组合物包含由式（1）表示的2,2'-双取代-7,8-双取代-6-烷基氨基苯并吡喃衍生物或其药学上可接受的盐。 在式（1）中，R 1是C 1-10烷基，苄基或取代的苄基，苯乙基，2-嘧啶基甲基，噻吩，2-甲基噻吩甲基，5-甲基-2-噻吩甲基，3-噻吩甲基，吲哚基甲基，苯并二氧杂环丙基甲基 ，萘基甲基或呋喃基甲基，每个R 2和R 3是H，C 1-6烷基，卤素或苯基和取代的苯基，R 4是C 1-10烷基，苯基或取代的苯基或杂环基 选自噻吩和呋喃（其中苄基，苯基或杂环基团能够被1-4个选自C1-6烷基，C1-6卤代烷基，硝基，氰基和C1的取代基取代） -6烷氧基），n为1〜5的整数。

公开(公告)号：KR1020060104269A

公开(公告)日：2006-10-09

申请号：KR1020050026264

申请日：2005-03-30

Applicant: 한국화학연구원

Inventor： 공영대 ,  서진수 ,  전문국 ,  이종철 ,  박우규 ,  조희영

IPC: C07D311/58

Abstract: 본 발명은 하기 화학식 1로 표시되는 2,2' 위치에 이중치환된 6-아미노술포닐 벤조피란 유도체, 약제학적으로 허용 가능한 그의 염 및 그를 유효성분으로 함유하는 5-HT
6 활성저해제에 관한 것이다.
본 발명의 2,2' 위치에 이중치환된 6-아미노술포닐 벤조피란 유도체는 5-HT
6 수용체에 대하여 억제활성 및 선택성이 우수하므로 이를 유효성분으로 함유하여 5-HT
6 활성에 관련된 세로토닌 재흡수로 유발되는 질환의 예방 및 치료제로서 유용하다.

(상기 식에서, R
1 , R
2 , R
3 및 n은 명세서에서 정의한 바와 같다.)
아미노술포닐벤조피란, 세로토닌, 항우울증, 항불안증, 항수면장애

公开(公告)号：KR1020060079498A

公开(公告)日：2006-07-06

申请号：KR1020040117711

申请日：2004-12-31

Applicant: 에스케이케미칼주식회사 ,  한국화학연구원

Inventor： 공영대 ,  서진수 ,  전문국 ,  곽의종 ,  조용백 ,  이남규 ,  이은주 ,  이정범 ,  이준원 ,  이석호 ,  동미숙 ,  김정란

IPC: C07D311/70

Abstract: 본 발명은 TGFβ 수용체 길항활성이 우수하여 간질환 예방 및 치료제로서는 물론 여러 섬유 증식성 질환 예를 들면 간섬유화, 간경화, 폐섬유증, 피부경화증, 신사구체 섬유증 등의 예방 및 치료제로서 유효한
N- (2,2-이중치환-2H-크로멘-6-일)싸이오우레아 유도체의 의약적 용도에 관한 것이다.

TGFβ 수용체 길항, 간경화, 콜라겐, 싸이오우레아, 고체상합성, 조합화학

公开(公告)号：KR100542324B1

公开(公告)日：2006-01-11

申请号：KR1020030037514

申请日：2003-06-11

Applicant: 한국화학연구원

Inventor： 공영대 ,  서진수 ,  유성은

IPC: C07D311/22

Abstract: 본 발명은 신규 2,2-디메틸-3-하이드록시-4-알콕시-6-알킬 아미노 벤조피란 유도체와, 조합화학 합성기술중 하나인 고체상 평형합성법을 이용하여 상기한 신규 화합물을 고효율로 합성하는 방법, 그리고 상기한 신규 화합물이 우수한 지질 과산화 억제 효과를 나타내므로 지질 과산화의 촉진 또는 산화물질의 축적으로 유발되는 질환의 예방 및 치료제로 사용하는 용도에 관한 것이다.
조합화학 합성, 고체상 평형 합성, 항산화제, 지질 과산화 억제, 뇌신경질환 치료제, 고혈압치료제, 당뇨병치료제, 약리적 효능, 벤조피란, 라이브러리

公开(公告)号：KR1020040022382A

公开(公告)日：2004-03-12

申请号：KR1020030037592

申请日：2003-06-11

Applicant: 한국화학연구원

Inventor： 공영대 ,  전용석 ,  황종연 ,  유성은

IPC: C07D311/74

Abstract: PURPOSE: 2,2-Dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran derivatives and a parallel synthesis of the derivatives on solid-phase are provided. The compounds have improved lipid peroxidation inhibiting activity, and are thus useful for the prevention and treatment of disease caused by stimulation of lipid peroxidation or accumulation of oxidizing materials. CONSTITUTION: 2,2-dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran derivatives are represented by the formula(5a), wherein R1 is C1-C10 saturated, unsaturated or cyclic alkyl, benzyl or substituted benzyl; R2 is C1-C10 saturated, unsaturated or cyclic alkyl, benzyl, substituted benzyl, or penethyl; and R3a is C2-C10 unsaturated or cyclic alkyl, phenyl, substituted phenyl, or 5- to 7-membered hetero ring containing a hetero atom selected from oxygen and sulfur in which the substituted benzyl or substituted phenyl is benzyl or phenyl substituted by 1 to 4 substituents selected from halogen atom, nitro, C1-C10 alkyl, C1-C10 alkoxy and C1-C10 haloalkyl. A parallel synthesis of the 2,2-dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran derivatives of the formula(5) on solid-phase comprises the steps of: selectively introducing R1 substituent to nitrogen of benzopyran of a compound of the formula(1) to prepare N-alkyl substituted carbamate resin of the formula(2); adding meta-chlorobenzoic acid and alcohol into the compound of the formula(2) and reacting them to prepare 2,2-dimethyl-3-hydroxy-6-alkyl amino benzopyran resin of the formula(3); reacting 3-hydroxy of the compound of the formula(3) with electrophile selected from carbonyl halide compounds containing R3 to prepare 2,2-dimethyl-3-ester-4-alkoxy-6-alkyl amino benzopyran resin of the formula(4); and treating the compound of the formula(4) with trifluoroacetic acid(TFA) containing a dichloromethane solution or organic acid containing an organic solvent, wherein (P) is a polymer type solid support selected from polystyrene-divinylbenzene, methacrylic acid-dimethylacrylamide and hydroxy methacrylic acid.

Abstract translation: 目的：提供2,2-二甲基-3-酯-4-烷氧基-6-烷基氨基苯并吡喃衍生物和固相衍生物的平行合成。 所述化合物具有改善的脂质过氧化抑制活性，因此可用于预防和治疗由脂质过氧化或氧化物质的积累引起的疾病。 构成：2,2-二甲基-3-酯-4-烷氧基-6-烷基氨基苯并吡喃衍生物由式（5a）表示，其中R1是C1-C10饱和，不饱和或环状烷基，苄基或取代的苄基; R2是C1-C10饱和，不饱和或环状烷基，苄基，取代的苄基或penethyl; R3a是C2-C10不饱和或环状烷基，苯基，取代的苯基或含有选自氧和硫的杂原子的5至7元杂环，其中取代的苄基或取代的苯基是苄基或被1至 4个选自卤素原子，硝基，C 1 -C 10烷基，C 1 -C 10烷氧基和C 1 -C 10卤代烷基的取代基。 在固相上平行合成式（5）的2,2-二甲基-3-酯-4-烷氧基-6-烷基氨基苯并吡喃衍生物包括以下步骤：选择性地将R 1取代基引入到苯并吡喃的氮 式（1）的化合物，制备式（2）的N-烷基取代的氨基甲酸酯树脂; 向式（2）的化合物中加入间氯苯甲酸和醇，并使其反应制备式（3）的2,2-二甲基-3-羟基-6-烷基氨基苯并吡喃树脂; 使式（3）化合物的3-羟基与选自含有R 3的羰基卤化合物的亲电试剂反应制备式（4）的2,2-二甲基-3-酯-4-烷氧基-6-烷基氨基苯并吡喃树脂， ; 并用含有二氯甲烷溶液或含有机溶剂的有机酸的三氟乙酸（TFA）处理式（4）化合物，其中（P）是选自聚苯乙烯 - 二乙烯基苯，甲基丙烯酸 - 二甲基丙烯酰胺和羟基的聚合物型固体载体 甲基丙烯酸。

公开(公告)号：KR1020040002538A

公开(公告)日：2004-01-07

申请号：KR1020030037514

申请日：2003-06-11

Applicant: 한국화학연구원

Inventor： 공영대 ,  서진수 ,  유성은

IPC: C07D311/22

Abstract: PURPOSE: Provided are 2,2-Dimethyl-3-hydroxy-4-alkoxy-6-alkyl amino benzopyran derivatives and a method for manufacturing the same in higher yield using parallel synthesis on the solid-phase. The derivatives have excellent lipid peroxidation and are thus used for prevention and treatment of diseases associated with lipid peroxidation. CONSTITUTION: 2,2-Dimethyl-3-hydroxy-4-alkoxy-6-alkyl amino benzopyran derivatives are characteristically represented by the formula(4a), wherein R¬1a represents an aryl group, a benzyl group or a substituted benzyl group, a naphthylmethyl group, or a penethyl group; and R¬2 represents a C1-C10 alkyl group, benzyl group or a substituted benzyl group, wherein a substituent is selected from a halogen atom, a nitro group, a C1-C10 alkyl group, C1-C10 alkoxy group and C1-C10 haloalkyl group.

Abstract translation: 目的：提供2,2-二甲基-3-羟基-4-烷氧基-6-烷基氨基苯并吡喃衍生物及其在固相上使用平行合成以更高产率制备该方法。 该衍生物具有优异的脂质过氧化作用，因此用于预防和治疗与脂质过氧化相关的疾病。 构成：2,2-二甲基-3-羟基-4-烷氧基-6-烷基氨基苯并吡喃衍生物的特征是由式（4a）表示，其中R 1a表示芳基，苄基或取代的苄基， 萘基甲基或苯乙基; R 2表示C1-C10烷基，苄基或取代的苄基，其中取代基选自卤素原子，硝基，C1-C10烷基，C1-C10烷氧基和C1-C10 卤代烷基。