公开(公告)号：KR100754325B1

公开(公告)日：2007-09-05

申请号：KR1020060052759

申请日：2006-06-12

Applicant: 한국과학기술연구원

Inventor： 배애님 ,  조용서 ,  차주환 ,  추현아 ,  임혜원 ,  레디도다레디무니크말 ,  고훈영

IPC: A61K31/517 ,  A61P25/04

CPC classification number: A61K31/517

Abstract: 3-(4-Chloro)-4-oxo-2-thioxo-1,2,3,4-tetrahydro-quinazoline derivatives as T-type calcium channel antagonists are provided to treat neurogenic pain, epilepsy, hypertension or angina pectoris by inhibiting the T-type calcium channel without side effects such as pharmacokinetic interactions. 3-(4-chloro)-4-oxo-2-thioxo-1,2,3,4-tetrahydro-quinazoline derivatives represented by the formula(I) is used as a pharmaceutical composition, wherein X is (3-piperidin-1-yl-propyl)-amide, [3-(2-ethyl-piperidin-1-yl)-propyl]-amide, [3-(4-methyl-piperidin-1-yl)-propyl]-amide, 2-(butyl-methyl-amino)-ethyl-amide, (3-pyrrolidin-1-yl-propyl)-amide, (3-azepan-1-yl-propyl)-amide, [3-(4-ethyl-piperazin-1-yl)-propyl]-amide, [3-(benzyl-methyl-amide)-propyl]-amide or (2-dimethylamino-ethyl)-amide, and the compound represented by the formula(I) includes 3-(4-chloro-benzyl)-7-(4-methyl-piperazine-1-carbonyl)-2-thioxo-2,3-dihydro-1H-quinazolin-4-one.

Abstract translation: 提供3-（4-氯）-4-氧代-2-硫代-1,2,3,4-四氢 - 喹唑啉衍生物作为T型钙通道拮抗剂，用于通过抑制神经源性疼痛，癫痫，高血压或心绞痛来治疗 T型钙通道没有副作用，如药代动力学相互作用。 使用由式（I）表示的3-（4-氯）-4-氧代-2-硫代-1,2,3,4-四氢 - 喹唑啉衍生物作为药物组合物，其中X是（3-哌啶-4-基） 丙基） - 酰胺，[3-（2-乙基 - 哌啶-1-基） - 丙基] - 酰胺，[3-（4-甲基 - 哌啶-1-基） - 丙基] - 酰胺，2 - （丁基 - 甲基 - 氨基） - 乙基 - 酰胺，（3-吡咯烷-1-基 - 丙基） - 酰胺，（3-氮杂环庚烷-1-基 - 丙基） - 酰胺，[3-（4-乙基 - -1-基） - 丙基] - 酰胺，[3-（苄基 - 甲基 - 酰胺） - 丙基] - 酰胺或（2-二甲基氨基 - 乙基） - 酰胺，由式（I）表示的化合物包括3- （4-氯 - 苄基）-7-（4-甲基 - 哌嗪-1-羰基）-2-硫代-2,3-二氢-1H-喹唑啉-4-酮。

公开(公告)号：KR100743255B1

公开(公告)日：2007-07-27

申请号：KR1020060040614

申请日：2006-05-04

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  추현아 ,  배애님 ,  차주환 ,  고훈영 ,  김화실 ,  임혜원 ,  서선희

IPC: C07D209/48

Abstract: Novel 1,3-dioxoisoindole derivatives having selective antagonism of T-type calcium channel are provided to treat brain diseases including epilepsy, hypertension and angina pectoris, heart disease and nerve system pain by inhibiting the T-type calcium channel as a representative low-voltage activated calcium channel. The 1,3-dioxoisoindole derivatives represented by the formula(1) or their pharmaceutically acceptable salts are provided, wherein R1 is phenyl group or benzyl group which is substituted or unsubstituted by halogen atom, C1-C6 alkoxy group, C1-C6 alkyl group, or cyano group; R2 is a hetero ring group selected from piperidinyl group, pyrolidinyl group, morpholinyl group and piperazinyl group which is substituted or unsubstituted by C1-C6 alkyl substituent; and n is 1 or 2, provided that a compound in which R2 is morpholinyl group when R1 is C1-C6 alkyl-substituted phenyl group is excluded.

Abstract translation: 通过抑制T型钙通道作为代表性的低电压来提供具有T型钙通道选择性拮抗作用的新型1,3-二氧代异吲哚衍生物来治疗包括癫痫，高血压和心绞痛，心脏病和神经系统疼痛的脑疾病 激活钙通道。 由式（1）表示的1,3-二氧代异吲哚衍生物或它们的药学上可接受的盐，其中R1是被卤素原子，C1-C6烷氧基，C1-C6烷基取代或未被取代的苯基或苄基 或氰基; R2是选自哌啶基，吡咯烷基，吗啉基和由C1-C6烷基取代基取代或未取代的哌嗪基的杂环基; 并且n是1或2，条件是当R 1是C 1 -C 6烷基取代的苯基时，其中R 2是吗啉基的化合物被排除在外。

公开(公告)号：KR100531117B1

公开(公告)日：2005-11-28

申请号：KR1020030029741

申请日：2003-05-12

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  차주환

IPC: C07D309/32

Abstract: 본 발명은 신규 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법에 관한 것으로서, 더욱 상세하게는 1-치환된-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올 유도체와 알데히드 유도체를 루이스 산 촉매 하에서 반응시켜 제조된 2,6-위치에 다양한 치환체가 도입된 다음 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법에 관한 것이다.

상기 화학식 1에서, R
1 및 R
2 는 각각 수소원자, C
1 ∼C
10 의 포화 또는 불포화된 직쇄, 분쇄 또는 싸이클릭 알킬기, 및 방향족기 중에서 선택된다.

公开(公告)号：KR100522133B1

公开(公告)日：2005-10-18

申请号：KR1020020004657

申请日：2002-01-26

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  한예선 ,  차주환 ,  김욱현 ,  이종수 ,  윤홍철

IPC: C12N9/02

CPC classification number: C12N9/0006

Abstract: 본 발명은 효모의 한 종류인 클루이베로마이세스 마르시아누스
(
Kluyveromyces marxianus )로부터 분리, 정제하여 얻은 카르보닐 환원효소 (Carbonyl Reaductase, CR) 및 이를 분리, 정제하는 방법에 관한 것이다. 본 발명에 의하여 얻어진 환원효소에 의한 환원반응은 미생물에 의한 환원반응 및 화학적 합성방법으로 얻어진 환원효소에 의한 환원반응보다 입체선택성이 높고, 비용과 시간이적인 측면에서 우수하다.

公开(公告)号：KR100519714B1

公开(公告)日：2005-10-10

申请号：KR1020030018240

申请日：2003-03-24

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  차주환 ,  전보경

IPC: C07C17/02

Abstract: 본 발명은 인듐할라이드(III)염을 사용하여 알릴알코올에서 알릴할라이드를 제조하는 방법에 관한 것으로, 인듐할라이드(III)염 (화학식 1)을 사용하여 알릴알코올(화학식 2)에서 알릴할라이드(화학식 3)를 제조(화학식 4)하는 것을 특징으로 하며, 본 발명에 의하여 출발물질인 알코올로부터 다양한 알릴할라이드를 한 단계의 반응으로 손쉽게 제조할 수 있다.
(화학식 4)

상기 화학식 I ∼ IV에서, R
1 , R
2 , R
3 = 알킬기, 방향족 화합물, 고리화합물 치환기를 말하며, X는 Cl, Br, I와 같은 할로겐 원소를 말한다.

公开(公告)号：KR100466797B1

公开(公告)日：2005-01-24

申请号：KR1020010089276

申请日：2001-12-31

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  고훈영 ,  배애님 ,  강경호 ,  김상희

IPC: C07D223/16

Abstract: PURPOSE: Benzoazepine derivatives and a preparation process thereof using indium are provided, thereby rapidly and easily preparing the benzoazepine derivatives using an appropriate amount of indium powder. CONSTITUTION: Benzoazepine derivatives are represented by the formula IV, wherein X is H, F, Cl, Br, I, alkyl or alkoxy. The benzoazepine derivatives represented by the formula III are also provided, wherein R is methyl, ethyl or hydrogen; and X is H, F, Cl, Br, I, alkyl or alkoxy. A process for preparing benzoazepine derivatives of the formula IV comprises the steps of: (1) stirring 2-nitro benzaldehyde derivatives of the formula I and methyl 2-(bromomethyl) acrylate or ethyl 2-(bromomethyl) acrylate in water or aqueous organic solvent, together with indium coil or indium thin layer and acid to prepare a compound of the formula III; and (2) reacting the compound of the formula III with base in an organic solvent, wherein the aqueous organic solvent in the step (1) is tetrahydrofuran solution, acetonitrile solution, N,N-dimethylformamide solution, methylalcohol solution or ethylalcohol solution; the base in the step (2) is sodium hydride, potassium butoxide, sodium bicarbonate, sodium carbonate, potassium carbonate or cesium carbonate; and the organic solvent in the step (2) is tetrahydrofuran, N,N-dimethylformamide, methylsulfoxide, dimethylsulfoxide or dichloromethane.

Abstract translation: 目的：提供苯并氮杂衍生物及其使用铟的制备方法，由此使用适量的铟粉迅速且容易地制备苯并吖庚因衍生物。 构成：苯并氮杂衍生物由式Ⅳ表示，其中X是H，F，Cl，Br，I，烷基或烷氧基。 还提供了由式III表示的苯并吖庚因衍生物，其中R是甲基，乙基或氢; X是H，F，Cl，Br，I，烷基或烷氧基。 制备式Ⅳ的苯并吖庚因衍生物的方法包括以下步骤：（1）将式I的2-硝基苯甲醛衍生物和2-（溴甲基）丙烯酸甲酯或2-（溴甲基）丙烯酸乙酯在水或含水有机溶剂 与铟线圈或铟薄层和酸一起制备式III的化合物; （2）使式III化合物与碱在有机溶剂中反应，其中步骤（1）中的含水有机溶剂为四氢呋喃溶液，乙腈溶液，N，N-二甲基甲酰胺溶液，甲醇溶液或乙醇溶液; 步骤（2）中的碱为氢化钠，丁醇钾，碳酸氢钠，碳酸钠，碳酸钾或碳酸铯; 步骤（2）中的有机溶剂为四氢呋喃，N，N-二甲基甲酰胺，甲基亚砜，二甲基亚砜或二氯甲烷。

公开(公告)号：KR1020040039033A

公开(公告)日：2004-05-10

申请号：KR1020020066652

申请日：2002-10-30

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  전보경

IPC: C07C209/32

Abstract: PURPOSE: A method for reducing a nitro compound into an amine compound by using an indium metal wire is provided, to prevent the conglomeration of indium metal and to allow the reduction reaction to be carried out under a milder condition. CONSTITUTION: The method comprises the step of reducing a nitro compound represented by the formula 1 into an amine compound represented by the formula 2 by using an indium metal wire in an aqueous solution, wherein R is an aliphatic or aromatic compound. Preferably the reaction is carried out at a temperature of 20-25 deg.C; and the amount of the indium metal is 1.5-2.0 equivalences per a nitro group. Optionally the reaction is carried out in the presence of HCl or HBr which is added to make the pH of the reaction mixture be 1-2.

Abstract translation: 目的：提供通过使用铟金属线将硝基化合物还原成胺化合物的方法，以防止铟金属的聚集并允许在较温和的条件下进行还原反应。 构成：该方法包括通过在水溶液中使用铟金属线将式1所示的硝基化合物还原成由式2表示的胺化合物的步骤，其中R是脂族或芳族化合物。 反应优选在20-25℃的温度下进行; 并且铟金属的量相对于硝基为1.5-2.0当量。 任选地，反应在HCl或HBr的存在下进行，其加入以使反应混合物的pH为1-2。

公开(公告)号：KR1020030065890A

公开(公告)日：2003-08-09

申请号：KR1020020005946

申请日：2002-02-01

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  석미영 ,  공재양 ,  정대영

IPC: C07D453/02

Abstract: PURPOSE: Provided are Quinuclidine compounds which are useful for treatment of brain-nervous diseases caused by cholinergic neurotransmission such as Alzheimer's disease and a preparation method thereof. CONSTITUTION: A quinuclidine compounds of the formula (I) and pharmaceutically acceptable salts thereof are provided, wherein n is an integer of 1 to 5; R is a substituent on a benzene ring, hydrogen, F, Cl, methoxy, OH, NH2, NO2, 3,4-dimethoxy, 2,4-dimethoxy, cyano, C1-6 alkyl, 1,2 or 3 fluorine substituted C1-6 alkyl, 4-methoxybenzyloxy, t-butoxycarbonyl, C2-6 alkenyl, 1,2 or 3 fluorine substituted C2-6 alkenyl, C2-6 alkynyl, 1,2 or 3 fluorine substituted C2-6 alkynyl, and C3-7 cycloalkyl. A method for preparing the quinuclidine compounds of the formula (I) comprises reacting a compound of the formula (II) with a compound of the formula (III) or (IV), wherein R1 and R2 are independently C1-6 alkyl, aryl or arylalkyl.

Abstract translation: 目的：提供可用于治疗由胆碱能神经传递如阿尔茨海默病引起的脑神经疾病的奎宁环化合物及其制备方法。 构成：提供式（I）的奎宁环化合物及其药学上可接受的盐，其中n为1至5的整数; R是苯环上的取代基，氢，F，Cl，甲氧基，OH，NH2，NO2,3,4-二甲氧基，2,4-二甲氧基，氰基，C1-6烷基，1,2或3个氟取代的C1 -6烷基，4-甲氧基苄氧基，叔丁氧基羰基，C2-6烯基，1,2或3个氟取代的C2-6烯基，C2-6炔基，1,2或3个氟取代的C2-6炔基，C3-7 环。 制备式（I）的奎宁环化合物的方法包括使式（II）的化合物与式（III）或（IV）的化合物反应，其中R 1和R 2独立地为C 1-6烷基，芳基或 芳。

公开(公告)号：KR100373485B1

公开(公告)日：2003-02-25

申请号：KR1019990041612

申请日：1999-09-28

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이희윤

IPC: C07D295/22

Abstract: PURPOSE: Provided is a novel isooxazol piperazin derivative which is used as an antagonist against dopamine-1 receptor related to the central nerve system disorders. CONSTITUTION: A novel isooxazol piperazin derivative represented by the formula (1) is manufactured by reacting secondary amine of the formula (2) with aldehyde of the formula (3) in the presence of NaBh(OAc)3, NaBH3CN, or NaBH4 as a reductant and methylene chloride as a solvent at room temperature for 3-24 hours, preferably 12-14 hours. In the formula (1), n is an integer of between 1 and 4; R1 is a phenyl group at an ortho, meta, or para position substituted by more than one group among halogen, trifluoromethyl, -NO2, alkyl group of C1-C3 , and alkoxy group of C1-C3, or an alkyl group of C1-C3, hydroxy group, 4-(2-keto-1-benzimidazolerynyl), 1-(2-(trifluoromethyl)benzene, 4-(4-chlorophenyl)-4-hydroxy, 1-(2-pyrimidyl), or 1-benzyl group; R2-R5 is hydrogen; R6 is a phenyl group at an ortho, meta, or para position substituted by more than one group among halogen group, trifluoromethyl group , -CN, -NO2, an alkyl group of C1-C3, phenoxy group, and alkoxy group of C1-C3 and an unsaturated 5 or 6 hetero ring group having more than one atom from an alkyl group of C-C3, alkoxy group of C1-C3, thiophenyl group, (2-phenyl)vinyl group, pyridyl group, and from oxygen, sulfur, and nitrogen; and Q is isoxazol (A) or 4,5-dihydroisoxazole derivative (B).

Abstract translation: 用途：提供了一种新的异恶唑哌嗪衍生物，其用作针对与中枢神经系统疾病相关的多巴胺-1受体的拮抗剂。 结构式（1）表示的新型异恶唑哌嗪衍生物是通过使式（2）的仲胺与式（3）的醛在NaBh（OAc）3，NaBH3CN或NaBH4存在下反应制备的 还原剂和二氯甲烷作为溶剂在室温下反应3-24小时，优选12-14小时。 式（1）中，n为1〜4的整数， R 1是在卤素，三氟甲基，-NO 2，C 1 -C 3的烷基和C 1 -C 3的烷氧基中的多于一个基团取代的邻位，间位或对位的苯基，或者C1- C3-羟基，4-（2-酮-1-苯并咪唑基），1-（2-（三氟甲基）苯，4-（4-氯苯基）-4-羟基，1-（2-嘧啶基） 苄基; R 2 -R 5是氢; R 6是在卤素基团，三氟甲基，-CN，-NO 2，C 1 -C 3烷基，C 1 -C 3烷氧基， 苯氧基和C 1 -C 3的烷氧基以及具有超过一个来自C 1 -C 3的烷基，C 1 -C 3的烷氧基，噻吩基，（2-苯基）乙烯基的不饱和5或6个杂环基 ，吡啶基和氧，硫和氮;并且Q是异恶唑（A）或4,5-二氢异恶唑衍生物（B）。

公开(公告)号：KR100362706B1

公开(公告)日：2002-12-11

申请号：KR1020000021258

申请日：2000-04-21

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  김유승 ,  고훈영 ,  최경일 ,  배애님 ,  이정규

IPC: C07C209/32

Abstract: 본 발명은 인듐 금속을 이용하여 니트로기(-NO
2 )를 갖는 화합물을 아민(-NH
2 ) 화합물로 환원시키는 방법을 제공한다. 보다 구체적으로는 인듐 금속을 이용하여 화학식 1을 갖는 지방족 또는 방향족 화합물을 화학식 2의 화합물로 환원시키는 방법을 제공한다.
[화학식 1]

[화학식 2]

상기 화학식 1 및 2에서, R은 지방족 또는 방향족 화합물을 나타내며, n은 1-5의 정수, 바람직하게는 1-3의 정수, 가장 바람직하게는 1 또는 2이다.
인듐 금속을 이용한 본 발명의 환원 반응은 상온에서 짧은 시간 내에 진행될 뿐만 아니라 수개의 니트로기를 짧은 시간 내에 한번에 환원시킬 수 있다. 또한 분자내 다른 관능기에 영향을 미치지 아니하고 니트로기만 선택적으로 환원시킬 수 있으며, 수용액 상에서 반응이 쉽게 진행되므로 환경친화적 산업 공정이다는 장점을 가지고 있다. 따라서 화학 공업 분야에서 다양하게 응용될 수 있다.