公开(公告)号：KR100380322B1

公开(公告)日：2003-04-16

申请号：KR1020000009063

申请日：2000-02-24

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  김보형

IPC: C07D501/16

CPC classification number: Y02P20/55

Abstract: PURPOSE: Provided is an isothiazol cephem derivative which has broad range of antimicrobial activity. And its producing method is also provided. CONSTITUTION: The cephalosporin compound represented by formula (1) and its pharmaceutically acceptable salts are produced. In the formula, R1 is hydrogen or an amine protecting group generally used in cephalosporin compound; R2 is hydrogen or an oxim protecting group; R3 is hydrogen or a chloro group; R5 is hydrogen or an ester producing group, a salt producing atom or a carboxy protecting group; and R4 is ring substituent having Q group, in which Q is hydrogen, halogen, hydroxy, mercapto, cyano, carboxy, carboxylic acid ester, carbamoyloxymethyl, N,N-dimethylcarbamoyloxymethyl, carbamoyl, N,N-dimethylcarbamoyl, C1 to C4 alkyl, C1 to C4 alkyloxy, halogen substituted methyl, halogen substituted C1 to C4 alkyloxy, aryl or hetero ring substituent. The cephalosporin derivative of the formula (1) is produced by reacting a compound of formula (7) with a compound of formula (8).

Abstract translation: 目的：提供具有广泛抗微生物活性的异噻唑头孢烯衍生物。 并提供其制作方法。 构成：由式（1）表示的头孢菌素化合物及其药学上可接受的盐被制备。 在该式中，R1是氢或通常用于头孢菌素化合物中的胺保护基; R2是氢或肟保护基; R3是氢或氯基; R5是氢或产酯基团，产盐原子或羧基保护基团; 其中Q为氢，卤素，羟基，巯基，氰基，羧基，羧酸酯，氨基甲酰氧基甲基，N，N-二甲基氨基甲酰氧基甲基，氨基甲酰基，N，N-二甲基氨基甲酰基，C1-C4烷基， C1至C4烷氧基，卤素取代的甲基，卤素取代的C1至C4烷氧基，芳基或杂环取代基。 式（1）的头孢菌素衍生物通过使式（7）的化合物与式（8）的化合物反应来制备。

公开(公告)号：KR1020020043918A

公开(公告)日：2002-06-12

申请号：KR1020000073121

申请日：2000-12-04

Applicant: 한국과학기술연구원 ,  한국과학기술원 ,  한국화학연구원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  강경호 ,  차미영 ,  공재양 ,  정대영 ,  이희윤

IPC: C07D413/14

CPC classification number: C07D413/04 ,  C07D261/08 ,  C07D413/14

Abstract: PURPOSE: Provided are novel isoxazolylalkylpiperazine derivatives having selective activity for dopamine D3 and D4 receptor represented by the formula(1) and their manufacturing method by reductive amination in the presence of a reductant. The derivatives and their pharmaceutically acceptable salts are useful in the treatment of mental illness. CONSTITUTION: The novel isoxazolylalkylpiperazine derivative of the formula(1) is prepared by reacting amine compound represented by the chemical formula(2) with aldehyde compound shown in the chemical formula(3) in the presence of a reductant selected from NaBH(OAc)3, NaBH3CN and NaBH4 in a reductive amination reaction. In the formulae, R1,R2,R3,R4, and R5 are same or different each other and are hydrogen atom, halogen atom, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, hydroxy, hydroxymethyl, aryl, heteroaryl, amino group, C1-C6 alkylamino, carbonyl, C3-C8 cycloalkyl, or C3-C8 heterocyclic group; R6 is hydrogen atom, halogen atom, alkyl, C1-C6 alkoxy, aryl, pyridyl, heterocyclic, pyrimidyl group; X is CH or nitrogen atom; and n is 3 or 4.

Abstract translation: 目的：提供具有式（1）表示的多巴胺D3和D4受体选择性活性的新型异恶唑基烷基哌嗪衍生物及其制备方法，在还原胺存在下还原胺化。 衍生物及其药学上可接受的盐可用于治疗精神疾病。 构成：式（1）的新型异恶唑基烷基哌嗪衍生物通过使化学式（2）表示的胺化合物与化学式（3）所示的醛化合物在选自NaBH（OAc）3的还原剂存在下反应来制备 ，NaBH 3 CN和NaBH 4在还原胺化反应中。 在式中，R 1，R 2，R 3，R 4和R 5相同或不同，为氢原子，卤原子，C 1 -C 6烷基，C 1 -C 6烷氧基，C 2 -C 6烯基，羟基，羟甲基，芳基，杂芳基 ，氨基，C1-C6烷基氨基，羰基，C3-C8环烷基或C3-C8杂环基; R6是氢原子，卤素原子，烷基，C1-C6烷氧基，芳基，吡啶基，杂环基，嘧啶基; X是CH或氮原子; n为3或4。

公开(公告)号：KR1020020041711A

公开(公告)日：2002-06-03

申请号：KR1020000071399

申请日：2000-11-28

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이희윤 ,  손정훈 ,  공재양 ,  정대영

IPC: C07D401/04

Abstract: PURPOSE: A 4-aminopiperidine analogue and a producing method thereof are provided, therefore the compound can be useful as a ligand of a muscarine receptor, and it is thus used in study on Alzheimer disease. CONSTITUTION: The 4-aminopiperidine analogue is represented by formula(I), wherein R1, R2, R3, R4, R5, R6 and R7 are hydrogen, cycloalkyl having carbon number of 1 to 6, alkoxy, halogen, hydroxy, hydroxymethyl, aryl, heteroaryl, amino, alkylamino, alkenyl, carbonyl or hetero ring having carbon number of 5 to 7 wherein aryl is a ring having 6 atoms, two rings having 10 atoms or a stable resonance form having double bond to adjacent carbon; heteroaryl is a single ring aromatic group having carbon number of 5 to 6 or a double ring aromatic group having carbon number of 10 in which the heteroaryl has at least one hetero atom of N, O or S; hetero ring consists of 5 to 7 atoms having 1 to 3 of N, O or S; X is carbon or sulfur; and n is an integer of 1 to 2 wherein n is 1 when X is carbon and is 2 when X is sulfur. The 4-aminopiperidine analogue is produced by reacting piperidine or amine(II) with piperazine with ketone(III) in the presence of 1 to 3 equivalent of acetic acid, 2 to 10 equivalent of reducing agent and solvent at room temperature for 3 to 24 hours to produce 4-aminopiperidine(I) and adding NaHCO3 solution and organic solvent to 4-aminopiperidine(I); and drying the extracted 4-aminopiperidine(I), dissolving it, adding 1 to 10 equivalent of hydrogen chloride to the solution, and separating, washing and drying the hydrochloride of 4-aminopiperidine.

Abstract translation: 目的：提供4-氨基哌啶类似物及其制备方法，因此该化合物可用作毒蕈碱受体的配体，因此用于阿尔茨海默病的研究。 构成：4-氨基哌啶类似物由式（I）表示，其中R 1，R 2，R 3，R 4，R 5，R 6和R 7为氢，碳数为1至6的环烷基，烷氧基，卤素，羟基，羟甲基，芳基 碳原子数为5〜7的杂芳基，氨基，烷基氨基，烯基，羰基或杂环，其中芳基为6原子的环，2个环为10个原子或具有与相邻碳原子双键的稳定共振形式; 杂芳基是碳数为5至6的单环芳基或碳数为10的双环芳基，其中杂芳基具有至少一个杂原子为N，O或S; 杂环由5至7个具有1至3个N，O或S的原子组成; X是碳或硫; n为1〜2的整数，X为碳时n为1，X为硫时为2。 4-氨基哌啶类似物通过哌啶或胺（II）与哌嗪与酮（III）在1至3当量的乙酸，2至10当量的还原剂和溶剂的存在下在室温下反应3至24 小时以产生4-氨基哌啶（I）并将NaHCO 3溶液和有机溶剂加入到4-氨基哌啶（I）中; 并将提取的4-氨基哌啶（I）干燥，溶解，向溶液中加入1〜10当量的氯化氢，分离，洗涤和干燥4-氨基哌啶的盐酸盐。

公开(公告)号：KR100303378B1

公开(公告)日：2001-09-24

申请号：KR1019990015261

申请日：1999-04-28

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  최경일 ,  배애님 ,  고훈영 ,  김유승 ,  차주환 ,  이지은

IPC: C07D501/22

CPC classification number: Y02P20/55

Abstract: 일반식(V)로표시되는 3-히드록시세펨유도체와일반식(III)으로표시되는알릴할라이드또는일반식(IV)로표시되는아세틸렌할라이드를용매와금속촉매존재하에반응시켜신규일반식(I)로표시되는세팜유도체및 이의제조방법. 일반식(I)의화합물은세펨항생제제조에중요한중간체로사용할수 있다. 일반식(I)에있어서, R은페닐아세틸, 2-[2-아미노(1,3-티아졸-4-일)-2-(히드록시알콕시이미노)에틴닐, 2-[2-아미노(1,3-티아졸-4-일)-2-(알콕시이미노)에틴닐또는 4-히드록시페닐글라이신유도체를표시하며, R는수소, 카르복실산염(무기염으로나트륨및 칼륨염, 유기염으로알킬아민염, 방향족아민염)으로카르복시보호기로는 4-메톡시벤질, 디페닐메틸, 4-니트로벤질, 알릴등 세팔로스포린화합물분야에서의분자보호기를표시하며, Q로표시되는알킬화합물에서, R, R및 R는각각수소, 할로겐, 메틸, 에틸기의알킬기, 히드록시기, 페닐또는알콕시카보닐기를표시한다.

公开(公告)号：KR1020010084201A

公开(公告)日：2001-09-06

申请号：KR1020000009063

申请日：2000-02-24

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  김보형

IPC: C07D501/16

CPC classification number: Y02P20/55

Abstract: PURPOSE: Provided is an isothiazol cephem derivative which has broad range of antimicrobial activity. And its producing method is also provided. CONSTITUTION: The cephalosporin compound represented by formula (1) and its pharmaceutically acceptable salts are produced. In the formula, R1 is hydrogen or an amine protecting group generally used in cephalosporin compound; R2 is hydrogen or an oxim protecting group; R3 is hydrogen or a chloro group; R5 is hydrogen or an ester producing group, a salt producing atom or a carboxy protecting group; and R4 is ring substituent having Q group, in which Q is hydrogen, halogen, hydroxy, mercapto, cyano, carboxy, carboxylic acid ester, carbamoyloxymethyl, N,N-dimethylcarbamoyloxymethyl, carbamoyl, N,N-dimethylcarbamoyl, C1 to C4 alkyl, C1 to C4 alkyloxy, halogen substituted methyl, halogen substituted C1 to C4 alkyloxy, aryl or hetero ring substituent. The cephalosporin derivative of the formula (1) is produced by reacting a compound of formula (7) with a compound of formula (8).

Abstract translation: 目的：提供具有广泛抗菌活性的异噻唑头孢烯衍生物。 并提供其生产方法。 构成：制备由式（1）表示的头孢菌素化合物及其药学上可接受的盐。 在该式中，R 1是氢或通常用于头孢菌素化合物中的胺保护基; R2是氢或肟基保护基; R3是氢或氯基; R5是氢或产酯基，产盐原子或羧基保护基; R4是具有Q基团的环取代基，其中Q是氢，卤素，羟基，巯基，氰基，羧基，羧酸酯，氨基甲酰氧基甲基，N，N-二甲基氨基甲酰氧基甲基，氨基甲酰基，N，N-二甲基氨基甲酰基， C1至C4烷氧基，卤素取代的甲基，卤素取代的C1至C4烷氧基，芳基或杂环取代基。 式（1）的头孢菌素衍生物通过使式（7）的化合物与式（8）的化合物反应来制备。

公开(公告)号：KR1020010029025A

公开(公告)日：2001-04-06

申请号：KR1019990041613

申请日：1999-09-28

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이지은 ,  이희윤 ,  공재양 ,  정대영 ,  정선호

IPC: C07D413/06

Abstract: PURPOSE: Provided is a method for manufacturing an iso-oxazole piperazin compound and its salts which can end up developing a lead compound for new drugs. CONSTITUTION: An isooxazol compound is manufactured by the next step: reacting the compound of the formula (2) with the compound of the formula (3) at room temperature, at 0-7 deg.C, in the presence of organic solvent, 0.1-2 equivalent, preferably 1 equivalent of base, and chlorinating agent for 30 minutes-4 hours, preferably 2 hours. Wherein, organic solvent is selected from benzene, methylene chloride, and tetrahydrofuran; a base is selected from methyl amine, ethyl amine, diethyl amine, dimethyl amine, trimethyl amine, cyclohexylamine, diethylisopropylamine, pyridine, or preferably triethylamine; And chlorinating agent is one of chlorine, N-chlorosuccinimide, and sodium hypochlorite. In the formula (1), (2), and (3), R1 and R6 are a phenyl group, benzyl group, halide phenyl group, phenyl group having substituted C1-C6 alkyl group, phenyl group having substituted C1-C6 alkoxy group, methyl phenyl group, or pyridyl group. R2-R5 is hydrogen, and X is nitrogen.

Abstract translation: 目的：提供一种制造异恶唑哌嗪化合物及其盐的方法，其可以最终形成用于新药的铅化合物。 构成：通过下一步骤制备异恶唑化合物：在室温，0-7℃，有机溶剂存在下，将式（2）化合物与式（3）化合物反应，得到0.1 -2当量，优选1当量碱和氯化剂30分钟-4小时，优选2小时。 其中有机溶剂选自苯，二氯甲烷和四氢呋喃; 碱选自甲胺，乙胺，二乙胺，二甲胺，三甲胺，环己胺，二乙基异丙胺，吡啶，或优选三乙胺; 而氯化剂是氯，N-氯代琥珀酰亚胺和次氯酸钠之一。 在式（1），（2）和（3）中，R 1和R 6是苯基，苄基，卤化苯基，具有取代的C 1 -C 6烷基的苯基，具有取代的C 1 -C 6烷氧基的苯基 ，甲基苯基或吡啶基。 R2-R5是氢，X是氮。

公开(公告)号：KR100264158B1

公开(公告)日：2000-08-16

申请号：KR1019980023118

申请日：1998-06-19

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  장문호 ,  김유승 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  공재양 ,  천혜경 ,  정대영

IPC: C07D453/00 ,  C07D261/20

Abstract: 일반식 (II)로 표시되는 카르보닐 화합물을 용매와 염기 존재하에 일반식 (III)으로 표시되는 포스포늄염 화합물이나 또는 일반식 (IV)로 표시되는 포스포네이트 화합물과 반응시켜 새로운 일반식 (I)로 표시되는 [(아릴)이소옥소졸릴]메틸렌-아자비시클로 화합물을 제조하는 것으로, 본 발명 화합물은 무스카린성 아세틸콜린 수용체에 높은 결합 친화도를 나타내므로 알쯔하이머씨 병 등의 뇌신경 질환 치료제로 유용하다.

상기 식들에서, R은 각각 수소, 할로, 알콕시, 시아노, 알킬, 알케닐, 알키닐, 히드록시, 아미노, 니트로, 4-메톡시벤질옥시, 3급-부톡시카르보닐아미노 또는 약제학적으로 가능한 염을, R
1 ,R
2 및R
R 는 각각 알킬, 아릴 또는 아랄킬을, X는 할로겐 원자를 각각 표시하며, n은 1 또는 2의 정수이다.

公开(公告)号：KR1020000007667A

公开(公告)日：2000-02-07

申请号：KR1019980027115

申请日：1998-07-06

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  장문호 ,  김유승 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  심상철

IPC: C07D501/24 ,  C07D501/20

Abstract: PURPOSE: A cephem compound for an oral administration having a broad spectrum antibacterial activity is prepared by esterifying cephalosporin compound in the presence of solvent. CONSTITUTION: The compound(I) is manufactured by reacting cephalosporin compound(Korea patent application No.1997-36921) and halide compound in the presence of solvent such as acetone, acetonitrile, dioxane, N,N-dimethylformamide, dimethylsulfoxide at -10 to 25°C for 10 min-12hr(preferably at 0 to 5°C for 10 min-1 hr). In formula(I), R1 = H or trityl, R2 = H, trityl, methyl or cyclopentyl; R3 = H, chloro, bromo or methoxy; R4 = acethoxyethyl, pyvaloyloxymethyl or isopropoxycarbonyloxymethyl. It shows a broad spectrum antibacterial activity about a staphylococcus aureus containing gram-positive bacterium and a gram-positive bacterium, especially methicillin-resistant staphylococcus aureus.

Abstract translation: 目的：通过在溶剂存在下酯化头孢菌素化合物来制备具有广谱抗菌活性的口服给药的头孢烯化合物。 构成：化合物（I）通过在-10℃下在溶剂如丙酮，乙腈，二恶烷，N，N-二甲基甲酰胺，二甲亚砜等溶剂存在下使头孢菌素化合物（韩国专利申请No.1997-36921）与卤化物反应制造而成 25℃10分钟-12小时（优选0-5℃10分钟-1小时）。 在式（I）中，R 1 = H或三苯甲基，R 2 = H，三苯甲基，甲基或环戊基; R3 = H，氯，溴或甲氧基; R4 =乙氧基乙基，吡喃酰氧基甲基或异丙氧羰基氧基甲基。 它显示了对含有革兰氏阳性菌和革兰氏阳性菌，特别是耐甲氧西林金黄色葡萄球菌的金黄色葡萄球菌的广谱抗菌活性。

公开(公告)号：KR100234013B1

公开(公告)日：1999-12-15

申请号：KR1019970053270

申请日：1997-10-17

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  고훈영 ,  최경일 ,  하영진 ,  차주환 ,  장문호 ,  배애님 ,  김명주

IPC: C07D499/887

Abstract: 본 발명은 일반식( III )의 알데히드와 일반식( II )의 아민 유도체를 용매 존재하에 축합반응시켜 중간체인 일반식( IV )의 이민화합물을 제조하고 카르복시 보호기를 제거하여 일반식(I)로 표시되는 페남 유도체를 제조하는 것으로 일반식(I)은 이성체를 포함한다. 일반식(I)의 화합물은 베타락타마제 저해제로서 기존의 항생제와 일정 비율로 병용하면 항균작용을 증진시키는 유용한 화합물이다.

公开(公告)号：KR1019990032286A

公开(公告)日：1999-05-15

申请号：KR1019970053271

申请日：1997-10-17

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  고훈영 ,  배애님 ,  김명주 ,  차주환 ,  장문호 ,  최경일 ,  하영진

IPC: C07D499/08

Abstract: 본 발명은 일반식( II )의 알데히드와 일반식( III )의 할로겐염 유도체를 이중결합시켜 중간체인 일반식( IV )의 비닐 화합물을 제조하고 카르복시 보호기를 제거하여 일반식(I)로 표시되는 신규한 2-베타-알케닐-페남 유도체를 제조하며, 이는 베타락타마제 저해제로서 기존의 항생제와 일정 비율로 병용하면 항균작용을 증진시키는 유용한 화합물이다.