公开(公告)号：KR100355343B1

公开(公告)日：2002-10-12

申请号：KR1019990050823

申请日：1999-11-16

Applicant: 한국과학기술연구원

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

IPC: C07D261/14

Abstract: 본발명은신규삼차아미노에틸이소옥사졸유도체및 그제조방법에관한것으로서, 상기이소옥사졸유도체는여러가지중추신경계장애와관련이있는도파민-1 수용체의길항제로서작용하며, 그구조는화학식 1과같다. [화학식 1] 그제조방법은아래의화학식 2의아민과화학식 3의토실레이트의치환반응을이용한것으로서, 그반응은반응식 1과같다. [화학식 2] [화학식 3] [반응식 1] 상기화학식 1, 2, 3 및반응식 1에서, R는페닐, 할로겐원자에의해치환된페닐, 트리플루오로메틸에의해치환된페닐, 페닐기의 2, 3 또는 4 위치에트리플루오로메틸에의해치환된페닐메틸, 디페닐메틸, 페닐기의 2, 3 또는 4 위치에할로겐원자에의해치환된디페닐메틸, 벤질, 3-히드로벤즈이미다졸-2-온이며; R내지 R는모두수소이며; R는니트로기, 페녹시기, 메톡시기, 트리플루오로메틸기및 할로겐기로구성되는군에서선택되는하나이상에의해치환된페닐, 페닐기에의해치환된비닐또는 O, S 및 N으로구성되는군에서선택되는한가지원자에의해치환된 5환또는 6환의불포화또는포화헤테로고리화합물이며; X는질소또는 C-H이다.

公开(公告)号：KR100343948B1

公开(公告)日：2002-07-24

申请号：KR1019990050824

申请日：1999-11-16

Applicant: 한국과학기술연구원

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

IPC: C07D403/02

Abstract: 본발명은화학식 1을갖는이소옥사졸피페라진계열의화합물또는그의허용되는염 및그 제조방법과관한것으로, 상기화합물은아래의화학식 1을갖고, 그제조방법은아래의화학식 2의화합물과화학식 3의화합물을 1,3-쌍극자고리화첨가반응시키는것으로구성된다. 본발명은또한상기제조방법을용액상조합합성에응용하여제조된라이브러리에관한것이다. [화학식 1] [화학식 2] [화학식 3] 상기화학식 1, 2 및 3에서 R은 C-C의방향족탄화수소, C-C의알킬기에의해치환된 C-C의방향족탄화수소, C-C의알콕시기에의해치환된 C-C의방향족탄화수소, 할로겐에의해치환된 C-C의방향족탄화수소또는 C-C의아릴알킬이며; R-R는서로독립적으로수소, 할로겐, 메틸또는에틸이며; R-R은서로독립적으로수소, 할로겐에의해치환된페녹시, -OC(O)R, -NRR,,또는이며, 상기식 중 Y는 O 또는 S이고, R은 C-C의알킬기이고, R및 R은서로독립적으로 C-C의알킬기이고, R은수소, C-C의알킬기또는페닐이고, R는서로독립적으로수소또는 C-C의알킬기이고, n는 1-2의정수이고, k는 n=1이면 5, n=2이면 6이고, m은 n=1이면 4, n=2이면 5이다.

公开(公告)号：KR100343947B1

公开(公告)日：2002-07-22

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: 본발명은화학식 1을갖는이소옥사졸피페라진계열의화합물또는그 염의제조방법및 상기방법에의해만들어진라이브러리에관한것으로, 상기방법은화학식 2의화합물과화학식 3의화합물을염기및 염소화제의존재하에 1,3-쌍극자고리화첨가반응시켜화학식 1 또는그 염의화합물을제조하는것으로구성된다. 그화학식 1, 2, 3과반응식 1은다음과같다. 상기화학식 1, 2, 3과반응식 1에서, R및 R는페닐, 벤질, 할로겐화페닐, C-C의알킬기로치환된페닐, C-C의알콕시기로치환된페닐, (트리플루오로)메틸페닐, 피리딜등의페닐유도체를말하며, R-R는수소이며, X는질소이며,는이중결합또는삼중결합을의미하며,는이중결합또는단일결합을의미한다.

公开(公告)号：KR1020020043413A

公开(公告)日：2002-06-10

申请号：KR1020000073122

申请日：2000-12-04

Applicant: 한국과학기술연구원 ,  한국과학기술원 ,  한국화학연구원 ,  학교법인 성신학원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  공재양 ,  정대영 ,  정선호 ,  정지영 ,  이희윤

IPC: C07D413/14

CPC classification number: C07D413/04 ,  C07D261/08

Abstract: PURPOSE: Provided are novel 4,5-dihydroisoxazolylalkylpiperazine derivatives having selective biological activity to dopamine D3 and D4 receptors, and their preparation method by reductive amination in the presence of reductant. CONSTITUTION: 4,5-dihydroisoxazolylalkylpiperazine derivative is represented by the formula(1), wherein R1, R2, R3, R4 and R5 are identical or different from each other, and represents individually hydrogen atom, halogen atom, C1-C6 alkyl group, C1-C6 alkoxy group, C2-C6 alkenyl group, hydroxy group , hydroxymethyl group, aryl group, heteroaryl group, amino group, C1-C6 alkyl amino group, carbonyl group, C3-C8 cycloalkyl group, or C3-C8 heterocyclic group; R6 represents hydrogen atom, halogen atom, alkyl group, C1-C6 alkoxy group, aryl group, pyridyl group, heterocyclic group or pyrimidyl group; X represents CH or nitrogen atom; and n is 3 or 4.

Abstract translation: 目的：提供对多巴胺D3和D4受体具有选择性生物活性的新型4,5-二氢异恶唑烷基哌嗪衍生物及其在还原剂存在下还原胺化的制备方法。 构成：4,5-二氢异恶唑基烷基哌嗪衍生物由式（1）表示，其中R 1，R 2，R 3，R 4和R 5彼此相同或不同，并且表示单独的氢原子，卤素原子，C1-C6烷基， C1-C6烷氧基，C2-C6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表示氢原子，卤素原子，烷基，C1-C6烷氧基，芳基，吡啶基，杂环基或嘧啶基; X表示CH或氮原子; n为3或4。

公开(公告)号：KR1020010046869A

公开(公告)日：2001-06-15

申请号：KR1019990050824

申请日：1999-11-16

Applicant: 한국과학기술연구원

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

IPC: C07D403/02

Abstract: PURPOSE: The piperazinylethyl triazole derivatives and a producing method thereof are provided, thereby the piperazinylethyl triazole compounds can be produced in higher yield and purity. CONSTITUTION: The piperazinylethyl triazole derivatives are represented by formula (1), in which R1 is C6 to C10 aromatics, C6 to C10 aromatic carbohydrate substituted with C1 to C6 alkyl, C6 to C10 aromatic carbohydrate substituted with C1 to C4 alkoxy, C6 to C10 aromatic carbohydrate substituted with halogen or C7 to C10 arylalkyl; R2 to R5 are independently hydrogen, halogen, methyl or ethyl; R6 to R7 are independently hydrogen, phenoxy substituted with halogen, -OC(O)R8 or -NR9R10; Y is O or S; R8 is C1 to C6 alkyl; R9 and R10 is independently C1 to C6 alkyl; R11 is hydrogen, C1 to C6 alkyl or phenyl; R12 is independently hydrogen or C1 to C6 alkyl; n is an integer of 1 or 2; k is 5 or 6 when n is 1 or 2, respectively; and m is 4 or 5 when n is 1 or 2, respectively. The piperazinylethyl triazole derivatives is produced by separation and purification using acid.

Abstract translation: 目的：提供哌嗪基乙基三唑衍生物及其制备方法，从而可以更高的产率和纯度制备哌嗪基乙基三唑化合物。 构成：哌嗪基乙基三唑衍生物由式（1）表示，其中R1为C6至C10芳族化合物，C6至C10芳族碳水化合物被C1至C6烷基取代，C6至C10芳族碳水化合物被C1至C4烷氧基取代，C6至C10 用卤素或C 7至C 10芳基烷基取代的芳族碳水化合物; R2至R5独立地为氢，卤素，甲基或乙基; R6至R7独立地为氢，被卤素取代的苯氧基，-OC（O）R8或-NR9R10; Y为O或S; R8是C1-C6烷基; R9和R10独立地为C1至C6烷基; R11是氢，C1-C6烷基或苯基; R 12独立地为氢或C 1至C 6烷基; n是1或2的整数; 当n分别为1或2时，k为5或6; 当n分别为1或2时，m为4或5。 哌嗪基乙基三唑衍生物通过使用酸的分离和纯化而产生。

公开(公告)号：KR1020010046868A

公开(公告)日：2001-06-15

申请号：KR1019990050823

申请日：1999-11-16

Applicant: 한국과학기술연구원

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

IPC: C07D261/14

Abstract: PURPOSE: A novel tertiary aminoethyl isooxazol derivative is provided, which acts as an antagonist of dopamine-1 receptor relating to various central nervous system disorders. And a method for preparing the same is also provided. CONSTITUTION: The tertiary aminoethyl isooxazol derivative is represented by the formula (1) and is prepared by dissolving a compound represented by the formula (2) and a compound represented by the formula (3) in a solvent to react them with each other in the presence of base. In the formulae 1-3, R1 is phenyl, phenyl substituted by halogen atom, phenyl substituted by trifluoromethyl, phenyl methyl having a trifluoromethyl substituent in 2, 3 or 4 position of the phenyl group, diphenylmethyl having a halogen atom substituent in 2, 3 or 4 position of the phenyl group, benzyl or 3-hydrobenzimidazole-2-one, each R2-R5 is hydrogen, R6 is phenyl substituted by at least one selected from the group consisting of nitro group, phynoxy group, methoxy group, trifluoromethyl group and halogen group, vinyl substituted by phenyl group or C5 or C6 unsaturated or saturated hetero cyclic compound substituted by O, S or N, and X is nitrogen or carbon.

Abstract translation: 目的：提供一种新的叔氨基乙基异恶唑衍生物，其作为与各种中枢神经系统疾病有关的多巴胺-1受体的拮抗剂。 还提供了制备该方法。 构成：叔氨基乙基异恶唑衍生物由式（1）表示，通过将式（2）表示的化合物和式（3）表示的化合物溶解在溶剂中，使其在 存在基地 式1-3中，R 1为苯基，被卤素原子取代的苯基，被三氟甲基取代的苯基，苯基2,3或4位中具有三氟甲基取代基的苯基甲基，2,3或4位的卤素原子取代基的二苯基甲基 或4位，苯基或3-氢苯并咪唑-2-酮，每个R 2 -R 5是氢，R 6是被选自硝基，环氧基，甲氧基，三氟甲基中的至少一个取代的苯基 卤素基，被苯基取代的乙烯基或被O，S或N取代的C5或C6不饱和或饱和杂环化合物，X是氮或碳。

公开(公告)号：KR1020010029024A

公开(公告)日：2001-04-06

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: 目的：提供一种新的异恶唑哌嗪衍生物，其用作与中枢神经系统疾病相关的多巴胺-1受体的拮抗剂。 构成：由式（1）表示的新型异恶唑哌嗪衍生物通过在NaBh（OAc）3，NaBH 3 CN或NaBH 4存在下，使式（2）的仲胺与式（3）的醛反应，作为 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。 在式（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烷基和C 1 -C 3烷氧基中被多个基团取代的邻位，间位或对位的苯基，或C1- C3，羟基，4-（2-酮-1-苯并咪唑啉基），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烷基， 苯氧基，C1-C3烷氧基，C1-C3烷氧基，噻吩基，（2-苯基）乙烯基等）中具有1个以上原子的不饱和5或6个杂环基 ，吡啶基和氧，硫和氮; Q是异恶唑（A）或4,5-二氢异恶唑衍生物（B）。

公开(公告)号：KR100394086B1

公开(公告)日：2003-08-06

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: The present invention relates to a novel isoxazolylalkylpiperazine derivatives having selective biological activity at dopamine D3 or D4 receptors represented by the following formula (1), and its preparation method through reductive amination reaction in the presence of reducing agent, wherein R1, R2, R3, R4, R5, R6, X and n are the same as defined in the specification.

Abstract translation: 本发明涉及对下式（1）所示的多巴胺D3或D4受体具有选择性生物活性的新型异恶唑烷基哌嗪衍生物及其在还原剂存在下通过还原胺化反应的制备方法，其中R1，R2，R3， R4，R5，R6，X和n与说明书中的定义相同。

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。