公开(公告)号：KR1020100005476A

公开(公告)日：2010-01-15

申请号：KR1020080065522

申请日：2008-07-07

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  이재균 ,  오유나 ,  추현아 ,  배애님 ,  임혜원 ,  서선희

IPC: C07D403/12

CPC classification number: C07D401/12 ,  A61K31/454

Abstract: PURPOSE: An isoindolinone derivative having pharmaceutical activation to T-type calcium channel is provided to have antagonistic activity to T-type calcium channel and use as a therapeutic agent for hypertension, cancer, and neurogenic pain. CONSTITUTION: An isoindolinone derivative is denoted by chemical formula 1. In chemical formula 1, R1 is hydrogen atom, halogen atom, alkoxy group of C1-C6, haloalkyl group of C1-C6, nitro group, cyano group, or hydroxyl group. R2 is hydrogen atom, alkyl group of C1-C6, or aryl group. The isoindolinone derivative is obtained by reacting piperidinyl propylamine derivative of chemical formula 9 with isoindolinone carboxylic acid derivative of chemical formula 8 through amide reaction. A pharmaceutical composition for treating hypertension, cancer, epilepsy, and neurogenic pain contains the isoindolinone derivative and its pharmaceutically acceptable salt.

Abstract translation: 目的：提供具有T型钙通道药学活性的异吲哚啉酮衍生物，对T型钙通道具有拮抗作用，用作高血压，癌症和神经源性疼痛的治疗剂。 构成：异吲哚啉酮衍生物由化学式1表示。在化学式1中，R 1为氢原子，卤素原子，C 1 -C 6烷氧基，C 1 -C 6卤代烷基，硝基，氰基或羟基。 R2是氢原子，C1-C6烷基或芳基。 异吲哚啉酮衍生物通过化学式9的哌啶基丙胺衍生物与化学式8的异吲哚酮羧酸衍生物反应而得到。 用于治疗高血压，癌症，癫痫和神经原性疼痛的药物组合物含有异吲哚啉酮衍生物及其药学上可接受的盐。

公开(公告)号：KR100879636B1

公开(公告)日：2009-01-21

申请号：KR1020070084322

申请日：2007-08-22

Applicant: 한국과학기술연구원

Inventor： 남길수 ,  임혜원 ,  배애님 ,  추현아 ,  최경일 ,  나승렬

IPC: A61K31/517 ,  A61P25/00

CPC classification number: A61K31/517 ,  A61K31/5377

Abstract: A pharmaceutical composition for preventing and treating the disease related to the central nervous system, and a food composition are provided to obtain the effect on emesis, nausea, alcoholism, drugs abuse, depression, compulsion neurosis, anxiety, etc. A pharmaceutical composition for preventing and treating the disease related to the central nervous system comprises a quinoline derivative compound represented by the formula 1 or its pharmaceutically acceptable salt as an active ingredient, wherein R1 is H, a C1-C6 alkyl group, a phenyl group or a benzyl group; R2 is a heterocyclic group selected from morpholine, pyrrolidine and piperidine; the phenyl group or the benzyl group can be substituted with a substituent selected from a halogen atom, a C1-C6 alkyl group and a C1-C6 alkoxy group; and n is an integer of 1-6.

Abstract translation: 提供了用于预防和治疗与中枢神经系统有关的疾病的药物组合物和食物组合物，以获得对呕吐，恶心，酒精中毒，药物滥用，抑郁，强迫性神经症，焦虑等的作用。 并且治疗与中枢神经系统相关的疾病包括由式1表示的喹啉衍生物化合物或其药学上可接受的盐作为活性成分，其中R1是H，C1-C6烷基，苯基或苄基; R2是选自吗啉，吡咯烷和哌啶的杂环基; 苯基或苄基可以被选自卤素原子，C1-C6烷基和C1-C6烷氧基的取代基取代; n为1-6的整数。

公开(公告)号：KR100645371B1

公开(公告)日：2006-11-14

申请号：KR1020050061697

申请日：2005-07-08

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  배애님 ,  차주환 ,  고훈영 ,  신철

IPC: C07D493/04

Abstract: Novel bicyclic tetrahydrofuran derivatives, and a process for preparing the same compounds are provided to improve efficiency of preparation, so that they are useful as intermediates for synthesis of natural products. The bicyclic tetrahydrofuran derivatives represented by the formula(1) are provided, wherein n is 1 or 2; R is phenyl group or substituted phenyl group by C1-C6 alkyl group, C1-C6 alkoxy group, hydroxy group or C1-C6 hydroxyalkyl group; and R1 is C1-C6 alkyl group. The bicyclic tetrahydrofuran derivatives represented by the formula(1) are prepared by intramolecular cyclizing tetrahydrofuran-allenol derivatives in the presence of alcohol compounds, transition metal catalyst and carbon monoxide(CO), wherein the transition metal catalyst is palladium chloride or copper chloride; and the reaction temperature is 0 to 25 deg.C.

Abstract translation: 新型双环四氢呋喃衍生物及其制备方法可提高制备效率，因此它们可用作合成天然产物的中间体。 提供由式（1）表示的双环四氢呋喃衍生物，其中n是1或2; R 1为C 1 -C 6烷基，C 1 -C 6烷氧基，羟基或C 1 -C 6羟烷基的苯基或取代的苯基; 并且R 1是C 1 -C 6烷基。 由式（1）表示的双环四氢呋喃衍生物是在醇化合物，过渡金属催化剂和一氧化碳（CO）存在下通过分子内环化四氢呋喃 - 烯醇衍生物制备的，其中过渡金属催化剂为氯化钯或氯化铜; 反应温度为0〜25℃。

公开(公告)号：KR1020060026315A

公开(公告)日：2006-03-23

申请号：KR1020040075192

申请日：2004-09-20

Applicant: 한국과학기술연구원

Inventor： 배애님 ,  고훈영 ,  조용서 ,  차주환 ,  임혜원 ,  정희경

IPC: C07D413/14 ,  C07D413/12

Abstract: 본 발명은 T-타입 칼슘채널(T-type calcium channel)에 대한 선택적인 길항작용이 우수하여 이와 관련된 뇌질환 및 심장질환의 치료 및 예방에 유효한 피페라지닐알킬 이소옥사졸 유도체와 용액상 조합 합성을 이용한 이 화합물의 제조방법 그리고 이 화합물의 T-타입 칼슘 길항제로서의 의약적 용도에 관한 것이다.
피페라지닐알킬 이소옥사졸, T-타입 칼슘채널, 간질, 고혈압

公开(公告)号：KR100488444B1

公开(公告)日：2005-05-11

申请号：KR1020010089274

申请日：2001-12-31

Applicant: 한국과학기술연구원

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

IPC: C07D215/56

Abstract: 다음 화학식 6의 헤테로고리 화합물 및 그의 제조 방법;
화학식 6

식 중에서, R은 H이거나 Cl, F, Br 및 I에서 선택되는 할로겐 원소이고; R
1 와 R
2 는 서로 독립적으로 H, 알킬기 또는 -OH기이며, Y는 -Ts(토실), -Ms(메실) 또는 -Ac(아세틸)임.

公开(公告)号：KR1020050028095A

公开(公告)日：2005-03-22

申请号：KR1020030064384

申请日：2003-09-17

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  강현정

IPC: C07D493/08

CPC classification number: C07D493/08 ,  A61K31/343

Abstract: A 8-membered cyclic compound having diexomethylene groups and a preparation method thereof are provided, which compound is useful as an intermediate for preparing other cyclic compound through Diels-Alder reaction, and has improved activity. The 8-membered cyclic compound having diexomethylene groups represented by formula (1) is provided, wherein R1 is phenyl; R2 and R3 are independently hydrogen; or R1, R2 and R3 together form 5- to 10-membered aliphatic or aromatic rings. The method for preparing the 8-membered cyclic compound having diexomethylene groups represented by formula (1) comprises cyclization of trimethylsilanylmethyl-alenol derivatives in the presence of Lewis acid in solvent at -90 deg. C to the room temperature, wherein the solvent is selected from diethylether, tetrahydrofuran, dichloromethane and chloroform; and the Lewis acid is trimethylsillyl trifluoromethanesulfonate(TMSOTf).

Abstract translation: 提供具有阴离子亚甲基的8元环状化合物及其制备方法，该化合物可用作通过Diels-Alder反应制备其它环状化合物的中间体，并且具有改善的活性。 提供了由式（1）表示的具有正亚烷基的8元环状化合物，其中R 1是苯基; R2和R3独立地是氢; 或R 1，R 2和R 3一起形成5至10元脂族或芳环。 由式（1）表示的具有阴离子亚甲基的8-元环状化合物的制备方法包括在路易斯酸存在下，在-90℃的溶剂中使三甲基硅烷基甲基 - 烯醇衍生物环化。 C至室温，其中溶剂选自乙醚，四氢呋喃，二氯甲烷和氯仿; 路易斯酸是三甲基甲硅烷基三氟甲磺酸酯（TMSOTf）。

公开(公告)号：KR1020050028094A

公开(公告)日：2005-03-22

申请号：KR1020030064383

申请日：2003-09-17

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  강현정

IPC: C07D493/08

CPC classification number: C07D493/08

Abstract: A 7-membered cyclic compound having diexomethylene groups and a preparation method thereof are provided, which compound is useful as an intermediate for preparing other cyclic compound through Diels-Alder reaction, and has improved activity. The 7-membered cyclic compound having diexomethylene groups represented by formula (1) is provided, wherein R1 is C1-C6 alkyl; R2 and R3 are independently hydrogen; or R1, R2 and R3 together form 5- to 10-membered aliphatic or aromatic rings. The method for preparing the 7-membered cyclic compound having diexomethylene groups represented by formula (1) comprises cyclization of trimethylsilanylmethyl-alenol derivatives in the presence of Lewis acid in solvent at -90 deg. C to the room temperature, wherein the solvent is selected from diethylether, tetrahydrofuran, dichloromethane and chloroform; and the Lewis acid is trimethylsillyl trifluoromethanesulfonate(TMSOTf).

Abstract translation: 提供了具有阴离子亚甲基基团的7-元环状化合物及其制备方法，该化合物可用作通过Diels-Alder反应制备其它环状化合物的中间体，并具有改进的活性。 提供了由式（1）表示的具有正亚烷基的7-元环状化合物，其中R 1为C 1 -C 6烷基; R2和R3独立地是氢; 或R 1，R 2和R 3一起形成5至10元脂族或芳环。 由式（1）表示的具有阴离子亚甲基的7-元环状化合物的制备方法包括在路易斯酸存在下，在-90℃的溶剂中使三甲基硅烷基甲基 - 烯醇衍生物环化。 C至室温，其中溶剂选自乙醚，四氢呋喃，二氯甲烷和氯仿; 路易斯酸是三甲基甲硅烷基三氟甲磺酸酯（TMSOTf）。

公开(公告)号：KR100465277B1

公开(公告)日：2005-01-13

申请号：KR1020020004200

申请日：2002-01-24

Applicant: 한국과학기술연구원

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

IPC: C07D453/02 ,  C07D471/08 ,  C07D261/06

Abstract: PURPOSE: Azabicyclic compounds having an oxime moiety and a preparation method thereof are provided, which can be useful for treatment of cerebral nervous diseases caused by choline neurotransmission disorders including Alzheimer's disease. CONSTITUTION: An azabicyclic compounds having an oxime moiety represented by the formula(I) and pharmaceutically acceptable salts thereof are provided, wherein n is 1 or 2; m is 0 or 1; and R is at least one substituent selected from the group consisting of hydrogen, F, Cl, methoxy, OH, NH2, NO2, 3, 4-dimethoxy, 2, 4-dimethoxy, cyano, C1-C6 alkyl, 1, 2 or 3 fluorine atom substituted C1-C6 alkyl, 4-methoxybenzyloxy, t-butoxycarbonyl, C2-C6 alkenyl, 1, 2 or 3 fluorine atom substituted C2-C6 alkynyl, C3-C7 cycloalkyl and aromatic atom group, in which the aromatic atom group is selected from phenyl, 2- or 3-thienyl, 2- or 3-puridyl, 2- or 3-pyrrolyl; and the substituent of the aromatic atom group is selected from the group consisting of Cl, Br, F, trifluoromethyl, NH2, NO2 and C1-C4 straight or branched chain alkyl.

Abstract translation: 目的：提供具有肟部分的氮杂双环化合物及其制备方法，其可用于治疗由包括阿尔茨海默病在内的胆碱神经传递障碍引起的脑神经疾病。 构成：提供了具有由式（I）表示的肟部分的氮杂双环化合物及其药学上可接受的盐，其中n是1或2; m是0或1; 和R是至少一个选自氢，F，Cl，甲氧基，OH，NH 2，NO 2，3,4-二甲氧基，2,4-二甲氧基，氰基，C 1 -C 6烷基，1,2或3个 3个氟原子取代的C 1 -C 6烷基，4-甲氧基苄氧基，叔丁氧基羰基，C 2 -C 6烯基，1,2或3个氟原子取代的C 2 -C 6炔基，C 3 -C 7环烷基和芳族原子基团， 选自苯基，2-或3-噻吩基，2-或3-嘌呤基，2-或3-吡咯基; 并且芳族原子基团的取代基选自Cl，Br，F，三氟甲基，NH 2，NO 2和C 1 -C 4直链或支链烷基。

公开(公告)号：KR100451414B1

公开(公告)日：2004-10-06

申请号：KR1020010089275

申请日：2001-12-31

Applicant: 한국과학기술연구원

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

IPC: C07D209/36

Abstract: PURPOSE: Indol derivatives and a preparation process thereof are provided, thereby rapidly preparing indol derivatives under mild conditions in higher yield. CONSTITUTION: Indol derivatives are represented by the formula 6, wherein R is H, or halogen selected from Cl, F, Br and I; and Y is -Ts(tosyl), -Ms(mesyl) or -Ac(acetyl). A process for preparing the indol derivatives of the formula 6 comprises the steps of: reacting a compound of the formula 1 with a compound of the formula 2 in the presence of indium metal and acid to simultaneously perform allylation of aldehyde and reduction of nitro group, thereby preparing a compound of the formula 3; protecting amine group of the compound of the formula 3 to prepare a compound of the formula 4; oxidizing secondary alcohol of the compound of the formula 4 to prepare a compound of the formula 5; and cyclization of the compound of the formula 5 in the presence of organic base, wherein the oxidation of secondary alcohol uses pyridinium chlorochromate(PCC) or pyridinium dichromate(PDC) or Swern's oxidation or Dess-Martin periodinane oxidation; and the organic base is diisopropylethylamine, DBU (1,8-diazabicyclo£5.4.0|undec-7-ene), DBN (1,5-diazabicyclo£4.3.0|non-5-ene), triethylamine or pyridine.

Abstract translation: 目的：提供吲哚衍生物及其制备方法，由此在温和条件下以较高的产率快速制备吲哚衍生物。 构成：吲哚衍生物由式6表示，其中R是H或选自Cl，F，Br和I的卤素; Y是-Ts（甲苯磺酰基），-Ms（甲磺酰基）或-Ac（乙酰基）。 制备式6吲哚衍生物的方法包括以下步骤：使式1化合物与式2化合物在铟金属和酸存在下反应，同时进行醛的烯丙基化和硝基的还原， 由此制备式3的化合物; 保护式3化合物的胺基以制备式4化合物; 氧化式4化合物的仲醇以制备式5化合物; 在有机碱存在下环化式5化合物，其中仲醇的氧化使用氯铬酸吡啶鎓（PCC）或重铬酸吡啶鎓（PDC）或斯文氧化或戴斯 - 马丁氧化剂氧化; DBU（1,8-二氮杂双环〔5.4.0〕十一碳-7-烯），DBN（1,5-二氮杂双环〔4.3.0〕壬-5-烯），三乙胺或吡啶组成的有机碱。

公开(公告)号：KR100441404B1

公开(公告)日：2004-07-23

申请号：KR1020020004199

申请日：2002-01-24

Applicant: 한국과학기술연구원

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

IPC: C07D453/02 ,  C07D471/08 ,  C07D261/06

Abstract: PURPOSE: An alkenyl azabicyclic compound and a preparation method thereof are provided, which can be useful for treatment of cerebral nervous diseases caused by choline neurotransmission disorders. CONSTITUTION: An alkenyl azabicyclic compound represented by the formula(I) and pharmaceutically acceptable salts thereof are provided, wherein n is 1 or 2; and R is selected from the group consisting of hydrogen, F, Cl, methoxy, OH, NH2, NO2, 3,4-dimethoxy, 2,4-dimethoxy, cyano, C1-C6 alkyl, 1, 2 or 3 fluorine substituted C1-C6 alkyl, 4-methoxybenzyloxy, t-butoxycarbonyl, C2-C6 alkenyl, 1, 2 or 3 fluorine substituted C2-C6 alkynyl and C3-C7 cyloalkyl. A method for preparing the alkenyl azabicyclic compound of the formula(I) comprises a compound of the formula(II) with a compound of the formula(III) or formula(IV), wherein R1, R2 and R3 are independently C1-C6 alkyl, aryl or arylalkyl.

Abstract translation: 目的：提供烯基氮杂双环化合物及其制备方法，其可用于治疗由胆碱神经传递紊乱引起的脑神经疾病。 构成：提供由式（I）表示的烯基氮杂双环化合物及其药学上可接受的盐，其中n是1或2; 并且R选自氢，F，Cl，甲氧基，OH，NH 2，NO 2，3,4-二甲氧基，2,4-二甲氧基，氰基，C 1 -C 6烷基，1,2或3个氟取代的C 1 -C 6烷基，4-甲氧基苄氧基，叔丁氧基羰基，C 2 -C 6烯基，1,2或3个氟取代的C 2 -C 6炔基和C 3 -C 7环烷基。 用于制备式（I）的烯基氮杂双环化合物的方法包括式（II）的化合物与式（III）或式（IV）的化合物，其中R 1，R 2和R 3独立地为C 1 -C 6烷基 ，芳基或芳基烷基。