公开(公告)号：KR101357674B1

公开(公告)日：2014-02-06

申请号：KR1020130081165

申请日：2013-07-10

Applicant: 한국화학연구원

Inventor： 김영섭 ,  유시용 ,  홍경식 ,  최춘환 ,  차미란 ,  박우규

IPC: A61K31/343 ,  A61K31/045 ,  A61K31/05 ,  A61K36/65

Abstract: 본 발명에 따른 작약 종자의 추출물, 이의 분획물 또는 이로부터 분리한 화합물은 BACE-1 활성을 저해시켜 알츠하이머형 치매, 파킨슨 병, 진행성 핵상마비 등 퇴행성 뇌질환의 예방 또는 치료에 유용하게 사용될 수 있다.

公开(公告)号：KR100999386B1

公开(公告)日：2010-12-09

申请号：KR1020080054697

申请日：2008-06-11

Applicant: 한국화학연구원

Inventor： 박우규 ,  공재양 ,  조희영 ,  정대영 ,  최길돈 ,  채종학

IPC: A61K31/167 ,  A61K31/17 ,  A61K31/496 ,  A61K31/551

Abstract: 본 발명은 히스타민 H
3 수용체에 대한 길항 작용을 갖는 화합물 및 이를 함유하는 중추 신경계 질환의 예방 및 치료용 약학적 조성물에 관한 것으로, 본 발명의 화합물은 히스타민 H
3 수용체에 대한 친화력이 우수하므로, 중추신경계 질환, 특히 수면 장애, 각성장애, 수면발작(narcolepsy), 인지기능 장애, 주의력결핍 과잉행동장애, 비만증, 간질, 정신분열증, 우울증, 통증 및 약물남용/중독 등의 예방 및 치료에 유용하게 사용될 수 있다.
히스타민, 히스타민 H3 수용체, 길항제, 중추 신경계 질환, 수면장애, 인지기능 장애, 정신질환

公开(公告)号：KR1020090128768A

公开(公告)日：2009-12-16

申请号：KR1020080054697

申请日：2008-06-11

Applicant: 한국화학연구원

Inventor： 박우규 ,  공재양 ,  조희영 ,  정대영 ,  최길돈 ,  채종학

IPC: A61K31/167 ,  A61K31/17 ,  A61K31/496 ,  A61K31/551

Abstract: PURPOSE: A pharmaceutical composition for preventing and treating narcolepsy, congnitive disorder, ADHD(attention-deficit hyperactivity disorder), obesity, epilepsy, schizophrenia, depression, and pain. CONSTITUTION: A pharmaceutical composition for preventing and treating central nervous system disease contains a compound having histamine H3 receptor antagonism. The compound is 4-[3-methyl-3-(1-methyl-pyperidine-4-yl)-ureido]-benzoic acid ethyl ester of chemical formula 1, 1-benzyloxy-3-(4-pyridine-2-yl-piperazine-1-yl)-propan-2-ol of chemical formula 2, N-{4-[4-(2-bromo-4-fluoro-phenyutiocarbamoyl)-[1,4]diazepan-1-yl-methyl]-phenyl}-aceteamide of chemical formula 3, 2-[4-(5-bromo-2H-1λ4-thiophene-2-carbonyl)-[1,4]diazepan-1-yl]-N-phenethyl-aceteamide of chemical formula 4. 1-[benzyl-(2,2-diethoxy-ethyl)-amino]-3-(4-chloro-phenoxy)-propan-2-ol of chemical formula 5, and 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[2-(1-benzyl-piperidine-4-yl) ethyl]-amide of chemical formula 6.

Abstract translation: 目的：预防和治疗发作性睡病，认知障碍，ADHD（注意力缺陷多动障碍），肥胖，癫痫，精神分裂症，抑郁症和疼痛的药物组合物。 构成：用于预防和治疗中枢神经系统疾病的药物组合物含有具有组胺H3受体拮抗作用的化合物。 化合物是化学式1的4- [3-甲基-3-（1-甲基 - 哌啶-4-基） - 脲基] - 苯甲酸乙酯，1-苄氧基-3-（4-吡啶-2-基 - 哌嗪-1-基） - 丙-2-醇，N- {4- [4-（2-溴-4-氟 - 苯基氨基甲酰基） - [1,4]二氮杂环庚烷-1-基 - 甲基 ] - 苯基} - 乙酰胺，2- [4-（5-溴-2H-1λ4-噻吩-2-羰基） - [1,4]二氮杂环庚烷-1-基] -N-苯乙基 - 乙酰胺 化学式4.化学式5的1- [苄基 - （2,2-二乙氧基 - 乙基） - 氨基] -3-（4-氯 - 苯氧基） - 丙-2-醇和5-氯-1,3- - 二甲基-1H-吡唑-4-磺酸 - [2-（1-苄基 - 哌啶-4-基）乙基] - 酰胺。

公开(公告)号：KR1020090078939A

公开(公告)日：2009-07-21

申请号：KR1020080004805

申请日：2008-01-16

Applicant: 한국화학연구원 ,  한국식품연구원

Inventor： 김영섭 ,  유시용 ,  연규환 ,  홍경식 ,  이병회 ,  유미영 ,  최연희 ,  김현기 ,  박우규 ,  고우석 ,  권대영 ,  하태열

IPC: A61K31/192 ,  A61K31/045 ,  A61K31/343 ,  A61P25/28

Abstract: A composition for preventing and treating neutodegenerative disease, which contains a polyphenol compound as an active ingredient is provided to have the effects of beta-amyloid coagulation inhibition, caspase-3 activity suppression and acetylcholinesterase activation suppression. A composition for preventing and treating neurodegenerative diseases comprises salvianolic acid, bakuchiol, epsilon-viniferin, rhapontigenin, piceatannol, luteolin, myricetin, or their mixture as an active ingredient. The neurodegenerative diseases are Alzheimer's disease, Pick's disease, Creutzfeldt-jakob, Parkinson's disease, Lou Gehrig's Disease, or Huntington's disease. The composition suppresses BACE-1[beta-site APP(amyloid precursor protein)-cleaving enzyme 1], caspase or acetylcholine esterase. The composition further comprises medicinal herb. The medicinal herb is Salviae Miltiorrhizae Radix, Psoraleae Semen, Vitidis Fructus, Rhei Rhizoma, Digitalis Folium, Schizonepeta Herba, Taraxaci Herba, Humuli Herba, Lonicerae Folium or their mixture.

Abstract translation: 提供含有多酚化合物作为活性成分的用于预防和治疗神经变性疾病的组合物，以具有β-淀粉样蛋白凝结抑制，半胱天冬酶-3活性抑制和乙酰胆碱酯酶活化抑制的作用。 用于预防和治疗神经变性疾病的组合物包括salvianolic acid，bakuchiol，ε-viniferin，rhapontigenin，piceatannol，木犀草素，杨梅宁或其混合物作为活性成分。 神经变性疾病是阿尔茨海默氏病，皮克病，克雅氏综合征，帕金森氏病，卢格里希氏病或亨廷顿舞蹈病。 该组合物抑制BACE-1β-位点APP（淀粉样蛋白前体蛋白）切割酶1]，半胱天冬酶或乙酰胆碱酯酶。 该组合物还包含药草。 药用草药是丹参，枸杞子，枸杞子，枸杞子，洋地黄属，荆芥草，竹aci草，虎嘴草，金银花或其混合物。

公开(公告)号：KR1020080094475A

公开(公告)日：2008-10-23

申请号：KR1020070038962

申请日：2007-04-20

Applicant: 한국화학연구원

Inventor： 공재양 ,  박우규 ,  조희영 ,  정대영 ,  최길돈 ,  배애님

IPC: A61K31/551 ,  A61K31/435 ,  A61K31/40 ,  A61P25/18

CPC classification number: A61K31/4468 ,  A61K9/0095 ,  A61K9/08 ,  A61K9/10 ,  A61K9/20 ,  A61K9/48 ,  A61K31/40 ,  A61K31/495 ,  A61K31/496 ,  A61K31/551

Abstract: 12 compounds are provided to show excellent binding affinity to serotonin 5-HT2A receptor, thereby being usefully used as a prophylactic or a therapeutic agent of central nervous system diseases such as anxiety, hypochondria, stroke, neurosis, psychosis, schizophrenia, suicidal tendency, Alzheimer's disease, Parkinson's disease, Huntington's chorea, sleep disorders, appetite disorders, cocaine, withdrawal symptoms caused by drug abuse, and migraine. A pharmaceutical composition for preventing and treating central nervous system diseases related to serotonin 5-HT2A receptor comprises a compound selected from the group consisting of naphthalene-2-sulfonic acid methyl-(1-methyl-piperidin-4-yl)-amide, 1-(5-bromo-2-methoxy-benzenesulfonyl)-4-(2-thiopen-2-yl-ethyl)-piperazine, 1-(1-benzyl-piperidin-4-yl)-3-(4-trifluoromethylsulfanyl-phenyl)-urea, 8-[4-(3-phenyl-aryl)-piperazin-1-sulfonyl]-quinoline, 1-(1-benzyl-pyrrolidin-3-yl)-3-(4-trifluoromethylsulfanyl-phenyl)-urea, 1-(4-butoxy-benzenesulfonyl)-4-methyl-[1,4]diazepane, 1-[4-(3,4-dimethyl-phenyl)-piperazin-1-yl]-3-phenoxy]-propan-2-one, biphenyl-4-sulfonic acid [2-(1-methyl-pyrrolidin-2-yl)-ethyl]-amide, 1-(2,5-dichloro-benzenesulfonyl)-4-penethyl-piperazine, 1-penethyl-4-(toluene-4-sulfonyl)-piperazine, 1-(2-fluoro-5-methyl-benzenesulfonyl)-4-penethyl-piperazine, and 1-(4-bromo-benzenesulfonyl)-4-penethyl-piperazine or a pharmaceutically acceptable salt thereof. The composition is formulated into tablet, capsule, solution, syrup, suspension and injection.

Abstract translation: 提供了12种化合物以显示与5-羟色胺5-HT2A受体的极好的结合亲和力，从而有效地用作中枢神经系统疾病如焦虑症，hypochondria，中风，神经症，精神病，精神分裂症，自杀倾向，阿尔茨海默氏症的预防或治疗剂 疾病，帕金森病，亨廷顿舞蹈病，睡眠障碍，食欲障碍，可卡因，药物滥用引起的戒断症状和偏头痛。 用于预防和治疗与5-羟色胺5-HT 2A受体相关的中枢神经系统疾病的药物组合物包括选自萘-2-磺酸甲基 - （1-甲基 - 哌啶-4-基） - 酰胺，1 - （5-溴-2-甲氧基 - 苯磺酰基）-4-（2-噻吩-2-基 - 乙基） - 哌嗪，1-（1-苄基 - 哌啶-4-基）-3-（4-三氟甲硫基 - 苯基） - 脲，8- [4-（3-苯基 - 芳基） - 哌嗪-1-磺酰基] - 喹啉，1-（1-苄基 - 吡咯烷-3-基）-3-（4-三氟甲硫基 - 苯基） - 脲，1-（4-丁氧基苯磺酰基）-4-甲基 - [1,4]二氮杂环庚烷，1- [4-（3,4-二甲基 - 苯基） - 哌嗪-1-基] -3-苯氧基] - 丙-2-酮，联苯-4-磺酸[2-（1-甲基 - 吡咯烷-2-基） - 乙基] - 酰胺，1-（2,5-二氯 - 苯磺酰基）-4-苯乙基 - 哌嗪 ，1-苯乙基-4-（甲苯-4-磺酰基） - 哌嗪，1-（2-氟-5-甲基 - 苯磺酰基）-4-辛基 - 哌嗪和1-（4-溴 - 苯磺酰基）-4- 哌嗪或其药学上可接受的盐。 将组合物配制成片剂，胶囊，溶液，糖浆，悬浮液和注射剂。

公开(公告)号：KR100838645B1

公开(公告)日：2008-06-16

申请号：KR1020060095156

申请日：2006-09-28

Applicant: 한국화학연구원

Inventor： 임희종 ,  정명희 ,  최일영 ,  박우규

IPC: C07D211/56 ,  A61K31/4406

Abstract: 본 발명은 하기 화학식 Ⅰ로 표시되는 (3R)-아미노-(4R)-아릴피페리딘 화합물 또는 이의 약제학적으로 허용 가능한 염에 관한 것이고, 또한 상기 3R)-아미노-(4R)-아릴피페리딘 화합물 또는 이의 약제학적으로 허용 가능한 염을 유효성분으로 함유하는 알쯔하이머 또는 다운증후군의 예방 또는 치료용 조성물, 또는 베타-세크리테아제(BACE)의 활성 억제제 조성물에 관한 발명이다.
[화학식 Ⅰ]

본 발명에 따른 3R)-아미노-(4R)-아릴피페리딘 화합물은 베타-세크리테아제(BACE)의 활성을 억제하여 신경세포를 손상시키는 베타-아밀로이드 단백질의 생성을 억제함으로써 알츠하이머 질환을 치료하거나 예방하는데 효과적으로 사용될 수 있다.
알츠하이머 질환, 피페리딘 화합물, 베타-세크리테아제, 노화, 신경퇴행성 질환, 베타-아밀로이드

公开(公告)号：KR100808685B1

公开(公告)日：2008-02-29

申请号：KR1020060101544

申请日：2006-10-18

Applicant: 한국화학연구원

Inventor： 공재양 ,  최일영 ,  임희종 ,  명도 ,  정명희 ,  박우규

IPC: C07D401/08 ,  C07D417/08 ,  C07D413/08

Abstract: A novel piperazine derivative is provided to show excellent antagonism against a dopamine receptor D4, thereby being effective as a therapeutic agent for schizophrenia. A piperazine derivative having a cycloalkyl bicyclic heterocycle group is represented by a formula(1), where R1 is a group represented by the structural formula(1) or (2); X is H, halogen, nitro, cyano, C1-6 alkyl, or C1-6 alkoxy; Y is NH, S or O; R2 is phenyl or pyridine, which may be substituted or unsubstituted by a substituent selected from the group consisting of halogen, C1-6 alkyl, C1-6 alkoxy, and cyano; n is an integer from 1 to 3. A method for preparing a piperazine compound represented by the formula(1b) comprises the steps of: (a) subjecting cyclopentanone carboxylic acid coupled to a Wang resin and represented by the formula(3) with a piperazine to a reducing amination to obtain a compound represented by the formula(3a); and (b) applying microwave to the compound of the formula(3a) with an amine compound represented by the formula(3b) to synthesize the compound of the formula(1b), where R2, X, Y, and n are the same as defined above, and A is Wang resin. A therapeutic agent for schizophrenia comprises the compound of the formula(1) or a pharmaceutically acceptable salt thereof.

Abstract translation: 提供了一种新的哌嗪衍生物，以显示对多巴胺受体D4的极好的拮抗作用，从而作为精神分裂症的治疗剂是有效的。 具有环烷基双环杂环基的哌嗪衍生物由式（1）表示，其中R 1是由结构式（1）或（2）表示的基团。 X是H，卤素，硝基，氰基，C 1-6烷基或C 1-6烷氧基; Y是NH，S或O; R2是苯基或吡啶，其可以被选自卤素，C 1-6烷基，C 1-6烷氧基和氰基的取代基取代或未取代。 n为1〜3的整数。由式（1b）表示的哌嗪化合物的制备方法包括以下步骤：（a）将与式（3）表示的Wang树脂偶联的环戊酮羧酸与 哌嗪还原胺化得到式（3a）表示的化合物; 和（b）用式（3b）表示的胺化合物向式（3a）化合物施加微波以合成式（1b）化合物，其中R 2，X，Y和n与 A为王树脂。 精神分裂症的治疗剂包括式（1）的化合物或其药学上可接受的盐。

公开(公告)号：KR1020080018029A

公开(公告)日：2008-02-27

申请号：KR1020060080067

申请日：2006-08-23

Applicant: 한국화학연구원

Inventor： 정영식 ,  박노상 ,  박우규 ,  공재양

IPC: A61K31/216 ,  A61P25/08

Abstract: Muscarinic receptor antagonists or agents are provided to struggle with the muscarinic receptor, prevent and treat nervous system diseases such as convulsion, Parkinson's disease and epilepsy, and detoxify the poisoning of nerve agents or organophosphate fertilizer. The muscarinic receptor antagonists or agents contain 2-phenyl-2-carboxylic acid derivatives represented by the formula(1) or pharmaceutically acceptable salts thereof as effective ingredients, wherein X is hydrogen, halogen, amino, nitro, C1-C5 linear or branched chain alkyl or C1-C5 alkoxy and is positioned in an ortho-, metha- or para-site; Y is C1-C7 linear or branched chain alkyl; R1 and R2 are each independently C1-C7 linear or branched chain alkyl and form a ring together; and n is an integer from 1 to 4.

Abstract translation: 提供毒蕈碱受体拮抗剂或药物与毒蕈碱受体作斗争，预防和治疗神经系统疾病如惊厥，帕金森病和癫痫，并解毒神经药物或有机磷酸盐肥料的中毒。 毒蕈碱受体拮抗剂或药剂含有由式（1）表示的2-苯基-2-羧酸衍生物或其药学上可接受的盐作为有效成分，其中X为氢，卤素，氨基，硝基，C 1 -C 5直链或支链 烷基或C 1 -C 5烷氧基并位于邻位，间位或对位; Y是C 1 -C 7直链或支链烷基; R1和R2各自独立地为C1-C7直链或支链烷基并形成环; n为1〜4的整数。

公开(公告)号：KR1020080004304A

公开(公告)日：2008-01-09

申请号：KR1020060063140

申请日：2006-07-05

Applicant: 한국화학연구원

Inventor： 성철민 ,  박노상 ,  최진일 ,  박철민 ,  박우규 ,  공재양

IPC: C07D401/04 ,  C07D403/04 ,  A61P25/00

Abstract: A novel substituted-1H-quinazoline-2,4-dione derivative is provided which shows excellent selectivity to a 5-HT6 receptor compared to other receptors, and inhibits the concentration increase of cAMP caused by 5-HT and apomorphine -induced hyperactivity of a rat, thereby being usefully used for central nervous system diseases related to the 5-HT6 receptor. A method for preparing a substituted-1H-quinazoline-2,4-dione derivative represented by the formula(1) comprises the steps of: (a) reacting anthranilic acid anhydride represented by the formula(2) with an amine compound to prepare an intermediate represented by the formula(I); (b) subjecting the intermediate of the formula(I) to cyclization to obtain an intermediate represented by the formula(II); (c) reacting the intermediate of the formula(II) with a compound represented by the formula(5) to prepare the derivative of the formula(1). In the formulae, each R^1, R^2 and R^3 is independently H, halogen, amino, cycloamino, nitro, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, piperazinyl, or N-methyl piperazinyl; R^4 is H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkoxy, aryloxy, acyl amino, arylsulfonylamino, arylsulfonylureido, alkylcarboxylate, arylcarboxylate, aralkylcarboxylate, alkylureido, or arylureido; R^5 is H, alkyl, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; R^6 is H, alkyl or aryl; X is F, Cl, Br, I or trifluoroacetate; and Y is Cl, Br, I, methane sulfonate, or p-toluenesulfonate. A pharmaceutical composition as an antagonist of 5-HT6 serotonin receptor comprises the compound of the formula(1), a pharmaceutically acceptable salt thereof or a prodrug thereof as an effective ingredient.

Abstract translation: 提供了一种新的取代的1H-喹唑啉-2,4-二酮衍生物，其与其他受体相比显示出对5-HT6受体的优异选择性，并且抑制由5-HT引起的cAMP和阿扑吗啡诱导的多动症的浓度增加 大鼠，因此有用地用于与5-HT6受体相关的中枢神经系统疾病。 由式（1）表示的取代的1H-喹唑啉-2,4-二酮衍生物的制备方法包括以下步骤：（a）使式（2）所示的邻氨基苯甲酸酐与胺化合物反应，制备 由式（I）表示的中间体; （b）使式（I）的中间体环化以获得由式（II）表示的中间体; （c）使式（II）的中间体与由式（5）表示的化合物反应以制备式（1）的衍生物。 式中，R 1，R 2和R 3各自独立地为H，卤素，氨基，环氨基，硝基，氰基，烷基，卤代烷基，烷氧基，卤代烷氧基，哌嗪基或N-甲基哌嗪基; 酰基氨基，芳基磺酰基氨基，芳基磺酰基脲基，烷基羧酸酯，芳基羧酸酯，芳烷基羧酸酯，烷基脲基或芳基脲基; R 4是H，烷基，环烷基，卤代烷基，芳基，杂芳基，芳烷基，杂芳基烷基，烷氧基， R 5是H，烷基，环烷基，卤代烷基，芳基，芳基烷基，杂芳基或杂芳基烷基; R 6是H，烷基或芳基; X是F，Cl，Br，I或三氟乙酸盐; Y是Cl，Br，I，甲磺酸盐或对甲苯磺酸盐。 作为5-HT 6 5-羟色胺受体的拮抗剂的药物组合物包含式（1）的化合物，其药学上可接受的盐或其前药作为有效成分。

公开(公告)号：KR100753907B1

公开(公告)日：2007-08-31

申请号：KR1020060037547

申请日：2006-04-26

Applicant: 한국화학연구원

Inventor： 정영식 ,  성철민 ,  박노상 ,  최진일 ,  공재양 ,  박우규

IPC: C07C219/12 ,  C07D211/40 ,  C07D451/04

Abstract: Provided are a novel 2-phenylindane-2-carboxylic acid ester derivative and its pharmaceutically acceptable salt, a method for preparing the derivative, and an agent for treating or preventing convulsions, Parkinson's disease or epilepsy containing the derivative. A 2-phenylindane-2-carboxylic acid ester derivative is represented by a formula 1, wherein X is H, a halogen atom, an amino group, a nitro group, a substituted or unsubstituted C1-C5 linear or branched alkyl group, or a substituted or unsubstituted C1-C5 alkoxy group; Y is a substituted or unsubstituted C1-C7 linear or branched alkyl group, or a substituted or unsubstituted C3-C7 cycloalkyl group; Z is H, a halogen atom, a substituted or unsubstituted C1-C5 alkyl group, a substituted or unsubstituted C1-C5 alkoxy group, or a substituted or unsubstituted C5-C7 cycloalkyl or aryl group fused with the two carbon atoms adjacent to the benzene ring of the indane ring; and R1 and R2 are independently a substituted or unsubstituted C1-C7 alkyl group, can form a ring together, or can independently form a ring together with Y.

Abstract translation: 本发明提供一种新的2-苯基茚满-2-羧酸酯衍生物及其药学上可接受的盐，该衍生物的制备方法，以及含有该衍生物的惊厥，帕金森氏病或癫痫的治疗或预防剂。 2-苯基茚满-2-羧酸酯衍生物由式1表示，其中X为H，卤素原子，氨基，硝基，取代或未取代的C1-C5直链或支链烷基或 取代或未取代的C 1 -C 5烷氧基; Y是取代或未取代的C 1 -C 7直链或支链烷基，或取代或未取代的C 3 -C 7环烷基; Z是H，卤素原子，取代或未取代的C1-C5烷基，取代或未取代的C1-C5烷氧基，或取代或未取代的C5-C7环烷基或芳基，其与苯相邻的两个碳原子 茚满环的环; 并且R 1和R 2独立地为取代或未取代的C 1 -C 7烷基，可以一起形成环，或者可以与Y一起独立地形成环。