公开(公告)号：KR1020080029296A

公开(公告)日：2008-04-03

申请号：KR1020060095156

申请日：2006-09-28

Applicant: 한국화학연구원

Inventor： 임희종 ,  정명희 ,  최일영 ,  박우규

IPC: C07D211/56 ,  A61K31/4406

Abstract: A (3R)-amino-(4R)-aryl piperidine compound is provided to inhibit generation of beta-amyloid proteins damaging neurons by inhibiting the activity of beta-secretase(BACE), thereby being effectively used for preventing or treating Alzheimer's disease. A (3R)-amino-(4R)-aryl piperidine compound is represented by a formula(I), wherein R^1 is -(CH)n-Ar, -(CH)n-CO-Ar, -(CH)n-SO2-Ar, or -(CH)n-CO-NH-Ar(where n is an integer from 0 to 3, Ar is a group represented by the structural formula(1) or (2); R^2 is H or halogen substituted or unsubstituted phenyl; and R^3 is H, -CO-R^6, -SO2-R^7, -CO-(CH2)m-R^8, -CO-NH-(CH2)m-R^9, -COO-(CH2)m-R^10, -CO-N(R^11)-(CH2)m-COO-R^12, -CO-NH-C(R^13))(R^14)-(CH2)m-COO-R^15 or -CO-C(R^16)(R^17)-NH-COO-(CH2)m-R^18(where each R^6 to R^18 is H, halogen, hydroxy or C1-6 alkyl which may be substituted or unsubstituted by C1-3 alkoxy, C1-3 alkylsulfonyl or the Ar same as defined above the R^1 and m is an integer from 0 to 2). In the structural formula(1) or (2), each Y^1 and Y^2 is independently H, phenyl, phenoxy, C1-3 alkoxy or -CO-N(R^4)R^5(wherein each R^4 and R^5 is independently C1-3 alkyl). A pharmaceutical composition for preventing or treating Alzheimer's disease or Down's syndrome comprises the compound of the formula(1) or a pharmaceutically acceptable salt thereof as an effective ingredient.

Abstract translation: 提供（3R） - 氨基 - （4R） - 芳基哌啶化合物，通过抑制β-分泌酶（BACE）的活性来抑制损伤神经元的β-淀粉样蛋白的产生，从而有效地用于预防或治疗阿尔茨海默氏病。 （3R） - 氨基 - （4R） - 芳基哌啶化合物由式（I）表示，其中R 1是 - （CH）n -Ar， - （CH）n -CO-Ar， - （CH） n-SO 2 -Ar或 - （CH）n -CO-NH-Ar（其中n是0至3的整数，Ar是由结构式（1）或（2）表示的基团; R 2是 H或卤素取代或未取代的苯基; R 3是H，-CO-R 6，-SO 2 -R 7，-CO-（CH 2）m R 8，-CO-NH-（CH 2）m R 9 ，-COO-（CH 2）m R 10，-CO-N（R 11） - （CH 2）m -COO-R 12，-CO-NH-C（R 13））（R 14） （CH 2）m -COO-R 15或-CO-C（R 16）（R 17）-NH-COO-（CH 2）m R 18（其中每个R 6至R 18是H，卤素 ，可以被C 1-3烷氧基取代或未取代的羟基或C 1-6烷基，C 1-3烷基磺酰基或与上述R 1相同的Ar，m是0-2的整数。 在结构式（1）或（2）中，每个Y 1和Y 2独立地是H，苯基，苯氧基，C 1-3烷氧基或-CO-N（R 4）R 5（其中每个R' 4和R 5独立地是C 1-3烷基）。 用于预防或治疗阿尔茨海默病或唐氏综合症的药物组合物包含式（1）化合物或其药学上可接受的盐作为有效成分。

公开(公告)号：KR1020050100090A

公开(公告)日：2005-10-18

申请号：KR1020040025267

申请日：2004-04-13

Applicant: 한국화학연구원

Inventor： 최일영 ,  홍중연 ,  변경희 ,  정명희 ,  임희종 ,  박우규

IPC: C07D471/04

Abstract: 본 발명은 다음 화학식 1로 표시되는 후퍼진(huperzine) B 유도체와 이의 제조방법에 관한 것으로서, 더욱 상세하게는 다음 화학식 2로 표시되는 카르복실산 화합물을 출발물질로 사용하고, C5 위치의 카르복실기를 아민화 및
N -알켄일화하여 다음 화학식 4로 표시되는 화합물을 반응 중간체로 합성한 후에, 이 중간체 화합물을 복분해반응(Ring Closing Metathesis, RCM)한 후에 메틸보호기를 제거하는 일련의 제조과정을 거쳐 합성하게 되는, 다음 화학식 1로 표시되는 후퍼진 B 유도체와 이의 제조방법에 관한 것이다. 본 발명에 따른 상기 화학식 1로 표시되는 화합물은 치매치료 효과가 있는 것으로 잘 알려져 있는 후퍼진 B 화합물의 유도체로서 화합물 그 자체의 의약적 활성이 기대된다.

公开(公告)号：KR100390777B1

公开(公告)日：2003-07-10

申请号：KR1020000078674

申请日：2000-12-19

Applicant: 한국화학연구원

Inventor： 최일영 ,  정명희 ,  양준연 ,  이효원

IPC: C07D215/22

Abstract: PURPOSE: Provided is a process for preparing pyridone derivative represented by the formula(1) and useful as a therapeutics of Alzheimer's disease(AD). CONSTITUTION: The process for preparing pyridione derivative of the formula(1) comprises the steps of; reacting 1,4-cyclohexanedione monoketal of the formula(2) with secondary amine under acid catalyst; then treating the resultant with propiolamide of the formula(3) to obtain the compound of the formula(1). In the formulae, R1 and R2 represent individually C1-C6 alkyl group or R1 and R2 bind together to form 5-8 membered hetero ring.

Abstract translation: 目的：提供一种制备式（1）代表的吡啶酮衍生物并用作阿尔茨海默病（AD）治疗剂的方法。 构成：制备式（1）的吡啶酮衍生物的方法包括以下步骤： 在酸催化剂下使式（2）的1,4-环己烷二酮单缩酮与仲胺反应; 然后用式（3）丙酰胺处理得到式（1）化合物。 在式中，R 1和R 2分别代表C 1 -C 6烷基或R 1和R 2结合在一起形成5-8元杂环。

公开(公告)号：KR100336971B1

公开(公告)日：2002-05-17

申请号：KR1019990026908

申请日：1999-07-05

Applicant: 한국화학연구원

Inventor： 정명희 ,  박준규 ,  조귀웅 ,  오정숙 ,  유복심 ,  공재양

IPC: C07D263/52

Abstract: 본발명은무스카린수용체작용물질(muscarinic receptor agonist)로서기억항진및 노인성치매치료제로유효한다음화학식 1로표시되는 1,2,5,6-테트라하이드로피리딜벤즈아졸유도체와이의약제학적으로허용가능한염, 그리고이들의제조방법에관한것이다. 상기화학식 1에서 : X는산소원자또는황원자를나타내고; R은수소원자, 할로겐원자, 니트로기, 탄소원자수 1 ∼ 4의저급알킬기또는탄소원자수 1 ∼ 4의저급알콕시기를나타낸다.

公开(公告)号：KR100322238B1

公开(公告)日：2002-02-07

申请号：KR1019990034974

申请日：1999-08-23

Applicant: 한국화학연구원

Inventor： 정명희 ,  박준규 ,  조귀웅 ,  이미정 ,  최승원 ,  공재양

IPC: C07D401/04

Abstract: 본발명은 5-(4-치환된-[1,2,5]티아디아졸-3-일)-3-메틸-1,2,3,4-테트라하이드로피리미딘유도체에관한것으로더욱상세하게는무스카린수용체작용물질(muscarinic receptor agonist)로서기억항진및 노인성치매치료제로유용한다음화학식 1로표시되는 5-(4-치환된-[1,2,5]-티아디아졸-3-일)-3-메틸-1,2,3,4-테트라하이드로피리미딘유도체와이의약제학적으로허용가능한염, 그리고이의제조방법에관한것이다. 상기화학식 1에서 : X는산소원자또는황원자를나타내고; R은수소원자, 탄소원자수 1 ∼ 5의저급알킬기, 알릴기, 프로파질기, 벤질기, 4-메틸벤질, 또는 4-클로로벤질기를나타낸다.

公开(公告)号：KR1020010018854A

公开(公告)日：2001-03-15

申请号：KR1019990034974

申请日：1999-08-23

Applicant: 한국화학연구원

Inventor： 정명희 ,  박준규 ,  조귀웅 ,  이미정 ,  최승원 ,  공재양

IPC: C07D401/04

Abstract: PURPOSE: Provided is a method for manufacturing a 5-(4-substituted-£1,2,5|thiadiazol-3-il)-3-methyl-1,2,3,4-tetrahydropyrimidine derivative which is effective on improving memory and treating Alzheimer's disease. CONSTITUTION: A 5-(4-substituted-£1,2,5|thiadiazol-3-il)-3-methyl-1,2,3,4-tetrahydropyrimidine derivative represented by the formula (1) is manufactured by the following steps of: i) reacting 5-pyrimidine carboxylaldehyde of the formula (2) with KCN/HOAc to synthesize hydroxy-pyrimidine-5-il-acetonitrile of the formula (3); ii) reacting hydroxy-pyrimidine-5-il-acetonitrile of the formula (3) with ammonium chloride and ammonium hydroxide to obtain amino-pyrimidine-5-il-acetonitrile of the formula (4) and reacting again amino-pyrimidine-5-il-acetonitrile with S2CL2 to obtain 5-(4-chloro-£1,2,5|thiadiazol-3-il)pyrimidine of the formula (5); iii) reacting 5-(4-chloro-£1,2,5|thiadiazol-3-il)pyrimidine with NaSH and alkylhalide to obtain a compound of the formula (6a); iv) reacting the compound of the formula (6a) with CH3L or methylfluoromethansulfonate at room temperature to obtain 5-(4-substituted sulfanil-£1,2,5|thiadiazol-3-il)-3-methylpyrimidium iodide of the formula (7a); and v) reducing 5-(4-substituted sulfanil-£1,2,5|thiadiazol-3-il)-3-methylpyrimidium iodide with NaBH4 to obtain a 5-(4-substituted-£1,2,5|thiadiazol-3-il)-3-methyl-1,2,3,4-tetrahydropyrimidine derivative. In the formula (1), X is oxygen atom or sulfur atom; R is hydrogen atom, low alkyl group having 1-5 carbon, propargyl group, benzil group, 4-methylbenzil group, or 4-chlorobenzil group.

Abstract translation: 目的：提供一种有效提高记忆力的5-（4-取代-1,2,5 |噻二唑-3-基）-3-甲基-1,2,3,4-四氢嘧啶衍生物的方法 并治疗阿尔茨海默病。 构成：由式（1）表示的5-（4-取代-1,2,5-二噻唑-3-基）-3-甲基-1,2,3,4-四氢嘧啶衍生物由以下制备 步骤：i）使式（2）的5-嘧啶羧醛与KCN / HOAc反应合成式（3）的羟基 - 嘧啶-5-基 - 乙腈; ii）将式（3）的羟基 - 嘧啶-5-基 - 乙腈与氯化铵和氢氧化铵反应，得到式（4）的氨基 - 嘧啶-5-基 - 乙腈，再次使氨基 - 嘧啶-5-基 - （2-氯苯基）乙腈与S2CL2反应，得到式（5）的5-（4-氯-1,2,5,5-thiadiazol-3-il）嘧啶; iii）使5-（4-氯-1,2,5-噻二唑-3-基）嘧啶与NaSH和烷基卤反应，得到式（6a）化合物; iv）在室温下使式（6a）化合物与CH 3 L或甲基氟代甲磺酸酯反应，得到式（5）的5-（4-取代的磺胺 - 1,2,5-二噻唑-3-基）-3-甲基嘧啶碘化物 图7a）; 和v）用NaBH 4还原5-（4-取代的磺胺 - 1,2,5 - 噻二唑-3-基）-3-甲基嘧啶碘化物，得到5-（4-取代的1,2,5-thiadiazol -3-i）-3-甲基-1,2,3,4-四氢嘧啶衍生物。 在式（1）中，X是氧原子或硫原子; R是氢原子，具有1-5个碳的低级烷基，炔丙基，苯偶酰基，4-甲基苯甲酰基或4-氯苯甲基。

公开(公告)号：KR1020000011489A

公开(公告)日：2000-02-25

申请号：KR1019990026907

申请日：1999-07-05

Applicant: 한국화학연구원

Inventor： 정명희 ,  박준규 ,  조귀웅 ,  오정숙 ,  유복심 ,  정대영

IPC: C07D239/06 ,  A61K31/505

Abstract: PURPOSE: Title derivatives are prepared which has a good therapeutic activity of dys-mnesia and senile athymia. CONSTITUTION: Title compounds (formula 1; R is -H, -CH3, -CH2CH3, -CH2(CH2)3CH3, -CH2CH=CH2, etc.) and their pharmaceutical salt are prepared. Thus, 1.24 g of hydroxylamine hydrochloride is dissolved in water, and controlled to pH 7 by NaHCO3 saturated aqueous solution. The solution is refluxed for 2 hours in a mixed solution of 5-acetylpyrimidine and 50 ml of benzene using Dean-Stark column. Obtained solution is concentrated under reduced pressure to give 1.28 g of 1-pyrimidin-5-yl-(E)-ethanone oxime(yield 78 %).

Abstract translation: 目的：制备具有良好的失眠症和老年性无精症治疗活性的标题衍生物。 构成：制备标题化合物（式1; R为-H，-CH 3，-CH 2 CH 3，-CH 2（CH 2）3 CH 3，-CH 2 CH = CH 2等）及其药物盐。 因此，将1.24g盐酸羟胺溶于水中，并通过NaHCO 3饱和水溶液控制至pH7。 使用Dean-Stark柱，将溶液在5-乙酰基嘧啶和50ml苯的混合溶液中回流2小时。 得到的溶液在减压下浓缩，得到1.28g 1-嘧啶-5-基 - （E） - 乙酮肟（产率78％）。

公开(公告)号：KR1019990083132A

公开(公告)日：1999-11-25

申请号：KR1019990012805

申请日：1999-04-12

Applicant: 한국화학연구원

Inventor： 정명희 ,  박준규 ,  조귀웅 ,  오정숙 ,  천혜경 ,  정대영

IPC: C07D239/06 ,  A61K31/505

Abstract: 본발명은노인성치매치료제로유효한다음화학식 1로표시되는 1,2,3,4-테트라하이드로피리미딘유도체와이의약제학적으로허용가능한염, 그리고이들의제조방법에관한것이다. 상기화학식 1에서 : R은 -H, -CH, -CHCH, -CH(CH)CH, -CHCH=CH, -CHC≡CH,,또는을나타낸다. 본발명에따른상기화학식 1로표시되는 1,2,3,4-테트라하이드로피리미딘유도체는무스카린수용체작용물질로서치매치료제에응용될수 있고, 상기유도체는테트라하이드로피리딘의등배전자로서이미임상적으로치매치료제에쓰였던아레콜린및 밀라멜린약제와동등한치료효과를갖는다.

公开(公告)号：KR1019940002256A

公开(公告)日：1994-02-17

申请号：KR1019920011978

申请日：1992-07-06

Applicant: 한국화학연구원

Inventor： 김완주 ,  정명희 ,  조귀웅

IPC: C07D501/46

Abstract: 본 발명은 다음 일반식(I)로 표시되는 신규한 3-암모니움 세펨 유도체를 제공한다.

윗식에서, R
1 은 수소 또는 다음 일반식(A)로 표시되는 헤테르 아르알카노일기이며,

公开(公告)号：KR100051127B1

公开(公告)日：1992-04-29

申请号：KR1019890015203

申请日：1989-10-23

Applicant: 한국화학연구원

Inventor： 김완주 ,  박명환 ,  오종훈 ,  정명희 ,  김봉진

IPC: C07D498/04 ,  C07D498/06