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：KR100055728B1

公开(公告)日：1992-10-24

申请号：KR1019900004222

申请日：1990-03-29

Applicant: 한국화학연구원

Inventor： 김완주 ,  이태석 ,  박태호 ,  김봉진 ,  조귀웅

IPC: C07D401/04