公开(公告)号：KR100847448B1

公开(公告)日：2008-07-21

申请号：KR1020070028181

申请日：2007-03-22

Applicant: 한국화학연구원

Inventor： 안미자 ,  정명희 ,  조남옥 ,  이병호

IPC: C07D271/06 ,  C07D413/06 ,  A61K31/535 ,  A61P3/04

Abstract: 3-Aryl-5-alkyl-1,2,4-oxadiazole derivatives are provided to reduce eating by competing with MCH R1(melanin-concentrating hormone receptor subtype-1) associated with obesity, so that the compounds are useful for preventing or treating obesity. The 3-aryl-5-alkyl-1,2,4-oxadiazole derivatives represented by the formula(1) are useful as antagonist of MCH R1, wherein R1 is (C3-C5) branched alkyl, (C1-C3)dialkylamino(C1-C3)alkyl or (C1-C3) linear alkyl which is optionally substituted by pyridine, piperidine or (C5-C7) cycloalkyl; R2 is halogen-substituted phenyl, CF3-substituted phenyl, phenyl substituted by phenoxy which is optionally substituted by halogen or (benzo[1,3]dioxol-5-yl)phenyl; and X is -NHCO or -NHCONH-. A method for preparing the 3-aryl-5-alkyl-1,2,4-oxadiazole derivatives represented by the formula(1a) comprises the steps of: (1) reacting 4-aminobenzonitrile represented by the formula(2) with organic acid(R2COOH) in the presence of solvent and binding reagent to prepare amide compounds represented by the formula(3); (2) reacting the amide compounds represented by the formula(3) with hydroxylamine hydrochloride in the presence of solvent to prepare amidoxime represented by the formula(4); and (3) reacting the amidoxime represented by the formula(4) with another organic acid(R1COOH) in the presence of solvent and binding reagent to prepare 1,2,4-oxadiazole ring.

Abstract translation: 提供3-芳基-5-烷基-1,2,4-恶二唑衍生物以通过与与肥胖相关的MCH R1（黑色素浓缩激素受体亚型-1）竞争来减少进食，使得该化合物可用于预防或治疗 肥胖。 由式（1）表示的3-芳基-5-烷基-1,2,4-恶二唑衍生物可用作MCH R 1的拮抗剂，其中R 1是（C 3 -C 5）支链烷基，（C 1 -C 3）二烷基氨基（ C1-C3）烷基或任选被吡啶，哌啶或（C5-C7）环烷基取代的（C1-C3）直链烷基; R 2是卤素取代的苯基，CF 3取代的苯基，被苯氧基取代的苯基，其被卤素或（苯并[1,3]二氧杂环戊烯-5-基）苯基任选取代; X是-NHCO或-NHCONH-。 制备由式（1a）表示的3-芳基-5-烷基-1,2,4-恶二唑衍生物的方法包括以下步骤：（1）使由式（2）表示的4-氨基苄腈与有机酸 （R2COOH）在溶剂和结合试剂存在下反应制备式（3）表示的酰胺化合物。 （2）在溶剂存在下使式（3）表示的酰胺化合物与羟胺盐酸盐反应，制备由式（4）表示的偕胺肟; 和（3）在溶剂和结合试剂的存在下使由式（4）表示的偕胺肟与另一种有机酸（R1COOH）反应以制备1,2,4-恶二唑环。

公开(公告)号：KR100621192B1

公开(公告)日：2006-09-19

申请号：KR1020040081725

申请日：2004-10-13

Applicant: 한국화학연구원

Inventor： 정명희 ,  최일영 ,  안미자 ,  임희종 ,  박우규

IPC: C07D413/04

Abstract: 본 발명은 무스카린 수용체 작용물질로서 작용하는 신규 1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸 유도체와 이의 제조방법, 그리고 상기 신규 화합물을 유효성분으로 함유하는 약제조성물에 관한 것이다.
본 발명에 따른 1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸 유도체는 무스카린 수용체 작용물질(muscarinic receptor agonist)로서 활성을 나타내므로 기억항진 및 노인성 치매 치료제, 뇌질환 및 중추신경계에 관련된 치료약물에 응용될 수 있고, 테트라하이드로피리딘의 등배전자(bioisoster)로 작용하여 이미 임상적으로 치매 치료제에 사용되는 아레콜린 및 밀라멜린 약제와 대등한 치료효과를 나타낸다.
노인성 치매 치료제, 무스카린 수용체 작용물질, 1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸 유도체

公开(公告)号：KR100599252B1

公开(公告)日：2006-07-13

申请号：KR1020040025050

申请日：2004-04-12

Applicant: 한국화학연구원

Inventor： 정명희 ,  최일영 ,  안미자 ,  이병호

IPC: C07D413/04 ,  C07D271/06

Abstract: 본 발명은 심근세포의 소듐(Na
+ )과 프로톤(H
+ )의 교환을 효과적으로 억제하는 1,2,4-옥사디아졸이 치환된 벤조일구아니딘 유도체와 이 화합물의 제조방법, 그리고 상기 화합물을 심경색, 협심증 및 부정맥 등의 심혈관계 질환 치료 및 예방제로 사용하는 의약적 용도에 관한 것이다.
심경색, 허혈, 심장병, NHE-억제제, 벤조일 구아니딘, 1,2,4-옥사디아졸, Na+/H+-교환 억제

公开(公告)号：KR1020050099836A

公开(公告)日：2005-10-17

申请号：KR1020040025050

申请日：2004-04-12

Applicant: 한국화학연구원

Inventor： 정명희 ,  최일영 ,  안미자 ,  이병호

IPC: C07D413/04 ,  C07D271/06

Abstract: 본 발명은 심근세포의 소듐(Na
+ )과 프로톤(H
+ )의 교환을 효과적으로 억제하는 1,2,4-옥사디아졸이 치환된 벤조일구아니딘 유도체와 이 화합물의 제조방법, 그리고 상기 화합물을 심경색, 협심증 및 부정맥 등의 심혈관계 질환 치료 및 예방제로 사용하는 의약적 용도에 관한 것이다.

公开(公告)号：KR1020030073444A

公开(公告)日：2003-09-19

申请号：KR1020020013001

申请日：2002-03-11

Applicant: 주식회사 코오롱 ,  한국화학연구원

Inventor： 정명희 ,  박정미 ,  최일영 ,  안미자 ,  조성민

IPC: C07D401/04

Abstract: PURPOSE: Provided are 1,2,5,6-tetrahydropyridinylbenzimidazole derivatives which are used in treating dementia and brain diseases as a muscarine receptor modulator, and operated as a bioisostere of tetrahydropyridine with the same effects as the existent dementia treatment drugs of arecoline and milameline. CONSTITUTION: 1,2,5,6-tetrahydropyridinylbenzimidazole derivatives are expressed by the formula 1 where X is NH or NCH3, and R is hydrogen, NH2, Cl, NO2 or OCH3. In the formula 1, HA is an inorganic salt or an organic salt selected from the group consisting of HCl, oxalic acid, p-toluene sulfonic acid, tartaric acid and fumaric acid.

Abstract translation: 目的：提供1,2,5,6-四氢吡啶基苯并咪唑衍生物，其用于治疗痴呆和脑疾病作为毒蕈碱受体调节剂，并作为四氢吡啶的生物电子等排体作用与槟榔碱和米兰的现有痴呆症治疗药物相同 。 构成：1,2,5,6-四氢吡啶基苯并咪唑衍生物由式1表示，其中X是NH或NCH 3，R是氢，NH 2，Cl，NO 2或OCH 3。 在式1中，HA是选自HCl，草酸，对甲苯磺酸，酒石酸和富马酸的无机盐或有机盐。

公开(公告)号：KR1020020017137A

公开(公告)日：2002-03-07

申请号：KR1020000050262

申请日：2000-08-29

Applicant: 한국화학연구원

Inventor： 정명희 ,  이미정 ,  공재양

IPC: C07D417/14

Abstract: PURPOSE: Provided are 5-(4-Substituted-(1,2,5)thiadiazole-3-yl)-3-methyl-1,2,3,4-tetrahydropyrimidine derivatives which are a muscarinic receptor agonists and used as therapeutic agents in Alzheimer's disease. Also, provided are their pharmaceutically acceptable salt, their preparation process and their use. CONSTITUTION: 5-(4-Substituted-(1,2,5)thiadiazole-3-yl)-3-methyl-1,2,3,4-tetrahydropyrimidine derivatives are represented by the formula(1), wherein X represents dialkylamine group, piperidinyl group, morpholinyl group or N-methylpiperazinyl group. They are as follows: 3-dimethyl-(4-(3-methyl-1,2,3,4-tetrahydropyrimidine-5-yl)-(1,2,5)thiadiazole-3-yl)amine; 3-methyl-5-(4-pyrrolidine-1-yl-(1,2,5)thiadiazole-3-yl)-1,2,3,4-tetrahydropyrimidine; 3-methyl-5-(4-piperidine-1-yl-(1,2,5)thiazol-3-yl)-1,2,3,4-tetrahydropyrimidine; 4-(4-(3-methyl-1,2,3,4-tetrahydropyrimidine-5-yl)-(1,2,5)thiadiazole-3-yl)morpholine or 3-methyl-5-(4-(4-methylpiperazin-1-yl)-(1,2,5)thiadiazole-3-yl)-1,2,3,4-tetrahydropyrimidine. The therapeutic agent in Alzheimer's disease contains 5-(4-Substituted-(1,2,5)thiadiazole-3-yl)-3-methyl-1,2,3,4-tetrahydropyrimidine derivative or its pharmaceutically acceptable salt.

Abstract translation: 目的：提供作为毒蕈碱受体激动剂并用作治疗剂的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 在阿尔茨海默病。 此外，还提供其药学上可接受的盐，其制备方法及其用途。 构成：5-（4-取代的 - （1,2,5）噻二唑-3-基）-3-甲基-1,2,3,4-四氢嘧啶衍生物由式（1）表示，其中X表示二烷基胺 哌啶基，吗啉基或N-甲基哌嗪基。 它们如下：3-二甲基 - （4-（3-甲基-1,2,3,4-四氢嘧啶-5-基） - （1,2,5）噻二唑-3-基）胺; 3-甲基-5-（4-吡咯烷-1-基 - （1,2,5-）噻二唑-3-基）-1,2,3,4-四氢嘧啶; 3-甲基-5-（4-哌啶-1-基 - （1,2,5）噻唑-3-基）-1,2,3,4-四氢嘧啶; 4-（4-（3-甲基-1,2,3,4-四氢嘧啶-5-基） - （1,2,5）噻二唑-3-基）吗啉或3-甲基-5-（4-（ 4-甲基哌嗪-1-基） - （1,2,5-）噻二唑-3-基）-1,2,3,4-四氢嘧啶。 阿尔茨海默病中的治疗剂含有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或其药学上可接受的盐。

公开(公告)号：KR100319490B1

公开(公告)日：2002-01-05

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: 본발명은무스카린수용체작용물질(muscarinic receptor agonist)로서기억항진및 노인성치매치료제로유용한다음화학식 1로표시되는 1,2,3,4-테트라하이드로피리미딘유도체와이의약제학적으로허용가능한염, 그리고이의제조방법에관한것이다. 상기화학식 1에서 : R은 -H, -CH, -CHCH, -CH(CH)CH, -CHCH=CH, -CHC≡CH,,,또는을나타낸다.

公开(公告)号：KR100094382B1

公开(公告)日：1996-01-17

申请号：KR1019920011978

申请日：1992-07-06

Applicant: 한국화학연구원

Inventor： 김완주 ,  정명희 ,  조귀웅

IPC: C07D501/46

公开(公告)号：KR1019930007811B1

公开(公告)日：1993-08-20

申请号：KR1019900016941

申请日：1990-10-23

Applicant: 한국화학연구원

Inventor： 김완주 ,  정명희 ,  하재두

IPC: C07D501/24

Abstract: 3-Vinylcephem derivatives of formula (I) which are useful as an oral antibiotics and it's intermediates were prepd. from 7- aminocephalosporin. In (I), R1=H or aralkanoyl as (A) or oxyimino substd. aralkanoyl or hetero aralkanoyl as (B), R2=Cl, Br, R3= phenyl or mono substd. phenyl or cyclohexadienyl, R4= 2- aminothiazolyl, R5= methylacetic acid or dimethylacetic acid. Cpd. (I) have better absorption and antibacterial activity against Gram negative bacteria for oral use than existing oral cephems.

Abstract translation: 可用作口服抗生素的式（I）的3-乙烯基头孢烯衍生物及其中间体是制备的。 来自7-氨基头孢菌素。 在（I）中，R 1 = H或芳烷酰基（A）或氧亚氨基。 芳烷酰基或杂芳烷酰基作为（B），R 2 = Cl，Br，R 3 =苯基或单子取代。 苯基或环己二烯基，R 4 = 2-氨基噻唑基，R 5 =甲基乙酸或二甲基乙酸。 CPD。 （I）对口腔使用革兰氏阴性细菌的吸收和抗菌活性比现有的口腔流行病好。

公开(公告)号：KR1019910002869A

公开(公告)日：1991-02-26

申请号：KR1019890010466

申请日：1989-07-24

Applicant: 한국화학연구원

Inventor： 김완주 ,  고광윤 ,  정명희 ,  조귀웅 ,  김문환

IPC: C07D501/36

Abstract: 내용 없음.