公开(公告)号：KR100336972B1

公开(公告)日：2002-05-17

申请号：KR1019990026909

申请日：1999-07-05

Applicant: 한국화학연구원

Inventor： 정명희 ,  박준규 ,  조귀웅 ,  최승원 ,  공재양

IPC: C07D263/52

Abstract: 본발명은 1,2,3,6-테트라하이드로피리딜벤즈아졸유도체와이의제조방법에관한것으로서, 더욱상세하게는무스카린수용체작용물질(muscarinic receptor agonist)로서기억항진및 노인성치매치료제로유용한다음화학식 1로표시되는 1,2,3,6-테트라하이드로피리딜벤즈아졸유도체와이의약제학적으로허용가능한염, 그리고이의제조방법에관한것이다. 상기화학식 1에서 : X는산소원자또는황원자를나타내고; R은수소원자, 할로겐원자, 니트로기, 탄소원자수 1 ∼ 4의저급알킬기또는탄소원자수 1 ∼ 4의저급알콕시기를나타낸다.

公开(公告)号：KR100297804B1

公开(公告)日：2001-09-22

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: PURPOSE: Provided are a 1,2,3,4-tetrahydropyrimidine derivative represented by the formula(1), which is useful as a muscarinic receptor agonist in treating imbecility, a pharmaceutically acceptable salt and method for preparation thereof. CONSTITUTION: The 1,2,3,4-tetrahydropyrimidine derivative is represented by the formula(1), wherein R is H, -CH3, -CH2CH3, -CH2(CH2)3CH3, -CH2CH=CH2, CH2C≡CH, C6H5CH2, P-CH2C6H4CH3, P-CH2C6H4-Cl. It is prepared by the following steps of: (a) condensing 5-pyrimidinecarboxylaldehyde represented by the formula(2) and hydroxylamine, to produce compound represented by the formula(3), wherein R1 is -H or -CH3; (b) condensing a compound represented by the formula(3), wherein R1 is H and a compound represented by R2-X, to produce compound represented by the formula(4), wherein R2 is -CH2CH3, -CH2(CH2)3CH3, -CH2CH=CH2, CH2C≡CH, C6H5CH2, P-CH2C6H4CH3, P-CH2C6H4-Cl and X is halogen; (c) methylating a compound represented by the formula(3) or a compound represented by the formula(4) and CH3I, to produce a compound represented by the formula(5), wherein R is H, -CH3, -CH2CH3, -CH2(CH2)3CH3, -CH2CH=CH2, CH2C≡CH, C6H5CH2, P-CH2C6H4CH3, P-CH2C6H4-Cl; and (d) reducing a compound represented by the formula(5) and NaBH4, to produce 1,2,3,4-tetrahydropyrimidine derivative represented by the formula(1), wherein R is H, -CH3, -CH2CH3, -CH2(CH2)3CH3, -CH2CH=CH2, CH2C≡CH, C6H5CH2, P-CH2C6H4CH3, P-CH2C6H4-Cl.

公开(公告)号：KR1020000011490A

公开(公告)日：2000-02-25

申请号：KR1019990026908

申请日：1999-07-05

Applicant: 한국화학연구원

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

IPC: C07D263/52

Abstract: PURPOSE: Title derivatives are prepared which has a good therapeutic activity of dys-mnesia and senile athymia as a muscarinic receptor agonist. CONSTITUTION: Title compounds (formula 1; X is oxygen atom or sulfur atom; R is hydrogen atom, halogen atom, nitro group, C1- C4 lower alkyl group or C1- C4 lower alkoxy group) and their pharmaceutical salts are prepared. Thus, 2.04 g of aminophenol is dissolved in ethanol anhydride at room temperature, followed by addition of 2.00 g 3-pyridine carboxaldehyde, 6.62 g of iodobenzene diacetate is added in the obtained solution, and concentrated under reduced pressure after 10 minutes to give 1.17 g of white title compounds.

Abstract translation: 目的：制备标题衍生物，其作为毒蕈碱受体激动剂具有良好的失眠症和老年不育症的治疗活性。 构成：制备标题化合物（式1; X为氧原子或硫原子; R为氢原子，卤素原子，硝基，C 1 -C 4低级烷基或C 1 -C 4低级烷氧基）及其药物盐。 因此，在室温下将2.04g氨基苯酚溶于乙醇酐中，然后加入2.00g 3-吡啶甲醛，在所得溶液中加入6.62g二乙酸碘苯，10分钟后减压浓缩，得到1.17g 的白色标题化合物。

公开(公告)号：KR1019990041199A

公开(公告)日：1999-06-15

申请号：KR1019970061756

申请日：1997-11-21

Applicant: 한국화학연구원

Inventor： 박준규 ,  오정숙 ,  정명희 ,  조귀웅

IPC: C07D501/34

Abstract: 본 발명은 세팔로스포린 유도체의 부분입체 이성질체의 합성과 분리방법에 관한 것으로, 더욱 상세하게는 화학식 2의 화합물에 캄파설폰산을 첨가하여 염의 형태로 합성하고 재결정하여 다음 화학식 1a의 부분입체 이성질체의 1:1 혼합물을 합성하는 방법에 관한 것이다.


윗 식에서 R
1 은 -CH
3 ,-CH
2 OCH
3 ,-CH=CH
2 이며, R
2 는 -C(CH
3 )
3 ,-시클로프로필,-시클로헥실이다.
또한, 본 발명은 화학식 2의 화합물에 HCl을 첨가하여 염산염의 형태로 합성하고 재결정하여 다음 화학식 1b의 단일 부분입체 이성질체를 분리하는 방법에 관한 것이다.

윗 식에서 R
1 은 -CH
3 ,-CH
2 OCH
3 ,-CH=CH
2 이며, R
2 는 -C(CH
3 )
3 ,-시클로프로필,-시클로헥실이다.
또한, 본 발명은 화학식 2의 화합물에 p-톨루엔 설폰산을 첨가하여 토실레이트염의 형태로 합성하고 재결정하여 다음 화학식 1c의 단일 부분입체 이성질체를 분리하는 방법에 관한 것이다.

윗 식에서 R
1 은 -CH
3 ,-CH
2 OCH
3 ,-CH=CH
2 이며, R
2 는 -C(CH
3 )
3 ,-시클로프로필,-시클로헥실이다.
본 발명에 따라 항박테리아에 약효가 있는 경구용 세펨 유도체, 즉, 중간체 형태의 화합물을 부분입체 이성질체의 광학적으로 순수한 중간체 및 혼합형으로 분리, 용이하게 합성할 수 있다. 또한, 이를 중간체로 이용하여 하기 화학식 1의 C-7위치에 여러 가지 유도체를 도입함으로써, 신규 경구용 세팔로스포린 항생제의 합성 개발에 큰 효과를 기대할 수 있다.

윗 식에서, R
1 은 -CH
3 ,-CH
2 OCH
3 ,-CH=CH
2 이며, X는 Cl,p-TsO,캄파설폰산염이고, R
2 는 -C(CH
3 )
3 ,-시클로프로필,-시클로헥실이다.

公开(公告)号：KR1019970004048B1

公开(公告)日：1997-03-24

申请号：KR1019930024602

申请日：1993-11-18

Applicant: 한국화학연구원

Inventor： 김완주 ,  조귀웅 ,  정명희

IPC: C07D501/46

Abstract: 1 - (2,2 - dimethylpropanoyloxy) ethyl - 7 - amino -3 - methoxy methyl - 3 - cephem - 4 - carboxylate dissolved in ethyl acetate is added to mixture of ethyl acetate and p-toluene sulfonic acid hydrate at room temperature, then, (R,S)-1-(2,2-dimethylpropanoyloxy) sethyl-7-amino -3-methoxymethyl-3-cephem-4-carboxylate is yielded. Pure (S)-form is firstly separated by recrystaliztion using CHCl3, thereafter, (R)-form is yielded by condensation and recrystalization of residual solution.

Abstract translation: 溶于乙酸乙酯的1-（2,2-二甲基丙酰氧基）乙基-7-氨基-3-甲氧基甲基-3-头孢烯-4-羧酸甲酯在室温下加入到乙酸乙酯和对甲苯磺酸水合物的混合物中，然后 ，得到（R，S）-1-（2,2-二甲基丙酰氧基）甲苯基-7-氨基-3-甲氧基甲基-3-头孢烯-4-羧酸酯。 首先使用CHCl 3通过重结晶分离纯（S）型，然后通过残留溶液的冷凝和重结晶产生（R） - 形式。

公开(公告)号：KR100051126B1

公开(公告)日：1992-04-29

申请号：KR1019890015202

申请日：1989-10-23

Applicant: 한국화학연구원

Inventor： 김완주 ,  박명환 ,  오종훈 ,  정명희 ,  김봉진

IPC: C07D487/04

公开(公告)号：KR1019910009333B1

公开(公告)日：1991-11-11

申请号：KR1019890015203

申请日：1989-10-23

Applicant: 한국화학연구원

Inventor： 김완주 ,  박명환 ,  오종훈 ,  정명희 ,  김봉진

IPC: C07D498/04 ,  C07D498/06

CPC classification number: C07D519/00

Abstract: Quinolone derivs. of formula (I) and, when R1 is H, their acid addn. salts and hydrates are new. Z = halo or NH2; R1 = H or a cation. R2 = H, lower alkyl or formyl; m = 1-3; n = 1 or 2. Also claimed is the prepn. of (I) which comprises e.g. condensing corresp. quinolone deriv. with a leaving gp. in the 10-position with a diazabicycloamine. (I) may be orally or parenterally administered at a dose of 0.1-1.5 (0.2-0.8) g/kay to a 60 kg adult. Cpds. (I) are used for the treatment of bacterial infections. (I) have a better and wider range of activity against Gram positive and Gram negative bacteria than existing quinolone antibacterial agents, esp. norfloxacin, ciprofloxacin and ofloxacin. (I) also have a good antibacterial activity against methicillin resistant bacteria.

Abstract translation: 喹诺酮衍生物。 的式（I）化合物，当R 1为H时，其酸加成。 盐和水合物是新的。 Z =卤素或NH 2; R1 = H或阳离子。 R2 = H，低级烷基或甲酰基; m = 1-3; n = 1或2.还要求是prepn。 的（I），其包含例如 冷凝对应 喹诺酮衍生物 离开gp。 在10位与二氮杂双环胺。 （I）可以以0.1-1.5（0.2-0.8）g / kay的剂量口服或非肠道给药至60kg成人。 CPDS。 （I）用于治疗细菌感染。 （I）比现有的喹诺酮抗菌剂具有更好和更广泛的抗革兰氏阳性和革兰氏阴性菌的活性，特别是。 诺氟沙星，环丙沙星和氧氟沙星。 （I）对耐甲氧西林细菌也具有良好的抗菌活性。

公开(公告)号：KR1019910003957B1

公开(公告)日：1991-06-17

申请号：KR1019890010466

申请日：1989-07-24

Applicant: 한국화학연구원

Inventor： 김완주 ,  고광윤 ,  정명희 ,  조귀웅 ,  김문환

IPC: C07D501/36

Abstract: Cephem derivs. of formula (I) are prepd. by reacting an aq. soln. of cefotaxime of formula (II) with Na or K salt of methyl(ethyl)xanthinic acid, piperidine dithiocarbamic acid or 4- methylpiperazine dithiocarbamic acid at 40-35 deg.C for 24 hrs. to obtain a cpd. of formula (III), and reacting (III) with iodomethylpivalate-5-methyl-2-oxo-1,3-dioxolene at 0-5 deg.C in the presence of dicyclohexylamine. In the formulas, R1= methyl or carboxymethyl; R2= ethoxy, methoxy, 1-piperidinyl, 1-morpholinyl or 4-methylpiperazinyl; R3= H, pivaloyloxymethyl, etc. (I) have a broad spectrum antibacterial activity and a good oral absorption.

Abstract translation: Cephem派生。 式（I）的化合物是制备的。 通过水杨酸 SOLN。 （II）的头孢噻肟与甲基（乙基）黄豆酸，哌啶二硫代氨基甲酸或4-甲基哌嗪二硫代氨基甲酸的Na或K盐在40-35℃下反应24小时。 获得cpd。 的式（III）化合物，在0-5℃下，在二环己基胺的存在下，使（III）与新戊酸碘代甲酯-5-甲基-2-氧代-1,3-二氧杂环戊烯反应。 式中R1 =甲基或羧甲基; R2 =乙氧基，甲氧基，1-哌啶基，1-吗啉基或4-甲基哌嗪基; R3 = H，新戊酰氧基甲基等（I）具有广谱抗菌活性和良好的口服吸收。