公开(公告)号：KR1020030062542A

公开(公告)日：2003-07-28

申请号：KR1020020002789

申请日：2002-01-17

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  김유승 ,  고훈영 ,  최경일 ,  배애님 ,  차주환

IPC: C07D307/12

Abstract: PURPOSE: Provided is a method of making β-methyl substituted Baylis-Hillman product represented by the formula(1) with indium easily under mild condition. The product is useful as precursor for the synthesis of carbapenem antibiotics. CONSTITUTION: A method of preparation of making β-methyl substituted Baylis-Hillman product comprises the steps of: making a compound of the formula (IV) by mixing and reacting a compound of the formula (II) with a compound of the formula(III) in a solvent, followed by addition of indium, stirring, reacting with acid and extraction; and adding the compound of the formula(IV) and base. In the formula (IV), R is alkyl, cycloalkyl, aryl or heterocyclic compound; R1 is alkyl, aryl or heterocyclic compound.

Abstract translation: 目的：提供在温和条件下容易地用铟制备由式（1）表示的β-甲基取代的Baylis-Hillman产品的方法。 该产品可用作合成碳青霉烯类抗生素的前体。 构成：制备β-甲基取代的Baylis-Hillman产品的方法包括以下步骤：通过将式（II）化合物与式（III）的化合物混合和反应来制备式（Ⅳ）化合物 ），然后加入铟，搅拌，与酸反应并萃取; 并加入式（IV）和碱的化合物。 在式（Ⅳ）中，R是烷基，环烷基，芳基或杂环化合物; R1是烷基，芳基或杂环化合物。

公开(公告)号：KR1020030058741A

公开(公告)日：2003-07-07

申请号：KR1020010089275

申请日：2001-12-31

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  김유승 ,  고훈영 ,  최경일 ,  강경호 ,  배애님

IPC: C07D209/36

Abstract: PURPOSE: Indol derivatives and a preparation process thereof are provided, thereby rapidly preparing indol derivatives under mild conditions in higher yield. CONSTITUTION: Indol derivatives are represented by the formula 6, wherein R is H, or halogen selected from Cl, F, Br and I; and Y is -Ts(tosyl), -Ms(mesyl) or -Ac(acetyl). A process for preparing the indol derivatives of the formula 6 comprises the steps of: reacting a compound of the formula 1 with a compound of the formula 2 in the presence of indium metal and acid to simultaneously perform allylation of aldehyde and reduction of nitro group, thereby preparing a compound of the formula 3; protecting amine group of the compound of the formula 3 to prepare a compound of the formula 4; oxidizing secondary alcohol of the compound of the formula 4 to prepare a compound of the formula 5; and cyclization of the compound of the formula 5 in the presence of organic base, wherein the oxidation of secondary alcohol uses pyridinium chlorochromate(PCC) or pyridinium dichromate(PDC) or Swern's oxidation or Dess-Martin periodinane oxidation; and the organic base is diisopropylethylamine, DBU (1,8-diazabicyclo£5.4.0|undec-7-ene), DBN (1,5-diazabicyclo£4.3.0|non-5-ene), triethylamine or pyridine.

Abstract translation: 目的：提供吲哚衍生物及其制备方法，从而在温和条件下以更高的收率快速制备吲哚衍生物。 构成：吲哚衍生物由式6表示，其中R是H，或选自Cl，F，Br和I的卤素; 和Y是-T（甲苯磺酰基），-Ms（甲磺酰）或-Ac（乙酰基）。 制备式6的吲哚衍生物的方法包括以下步骤：在铟金属和酸的存在下使式1的化合物与式2的化合物反应，以同时进行醛的还原和烯基的还原， 从而制备式3的化合物; 保护式3化合物的胺基以制备式4的化合物; 氧化式4化合物的仲醇制备式5的化合物; 在有机碱的存在下环化式5的化合物，其中仲醇的氧化使用氯铬酸吡啶鎓（PCC）或重铬酸吡啶鎓（PDC）或Swern的氧化或Dess-Martin氧化氧化; 有机碱是二异丙基乙胺，DBU（1,8-二氮杂双环{5.4.0 |十一-7-烯），DBN（1,5-二氮杂双环{4.3.0 |非-5-烯），三乙胺或吡啶。

公开(公告)号：KR1020030056992A

公开(公告)日：2003-07-04

申请号：KR1020010087362

申请日：2001-12-28

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  한예선 ,  이종수 ,  윤홍철

IPC: C07D209/48

CPC classification number: C07D209/48

Abstract: PURPOSE: Carbonyl compounds and a preparation process thereof using carbonyl reductase isolated from Kluyveromyces marxianus are provided. The carbonyl compounds are useful as intermediates for preparing beta-lactam family antimicrobial agents. CONSTITUTION: Carbonyl compounds represented by the formula(Ia) and (Ib) are provided, wherein R is methyl, ethyl, propyl, isopropyl, isobutyl and allyl containing saturated or unsaturated alkyl, or phenyl containing aryl; R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, halogen atoms including Br, Cl, F and I, methyl and ethyl containing C1-C4 alkyl, hydroxy, C1-C4 alkoxy, acetoxy containing ester, and phenyl. A process for preparing the carbonyl compound of the formula(Ia) and (Ib) comprises the steps of: mixing a compound of formula(VI) with β-NADPH and a pH 5.0 to 8.0 buffer solution; adding carbonyl reductase isolated from Kluyveromyces marxianus into the mixture; and reacting the mixture at 20 to 40 deg. C for 5 hours to 5 days.

Abstract translation: 目的：提供羰基化合物及其使用从马克斯克鲁维酵母分离的羰基还原酶的制备方法。 羰基化合物可用作制备β-内酰胺家族抗微生物剂的中间体。 构成：提供由式（Ia）和（Ib）表示的羰基化合物，其中R是含有饱和或不饱和的烷基或含苯基的芳基的甲基，乙基，丙基，异丙基，异丁基和烯丙基; R 1，R 2，R 3和R 4独立地选自氢，包括Br，Cl，F和I的卤素原子，含有C 1 -C 4烷基，羟基，C 1 -C 4烷氧基，含乙酰氧基的酯和苯基的甲基和乙基 。 制备式（Ia）和（Ib）的羰基化合物的方法包括以下步骤：将式（VI）化合物与β-NADPH和pH 5.0-8.0缓冲溶液混合; 将从马克斯克鲁维酵母分离的羰基还原酶加入到混合物中; 并使混合物在20至40℃下反应。 C为5小时至5天。

公开(公告)号：KR1020020095286A

公开(公告)日：2002-12-26

申请号：KR1020010033382

申请日：2001-06-14

Applicant: 한국과학기술연구원

Inventor： 김중협 ,  김유승 ,  최경일 ,  김동현 ,  남길수 ,  서재홍

IPC: C07D487/04

CPC classification number: C07D487/04

Abstract: PURPOSE: Provided is a method for preparing novel pyrazolpyrimidine derivative represented by the formula(1) and its pharmaceutically acceptable salts or hydrates. A pharmaceutical composition containing it is used as a therapeutic agent for impotency by inhibition of phosphodiesterase V. CONSTITUTION: The novel pyrazolpyrimidine derivative represented by the formula(1), wherein R1 and R2 are independently C1-C6 alkyl or C3-C6 cycloalkyl; R3 is substituted or unsubstituted C1-C6 alkyl, C3-C6 cycloalkyl or C3-C6 alkenyl; and X is O or NR4 wherein R4 is hydrogen, OH or C1-C6 alkyl, C3-C6 cycloalkyl or C3-C6 alkenyl substituted or unsubstituted by alkoxy group. It is manufactured by the steps of: converting pyrazolopyrimidinone of the formula(2) into pyrazolopyrimidinethione of the formula(3) by thione reaction; chlorosulfonating the compound of the formula(3) into chlorosulfone compound of the formula(4) and letting the compound of formula(4) react with secondary amine to make the final compound of the formula(1).

Abstract translation: 目的：提供由式（1）表示的新型吡唑嘧啶衍生物及其药学上可接受的盐或水合物的制备方法。 通过抑制磷酸二酯酶V将含有它的药物组合物用作阳性的治疗剂。构成：由式（1）表示的新型吡唑嘧啶衍生物，其中R 1和R 2独立地为C 1 -C 6烷基或C 3 -C 6环烷基; R3是取代或未取代的C1-C6烷基，C3-C6环烷基或C3-C6烯基; 且X为O或NR 4，其中R 4为氢，OH或C 1 -C 6烷基，C 3 -C 6环烷基或被烷氧基取代或未取代的C 3 -C 6烯基。 其通过以下步骤制备：通过硫酮反应将式（2）的吡唑并嘧啶酮转化为式（3）的吡唑并嘧啶硫酮; 将式（3）的化合物氯化为式（4）的氯砜化合物，并使式（4）的化合物与仲胺反应以制备式（1）的最终化合物。

公开(公告)号：KR100333492B1

公开(公告)日：2002-04-25

申请号：KR1019990019241

申请日：1999-05-27

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  장문호 ,  조영서 ,  최경일 ,  배애님 ,  김혜연 ,  주현진

IPC: C07D413/14

Abstract: 일반식(II)로표시되는옥사졸리디논유도체와일반식(III)으로표시되는이소옥사졸유도체를용매와환원제존재하에반응시켜 MRSA 균주를포함한그람양성균에우수한신규의일반식 (I)로표시되는이소옥사졸릴메틸렌옥사졸리디논유도체및 이의제조방법에관한것이다. 상기식들중, R은수소, 알킬, 브롬또는염소의할로겐, 시아노, 알콜시, 히드록시, 카르복시, 카르바모일, N,N'-디메틸카르바모일, 카르바모일옥시, 산소, 황, 질소원자를적어도한 개이상포함하고있는티오펜, 티아졸, 아미노티아졸, 이소티아졸, 이소옥사졸, 옥사졸, 테트라졸, 피리딘의불포화 5환또는 6환헤테로고리치환체, 알킬, 할로겐알콕시, 시아노또는페녹시가치환된벤젠고리치환체, 약제학적으로허용되는염의메탄설폰산염, 퓨마렌산염, 브롬산염, 시트릭산염, 인산염, 황산염, 염산염또는염이아닌아민을포함한다.

公开(公告)号：KR1020000067451A

公开(公告)日：2000-11-15

申请号：KR1019990015261

申请日：1999-04-28

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  최경일 ,  배애님 ,  고훈영 ,  김유승 ,  차주환 ,  이지은

IPC: C07D501/22

CPC classification number: Y02P20/55

Abstract: PURPOSE: Cepham derivatives prepared by the reaction of 3-hydroxy cephem derivatives and allylhalide or acetylene halide in a solvent in the presence of a metal catalyst and process for the preparation method thereof are provided which can be used as an intermediate for the manufacture of cephem antibiotics. CONSTITUTION: Cepham derivatives of formula (I) useful as an intermediate for producing cephem antibiotics are prepared by the reaction of 3-hydroxy cephem derivatives of formula (V) and allylhalide (III) or acetylene halide in a solvent in the presence of a metal catalyst at 0 to 100°C for 1 to 96 hr. In formula, R1 represents phenylacetyl, 2-£2-amino(1,3-thiazole-4-yl)-2-(hydroxyalkoxyimino)ethinyl, 2-£2-amino(1,3-thiazole-4-yl)-2-(alkoxyimino)ethinyl or 4-hydroxyphenylglycine derivative, R2 is H, carboxylic acid salts (sodium and potassium salt as inorganic salts, alkylamine salt, aromatic amine salt as organic salts), a molecular protecting group in the cephalosporin field of 4-methoxybenzyl, diphenylbenzyl, diphenylmethyl, 4-nitrobenzyl, allyl as a carboxyl protecting group, in a Q compound, R3, R4 and R5 represent each H, halogen, methyl, ethyl, hydroxy, phenyl or alkoxycarbonyl.

Abstract translation: 目的：提供在金属催化剂存在下，通过3-羟基头孢烯衍生物和烯丙基卤或乙炔卤化物在溶剂中反应制备的Cepham衍生物，其制备方法可用作中间体，用于制备头孢烯 抗生素。 构成：通过式（Ⅴ）的3-羟基头孢烯衍生物与烯丙基卤（III）或炔酰卤在溶剂中在金属存在下的反应制备用作产生头孢类抗生素的中间体的式（I）的头孢类衍生物 催化剂在0〜100℃下反应1〜96小时。 在式中，R 1表示苯乙酰基，2- {2-氨基（1,3-噻唑-4-基）-2-（羟基烷氧基亚氨基）乙炔基，2-（2-氨基（1,3-噻唑-4-基） 2-（烷氧基亚氨基）乙炔基或4-羟基苯基甘氨酸衍生物，R2是H，羧酸盐（作为无机盐的钠盐和钾盐，烷基胺盐，作为有机盐的芳族胺盐），四氢呋喃的头孢菌素领域中的分子保护基， 甲氧基苄基，二苯基苄基，二苯基甲基，4-硝基苄基，烯丙基作为羧基保护基，在Q化合物中，R 3，R 4和R 5各自表示H，卤素，甲基，乙基，羟基，苯基或烷氧基羰基。

公开(公告)号：KR100267260B1

公开(公告)日：2000-11-01

申请号：KR1019980027115

申请日：1998-07-06

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  장문호 ,  김유승 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  심상철

IPC: C07D501/24 ,  C07D501/20

Abstract: 본 발명은 경구 투여가 가능한 새로운 세펨 에스테르 화합물 및 이의 제조방법에 관한 것으로, 그램 양성균과 그램 음성균에 대해 광범위의 항균력을 나타내며, 특히 MRSA를 포함한 여러 내성균에 강한 항균력을 나타내는 약제학적으로 유용한 화합물이다.

(I)
일반식 (I)에 있어서, R
1 은 수소 또는 트리틸기를 표시하며, R
2 는 수소, 트리틸기, 메틸기 또는 시클로펜틸기를 표시하며, R
3 는 수소, 클로로, 브로모 또는 메톡시기를 표시하며, R
4 는 아세톡시에틸, 피발로일옥시메틸 또는 이소프로폭시카르보닐옥시에틸기를 표시한다.

公开(公告)号：KR1020000002400A

公开(公告)日：2000-01-15

申请号：KR1019980023118

申请日：1998-06-19

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  장문호 ,  김유승 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  공재양 ,  천혜경 ,  정대영

IPC: C07D453/00 ,  C07D261/20

Abstract: PURPOSE: The compound is provided which exhibits a high affinity for muscarinic acetylcholine receptor and is useful as therapeutic agent of cerebral nerve disease such as Alzheimer's disease. CONSTITUTION: The carbonyl compound of the formula (II), wherein, n is integer 1 or 2, is reacted with phosphonium salt compound of formula (III), in which R is H, halo, alkoxy, cyano, alkyl, alkenyl, alkinyl, hydroxy, amino, nitro, 4-methoxybenzyloxy, t-butoxycarbonylamino or its salt; R1, R2 and R3 are alkyl, aryl or aralkyl, respectively; X is halogen, or with phosphonate compound of the formula (IV) in the presence of solvent and base to give £(aryl) isooxozolyl| methylene-azabicyclo compound of the formula (I). Thus, 188mg of potassium t-butoxide and 482mg of diethyl 3-(4-methylphenyl)-5-isooxazolylmethylphosphonate being dissolved in tetrahydrofuran are stirred for 30 minutes at 22°C to give 3-£3-(4-methylphenyl)isooxazol-5-yl|methylene-1-azabicyclo£2.2.2|octane oxalic acid salt.

Abstract translation: 目的：提供对毒蕈碱性乙酰胆碱受体具有高亲和力的化合物，并且可用作脑神经疾病如阿尔茨海默病的治疗剂。 构成：其中n为1或2的式（II）的羰基化合物与式（III）的鏻盐化合物反应，其中R为H，卤素，烷氧基，氰基，烷基，烯基，炔基 ，羟基，氨基，硝基，4-甲氧基苄氧基，叔丁氧基羰基氨基或其盐; R1，R2和R3分别是烷基，芳基或芳烷基; X为卤素，或与式（IV）的膦酸酯化合物在溶剂和碱存在下反应，得到（芳基）异恶唑基| 式（I）的亚甲基 - 氮杂二环化合物。 因此，将188mg叔丁醇钾和482mg 3-（4-甲基苯基）-5-异恶唑甲基膦酸二乙酯溶于四氢呋喃中，在22℃下搅拌30分钟，得到3- {3-（4-甲基苯基）异恶唑-4-基） 5-基|亚甲基-1-氮杂双环{2.2.2 |辛酸草酸盐。

公开(公告)号：KR100215551B1

公开(公告)日：1999-08-16

申请号：KR1019970015200

申请日：1997-04-23

Applicant: 한국과학기술연구원 ,  학교법인 중앙대학교 ,  한미사이언스 주식회사

Inventor： 조용서 ,  장문호 ,  고훈영 ,  최경일 ,  배애님 ,  하영진

IPC: C07D499/87

Abstract: 일반식(Iv)로 표시되는 알데히드와 일반식(Ⅲ)으로 표시되는 아민화합물올 용매존재하에 축합반응시켜 중간체인 일반식(V)의 이민화합물을 제조하고, 일반식(V)로 표시되는 이민화합물의 C-3 위치의 보호기인 R
3 를 제거하여 신규한 일반식(I)로 표시되는 2-베타-이민-페남유도체를 제조하는 것으로 일반식(I)은 이성체를 포합한다. 일반식(I)의 화합물은 베타락타마제 제해제로서 기존의 항생제와 일정 비율로 병용하면 항균작용을 증진시키는 유용한 화합물이다.

상기 일반식들에 있어서, Q는 수소, 메틸, 시아노메틸, 카르복시메틸, 알콕시카르보닐메틸, 디히드록시 벤질유도체, 알릴, 아세 틸유도체, 아미 도알콕시메틸,2-카르복시에톡시유도체, 플루오르알콕시유도체, 피리듐아세틸유도체를 나타내며, R3는 수소, 카르복실산 염, 카르복시 보호기로는 4-메톡시벤질, 디페닐메틸,4-니트로벤질 그리고 알릴 등의 페니실린이나 세팔로스포린 화합물 분야에서 분자의 보호기로 유용한 것을 나타내고, n은 0 ∼ 2의 정수이다.

公开(公告)号：KR1019960022537A

公开(公告)日：1996-07-18

申请号：KR1019940035869

申请日：1994-12-22

Applicant: 한국과학기술연구원

Inventor： 장문호 ,  고훈영 ,  김유승 ,  최경일 ,  조용서 ,  배애남

IPC: C07D501/36 ,  C07D501/24

Abstract: 본 발명은 하기 일반식(I)의 화합물 또는 그의 제약학적으로 허용되는 염 및 에스테르를 제공한다.

상기 식 중, R
1 은 수소 또는 아미노 보호기이고, R
2 는 수소, 카르복실산 에스테르 또는 카르복실산염 형성기, 또는 카르복시 보호기이거나, 또는 -COOR
2 는 -COO
를 나타내고, R
3 및 R
4 는 서로 동일하거나 상이한 것으로서, 각각 수소 또는 페놀성 히드록시 보호기이고, Q는 수소, 할로겐, C
2-4 알케닐, 할로-C
1-4 알킬, C
3-12 알카노일옥시알킬 또는 Q′-C
1-4 알킬-(여기서, Q′는 헤테로 원자로서 1개 이상의 질소 원자를 함유하고 황원자를 통해 C
1-4 알킬과 결합되는 5원 내지 6월 헤테로 고리임)이다.
또한, 본 발명은 상기 일반식(I)의 화합물의 제조 방법 및 이에 사용되는 중간제의 제조 방법도 제공한다.