公开(公告)号：KR100843352B1

公开(公告)日：2008-07-03

申请号：KR1020070009627

申请日：2007-01-30

Applicant: 한국과학기술연구원 ,  주식회사 디비하이텍

Inventor： 배애님 ,  조용서 ,  추현아 ,  차주환 ,  김지혜 ,  고훈영 ,  박우규 ,  공재양 ,  채명윤 ,  조인선 ,  황봉운 ,  이동하

IPC: C07D401/12 ,  A61K31/502

CPC classification number: C07D237/32

Abstract: A 1,2-dihydro-1-oxophthalazinyl piperazine derivative is provided to show selective antagonistic activity on serotonin 5-HT2a or 5-HT2c receptor, thereby being used for a pharmaceutical composition for treating and preventing central nervous system diseases. A 1,2-dihydro-1-oxophthalazinyl piperazine derivative is represented by a formula(1) and is prepared by reacting an amine compound represented by a formula(2) with a carboxylic acid compound represented by a formula(3). In the formulae, R1 is H, halogen, C1-10 alkyl, C1-10 alkoxy, phenyl, pyridyl or pyrimidyl; R2 is aryl selected from the group consisting of phenyl, pyridyl and pyrimidyl which may be substituted or unsubstituted by a substituent selected from the group consisting of halogen, nitro, C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, C1-10 haloalkoxy, and C1-6 acyl; and n is an integer from 0 to 5. A pharmaceutical composition for treating and preventing diseases such as anxiety, depression, stroke, obsessive neurosis, psychosis, schizophrenia, suicidal tendency, sleep disorders, appetite disorders, withdrawal symptoms caused by drug abuse, and migraine comprises the 1,2-dihydro-1-oxophthalazinyl piperazine derivative represented by the formula(1) or a pharmaceutically acceptable salt thereof.

Abstract translation: 提供1,2-二氢-1-氧酞嗪哌嗪衍生物以显示对5-羟色胺5-HT2a或5-HT2c受体的选择性拮抗活性，从而用于治疗和预防中枢神经系统疾病的药物组合物。 1,2-二氢-1-氧代吖嗪基哌嗪衍生物由式（1）表示，通过使由式（2）表示的胺化合物与由式（3）表示的羧酸化合物反应制备。 式中，R 1为H，卤素，C 1-10烷基，C 1-10烷氧基，苯基，吡啶基或嘧啶基; R 2是选自苯基，吡啶基和嘧啶基的芳基，其可以被选自卤素，硝基，C 1-10烷基，C 1-10卤代烷基，C 1-10烷氧基，C 1-10烷氧基， 10个卤代烷氧基和C1-6酰基; n为0〜5的整数。用于治疗和预防焦虑，抑郁，中风，强迫神经症，精神病，精神分裂症，自杀倾向，睡眠障碍，食欲障碍，药物滥用引起的戒断症状的药物组合物，以及 偏头痛包含由式（1）表示的1,2-二氢-1-氧代嗪嗪哌嗪衍生物或其药学上可接受的盐。

公开(公告)号：KR100645372B1

公开(公告)日：2006-11-14

申请号：KR1020050061706

申请日：2005-07-08

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  차주환 ,  배애님 ,  고훈영 ,  신철

IPC: C07D493/04

Abstract: Novel bicyclic tetrahydrofuran lactone derivatives, and a preparation process thereof are provided to serve useful intermediates for synthesis of natural products, and prepare the compounds simply. The bicyclic tetrahydrofuran lactone derivatives represented by the formula(1) are provided, wherein n is 1 or 2; R is phenyl group optionally substituted by C1-C6 alkyl group, C1-C6 alkoxy group, hydroxy group or C1-C6 hydroxyalkyl group. The bicyclic tetrahydrofuran lactone derivatives represented by the formula(1) are prepared by intramolecular cyclizing tetrahydrofuran-allenic acid derivatives represented by the formula(2) in the presence of phenyl halide, palladium catalyst and base, wherein the reaction solvent is diethylether, tetrahydrofuran, dichloromethane, dimethylformamide, ethylacetate or chloroform; the palladium catalyst is tetrakis(triphenylphosphin) palladium; the base is carbonate, hydrogen carbonate or sulfate of alkali metals or alkali earth metals; and the reaction temperature is 0 to 90 deg.C.

Abstract translation: 提供了新的双环四氢呋喃内酯衍生物及其制备方法，以提供用于合成天然产物的有用中间体，并简单地制备该化合物。 提供由式（1）表示的双环四氢呋喃内酯衍生物，其中n是1或2; R是任选被C1-C6烷基，C1-C6烷氧基，羟基或C1-C6羟烷基取代的苯基。 式（1）所示的双环四氢呋喃内酯衍生物是在苯基卤化物，钯催化剂和碱的存在下，通过式（2）表示的四氢呋喃 - 艾伦酸衍生物分子内环化制备的，其中反应溶剂为乙醚，四氢呋喃， 二氯甲烷，二甲基甲酰胺，乙酸乙酯或氯仿; 钯催化剂是四（三苯基膦）钯; 碱是碱金属或碱土金属的碳酸盐，碳酸氢盐或硫酸盐; 反应温度为0〜90℃。

公开(公告)号：KR100519715B1

公开(公告)日：2005-10-10

申请号：KR1020030018239

申请日：2003-03-24

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  차주환 ,  전보경

IPC: C07C17/272

Abstract: 본 발명은 인듐할라이드(III)염을 사용하여 알렌올에서 2-할로-1,3-다이엔을 제조하는 방법에 관한 것으로, 인듐할라이드(III)염 (화학식 1)을 사용하여 알렌올(화학식 2)에서 화학식 4의 반응을 통하여 2-할로-1,3-다이엔(화학식 3)을 제조하는 것을 특징으로 한다.
(화학식 4)

(상기 화학식 1 ∼ 화학식 4에서, R
1 , R
2 , R
3 , R
4 는 수소, 알킬기, 방향족 화합물, 고리화합물 치환기를 말하며, X는 Cl, Br, I와 같은 할로겐 원소를 말한다.)

公开(公告)号：KR100478901B1

公开(公告)日：2005-03-28

申请号：KR1020020002789

申请日：2002-01-17

Applicant: 한국과학기술연구원

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

IPC: C07D307/12

Abstract: 본 발명은 베일리스-힐만 생성물 및 이의 제조방법에 관한 것으로, 구체적으로는 베타위치가 치환된 베일리스-힐만 생성물 및 인듐을 이용하여 통상적인 방법으로는 제조하기 어려운 상기 베일리스-힐만 생성물을 온화한 조건과 용이한 방법으로 제조하는 방법에 관한 것이다.

公开(公告)号：KR1020040097444A

公开(公告)日：2004-11-18

申请号：KR1020030029741

申请日：2003-05-12

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  차주환

IPC: C07D309/32

Abstract: PURPOSE: 3,4-Diexomethylene tetrahydropyrane derivatives and a process for preparing the same derivatives are provided, which derivatives are useful as intermediate for preparing two or three cyclic compounds through Diels-Alder reaction. CONSTITUTION: The 3,4-diexomethylene tetrahydropyrane derivatives represented by formula (1) are provided, wherein R1 and R2 are selected from hydrogen, C1-C10 optionally saturated linear, branched chain or cyclic alkyl, and aromatics. The process for preparing the 3,4-diexomethylene tetrahydropyrane derivatives of formula (1) comprises reacting 1-substituted-3-trimethylsilanylmethyl-3,4-pentadiene-1-ol derivatives of formula (2) with aldehyde derivatives of formula (3) in solvent in the presence of Lewis acid catalyst at -100 deg. C to room temperature, wherein the Lewis acid catalyst is selected from trimethylsillyl trifluoromethanesulfonate(TMSOTF), aluminium halide, indium(III) halide, boron halide and titanium(IV) halide; and the solvent is selected from dimethylether, diethylether and tetrahydrofuran.

Abstract translation: 目的：提供3,4-二亚甲基四氢吡喃衍生物和制备相同衍生物的方法，该衍生物可用作通过Diels-Alder反应制备两种或三种环状化合物的中间体。 构成：提供由式（1）表示的3,4-阴离子亚甲基四氢吡喃衍生物，其中R 1和R 2选自氢，C 1 -C 10任选饱和的直链，支链或环烷基和芳族。 制备式（1）的3,4-二甲基四氢吡喃衍生物的方法包括使式（2）的1-取代-3-三甲基硅烷基甲基-3,4-戊二烯-1-醇衍生物与式（3）的醛衍生物反应， 在溶剂中，在-100度的路易斯酸催化剂存在下进行。 其中路易斯酸催化剂选自三甲基甲硅烷基三氟甲磺酸酯（TMSOTF），卤化铝，卤化铟（III），卤化硼和卤化钛（IV）; 溶剂选自二甲醚，二乙醚和四氢呋喃。

公开(公告)号：KR1020040083678A

公开(公告)日：2004-10-06

申请号：KR1020030018240

申请日：2003-03-24

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  장문호 ,  고훈영 ,  배애님 ,  차주환 ,  전보경

IPC: C07C17/02

Abstract: PURPOSE: Provided is a method for preparing various types of allyl halide compounds from allyl alcohols with ease by a one-step process at a high yield. CONSTITUTION: The method for preparing an allyl halide represented by formula 3 from an allyl alcohol represented by formula 2 comprises treating the allyl alcohol with an indium(III) halide salt represented by the formula of InX3 (wherein X is Cl, Br or I), through the reaction route of the following formula 4. In formulas 2 to 4, each of R1 to R3 represents H, Si, a halogen atom, an alkyl group, an aromatic substituent or a cyclic substituent. In the method, the reaction solvent is selected from acetonitrile and benzene.

Abstract translation: 目的：提供通过一步法以高收率容易地从烯丙醇制备各种烯丙基卤化物的方法。 构成：由式2表示的烯丙醇制备由式3表示的烯丙基卤的方法包括用式InX 3（其中X为Cl，Br或I）表示的卤化铟（III）处理烯丙醇， 在式2〜4中，R 1〜R 3各自表示H，Si，卤素原子，烷基，芳香族取代基或环状取代基。 在该方法中，反应溶剂选自乙腈和苯。

公开(公告)号：KR100419592B1

公开(公告)日：2004-02-19

申请号：KR1020010074837

申请日：2001-11-29

Applicant: 한국과학기술연구원

Inventor： 한예선 ,  고훈영 ,  임혜원 ,  차주환 ,  김욱현 ,  백정호

IPC: C12N15/53

CPC classification number: C12N9/0036

Abstract: The invention is a gene coding for a quinone oxidoreductase from Kluyveromyces marxianus and a protein having an amino acid sequence expressed therefrom, which can be advantageously used in a reduction reaction of a quinone compound and synthesis of intermediates for a biologically active compound.

Abstract translation: 本发明是编码来自马克斯克鲁维酵母的醌氧化还原酶的基因和具有由其表达的氨基酸序列的蛋白质，其可以有利地用于醌化合物的还原反应和用于生物活性化合物的中间体的合成。

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：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：KR1020030044179A

公开(公告)日：2003-06-09

申请号：KR1020010074837

申请日：2001-11-29

Applicant: 한국과학기술연구원

Inventor： 한예선 ,  고훈영 ,  임혜원 ,  차주환 ,  김욱현 ,  백정호

IPC: C12N15/53

CPC classification number: C12N9/0036

Abstract: PURPOSE: A quinone oxidoreductase gene from Kluyveromyces marxianus is provided to be used for the reduction reaction of the quinone compounds and for the intermediate synthesis of the biologically active compounds by way of the excellent quinone reduction activity thereof. CONSTITUTION: A gene codes the amino acid sequence of Kluyveromyces marxianus quinone oxidoreductase(kmQOR) presented at the sequence No. 2. The kmQOR has a molecular weight of about 42kDa. A recombinant vector contains the gene coded with the kmQOR, and is determined to be plasmid pQOR22b. An E. coli is transformed into the recombinant vector. In a method of preparing the kmQOR, the transformed E. coli is first cultured, and β-D-isopropyl-D-thiogalactopyranoside (IPTG) is then added to the cultured E. coli to induce the expression of kmQOR therefrom. The expressed kmQOR is collected, and purified.

Abstract translation: 目的：提供马克斯克鲁维酵母的醌氧化还原酶基因，用于醌类化合物的还原反应和生物活性化合物的中间合成，其优异的醌还原活性。 构成：A基因编码序列号2中提供的马克斯基黄酮醌氧化还原酶（kmQOR）的氨基酸序列。kmQOR的分子量约为42kDa。 重组载体含有用kmQOR编码的基因，并确定为质粒pQOR22b。 将大肠杆菌转化入重组载体。 在制备kmQOR的方法中，首先培养转化的大肠杆菌，然后将β-D-异丙基-D-硫代吡喃半乳糖苷（IPTG）加入到培养的大肠杆菌中以诱导其表达KmQOR。 收集并纯化表达的kmQOR。