公开(公告)号：KR100448002B1

公开(公告)日：2004-09-13

申请号：KR1020020005946

申请日：2002-02-01

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  석미영 ,  공재양 ,  정대영

IPC: C07D453/02

Abstract: PURPOSE: Provided are Quinuclidine compounds which are useful for treatment of brain-nervous diseases caused by cholinergic neurotransmission such as Alzheimer's disease and a preparation method thereof. CONSTITUTION: A quinuclidine compounds of the formula (I) and pharmaceutically acceptable salts thereof are provided, wherein n is an integer of 1 to 5; R is a substituent on a benzene ring, hydrogen, F, Cl, methoxy, OH, NH2, NO2, 3,4-dimethoxy, 2,4-dimethoxy, cyano, C1-6 alkyl, 1,2 or 3 fluorine substituted C1-6 alkyl, 4-methoxybenzyloxy, t-butoxycarbonyl, C2-6 alkenyl, 1,2 or 3 fluorine substituted C2-6 alkenyl, C2-6 alkynyl, 1,2 or 3 fluorine substituted C2-6 alkynyl, and C3-7 cycloalkyl. A method for preparing the quinuclidine compounds of the formula (I) comprises reacting a compound of the formula (II) with a compound of the formula (III) or (IV), wherein R1 and R2 are independently C1-6 alkyl, aryl or arylalkyl.

Abstract translation: 目的：提供用于治疗由胆碱能神经传递引起的脑神经疾病如阿尔茨海默氏病的奎宁环化合物及其制备方法。 构成：提供式（I）的奎宁环化合物及其药学上可接受的盐，其中n是1至5的整数; R为苯环上的取代基，氢，F，Cl，甲氧基，OH，NH2，NO2,3,4-二甲氧基，2,4-二甲氧基，氰基，C1-6烷基，1,2或3个氟取代的C1 -6烷基，4-甲氧基苄氧基，叔丁氧基羰基，C2-6烯基，1,2或3个氟取代的C2-6烯基，C2-6炔基，1,2或3个氟取代的C2-6炔基和C3-7 环。 用于制备式（I）奎宁环化合物的方法包括使式（II）化合物与式（III）或（IV）化合物反应，其中R 1和R 2独立地为C 1-6烷基，芳基或 芳。

公开(公告)号：KR100418915B1

公开(公告)日：2004-02-14

申请号：KR1020000071399

申请日：2000-11-28

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이희윤 ,  손정훈 ,  공재양 ,  정대영

IPC: C07D401/04

Abstract: PURPOSE: A 4-aminopiperidine analogue and a producing method thereof are provided, therefore the compound can be useful as a ligand of a muscarine receptor, and it is thus used in study on Alzheimer disease. CONSTITUTION: The 4-aminopiperidine analogue is represented by formula(I), wherein R1, R2, R3, R4, R5, R6 and R7 are hydrogen, cycloalkyl having carbon number of 1 to 6, alkoxy, halogen, hydroxy, hydroxymethyl, aryl, heteroaryl, amino, alkylamino, alkenyl, carbonyl or hetero ring having carbon number of 5 to 7 wherein aryl is a ring having 6 atoms, two rings having 10 atoms or a stable resonance form having double bond to adjacent carbon; heteroaryl is a single ring aromatic group having carbon number of 5 to 6 or a double ring aromatic group having carbon number of 10 in which the heteroaryl has at least one hetero atom of N, O or S; hetero ring consists of 5 to 7 atoms having 1 to 3 of N, O or S; X is carbon or sulfur; and n is an integer of 1 to 2 wherein n is 1 when X is carbon and is 2 when X is sulfur. The 4-aminopiperidine analogue is produced by reacting piperidine or amine(II) with piperazine with ketone(III) in the presence of 1 to 3 equivalent of acetic acid, 2 to 10 equivalent of reducing agent and solvent at room temperature for 3 to 24 hours to produce 4-aminopiperidine(I) and adding NaHCO3 solution and organic solvent to 4-aminopiperidine(I); and drying the extracted 4-aminopiperidine(I), dissolving it, adding 1 to 10 equivalent of hydrogen chloride to the solution, and separating, washing and drying the hydrochloride of 4-aminopiperidine.

Abstract translation: 目的：提供了4-氨基哌啶类似物及其生产方法，因此该化合物可用作毒蕈碱受体的配体，因此用于研究阿尔茨海默病。 构成：4-氨基哌啶类似物由式（I）表示，其中R1，R2，R3，R4，R5，R6和R7是氢，碳数为1-6的环烷基，烷氧基，卤素，羟基，羟甲基，芳基 杂芳基，氨基，烷基氨基，链烯基，羰基或杂环，其中芳基是具有6个原子的环，具有10个原子的两个环或具有与相邻碳双键的稳定的共振形式; 杂芳基为碳数为5至6的单环芳族基团或碳数为10的双环芳族基团，其中杂芳基具有至少一个N，O或S的杂原子; 杂环由5至7个具有1至3个N，O或S的原子组成; X是碳或硫; 并且n是1至2的整数，其中当X是碳时，n是1，当X是硫时，n是2。 4-氨基哌啶类似物是通过使哌啶或胺（II）与哌嗪与酮（III）在1至3当量乙酸，2至10当量还原剂和溶剂的存在下在室温下反应3至24 小时以产生4-氨基哌啶（I）并将NaHCO 3溶液和有机溶剂加入到4-氨基哌啶（I）中; 干燥提取的4-氨基哌啶（I），溶解，加入1至10当量的氯化氢至溶液中，分离，洗涤并干燥4-氨基哌啶的盐酸盐。

公开(公告)号：KR100394083B1

公开(公告)日：2003-08-06

申请号：KR1020000073122

申请日：2000-12-04

Applicant: 한국과학기술연구원 ,  한국과학기술원 ,  한국화학연구원 ,  학교법인 성신학원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  공재양 ,  정대영 ,  정선호 ,  정지영 ,  이희윤

IPC: C07D413/14

CPC classification number: C07D413/04 ,  C07D261/08

Abstract: The present invention relates to 4,5-dihydroisoxazolylalkylpiperazine derivatives having selective biological activity at dopamine D3 and D4 receptors represented by the following Formula (1), and its preparation method through reductive amination reaction in the presence of reducing agent,wherein R1, R2, X and n are the same as defined in the specification.

Abstract translation: 本发明涉及对下式（1）所示的多巴胺D3和D4受体具有选择性生物活性的4,5-二氢异恶唑烷基哌嗪衍生物及其在还原剂存在下通过还原胺化反应的制备方法，其中R1，R2， X和n与说明书中定义的相同。

公开(公告)号：KR1020030063853A

公开(公告)日：2003-07-31

申请号：KR1020020004199

申请日：2002-01-24

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  최경일 ,  조용서 ,  배애님 ,  차주환 ,  공재양 ,  정대영

IPC: C07D453/02 ,  C07D471/08 ,  C07D261/06

Abstract: PURPOSE: An alkenyl azabicyclic compound and a preparation method thereof are provided, which can be useful for treatment of cerebral nervous diseases caused by choline neurotransmission disorders. CONSTITUTION: An alkenyl azabicyclic compound represented by the formula(I) and pharmaceutically acceptable salts thereof are provided, wherein n is 1 or 2; and R is selected from the group consisting of hydrogen, F, Cl, methoxy, OH, NH2, NO2, 3,4-dimethoxy, 2,4-dimethoxy, cyano, C1-C6 alkyl, 1, 2 or 3 fluorine substituted C1-C6 alkyl, 4-methoxybenzyloxy, t-butoxycarbonyl, C2-C6 alkenyl, 1, 2 or 3 fluorine substituted C2-C6 alkynyl and C3-C7 cyloalkyl. A method for preparing the alkenyl azabicyclic compound of the formula(I) comprises a compound of the formula(II) with a compound of the formula(III) or formula(IV), wherein R1, R2 and R3 are independently C1-C6 alkyl, aryl or arylalkyl.

Abstract translation: 目的：提供一种烯基氮杂双环化合物及其制备方法，其可用于治疗由胆碱神经传递障碍引起的脑神经疾病。 构成：提供由式（I）表示的烯基氮杂双环化合物及其药学上可接受的盐，其中n为1或2; 并且R选自氢，F，Cl，甲氧基，OH，NH 2，NO 2，3,4-二甲氧基，2,4-二甲氧基，氰基，C 1 -C 6烷基，1,2或3个氟取代的C 1 C 1-6烷基，4-甲氧基苄氧基，叔丁氧基羰基，C 2 -C 6烯基，1,2或3个氟取代的C 2 -C 6炔基和C 3 -C 7环烷基。 制备式（I）的烯基氮杂双环化合物的方法包括式（II）化合物与式（III）或式（IV）化合物，其中R 1，R 2和R 3独立地为C 1 -C 6烷基 ，芳基或芳烷基。

公开(公告)号：KR1020000074954A

公开(公告)日：2000-12-15

申请号：KR1019990019241

申请日：1999-05-27

Applicant: 한국과학기술연구원

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

IPC: C07D413/14

Abstract: PURPOSE: Provided is an isooxazolyl methylene oxazolidinone derivative represented by the formula (I) which is superior in antibacterial activity. Also, a method for preparing the compound is provided. CONSTITUTION: An isooxazoly methylene oxazolidinone derivative is represented by the formula (I): wherein, R is hydrogen, alkyl, halogen such as bromine or chlorine, cyano, alkoxy, hydroxy, carboxy, carbamoyl, N,N'-dimethylcarbamoyl, carbamoyloxy, oxygen, sulfur, thiopene having more than one nitrogen atom, thiazole, aminothiazole, isothiazole, isooxazole, oxazole, tetrazole, 5 or 6-membered unsaturated heterocycle substituent of pyridine, alkyl, halogenalkoxy, benzene ring substituted with cyano or phenoxy group, pharmaceutically acceptable methanesulfonate, fumarate, bromate, citrate, phosphate, sulfate or amine not being salt. The isooxazoly methylene oxazolidinone derivative is prepared by reacting oxazolidine derivative represented by the formula (II) and isooxazole derivative represented by the formula (III) a using a reductant in the presence of a solvent.

Abstract translation: 目的：提供抗菌活性优异的由式（I）表示的异恶唑基亚甲基恶唑烷酮衍生物。 此外，提供了制备该化合物的方法。 构型：异恶唑基亚甲基恶唑烷酮衍生物由式（I）表示：其中R是氢，烷基，卤素如溴或氯，氰基，烷氧基，羟基，羧基，氨基甲酰基，N，N'-二甲基氨基甲酰基，氨基甲酰氧基， 氧，硫，具有多于一个氮原子的噻吩，噻唑，氨基噻唑，异噻唑，异恶唑，恶唑，四唑，吡啶，烷基，卤代烷氧基，被氰基或苯氧基取代的苯环的5或6元不饱和杂环取代基， 甲磺酸盐，富马酸盐，溴酸盐，柠檬酸盐，磷酸盐，硫酸盐或胺不是盐。 异恶唑亚甲基恶唑烷酮衍生物通过使用还原剂在溶剂存在下使式（II）表示的恶唑烷衍生物和由式（III）a表示的异恶唑衍生物反应来制备。

公开(公告)号：KR1020000073204A

公开(公告)日：2000-12-05

申请号：KR1019990016354

申请日：1999-05-07

Applicant: 한국과학기술연구원

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

IPC: C07D499/00

CPC classification number: Y02P20/55

Abstract: PURPOSE: A new penam derivative using indium and zinc and a preparation method thereof are provided CONSTITUTION: A novel penam derivative represented by formula(I) is prepared by reacting 6-oxopenam of the formula(I') with ally halide of the formula (II) or acetylene halide of the formula (III) in the presence of indium or zinc. In the formula(I): R1 is allyl derivative and acetylene derivative; R2 is hydrogen, carboxylic acid salt(sodium salt and potassium salt as inorganic salt, alkyl amine salt, aromatic amine salt as organic salt) or carboxy protecting group(4-methoxy benzyl, diphenylmethyl, 4-nitrobenzyl, useful thing as protecting group of molecule in penicillin or cephalosporin compound field); R3 is hydrogen, halogen, hydroxy, acetoxy group.

Abstract translation: 目的：提供使用铟和锌的新的penam衍生物及其制备方法构成：式（I）表示的新型penam衍生物通过式（I'）的6-氧代青霉素与式（I'）的式 II）或式（III）的炔酰卤在铟或锌的存在下进行。 在式（I）中：R 1是烯丙基衍生物和乙炔衍生物; R2为氢，羧酸盐（钠盐和钾盐为无机盐，烷基胺盐，芳族胺盐为有机盐）或羧基保护基（4-甲氧基苄基，二苯基甲基，4-硝基苄基，有用物质为保护基 分子在青霉素或头孢菌素化合物领域）; R3是氢，卤素，羟基，乙酰氧基。

公开(公告)号：KR1020000051062A

公开(公告)日：2000-08-16

申请号：KR1019990001300

申请日：1999-01-18

Applicant: 한국과학기술연구원

Inventor： 김유승 ,  배애님 ,  강순방 ,  금교창 ,  조상원

IPC: C07D501/04

Abstract: PURPOSE: A process for preparing 7-aminodesacetoxycephalosporanic acid useful as an important intermediate for preparing cephalosporin antibiotics is provided which comprises reaction of 3-substituted cephalosporin derivatives in the presence of metal indium or an indium compound. CONSTITUTION: A process comprises the steps of preparing a mixture of 7-aminodesacetoxycephalosporanic acid derivatives (I) and 3-exomethylenecephem derivatives (III) by the reaction of 3-substituted cephalosporin derivative (II) in a mixture solution of an organic solvent and water in the presence of solely indium metal or a mixture of indium metal and metal iodide at 10 to 80°C for 1 to 10 hrs and preparing 7-aminodesacetoxycephalosporanic acid (I) by the reaction of the obtained mixture with tetramethylsilylchloride at 20 to 30°C for 20 to 24 hrs.

Abstract translation: 目的：提供一种制备用作制备头孢菌素抗生素的重要中间体的7-氨基脱乙酸基头孢烷酸的方法，其包括在金属铟或铟化合物存在下3-取代头孢菌素衍生物的反应。 构成：一种方法包括通过3-取代头孢菌素衍生物（II）在有机溶剂和水的混合溶液中的反应制备7-氨基脱乙酸基头孢烷酸衍生物（I）和3-异二甲酰头孢烯衍生物（III）的混合物的步骤 在单独的铟金属或铟金属与金属碘化物的混合物的存在下，在10〜80℃下反应1〜10小时，并通过所得混合物与四甲基甲硅烷基氯反应，在20〜30℃下制备7-氨基脱乙酸基头孢烷酸（I） C为20至24小时。

公开(公告)号：KR1019950008319B1

公开(公告)日：1995-07-27

申请号：KR1019920012642

申请日：1992-07-15

Applicant: 한국과학기술연구원

Inventor： 장문호 ,  강한영 ,  고훈영 ,  배애님 ,  심상철

IPC: C07D501/20

Abstract: This is new cephalosphorin compd. and its parmaceutically acceptable salt of formula(I). In formula, R1 is H, or trityl, tert-butoxycarbonyl, or formyl; R2 H, p-methoxybenzyl, diphenylmethyl or salting compd. such as Na or K; R3 and R4 are same or different, and H, acetyl, or p-methoxybenzyl; X,Y are H, F, Cl, Br, or I; and Q hydrogen, chloro, vinyl, acetoxymethyl, halomethyl, pyridiniummethyl, N- ethyl pyridiniumyl thiomethyl, N- carboxymethyl pyridiniumyl thiomethyl, carbamoyloxymethyl, and N-methyl-tetrazolyl thiomethyl gp. This compd. is prepared by acylation of the aminothiazol compd of (II) with cephalosphorin of (III). This cephem compd. has good antibacterial activity.

Abstract translation: 这是新头孢菌素 和其药学上可接受的式（I）盐。 在式中，R 1是H或三苯甲基，叔丁氧基羰基或甲酰基; R2H，对甲氧基苄基，二苯甲基或盐析化合物。 如Na或K; R3和R4相同或不同，H，乙酰基或对甲氧基苄基; X，Y是H，F，Cl，Br或I; 和Q氢，氯，乙烯基，乙酰氧基甲基，卤代甲基，吡啶鎓甲基，N-乙基吡啶鎓硫代甲基，N-羧甲基吡啶鎓硫代甲基，氨基甲酰氧基甲基和N-甲基 - 四唑基硫代甲基gp。 这个compd 通过（II）的氨基噻唑化合物与（III）的头孢菌素的酰化制备。 这个cephem compd 具有良好的抗菌活性。

公开(公告)号：KR1019930007812B1

公开(公告)日：1993-08-20

申请号：KR1019910018791

申请日：1991-10-25

Applicant: 한국과학기술연구원

Inventor： 장문호 ,  강한영 ,  고훈영 ,  배애님 ,  조용서

IPC: C07D501/24

Abstract: Alkenyl cephalosporin derivs. of formula (I) and their pharmaceutical salts are new. 3-cephem compds. were obtained by witting reaction from a phosphonium cpd. of formula (II) with an aldehyde cpd. of formula (III) and then were deacylated to produce 7- amino-3-cephem derivs. The formula (I) derivs. are prepd. by acylation of 7-amino-3-cephem derivs with 2- aminothiazolyl-2-hydroxyimino- acetic acid compds. In (I), R1=H or a protecting gp. as in cephalosporin and penicillin cpds.; R2=H, C1-4 alkyl or substd. alkyl; R3=H or a deriv. of a carboxy gp., an atom for prepn. of a salt or carboxy protecting gp.

Abstract translation: 烯基头孢菌素衍生物。 的式（I）化合物及其药用盐是新的。 3-头孢烯 通过从cpd鏻反应得到。 式（II）与醛cpd反应。 的式（III），然后脱酰基以产生7-氨基-3-头孢烯衍生物。 公式（I）导出。 是prepd 通过7-氨基-3-头孢烯衍生物与2-氨基噻唑-2-羟基亚氨基 - 乙酸化合物的酰化反应。 在（I）中，R1 = H或保护gp。 如头孢菌素和青霉素cpds。 R2 = H，C1-4烷基或取代基。 烷基; R3 = H或衍生物。 的羧基，一个原子的制备。 的盐或羧基保护gp。

公开(公告)号：KR1019930007261B1

公开(公告)日：1993-08-04

申请号：KR1019910006288

申请日：1991-04-19

Applicant: 한국과학기술연구원

Inventor： 장문호 ,  강한영 ,  고훈영 ,  배애님 ,  김현미 ,  고성희

IPC: C07D501/24

CPC classification number: C07D257/04 ,  C07D501/00

Abstract: The cephene-4-carboxylic acid deriv. of formula (I) is prepd. by reacting an aldehyde cpd. of formula (II) with a phosphonium salt of formula (III) in the presence of a base and a solvent at 0-30 deg.C. In the formulas, R1 is methyl, ethyl, propyl, phenyl or benzyl; R2 is p-methoxy benzyl, diphenyl methyl or allyl; R3 is H, t- butoxy carbonyl or phenyl acetyl; R4 is H, t-butoxy carbonyl, formyl or phenyl acetyl. The solvent is pref. water, dichloromethane, ethylether and/or tetrahydrofurane. The deriv. of (I) is useful for antibiotics.

Abstract translation: 环丙烷-4-羧酸衍生物。 式（I）的化合物是制备的。 通过使醛cpd反应。 式（II）的化合物与式（III）的鏻盐在碱和溶剂的存在下在0-30℃下反应。 式中R1是甲基，乙基，丙基，苯基或苄基; R2是对甲氧基苄基，二苯基甲基或烯丙基; R3是H，叔丁氧基羰基或苯基乙酰基; R4是H，叔丁氧基羰基，甲酰基或苯基乙酰基。 溶剂优先。 水，二氯甲烷，乙醚和/或四氢呋喃。 衍生。 （I）可用于抗生素。