公开(公告)号：KR1020030081762A

公开(公告)日：2003-10-22

申请号：KR1020020020136

申请日：2002-04-12

Applicant: 동화약품주식회사

Inventor： 정용호 ,  최동락 ,  김익회 ,  신정한 ,  양진 ,  윤수혜

IPC: C07D401/04

CPC classification number: Y02P20/55

Abstract: PURPOSE: A quinoline carboxylic acid derivative with fluoropyrrolidine substituents and a preparation process thereof are provided. The compound has no toxicity and improved antimicrobial activity to both gram positive and negative bacteria. CONSTITUTION: A quinoline carboxylic acid derivative represented by the formula 1 in which 4-aminomethyl-4-fluoro-3-(Z)-alkoxyiminopyrrolidine is substituted at the 7-site of the quinolone scaffold, pharmaceutically acceptable acid adding salt and solvates thereof are provided. In the formula, Q is C-H, C-F, C-Cl, C-OCH3, C-OCHF2, C-CH3 or N; R is hydrogen, methyl or NH2; R1 is ethyl, cyclopropyl, t-butyl, or at least one fluoro substituted phenyl; R2 is hydrogen, C1-C5 alkyl, cyclopropyl, cyclopropyl methyl, C3-C6 alkenyl, C3-C6 alkynyl, phenyl or benzyl; and R3 or R4 is independently hydrogen, or C1-C3 alkyl, or R3 or R4 is hydrogen or C1-C3 alkyl bound nitrogen containing C3-C5 hetero ring compound. A process for preparing the quinoline carboxylic acid derivative represented by the formula 1 comprises the steps of: (1) reacting a quinolone scaffold compound of the formula 2 with a fluoro containing compound of the formula 3 in the presence of a solvent and a base to prepare a compound of the formula 4; and (2) deprotecting the compound of formula 4 with HX, wherein R3 or R4 is hydrogen; P is hydrogen or amine-protecting group; and X is F or Cl.

Abstract translation: 目的：提供具有氟吡咯烷取代基的喹啉羧酸衍生物及其制备方法。 该化合物对革兰氏阳性菌和阴性菌均无毒性和改善的抗微生物活性。 构成：在喹诺酮支架的7-位取代有4-氨基甲基-4-氟-3-（Z） - 烷氧基亚氨基吡咯烷的式1所示的喹啉羧酸衍生物，其药学上可接受的酸加成盐及其溶剂合物是 提供。 在该式中，Q为C-H，C-F，C-Cl，C-OCH 3，C-OCHF 2，C-CH 3或N; R是氢，甲基或NH 2; R 1是乙基，环丙基，叔丁基或至少一个氟取代的苯基; R 2是氢，C 1 -C 5烷基，环丙基，环丙基甲基，C 3 -C 6烯基，C 3 -C 6炔基，苯基或苄基; 并且R 3或R 4独立地是氢或C 1 -C 3烷基，或者R 3或R 4是氢或C 1 -C 3烷基键合的含有C 3 -C 5杂环化合物的氮。 制备由式1表示的喹啉羧酸衍生物的方法包括以下步骤：（1）在溶剂和碱的存在下使式2的喹诺酮支架化合物与式3的含氟化合物反应， 制备式4的化合物; 和（2）用HX使式4的化合物脱保护，其中R3或R4是氢; P是氢或胺保护基; X为F或Cl。

公开(公告)号：KR1020030075396A

公开(公告)日：2003-09-26

申请号：KR1020020014588

申请日：2002-03-18

Applicant: 동화약품주식회사 ,  이승택

Inventor： 이승택 ,  장진욱 ,  김주현 ,  장윤정 ,  정용호 ,  임문정 ,  성희진 ,  노양국 ,  신동혁 ,  장환봉

IPC: C07D311/40

Abstract: PURPOSE: A matrix metalloproteinase inhibitor and functional food containing flavonoid derivatives or extracts of Dalbergia odorifera containing the flavonoid derivatives are provided, thereby effectively treating diseases associated with matrix metalloproteinase. CONSTITUTION: Extracts of Dalbergia odorifera containing fisetin of formula 1 and 3'-hydroxydidzein of formula 2 are prepared by dissolving pulverized Dalbergia odorifera in a solvent selected from methanol, a mixed solvent of methanol and water and ethylacetate, filtering the solution, and concentrating the filtered solution under reduced pressure. A fraction of Dalbergia odorifera containing fisetin and 3'-hydroxydidzein is prepared by dissolving Dalbergia odorifera in methanol or a mixed solvent of water and methanol, filtering the solution, adding ethylacetate or butanol into the filtered solution, filtering the solution, and concentrating the filtered solution under reduced pressure.

Abstract translation: 目的：提供一种基质金属蛋白酶抑制剂和含有黄酮类衍生物的黄酮类衍生物或含有黄酮衍生物的提取物的功能性食品，从而有效治疗与基质金属蛋白酶相关的疾病。 构成：通过将粉碎的Dalbergia odorifera溶解在选自甲醇，甲醇和水与乙酸乙酯的混合溶剂的溶剂中，过滤该溶液并浓缩，得到含有式1的非瑟酮和式2的3'-氢氧根霉素的Dalbergia odorifera的提取物 在减压下过滤溶液。 通过将Dalbergia odorifera在甲醇或水和甲醇的混合溶剂中溶解，过滤该溶液，向过滤的溶液中加入乙酸乙酯或丁醇，过滤溶液，浓缩过滤的溶液，制备含有非丝氨酸和3'-羟基溶解素的Dalbergia odorifera的一小部分 溶液在减压下。

公开(公告)号：KR1020030050412A

公开(公告)日：2003-06-25

申请号：KR1020010080842

申请日：2001-12-18

Applicant: 동화약품주식회사

Inventor： 정용호 ,  오윤석 ,  임재경 ,  권오진 ,  강소연 ,  홍현수

IPC: C07D215/227

Abstract: PURPOSE: A process for preparing rebamipide is provided, thereby simplifying the preparing process of rebamipide and improving the preparation yield of rebamipide. CONSTITUTION: A process for preparing rebamipide of the formula(1) comprises the steps of: reacting 4-(bromomethyl)-1,2-dihydro-2-quinolinone of formula(2) with diethyl 2-£(4-chlorobenzoyl)amino|malonate of formula(3) to prepare a compound of formula(4); and reacting the compound of formula(4) under basic conditions, wherein R is alkyl having the carbon number of 1 to 6, wherein the diethyl 2-£(4-chlorobenzoyl)amino|malonate of formula(3) is prepared by reacting diethyl 2-aminomalonate hydrochloride with 4-chlorobenzoyl derivative of formula(6); and R is alkyl having the carbon number of 1 to 6 and X is OH or halogen atom.

Abstract translation: 目的：提供制备瑞巴派特的方法，从而简化了雷巴米特的制备过程，提高了瑞巴派特的制备成品率。 构成：制备式（1）的瑞巴派特的方法包括以下步骤：使式（2）的4-（溴甲基）-1,2-二氢-2-喹啉酮与2-（4-氯苯甲酰基）氨基 （3）的丙二酸酯以制备式（4）的化合物; 并在碱性条件下使式（4）的化合物反应，其中R是碳数为1至6的烷基，其中式（3）的2-（2-氯苯甲酰基）氨基丙二酸二乙酯是通过使二 2-氨基马来酸盐酸盐与式（6）的4-氯苯甲酰基衍生物反应; R为碳原子数1〜6的烷基，X为OH或卤素原子。

公开(公告)号：KR1020030008653A

公开(公告)日：2003-01-29

申请号：KR1020010043489

申请日：2001-07-19

Applicant: 동화약품주식회사 ,  서홍석

Inventor： 이진수 ,  김판수 ,  황연하 ,  유제만 ,  정용호 ,  서홍석 ,  김도희 ,  박용엽

IPC: A61K31/166

Abstract: PURPOSE: Provided is N,N-diisopropyl-4-(7-(4-aminophenoxy)heptoxy)-3-methoxybenzamide(DW1259) which has leukotriene-B4 receptor antagonistic action and has excellent effects on inhibition of bone absorption by effectively inhibiting the function of osteoclast cells. CONSTITUTION: The agent for prophylaxis and treatment of osteoporosis contains an effective amount of N,N-diisopropyl-4-(7-(4-aminophenoxy)heptoxy)-3-methoxybenzamide of formula(1). The compound has an excellent inhibition effect on a differentiation, formation, fusion process and bone absorption function of osteoclast cells, is excellent in an inhibition function of osteoclast cells as compared to any compound such as DW1231, DW1234, DW1166, DW1235 having structural similarity as well as HS-1141 and CGS-25019C and has increased efficacy in increasing the activity of osteoblast cells.

Abstract translation: 目的：提供具有白三烯-B4受体拮抗作用的N，N-二异丙基-4-（7-（4-氨基苯氧基）庚氧基）-3-甲氧基苯甲酰胺（DW1259），并且通过有效抑制 破骨细胞功能。 构成：用于预防和治疗骨质疏松症的药物含有有效量的式（1）的N，N-二异丙基-4-（7-（4-氨基苯氧基）乙氧基）-3-甲氧基苯甲酰胺。 该化合物对破骨细胞的分化，形成，融合过程和骨吸收功能具有优异的抑制作用，与​​具有结构相似性的任何化合物如DW1231，DW1234，DW1166，DW1235相比，破骨细胞的抑制功能优异 以及HS-1141和CGS-25019C，并且增加了成骨细胞活性的功效。

公开(公告)号：KR1020020076920A

公开(公告)日：2002-10-11

申请号：KR1020010017143

申请日：2001-03-31

Applicant: 동화약품주식회사

Inventor： 정용호 ,  이치우 ,  양왕용 ,  이학동 ,  박휘정 ,  장윤영 ,  이진수

IPC: C07D413/14

CPC classification number: C07D403/14 ,  C07D401/14 ,  C07D403/12 ,  C07D413/14

Abstract: PURPOSE: Provided are a methoxy-1,3,5-triazine derivative which inhibit the growth of Hepatitis C virus(HCV) and a pharmaceutical composition containing the same, therefore it can be useful for the prevention and treatment of hepatitis type B and hepatitis type C. CONSTITUTION: The methoxy-1,3,5-triazine derivative is represented by formula(1) and its pharmaceutically acceptable salt are provided. In the formula(1), R1 is H or C1-C8 alkyl; R2 is H, hydroxy, C1-C4 linear or branched chain alkyl, C1-C3 linear or branched chain alkoxy, C1-C3 hydroxyalkyl, C2-C6 dialkylamino, C3-C6 cycloalkyl, lactam, saturated or unsaturated 5 or 6 atom hetero ring compound optionally substituted with C1-C3 linear or branched chain alkyl substituted or unsubstituted, and containing one or two hetero atom selected from N, O and S; or bicyclo compound containing one or two hetero atom selected from N, O and S; n is an integer of 0 to 4; and R3 is 5-indazolyl or 6-indazolyl. The method for producing the methoxy-1,3,5-triazine derivative comprises the steps of: reacting 2,4-dichloro-6-methoxy-1,3,5-triazine of formula(4) with 5-aminoindazole or 6-aminoindazole of formula(5) in the presence of base to prepare aminoindazole substituted 2-chloro-6-methoxy-1,3,5-triazine derivative of formula(6); and reacting the compound of formula(6) with amine compound of formula(7) in the presence of amine to prepare methoxy-1,3,5-triazine derivative of formula(1).

Abstract translation: 目的：提供抑制丙型肝炎病毒（HCV）生长的甲氧基-1,3,5-三嗪衍生物和含有该丙氨酸病毒（HCV）的药物组合物，因此可用于预防和治疗乙型肝炎和肝炎 C型。构成：提供甲氧基-1,3,5-三嗪衍生物由式（1）表示，并提供其药学上可接受的盐。 在式（1）中，R 1是H或C 1 -C 8烷基; R2是H，羟基，C1-C4直链或支链烷基，C1-C3直链或支链烷氧基，C1-C3羟基烷基，C2-C6二烷基氨基，C3-C6环烷基，内酰胺，饱和或不饱和的5或6原子杂环 任选被取代或未取代的C 1 -C 3直链或支链烷基取代的，含有一个或两个选自N，O和S的杂原子的化合物; 或含有一个或两个选自N，O和S的杂原子的双环化合物; n为0〜4的整数。 并且R 3是5-吲唑基或6-吲唑基。 制备甲氧基-1,3,5-三嗪衍生物的方法包括以下步骤：使式（4）的2,4-二氯-6-甲氧基-1,3,5-三嗪与5-氨基吲唑或6- 式（5）的氨基吲唑在碱的存在下反应，制备式（6）的氨基吲唑取代的2-氯-6-甲氧基-1,3,5-三嗪衍生物; 并在胺的存在下使式（6）的化合物与式（7）的胺化合物反应，制得式（1）的甲氧基-1,3,5-三嗪衍生物。

公开(公告)号：KR1020020034759A

公开(公告)日：2002-05-09

申请号：KR1020000065270

申请日：2000-11-03

Applicant: 동화약품주식회사

Inventor： 황순봉 ,  윤성준 ,  김종우 ,  이경재 ,  황연하 ,  윤승원

IPC: C12N7/01

CPC classification number: C12N7/00 ,  C12N2710/14011 ,  C12Q1/68

Abstract: PURPOSE: Provided are a detecting method of hepatitis C virus(HCV) using recombinant mixed antigens derived from HCV and a diagnostic kit thereof, particularly by immuno chromatography using recombinant mixed antigens including core, NS3 and NS5A proteins of HCV gene as main components. CONSTITUTION: A recombinant Baculovirus(KCCM 10218) is manufactured by cotransfection of Baculovirus transfer vector including HCV derived core protein gene. HCV derived core protein is expressed from the recombinant Baculovirus(KCCM 10218) and has amino acid sequence of SEQ ID NO: 8. A recombinant Baculovirus(KCCM 10219) is manufactured by cotransfection of Baculovirus transfer vector including HCV derived NS3 protein gene. HCV derived NS3 proteins expressed from the recombinant Baculovirus(KCCM 10219) and has amino acid sequence of SEQ ID NO:9. An E.coli transformant(KCCM 10217) is transformed with a recombinant expression vector including HCV derived NS5A protein gene. HCV derived NS5A protein is expressed from the transformant and has amino acid sequence of SEQ ID NO: 10. The HCV diagnostic kit contains a mixed antigen consisting of core, NS3 and NS5A proteins derived from HCV.

Abstract translation: 目的：提供使用HCV衍生的重组混合抗原的丙型肝炎病毒（HCV）的检测方法及其诊断试剂盒，特别是使用包含HCV基因的核心，NS3和NS5A蛋白的重组混合抗原的免疫色谱作为主要成分。 构成：通过共转染包括HCV衍生的核心蛋白基因的杆状病毒转移载体来制备重组杆状病毒（KCCM 10218）。 HCV衍生的核心蛋白由重组杆状病毒（KCCM 10218）表达并具有SEQ ID NO：8的氨基酸序列。通过共转染包含HCV衍生的NS3蛋白基因的杆状病毒转移载体来制备重组杆状病毒（KCCM 10219）。 由重组杆状病毒（KCCM 10219）表达的HCV衍生的NS3蛋白，具有SEQ ID NO：9的氨基酸序列。 用包含HCV衍生的NS5A蛋白基因的重组表达载体转化大肠杆菌转化体（KCCM 10217）。 HCV衍生的NS5A蛋白由转化体表达，并具有SEQ ID NO：10的氨基酸序列。HCV诊断试剂盒含有由核心，NS3和源自HCV的NS5A蛋白组成的混合抗原。

公开(公告)号：KR1020020002461A

公开(公告)日：2002-01-09

申请号：KR1020017014647

申请日：2000-05-18

Applicant: 동화약품주식회사

Inventor： 윤성준 ,  정용호 ,  이치우 ,  이진수 ,  김남두 ,  진윤호 ,  송완진 ,  김익회 ,  양왕용 ,  최동락 ,  신정한

IPC: C07D471/04

CPC classification number: C07D401/04 ,  C07D471/04 ,  C07D487/10

Abstract: PURPOSE: Provided are optically active quinoline carboxylic acid derivatives, pharmaceutically acceptable salts thereof, solvates thereof, and a process for preparation thereof, which are useful for an antibacterial agent. CONSTITUTION: The optically active quinoline carboxylic acid derivatives are represented by the following formula(1), and contains optical activity-causing 4-aminomethyl-4-methyl-3 (Z)-alkoxyiminopyrrolidine substituents at the 7-position of the quinolone nuclei, their pharmaceutically acceptable salts, and their solvates. In the formula(1), Q is C-H, C-F, C-Cl or N; Y is H or NH2; R is a straight or branched alkyl group of Cl-C, an allyl group or a benzyl group, and * represents optically pure chiral carbon atom. Their preparation process comprises the steps of: condensing the quinolone nuclei-containing compound of formula(3), with the ketal compound of formula(2a), in the presence of an acid acceptor to give the optically active quinoline carboxylic acid derivative of formula(4); deketalizing the optically active quinoline carboxylic acid derivative of formula(4) to give the pyrrolidinone compound of formula(5); and reacting the pyrrolidinone compound of formula(5) with an alkoxylamine in the presence of a base to obtain the desired compound of formula(1).

Abstract translation: 目的：提供可用于抗菌剂的光学活性喹啉羧酸衍生物，其药学上可接受的盐，溶剂合物及其制备方法。 构成：光学活性喹啉羧酸衍生物由下式（1）表示，并且在喹诺酮核的7-位含有光学活性的4-氨基甲基-4-甲基-3（Z） - 烷氧基亚氨基吡咯烷取代基， 其药学上可接受的盐及其溶剂合物。 在式（1）中，Q是C-H，C-F，C-Cl或N; Y为H或NH 2; R是Cl-C，烯丙基或苄基的直链或支链烷基，*表示光学上纯的手性碳原子。 它们的制备方法包括以下步骤：在酸受体存在下将式（3）的喹诺酮核含有化合物与式（2a）的缩酮化合物缩合，得到式（3）的光学活性喹啉羧酸衍生物 4）; 对式（4）的光学活性喹啉羧酸衍生物进行缩酮化，得到式（5）的吡咯烷酮化合物; 并在碱的存在下使式（5）的吡咯烷酮化合物与烷氧基胺反应，得到所需的式（1）化合物。

公开(公告)号：KR100309888B1

公开(公告)日：2001-11-01

申请号：KR1019990031532

申请日：1999-07-31

Applicant: 동화약품주식회사

Inventor： 윤성준 ,  김종우 ,  한재진 ,  우제태 ,  케이지하수미 ,  나가이카즈오

IPC: A61K38/15

Abstract: 본발명은데스트룩신(destruxin) 유도체를유효성분으로함유하는골다공증예방및 치료제조성물에관한것으로본 발명곰팡이유래의사이클로뎁시펩타이드(cyclodepsipeptide)는파골세포에서부갑상선호르몬(PTH)의존재와관계없이파골세포활성저해능이매우뛰어난효과가있다.

公开(公告)号：KR1020010011926A

公开(公告)日：2001-02-15

申请号：KR1019990031532

申请日：1999-07-31

Applicant: 동화약품주식회사

Inventor： 윤성준 ,  김종우 ,  한재진 ,  우제태 ,  케이지하수미 ,  나가이카즈오

IPC: A61K38/15

Abstract: PURPOSE: A composition containing destruxin derivatives for prevention and treatment of osteoporosis is provided, inwhich cyclodepsipeptide derived from fungi shows excellent osteoclast activity-inhibition effect regardless of presence of PTH(parathyroid hormone) in osteoclast, therefore being used for prevention and treatment of osteoporosis. CONSTITUTION: The various destruxin derivatives can be prepared by a well known method, which is cyclodepsipeptides separated from various fungi(e.g., Metarhizium anisopliae). The composition containing destruxin derivatives for prevention and treatment of osteoporosis can be prepared in the form of tablets, capsules, troches, solution, suspension, or injections, dried powder for injection, a spray, suppositories, or a patch preparation by mixing with pharmaceutically acceptable carriers, and which can be administrated by oral path and parenteral path(e.g., in vein, under subcutaneous, abdominal cavity, or nasal cavity). The composition containing destruxin derivatives can be also administrated in the dosage of 0.1μg-100mg, desirably 100μg-1mg per day.

Abstract translation: 目的：提供含有用于预防和治疗骨质疏松症的destruxin衍生物的组合物，其中来自真菌的环缩酚肽显示出破骨细胞中存在PTH（甲状旁腺激素）的极好的破骨细胞活性抑制作用，因此用于预防和治疗骨质疏松症。 构成：各种destruxin衍生物可以通过众所周知的方法制备，该方法是从各种真菌（例如，Metarhizium anisopliae）分离的环糊精肽。 含有用于预防和治疗骨质疏松症的destruxin衍生物的组合物可以以片剂，胶囊剂，锭剂，溶液，悬浮液或注射剂的形式，注射用干燥粉末，喷雾剂，栓剂或贴剂制剂的形式制备， 载体，并且其可以通过口服途径和肠胃外途径施用（例如，在静脉，皮下，腹腔或鼻腔）。 含有destruxin衍生物的组合物也可以以0.1μg-100mg，优选每天100μg-1mg的剂量施用。

公开(公告)号：KR1020000031735A

公开(公告)日：2000-06-05

申请号：KR1019980047918

申请日：1998-11-10

Applicant: 동화약품주식회사

Inventor： 윤성준 ,  이상욱 ,  심형수 ,  박용균 ,  양왕용 ,  김종우 ,  박상진

IPC: C07D401/14

Abstract: PURPOSE: 2,5-pyrimidinedicarboxylic acids and the method for manufacturing it are provided, which have effect on restraining the proliferation of HBV(Hepatitis B Virus) and HIV(Human Immunodeficiency Virus). CONSTITUTION: In the formula 1, R1 represents hydrogen, alkyl group, hydroxy alkyl group, alkoxy alkyl group, dihydroxy alkyl group and dialkoxy alkyl group and R2 represents hydrogen and alkyl group. 2,5-pyridinedicarboxylic acids(formula 1) can form organic or inorganic salt such as chloric acid, phosphoric acid, oxalic acid, maleic acid and tartaric acid which is admitted pharmaceutically. 2,5-pyridinedicarboxylic acids are prepared from following reaction(reaction 1). Piperazines are piperazine(R1=hydrogen), 1-methylpiperazine(R1=methyl group), 1-ethylpiperazine(R1=ethyl group), 1-(2-hydroxyethyl)piperazine(R1=2-hydroxyethyl group. Nicotinic acids(formula 2) are reacted with acyl chloride, product of this reaction is reacted with piperazine compounds and 2,5-pyrimidinedicarboxylic acids are prepared from this reaction.

Abstract translation: 目的：提供2,5-嘧啶二羧酸及其制备方法，其具有抑制HBV（乙型肝炎病毒）和HIV（人类免疫缺陷病毒）增殖的作用。 构成：在式1中，R 1表示氢，烷基，羟基烷基，烷氧基烷基，二羟基烷基和二烷氧基烷基，R 2表示氢和烷基。 2,5-吡啶二羧酸（式1）可以形成有机或无机盐，例如药学上允许的氯酸，磷酸，草酸，马来酸和酒石酸。 从以下反应制备2,5-吡啶二羧酸（反应1）。 哌嗪是哌嗪（R1 =氢），1-甲基哌嗪（R1 =甲基），1-乙基哌嗪（R1 =乙基），1-（2-羟乙基）哌嗪（R1 = 2-羟乙基）烟酸（式2 ）与酰氯反应，将该反应产物与哌嗪化合物反应，并从该反应制备2,5-嘧啶二羧酸。