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：KR1020080092893A

公开(公告)日：2008-10-16

申请号：KR1020080034411

申请日：2008-04-14

Applicant: 동화약품주식회사

Inventor： 유제만 ,  최동락 ,  양진 ,  윤수혜 ,  김승환 ,  구세광

IPC: C07D471/04 ,  A61K31/4375

CPC classification number: C07D519/00

Abstract: A 1-cyclopropyl-6-fluoro-7-(8-methoxyimino-2,6-diaza-spiro[3.4]oct-6-yl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid aspartic acid salt is provided to improve physicochemical properties including solubility and stability as compared to phosphate or hydrochloride thereof, and minimize toxicity, so that the compound is useful as antimicrobial agent in food and medicines. A 1-cyclopropyl-6-fluoro-7-(8-methoxyimino-2,6-diaza-spiro[3.4]oct-6-yl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid aspartic acid salt represented by the formula(1) is prepared by reacting 1-cyclopropyl-6-fluoro-7-(8-methoxyimino-2,6-diaza-spiro[3.4]oct-6-yl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid with aspartic acid in inert organic solvent selected from ethyl acetate, methanol, ethanol, isopropanol, acetone, acetonitrile, hexane, isopropyl ether and water. An antimicrobial pharmaceutical composition comprises 1-cyclopropyl-6-fluoro-7-(8-methoxyimino-2,6-diaza-spiro[3.4]oct-6-yl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid aspartic acid salt, and is formulated as injection. The aspartic acid salt is D-aspartic acid salt, L-aspartic acid salt or racemic mixture thereof.

Abstract translation: 1-环丙基-6-氟-7-（8-甲氧基亚氨基-2,6-二氮杂 - 螺[3.4]辛-6-基）-4-氧代-1,4-二氢 - [1,8] 提供3-羧酸天冬氨酸盐以提高与其磷酸盐或盐酸盐相比的溶解度和稳定性的物理化学性质，并且使毒性最小化，使得该化合物可用作食品和药物中的抗微生物剂。 1-环丙基-6-氟-7-（8-甲氧基亚氨基-2,6-二氮杂 - 螺[3.4]辛-6-基）-4-氧代-1,4-二氢 - [1,8] 由式（1）表示的3-羧酸天冬氨酸盐通过1-环丙基-6-氟-7-（8-甲氧基亚氨基-2,6-二氮杂 - 螺[3.4]辛-6-基） - 4-氧代-1,4-二氢 - [1,8]二氮杂萘-3-羧酸与天冬氨酸在惰性有机溶剂中的溶液，选自乙酸乙酯，甲醇，乙醇，异丙醇，丙酮，乙腈，己烷，异丙醚和水。 抗微生物药物组合物包含1-环丙基-6-氟-7-（8-甲氧基亚氨基-2,6-二氮杂 - 螺[3.4]辛-6-基）-4-氧代-1,4-二氢 - [1,3' 8]萘啶-3-羧酸天冬氨酸盐，并配制成注射剂。 天冬氨酸盐是D-天冬氨酸盐，L-天冬氨酸盐或其外消旋混合物。

公开(公告)号：KR100953271B1

公开(公告)日：2010-04-16

申请号：KR1020080034411

申请日：2008-04-14

Applicant: 동화약품주식회사

Inventor： 유제만 ,  최동락 ,  양진 ,  윤수혜 ,  김승환 ,  구세광

IPC: C07D471/04 ,  A61K31/4375

CPC classification number: C07D519/00

Abstract: 본 발명은 1-시클로프로필-6-플루오로-7-(8-메톡시이미노-2,6-디아자-스피로[3.4]옥트-6-일)-4-옥소-1,4-디히드로-[1,8]나프티리딘-3-카르복실산 아스파르트산 염, 이의 제조방법 및 이를 포함하는 항균용 약학 조성물에 관한 것이다.
항균, 1-시클로프로필-6-플루오로-7-(8-메톡시이미노-2,6-디아자-스피로[3.4]옥트-6-일)-4-옥소-1,4-디히드로-[1,8]나프티리딘-3-카르복실산, 아스파르트산 염