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    • 3. 发明授权
    • 알킬 시스-4-아미노-3-메톡시-1-피페리딘 카르복실레이트 염산염의 제조방법
    • -4--3-1-顺式-4-氨基-3-甲氧基-1-哌啶羧酸烷基酯盐酸盐的制备方法
    • KR100323652B1
    • 2002-03-29
    • KR1019990047103
    • 1999-10-28
    • 동화약품주식회사한국화학연구원
    • 이철해김봉진정용호편도규송지섭정희정곽현정김은정
    • C07D213/89
    • 본발명은알킬트란스-4-브로모-3-하이드록시-1-피페리딘카르복실레이트를출발물질로하여알킬트란스-4-브로모-3-벤조일아미노카르보닐옥시-1-피페리딘카르복실레이트, 알킬시스-1-벤조일-2-옥소-헥사하이드로-옥사졸로[5,4-c] 피리딘-5-카르복실레이트, 알킬시스-2-옥소-헥사하이드로-옥사졸로[5,4-c] 피리딘-5-카르복실레이트, 시스-1--부톡시카르보닐-5-에톡시카르보닐-2-옥소-헥사하이드로옥사졸로[5,4-c] 피리딘, 알킬시스-4--부톡시카르보닐아미노-3-하이드록시-1-피페리딘카르복실레이트및 알킬시스-4--부톡시카르보닐아미노-3-메톡시-1-피페리딘카르복실레이트의중간물질을거쳐시사프라이드의중간체인알킬시스-4-아미노-3-메톡시-1-피페리딘카르복실레이트염산염을제조하는방법에관한것이다. 본발명은종래기술과는달리모든반응이온화한조건에서진행되고각 단계마다특별히정제과정을필요로하지않으며위험한나트륨하이드라이드나수소가스를사용하지않아종래기술의단점을모두극복함으로써산업화가용이한장점을가지고있으며또한알킬시스-4-아미노-3-메톡시-1-피페리딘카르복실레이트를취급이불편하고순도(80% 이하)가떨어지는종래기술의액상형태와는달리공업적으로다루기쉬운고순도(98% 이상)의분말형태로얻을수 있는장점이있다.
    • 6. 发明公开
    • 알킬 시스-4-아미노-3-메톡시-1-피페리딘 카르복실레이트 염산염의 제조방법
    • 苯基-3-氨基-3-甲氧基-1-哌啶羧酸盐氢氯化物的制备方法
    • KR1020010038923A
    • 2001-05-15
    • KR1019990047103
    • 1999-10-28
    • 동화약품주식회사한국화학연구원
    • 이철해김봉진정용호편도규송지섭정희정곽현정김은정
    • C07D213/89
    • PURPOSE: A method for producing alkyl cis-4-amino-3- methoxy-1-piperidine carboxylate hydrochloride is provided, thereby the titled compound having high purity can be easily produced because the further purification steps are not required and the production is performed under the mild conditions. CONSTITUTION: The method for producing alkyl cis-4-amino-3- methoxy-1-piperidine carboxylate hydrochloride represented by formula (I) comprises the steps of: reacting alkyl trans-4-bromo-3- hydroxypiperidine-1-carboxylate of formula (III) with benzoyl isocyanate in organic solvents to produce alkyl trans-4-bromo-3- benzoylaminocarbonyloxy-1-piperidine carboxylate of formula (IV); adding base such as kalium tert-butoxide into the compound of formula (IV) to produce alkyl cis-1-benzoyl-2-oxo- hexahydro-oxazolo(5,4,c) pyridine-5-carboxylate of formula (V); reacting the compound of formula (V) with lithium hydroxide·H2O to produce alkyl cis-2-oxo-hexahydro-oxazolo(5,4-c) pyridine-5-carboxylate of formula (VI); reacting the compound of formula (VI) with triethylamine, di-tert-butoxy dicarbonate, and dimethylaminopyridine to produce cis-1-tert- butoxycarbonyl-5- ethoxycarbonyl-2-oxo- hexahydro- oxazolo(5,4-c) pyridine of formula (VII); reacting the compound of formula (VII) with cesium carbonate to produce alkyl cis-4-tert- butoxycarbonyl amino-3-hydroxy-1-piperidine carboxylate of formula (VIII); adding sodium hydroxide, dimethyl sulfate, and benzyltriethyl ammonium chloride into the compound of formula (VIII) to produce alkyl cis-4-tert-butoxycarbonylamino- 3-methoxy-1-piperidine carboxylate of formula (IX); and adding hydrogen chloride dissolved organic solvent into the compound of formula (IX) to produce alkyl cis-4-amino-3- methoxy-1-piperidine carboxylate hydrochloride of formula (I).
    • 目的:制备顺式-4-氨基-3-甲氧基-1-哌啶羧酸烷基酯盐酸盐的方法,由于不需要进一步的纯化步骤,因此可以容易地制备具有高纯度的标题化合物,并且在 温和的条件。 构成:由式(I)表示的顺式-4-氨基-3-甲氧基-1-哌啶羧酸盐酸烷基酯盐酸盐的制备方法包括以下步骤:使反式-4-溴-3-羟基哌啶-1-羧酸烷基酯 (III)与有机溶剂中的苯甲酰异氰酸酯反应以制备式(IV)的反式-4-溴-3-苯甲酰氨基羰基氧基-1-哌啶羧酸烷基酯; 将碱如叔丁醇钾加入到式(IV)化合物中以制备式(V)的顺式-1-苯甲酰基-2-氧代六氢恶唑并(5,4,c)吡啶-5-羧酸烷基酯; 使式(Ⅴ)化合物与氢氧化锂·H 2 O反应生成式(Ⅵ)的烷基顺式-2-氧代 - 六氢 - 恶唑并(5,4-c)吡啶-5-羧酸酯; 使式(VI)化合物与三乙胺,二叔丁氧基二碳酸酯和二甲基氨基吡啶反应,得到顺式-1-叔丁氧基羰基-5-乙氧基羰基-2-氧代六氢 - 恶唑并(5,4-c)吡啶 式(Ⅶ); 使式(Ⅶ)化合物与碳酸铯反应制得式(Ⅷ)的顺式-4-叔丁氧基羰基氨基-3-羟基-1-哌啶羧酸烷基酯; 向式(Ⅷ)化合物中加入氢氧化钠,硫酸二甲酯和苄基三乙基氯化铵,得到式(Ⅸ)的顺式-4-叔丁氧基羰基氨基-3-甲氧基-1-哌啶羧酸烷基酯; 并向式(IX)化合物中加入氯化氢溶解的有机溶剂,得到式(I)的烷基顺式-4-氨基-3-甲氧基-1-哌啶羧酸盐酸盐。
    • 7. 发明公开
    • 자가미세유화형 약물전달시스템을 이용한 고지혈증치료용약제 조성물
    • 使用自我微量给药系统(SMEDDS)治疗高胆固醇血症的药物组合物
    • KR1020020042218A
    • 2002-06-05
    • KR1020000072016
    • 2000-11-30
    • 한국화학연구원
    • 조선행김은정육순홍
    • A61K9/10B82Y5/00
    • A61K9/1075A61K9/4808A61K31/366
    • PURPOSE: A pharmaceutical compositions for hypercholesterolemia treatment using of self microemulsifying drug delivery system is provided, thereby improving the solubility and bioavailability of a drug hardly dissolved. CONSTITUTION: The pharmaceutical composition useful for hyperlipidemia treatment using a self microemulsifying drug delivery system(SMEDDS) comprises 1 to 20 wt.% of statin, 5 to 60 wt.% of surfactant, 10 to 60 wt.% of solubilizing agent and 10 to 60 wt.% of co-surfactant, wherein the statin is lovastatin or simvastatin; the surfactant is selected from caster oils, substituted caster oils, twins, spans and bridge; the solubilizing agent is selected from fatty acid ester consisting of propyleneglycol monocaprylate, polyglycolide of oleic acid and linoleic acid, propyleneglycol monolaurate and polyglyceryl dioleate, vegetable oils consisting of coconut oil, olive oil, corn oil, caster oil, macadamia nut oil, apricot oil and unsaturated fatty acid, purified oil, and hydrophobic solubilizing agent; and the co-surfactant is selected from polyethyleneglycol, propylene glycol, dimethylisosorbid and diethyleneglycolmonoethylether.
    • 目的:提供使用自微乳化药物递送系统的高胆固醇血症治疗药物组合物,从而提高难溶性药物的溶解度和生物利用度。 构成:使用自微乳化药物递送系统(SMEDDS)用于高脂血症治疗的药物组合物包含1至20重量%的他汀类,5至60重量%的表面活性剂,10至60重量%的增溶剂和10至 60重量%的辅助表面活性剂,其中他汀类是洛伐他汀或辛伐他汀; 表面活性剂选自脚轮油,取代脚轮油,双胞胎,跨度和桥梁; 增溶剂选自由丙二醇单辛酸酯,油酸聚亚油酸和亚油酸组成的脂肪酸酯,单月桂酸丙二醇酯和聚甘油二油酸酯,由椰子油,橄榄油,玉米油,脚轮油,澳洲坚果油,杏仁油组成的植物油 和不饱和脂肪酸,纯化油和疏水增溶剂; 共表面活性剂选自聚乙二醇,丙二醇,二甲基异山梨醇酯和二乙二醇单乙醚。
    • 10. 发明公开
    • 2-아릴에테닐 카바페넴 유도체 및 그의 제조방법
    • 2-ARYLETHENYL CARBAPENEM衍生物及其制备方法
    • KR1020020006889A
    • 2002-01-26
    • KR1020000040396
    • 2000-07-14
    • 한국화학연구원
    • 이철해김재학정희정편도규곽현정송신섭김은정김봉진정원장
    • C07D205/08
    • PURPOSE: Provided are 2-arylethenyl carbapenem derivative of the formula(1) and its pharmaceutically acceptable salt which have therapeutic effect in methicillin resistant staphylococcus aureus(MRSA) infection. And its manufacturing method and an antibacterial composition containing it as an active ingredient are also provided. CONSTITUTION: 2-arylethenyl carbapenem derivative is represented by the formula(1), wherein R is halogen, nitro, hydroxy or cyano substituted phenyl or fused aryl group; or halogen or C1-3 alkyl group substituted monocyclic, bicyclic or tricyclic 5 or 6 membered hetero aryl group containing at least one of O, S or N atom; and M is hydrogen or zwitterion forming pharmaceutically acceptable salts.
    • 目的:提供式(1)的2-亚乙烯基碳青霉烯衍生物及其药用盐,其在耐甲氧西林金黄色葡萄球菌(MRSA)感染中具有治疗作用。 还提供其制造方法和含有它作为活性成分的抗菌组合物。 构成:2-亚乙烯基碳代青霉烯衍生物由式(1)表示,其中R是卤素,硝基,羟基或氰基取代的苯基或稠合芳基; 或含有O,S或N原子中的至少一个的卤素或C 1-3烷基取代的单环,双环或三环5或6元杂芳基; M是氢或两性离子形成药学上可接受的盐。