公开(公告)号：KR101959008B1

公开(公告)日：2019-03-18

申请号：KR1020170099101

申请日：2017-08-04

Applicant: 한국과학기술연구원 ,  대정화금주식회사

Inventor： 이강봉 ,  남윤식 ,  김경민 ,  장택수

IPC: G01N31/00 ,  C08B37/08 ,  C08L5/08 ,  G01N21/25 ,  G01N21/29 ,  G01N33/20

公开(公告)号：KR1020030034823A

公开(公告)日：2003-05-09

申请号：KR1020010066579

申请日：2001-10-27

Applicant: 한국과학기술연구원

Inventor： 김유승 ,  강순방 ,  금교창 ,  장민석 ,  장택수 ,  공재양 ,  정대영

IPC: C07D413/04

Abstract: PURPOSE: Isoxazole or isoxazoline substituted 1,2,5,6-tetrahydropyridine derivative having high affinity for an acetylcholine receiptor is provided, which compound is useful as a muscarine type acetylcholine receiptor agonist, a recognition improving agent and a treating agent of cerebral nervous disease such as Alzheimer's disease. CONSTITUTION: The isoxazole or isoxazoline substituted 1,2,5,6-tetrahydropyridine derivative represented by formula(1) and a pharmaceutically acceptable salt thereof are provided, wherein R2 is C1-4 alkyl; one of R3 and R4 is one functional group in claim 1 and another of them is H; R5 is hydrogen, hydroxy, hydroxy C1-6 alkyl, C1-6 alkoxymethyl, C1-6 alkoxy, acetoxy, C1-4 alkyl ester, nitrile, aryl, phenylthio, methylthiomethyl, phenylsulfoxide, dimethylthiomethyl, C1-4 alkylketo, C1-4 alkylketo oxime, C1-4 alkylketo C1-5 alkyl oxime, and N-pyrrolidine-2-on; R6 is hydrogen; and R5 and F6 form -CH2OCH2 together. The process for preparing the isoxazole or isoxazoline substituted 1,2,5,6-tetrahydropyridine derivative represented by formula comprises the steps of: reacting 3- or 4-pyridine aldehyde oxime compound of formula(2) with chlorox to prepare nitrile oxide of formula(4); and cycloadddition reaction of nitrile oxide of formula(4) with alkene or alkyne compound of formula(8) or formula(9) to prepare a compound of formula(5) or formula(6); reacting the compound of formula(5) or formula(6) with alkyl iodide to prepare alkyl pyridine salt of formula(7); and reducing the alkyl pyridine salt of formula(7).

Abstract translation: 目的：提供对乙酰胆碱受体具有高亲和力的异恶唑或异恶唑啉取代的1,2,5,6-四氢吡啶衍生物，该化合物可用作毒蕈碱型乙酰胆碱受体激动剂，识别改善剂和脑神经系统疾病的治疗剂 如阿尔茨海默病。 构成：提供由式（1）表示的异恶唑或异恶唑啉取代的1,2,5,6-四氢吡啶衍生物及其药学上可接受的盐，其中R 2为C 1-4烷基; R3和R4之一是权利要求1中的一个官能团，另一个是H; R5是氢，羟基，羟基C1-6烷基，C1-6烷氧基甲基，C1-6烷氧基，乙酰氧基，C1-4烷基酯，腈，芳基，苯硫基，甲硫基甲基，苯基亚砜，二甲硫甲基，C1-4烷基酮，C1-4 烷基酮肟，C 1-4烷基酮C 1-5烷基肟和N-吡咯烷-2-酮; R6是氢; R5和F6一起形成-CH 2 OCH 2。 制备由式表示的异恶唑或异恶唑啉取代的1,2,5,6-四氢吡啶衍生物的方法包括以下步骤：使式（2）的3-或4-吡啶醛肟化合物与氯氧反应制备式 （4）; 和式（4）的氧化腈与式（8）或式（9）的烯烃或炔化合物的环加成反应以制备式（5）或式（6）的化合物; 使式（5）或式（6）的化合物与烷基碘反应制备式（7）的烷基吡啶盐; 和还原式（7）的烷基吡啶盐。

公开(公告)号：KR101957460B1

公开(公告)日：2019-06-19

申请号：KR1020170088903

申请日：2017-07-13

Applicant: 한국과학기술연구원 ,  대정화금주식회사

Inventor： 이강봉 ,  남윤식 ,  옵시아니드스기이알렉산드르 ,  오영제 ,  올렉시오히엔코 ,  장택수

IPC: G01N27/12 ,  G01N33/00

公开(公告)号：KR100437973B1

公开(公告)日：2004-07-02

申请号：KR1020010066579

申请日：2001-10-27

Applicant: 한국과학기술연구원

Inventor： 김유승 ,  강순방 ,  금교창 ,  장민석 ,  장택수 ,  공재양 ,  정대영

IPC: C07D413/04

Abstract: PURPOSE: Isoxazole or isoxazoline substituted 1,2,5,6-tetrahydropyridine derivative having high affinity for an acetylcholine receiptor is provided, which compound is useful as a muscarine type acetylcholine receiptor agonist, a recognition improving agent and a treating agent of cerebral nervous disease such as Alzheimer's disease. CONSTITUTION: The isoxazole or isoxazoline substituted 1,2,5,6-tetrahydropyridine derivative represented by formula(1) and a pharmaceutically acceptable salt thereof are provided, wherein R2 is C1-4 alkyl; one of R3 and R4 is one functional group in claim 1 and another of them is H; R5 is hydrogen, hydroxy, hydroxy C1-6 alkyl, C1-6 alkoxymethyl, C1-6 alkoxy, acetoxy, C1-4 alkyl ester, nitrile, aryl, phenylthio, methylthiomethyl, phenylsulfoxide, dimethylthiomethyl, C1-4 alkylketo, C1-4 alkylketo oxime, C1-4 alkylketo C1-5 alkyl oxime, and N-pyrrolidine-2-on; R6 is hydrogen; and R5 and F6 form -CH2OCH2 together. The process for preparing the isoxazole or isoxazoline substituted 1,2,5,6-tetrahydropyridine derivative represented by formula comprises the steps of: reacting 3- or 4-pyridine aldehyde oxime compound of formula(2) with chlorox to prepare nitrile oxide of formula(4); and cycloadddition reaction of nitrile oxide of formula(4) with alkene or alkyne compound of formula(8) or formula(9) to prepare a compound of formula(5) or formula(6); reacting the compound of formula(5) or formula(6) with alkyl iodide to prepare alkyl pyridine salt of formula(7); and reducing the alkyl pyridine salt of formula(7).

Abstract translation: 目的：提供了对乙酰胆碱接受者具有高亲和力的异恶唑或异恶唑啉取代的1,2,5,6-四氢吡啶衍生物，该化合物可用作毒蕈碱型乙酰胆碱接受者激动剂，识别改善剂和脑神经疾病治疗剂 如阿尔茨海默病。 本发明提供了由式（1）表示的异恶唑或异恶唑啉取代的1,2,5,6-四氢吡啶衍生物及其药学上可接受的盐，其中R2为C1-4烷基; R 3和R 4中的一个是权利要求1中的一个官能团，另一个是H; R5是氢，羟基，羟基C1-6烷基，C1-6烷氧基甲基，C1-6烷氧基，乙酰氧基，C1-4烷基酯，腈，芳基，苯硫基，甲硫基甲基，苯基亚砜，二甲基硫代甲基，C1-4烷基酮基，C1-4 烷基酮肟，C 1-4烷基酮基C 1-5烷基肟和N-吡咯烷-2-酮; R6是氢; R5和F6一起形成-CH2OCH2。 制备由下式表示的异恶唑或异恶唑啉取代的1,2,5,6-四氢吡啶衍生物的方法包括以下步骤：使式（2）的3-或4-吡啶醛肟化合物与氯化氧反应以制备式 （4）; 和式（4）的氧化腈与式（8）或式（9）的烯烃或炔烃化合物的环加成加成反应以制备式（5）或式（6）的化合物; 使式（5）或式（6）的化合物与烷基碘反应以制备式（7）的烷基吡啶盐; 和还原式（7）的烷基吡啶盐。