公开(公告)号：KR1020010056060A

公开(公告)日：2001-07-04

申请号：KR1019990057477

申请日：1999-12-14

Applicant: 한국화학연구원

Inventor： 노재성 ,  신동성 ,  안미자

IPC: C07D498/12

Abstract: PURPOSE: Provided is a method for manufacturing 5-(hydroxy-protected)-5-(substituted or unsubstituted)2,3-anhydro-2-deoxyuridine compound in a high yield which is useful as an intermediate of a compound useful in treating acquired immune deficiency syndrome (AIDS). CONSTITUTION: The method for manufacturing 5-(hydroxy-protected)-5-(substituted or unsubstituted)2,3-anhydro-2-deoxyuridine compound is characterized by the next step of: reacting 5-(hydroxy protected)-5-(substituted or unsubstituted)-2-deoxyuridine of the formula (4) with 1,1-sulfonyldiimidazole of the formula (3) in the presence of base and polar or nonpolar organic solvent at 0-150 deg.C, preferably 25-90 deg.C. Optionally, 1.2-2.0 equivalents of the compound (3) are added per 1 equivalent of the compound (4) to improve its yield more.

Abstract translation: 目的：提供以高产率制备5-（羟基保护的）-5-（取代或未取代）2,3-脱水-2-脱氧尿苷化合物的方法，其可用作用于治疗所获得的化合物的中间体 免疫缺陷综合征（AIDS）。 构成：5-（羟基保护）-5-（取代或未取代）2,3-脱水-2-脱氧尿苷化合物的制备方法的特征在于下列步骤：使5-（羟基保护的）-5-（ 取代或未取代的）式（4）的脱氧尿苷与式（3）的1,1-磺酰基二咪唑在碱和极性或非极性有机溶剂存在下在0-150℃，优选25-90度 。C。 任选地，每1当量化合物（4）加入1.2-2.0当量的化合物（3），以提高其产率。

公开(公告)号：KR101250990B1

公开(公告)日：2013-04-04

申请号：KR1020100080755

申请日：2010-08-20

Applicant: 한국화학연구원

Inventor： 이규양 ,  김낙정 ,  서지희 ,  임채조 ,  이병호 ,  오광석 ,  안미자

IPC: C07D413/12 ,  C07D271/06 ,  A61K31/4245 ,  A61P3/00

Abstract: 본 발명은 하기 화학식 1로 표시되는 신규 1,2,4-옥사다이아졸 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 MCH(멜라닌 농축 호르몬) 관련 질환의 예방 또는 치료용 약학적 조성물에 관한 것으로, 본 발명에 따른 유도체는 MCH 수용체에 대한 길항제로 작용함으로써 MCH가 MCH 수용체에 결합함으로써 유발되는 비만, 당뇨병, 대사장애, 불안증 및 우울증과 같은 MCH 관련 질환을 예방 또는 치료하는데 유용하게 사용할 수 있다.
[화학식 1]

(상기 화학식 1에서, 상기 R
1 , R
2
및 R
3 는 본 명세서 내에 정의한 바와 같다.)

公开(公告)号：KR100666756B1

公开(公告)日：2007-01-15

申请号：KR1020050031355

申请日：2005-04-15

Applicant: 한국화학연구원

Inventor： 최일영 ,  변경희 ,  정명희 ,  임희종 ,  안미자 ,  박우규

IPC: C07D401/12

Abstract: 본 발명은 다음 화학식 1의 후퍼진-타크린 하이브리드(huperzine-tacrine hybrid) 유도체 및 이의 제조방법에 관한 것으로서, 본 발명의 후퍼진-타크린 하이브리드 유도체 는 치매치료에 효과가 있는 것으로 잘 알려져 있는 후퍼진 A 와 타크린 화합물의 혼합체로서 아세틸콜린에스트라제(AChE) 저해제로서의 활성을 보여준다.
[화학식 1]

(상기 화학식 1에서, X는 수소, 할로겐기 또는 C
1 ~C
6 의 알킬기이고, m은 1 내지 3이고, n은 1 또는 2이다.)
후퍼진-타크린 하이브리드, 치매, 후퍼진, 타크린, 아세틸콜린에스테라제 저해제

公开(公告)号：KR1020050012503A

公开(公告)日：2005-02-02

申请号：KR1020030051485

申请日：2003-07-25

Applicant: 주식회사 코오롱 ,  한국화학연구원

Inventor： 남궁미애 ,  정명희 ,  박정미 ,  최일영 ,  안미자 ,  박우규 ,  정용준 ,  김윤철

IPC: C07D401/04

Abstract: PURPOSE: A process for preparing 1,2,3,6-tetrahydropyridinyl-benzimidazole derivatives is provided, thereby preparing the 1,2,3,6-tetrahydropyridinyl-benzimidazole derivatives which are useful for treatment of dementia as a muscarinic receptor agonist with improved yield. CONSTITUTION: The process for preparing 1,2,3,6-tetrahydropyridinyl-benzimidazole derivatives represented by formula (1) and pharmaceutically acceptable salts thereof comprises the steps of: (a) reacting 4-pyridinecarboxalaldehyde of formula (2) with a compound of formula (3) and iodibenzene diacetate(IBD) in solvent to prepare a compound of formula (4); (b) reacting the compound of formula (4) with KOH/CH3I to prepare a 5/6-substituent isomer compound of formula (5); (c) reacting the compound of formula (5) with CH3I to prepare a compound of formula (7); and (d) reacting the compound of formula (7) with NaBH4, and treating a reaction product with acid, wherein X is NH or NCH3; R is H, NH2, Cl, NO2 or OCH3; and HA is an organic or inorganic salt selected from HCl, oxalic acid, p-toluenesulfonate, tartaric acid and fumaric acid.

Abstract translation: 目的：提供制备1,2,3,6-四氢吡啶基 - 苯并咪唑衍生物的方法，从而制备可用于治疗痴呆作为毒蕈碱受体激动剂的1,2,3,6-四氢吡啶基 - 苯并咪唑衍生物，其具有改进的 产量。 构成：由式（1）表示的1,2,3,6-四氢吡啶基 - 苯并咪唑衍生物及其药学上可接受的盐的制备方法包括以下步骤：（a）使式（2）的4-吡啶甲醛与式 式（3）和二苯乙酮（IBD）在溶剂中制备式（4）化合物; （b）使式（4）的化合物与KOH / CH 3 I反应以制备式（5）的5 / 6-取代的异构体化合物; （c）使式（5）的化合物与CH 3 I反应以制备式（7）的化合物; 和（d）使式（7）的化合物与NaBH 4反应，并用酸处理反应产物，其中X是NH或NCH 3; R是H，NH2，Cl，NO2或OCH3; 并且HA是选自HCl，草酸，对甲苯磺酸盐，酒石酸和富马酸的有机或无机盐。

公开(公告)号：KR1020060109085A

公开(公告)日：2006-10-19

申请号：KR1020050031355

申请日：2005-04-15

Applicant: 한국화학연구원

Inventor： 최일영 ,  변경희 ,  정명희 ,  임희종 ,  안미자 ,  박우규

IPC: C07D401/12

Abstract: Huperzine-tacrine hybrids and preparing process thereof is provided to improve inhibiting activity of acetylcholine esterase(AChE) associated with occurrence of neurodegenerative disease, and enhance their production yield. The huperzine-tacrine hybrid derivatives represented by the formula(1) having neurodegenerative disease-treating effect are provided, wherein X is hydrogen, halogen group or C1-C6 alkyl group, m is 1 to 3 and n is 1 or 2; and the neurodegenerative disease is dementia. The precursors of the huperzine-tacrine hybrid derivatives represented by the formula(6) are provided. The process for preparing the huperzine-tacrine hybrid derivatives comprises the steps of: (1) treating chloro acrydine represented by the formula(2) with hydroxylamine to prepare hydroxy compounds represented by the formula(3); (2) oxidizing the compounds of the formula(3) with an oxidizing agent selected from pyridinium chlorochromate(PCC), pyridinium dichromate(PDC), Jone's reagent and manganese dioxide to prepare aldehyde compounds represented by the formula(4); (3) condensing the aldehyde compounds of the formula(4) with pyridineamine represented by the formula(5) by using a molecular sieve to prepare immine, and reducing it to prepare compounds represented by the formula(6); and (4) deprotecting the compounds of the formula(6) by using trimethylsilyl iodide(TMSI).

Abstract translation: 提供石杉碱混合物及其制备方法，以改善与神经退行性疾病发生相关的乙酰胆碱酯酶（AChE）的抑制活性，提高其产量。 提供了具有神经变性疾病治疗效果的由式（1）表示的石杉碱 - 他克林杂合衍生物，其中X为氢，卤素基或C 1 -C 6烷基，m为1至3，n为1或2; 神经变性疾病是痴呆。 提供了由式（6）表示的石杉碱 - 他克林杂合衍生物的前体。 制备石杉木混合衍生物的方法包括以下步骤：（1）用羟胺处理由式（2）表示的氯丙酸，制备由式（3）表示的羟基化合物; （2）用选自氯铬酸吡啶鎓（PCC），重铬酸吡啶鎓（PDC），琼氏试剂和二氧化锰的氧化剂氧化式（3）的化合物，制备由式（4）表示的醛化合物。 （3）通过使用分子筛将式（4）的醛化合物与式（5）所示的吡啶胺缩合以制备赖氨酸，并将其还原以制备由式（6）表示的化合物; 和（4）通过使用三甲基甲硅烷基碘（TMSI）使式（6）的化合物脱保护。

公开(公告)号：KR1020050033328A

公开(公告)日：2005-04-12

申请号：KR1020030069320

申请日：2003-10-06

Applicant: 한국화학연구원

Inventor： 정명희 ,  안미자 ,  한인규 ,  최일영 ,  박우규

IPC: C07D413/14

Abstract: 1-Methyl-[1,2,4]oxadiazol-3- yl-1,2,5,6-tetrahydropyridine derivatives as a muscarinic receptor agonist and a preparation method thereof are provided, which compounds are useful for enhancement of memory, treatment of senile dementia, and prevention and treatment of diseases associated with the central nervous system. The 1-methyl-[1,2,4]oxadiazol-3- yl-1,2,5,6-tetrahydropyridine derivatives represented by formula (1) or pharmaceutically acceptable salts are provided, wherein R is C1-C10 alkyl, C1-C10 alkylamino, amide or 5- or 6-membered aliphatic, aromatic or hetero ring optionally substituted by one selected from halogen atom or C1-C10 alkyl. The method for preparing the 1-methyl-[1,2,4]oxadiazol-3- yl-1,2,5,6-tetrahydropyridine derivatives of formula (1) comprises the steps of: (a) cyclizating N-hydroxy-nicotineamidine of formula (2) and an organic compound of formula (3) to prepare a compound of formula (4); (b) 3-methylating the compound of formula (4) to prepare a compound of formula (5); and (c) reducting the compound of formula (5).

Abstract translation: 提供1-甲基 - [1,2,4]恶二唑-3-基-1,2,5,6-四氢吡啶衍生物作为毒蕈碱受体激动剂及其制备方法，该化合物可用于增强记忆，治疗 老年性痴呆，预防和治疗与中枢神经系统相关的疾病。 提供由式（1）表示的1-甲基 - [1,2,4]恶二唑-3-基-1,2,5,6-四氢吡啶衍生物或其药学上可接受的盐，其中R是C1-C10烷基，C1 -C 10烷基氨基，酰胺或任选被选自卤素原子或C 1 -C 10烷基的一个取代的5或6元脂族，芳族或杂环。 制备式（1）的1-甲基 - [1,2,4]恶二唑-3-基-1,2,5,6-四氢吡啶衍生物的方法包括以下步骤：（a）使N-羟基 - 式（2）的烟碱脒和式（3）的有机化合物以制备式（4）的化合物; （b）将式（4）化合物3-甲基化以制备式（5）化合物; 和（c）还原式（5）的化合物。

公开(公告)号：KR100871077B1

公开(公告)日：2008-11-28

申请号：KR1020070046077

申请日：2007-05-11

Applicant: 한국화학연구원

Inventor： 김낙정 ,  유성은 ,  이규양 ,  서지희 ,  안미자 ,  이병호 ,  오광석 ,  천혜경

IPC: C07D401/14 ,  C07D409/14 ,  C07D405/14 ,  A61K31/4439

Abstract: A pharmaceutical composition is provided to prevent and cure diseases relating to MCH using an aryl piperidine group-containing imidazole derivative as an active ingredient. A pharmaceutical composition includes an aryl piperidine group-containing imidazole derivative represented by a formula to an active ingredient. In the formula: R1 is group1, and group2 or group3; R4 is H, halogen, C1~C3 of a straight-chain or a side-chain alkyl, or C1~C3 of a straight-chain or a side-chain alkoxy; W is CH or N; Y is O, S or NR8; R8 is H or C1~C3 of a straight-chain or a side-chain alkyl; M is an integer of 1-2; R2 is H, halogen, C1~C3 of a straight-chain or a side-chain alkyl, or C1~C3 of a straight-chain or a side-chain alkoxy, NO2; R3 is C1~C3 of a straight-chain or a side-chain alkyl; A is CH; and N is an integer of 2-5.

Abstract translation: 提供了一种药物组合物，用于使用含芳基哌啶基的咪唑衍生物作为活性成分来预防和治疗与MCH有关的疾病。 药物组合物包含由式表示的含有芳基哌啶基的咪唑衍生物作为活性成分。 在公式中：R1是group1，group2或group3; R4是直链或侧链烷基的H，卤素，C1〜C3，或直链或侧链烷氧基的C1〜C3; W是CH或N; Y为O，S或NR8; R8是直链或侧链烷基的H或C1〜C3; M为1-2的整数; R2是直链或侧链烷基的H，卤素，C1〜C3，或直链或侧链烷氧基的C1〜C3; R3是直链或侧链烷基的C1〜C3; A是CH; N为2-5的整数。

公开(公告)号：KR1020060032771A

公开(公告)日：2006-04-18

申请号：KR1020040081725

申请日：2004-10-13

Applicant: 한국화학연구원

Inventor： 정명희 ,  최일영 ,  안미자 ,  임희종 ,  박우규

IPC: C07D413/04

Abstract: 본 발명은 무스카린 수용체 작용물질로서 작용하는 신규 1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸 유도체와 이의 제조방법, 그리고 상기 신규 화합물을 유효성분으로 함유하는 약제조성물에 관한 것이다.
본 발명에 따른 1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸 유도체는 무스카린 수용체 작용물질(muscarinic receptor agonist)로서 활성을 나타내므로 기억항진 및 노인성 치매 치료제, 뇌질환 및 중추신경계에 관련된 치료약물에 응용될 수 있고, 테트라하이드로피리딘의 등배전자(bioisoster)로 작용하여 이미 임상적으로 치매 치료제에 사용되는 아레콜린 및 밀라멜린 약제와 대등한 치료효과를 나타낸다.
노인성 치매 치료제, 무스카린 수용체 작용물질, 1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸 유도체

公开(公告)号：KR100553313B1

公开(公告)日：2006-02-20

申请号：KR1020030069320

申请日：2003-10-06

Applicant: 한국화학연구원

Inventor： 정명희 ,  안미자 ,  한인규 ,  최일영 ,  박우규

IPC: C07D413/14

Abstract: 본 발명은 무스카린 수용체 작용물질로서 작용하는 신규 1-메칠-[1,2,4]옥사다이아졸-3-일-1,2,5,6-테트라하이드로피리딘 유도체와 이의 제조방법, 그리고 상기 신규 화합물을 유효성분으로 함유하는 약제조성물에 관한 것이다.
본 발명에 따른 1-메칠-[1,2,4]옥사다이아졸-3-일-1,2,5,6-테트라하이드로피리딘 유도체는 무스카린 수용체 작용물질(muscarinic receptor agonist)로서 활성을 나타내므로 기억항진 및 노인성 치매 치료제, 뇌질환 및 중추신경계에 관련된 치료약물에 응용될 수 있고, 테트라하이드로피리딘의 등배전자(bioisoster)로 작용하여 이미 임상적으로 치매 치료제에 사용되는 아레콜린 및 밀라멜린 약제와 대등한 치료효과를 나타낸다.
노인성 치매 치료제, 무스카린 수용체 작용물질, 1-메칠-[1,2,4]옥사다이아졸-3-일-1,2,5,6-테트라하이드로피리딘 유도체

公开(公告)号：KR100453916B1

公开(公告)日：2004-10-20

申请号：KR1020020013001

申请日：2002-03-11

Applicant: 주식회사 코오롱 ,  한국화학연구원

Inventor： 정명희 ,  박정미 ,  최일영 ,  안미자 ,  조성민

IPC: C07D401/04

Abstract: PURPOSE: Provided are 1,2,5,6-tetrahydropyridinylbenzimidazole derivatives which are used in treating dementia and brain diseases as a muscarine receptor modulator, and operated as a bioisostere of tetrahydropyridine with the same effects as the existent dementia treatment drugs of arecoline and milameline. CONSTITUTION: 1,2,5,6-tetrahydropyridinylbenzimidazole derivatives are expressed by the formula 1 where X is NH or NCH3, and R is hydrogen, NH2, Cl, NO2 or OCH3. In the formula 1, HA is an inorganic salt or an organic salt selected from the group consisting of HCl, oxalic acid, p-toluene sulfonic acid, tartaric acid and fumaric acid.

Abstract translation: 用途：1,2,5,6-四氢吡啶基苯并咪唑衍生物作为毒蕈碱受体调节剂用于治疗痴呆症和脑疾病，并且作为四氢吡啶的生物电子等排体进行操作，其效果与现有的槟榔碱和咪唑啉的痴呆治疗药物相同 。 构成：1,2,5,6-四氢吡啶基苯并咪唑衍生物由式1表示，其中X是NH或NCH 3，R是氢，NH 2，Cl，NO 2或OCH 3。 在式1中，HA是选自HCl，草酸，对甲苯磺酸，酒石酸和富马酸的无机盐或有机盐。