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    3-아미도-1,2-벤조이소옥사졸 유도체, 그 염, 제조방법 및 용도
    1.
    发明授权
    3-아미도-1,2-벤조이소옥사졸 유도체, 그 염, 제조방법 및 용도 失效
    3-氨基-1,2-苯并恶唑衍生物，制备方法及其用途

    公开(公告)号：KR100789567B1

    公开(公告)日：2007-12-28

    申请号：KR1020010069013

    申请日：2001-11-06

    Applicant: 동화약품주식회사

    Inventor： 이진수 ,  안석훈 ,  진영구 ,  진상미 ,  구세광 ,  유제만 ,  정용호 ,  김은주 ,  조순기

    IPC: C07D261/20

    CPC classification number: C07D261/20

    Abstract: 본 발명은 하기 화학식 1로 표시되는 3-아미도-1,2-벤조이소옥사졸(3-amido-1,2-benzoisoxazole)유도체, 그의 염, 제조방법 및 용도에 관한 것으로 3-아미도-1,2-벤조이소옥사졸의 아민기에 아미노산 잔기를 도입하여 생체이용률을 개선하는 방법에 관한 것이다. 본 발명의 화합물은 류코트리엔-B-4 (Leukotriene-B-4)의 수용체 길항제, 골 흡수 억제 작용 및 골 형성 촉진 작용을 하는 골다공증의 억제 또는 치료에 유용하게 사용된다.

    (상기 식에서, R
    1 및 R
    2 는 명세서 내에서 정의한 바와 같다.)
    벤조이소옥사졸 유도체, 골다공증 치료제

    Ｎ-히드록시-4-｛5-〔4-（5-이소프로필-2-메틸-1,3-티아졸-4-일）페녹시〕펜톡시｝벤즈아미딘 2 에탄술폰산염, 이의제조방법 및 이를 포함하는 약학 조성물
    5.
    发明公开
    Ｎ-히드록시-4-｛5-〔4-（5-이소프로필-2-메틸-1,3-티아졸-4-일）페녹시〕펜톡시｝벤즈아미딘 2 에탄술폰산염, 이의제조방법 및 이를 포함하는 약학 조성물 失效
    N-羟基-4- {5- [4-（5-异丙基-2-甲基-1,3-噻唑-4-基）苯氧基]戊氧基}苯甲胺二乙酸盐，其制备方法和包含药物组合物 一样

    公开(公告)号：KR1020080094634A

    公开(公告)日：2008-10-23

    申请号：KR1020080036880

    申请日：2008-04-21

    Applicant: 동화약품주식회사

    Inventor： 이진수 ,  조순기 ,  성승규 ,  진영구 ,  박재훈 ,  김보경 ,  차자현 ,  조은희 ,  유제만

    IPC: C07D277/24 ,  A61K31/426 ,  A61P19/10

    CPC classification number: C07D277/24

    Abstract: An N- hydroxy-4- benzamidine 2 ethansulfonic acid salt is provided to show excellent solubility, stability, and bioavailability, as well as a higher initial release rate than 2 methansulfonic acid salt thereof. An N-hydroxy-4-benzamidine 2 ethansulfonic acid salt is represented by a formula(1) and is prepared by reacting N- hydroxy-4-benzamidine and ethanesulfonic acid in an inert solvent. A pharmaceutical composition for preventing and treating osteoporosis, bone fractures, allergic or inflammatory diseases comprises the N- hydroxy-4-benzamidine 2 ethansulfonic acid salt and a pharmaceutically acceptable carrier. An oral formulation for preventing and treating osteoporosis, bone fractures, and allergic inflammatory diseases, comprises the N- hydroxy-4-benzamidine 2 ethansulfonic acid salt along with (a) at least one carbonate selected from the group consisting of alkali metal carbonate, alkali metal bicarbonate and alkaline earth metal carbonate; (b) at least one disintegrant selected from the group consisting of sodium carboxymethyl starch, sodium carmellose, calcium carmellose and sodium croscarmellose; or a combination of (a) and (b).

    Abstract translation: 提供N-羟基-4-苄脒2乙磺酸盐以显示出优异的溶解性，稳定性和生物利用度，以及比其二甲基磺酸盐更高的初始释放速率。 N-羟基-4-苯甲脒2乙磺酸盐由式（1）表示，并通过N-羟基-4-苯甲脒和乙磺酸在惰性溶剂中反应制备。 用于预防和治疗骨质疏松症，骨折，过敏或炎性疾病的药物组合物包括N-羟基-4-苄脒2乙磺酸盐和药学上可接受的载体。 用于预防和治疗骨质疏松症，骨折和过敏性炎性疾病的口服制剂包括N-羟基-4-苯甲脒2乙磺酸盐以及（a）至少一种选自碱金属碳酸盐，碱金属的碳酸盐 金属碳酸氢盐和碱土金属碳酸盐; （b）至少一种选自羧甲基淀粉钠，羧甲纤维素钠，羧甲纤维素钙和交联羧甲纤维素钠的崩解剂; 或（a）和（b）的组合。

    신규한 벤즈아미딘 유도체, 그의 제조방법 및 이를포함하는 약학 조성물
    6.
    发明公开
    신규한 벤즈아미딘 유도체, 그의 제조방법 및 이를포함하는 약학 조성물 失效
    新颖的苯扎明衍生物，其制备方法和包含其的药物组合物

    公开(公告)号：KR1020070079043A

    公开(公告)日：2007-08-03

    申请号：KR1020070009859

    申请日：2007-01-31

    Applicant: 동화약품주식회사

    Inventor： 유제만 ,  이진수 ,  진영구 ,  이기영 ,  박재훈 ,  황연하 ,  구세광

    IPC: C07D277/22 ,  C07D413/04 ,  C07D401/04 ,  A61P19/10

    CPC classification number: C07D417/04 ,  C07D277/28 ,  C07D417/12

    Abstract: A novel benzamidine derivative is provided to effectively inhibit osteoclast differentiation at an extremely low concentration, and significantly increase the trabecular bone volume, thereby being used for preventing and treating osteoporosis. The benzamidine derivative is represented by the formula(1), wherein R1 is C1-6 alkyl which is unsubstituted or substituted with one group selected from pyridine and a group represented by the structural formula(1-a), C3-6 cycloalkyl, phenyl, benzyl; pyridinyl which is unsubstituted or substituted with C1-6 alkyl, guanidino, NR6R7, a group represented by the structural formula(1-b); or a group represented by the structural formula(1-a) which is unsubstituted or substituted with C1-6 alkyl; R2 is a primary or secondary amine, which is NR8R9, a compound represented by the structural formula(1-c), pyrrolidine, piperidine or imidazole, each R3 and R4 is independently H, halogen, hydroxy, C1-6 alkyl which is unsubstituted or substituted with halogen, C3-6 cycloalkylamino, C1-6 alkoxy, C1-6 alkanoyloxy, C2-6 alkenyloxy, phenyl-C1-6 alkoxy, phenoxy, C2-6 alkenoyloxy or phenyl-C1-6 alkanoyloxy, or C3-6 cycloalkyloxy which is substituted with one group selected from carboxy, esterified carboxy and amidated carboxy or aminooxy; R5 is H or hydroxy group; each X1 and X3 is independently O, S, NH, or N-C1-6 alkyl, N-C3-6 cycloalkyl, N-benzyl or N-phenyl; X2 is C3-7 alkylene, C1-3 alkylene-C2-7 alkenylene-C1-3 alkylene, C1-3 alkylene-O-C1-3 alkylene, C1-3 alkylene-S-C1-3 alkylene, C1-3 alkylene-NH-C1-3 alkylene, C1-3 alkylene-phenylene-C1-3 alkylene, C1-3 alkylene-pyridylene-C1-3 alkylene or C1-3 alkylene-naphthylene-C1-3 alkylene, C3-7 alkylene which is substituted with C1-3 alkyl and hydroxyl, C3-7 alkylene carbonyl, or C3-7 alkylene which is interrupted by piperazine; Q is CH or carbonyl; and n is an integer of 0 to 6..

    Abstract translation: 提供了一种新颖的苯甲脒衍生物，以极低浓度有效抑制破骨细胞分化，并显着增加小梁骨体积，从而用于预防和治疗骨质疏松症。 苯甲脒衍生物由式（1）表示，其中R 1是未被取代或被一个选自吡啶和由结构式（1-a）表示的基团，C 3-6环烷基，苯基 ，苄基; 吡啶基，其未被取代或被C 1-6烷基，胍基，NR 6 R 7，被结构式（1-b）表示的基团取代; 或由未被取代或被C 1-6烷基取代的结构式（1-a）表示的基团; R2是伯或仲胺，其为NR8R9，由结构式（1-c）表示的化合物，吡咯烷，哌啶或咪唑，每个R 3和R 4独立地为H，卤素，羟基，未被取代的C 1-6烷基 或被卤素取代，C 3-6环烷基氨基，C 1-6烷氧基，C 1-6烷酰氧基，C 2-6烯氧基，苯基-C 1-6烷氧基，苯氧基，C 2-6烯酰氧基或苯基-C 1-6烷酰氧基或C 3-6 被一个选自羧基，酯化的羧基和酰胺化的羧基或氨氧基的基团取代的环烷氧基; R5为H或羟基; 每个X 1和X 3独立地是O，S，NH或N-C 1-6烷基，N 3 -C 6环烷基，N-苄基或N-苯基; X2是C3-7亚烷基，C1-3亚烷基-C2-7亚烯基C1-3亚烷基，C1-3亚烷基-O-C1-3亚烷基，C1-3亚烷基-S-C1-3亚烷基，C1-3亚烷基 -NH-C 1-3亚烷基，C 1-3亚烷基 - 亚苯基-C 1-3亚烷基，C 1-3亚烷基 - 亚吡啶基-C 1-3亚烷基或C 1-3亚烷基 - 亚萘基-C 1-3亚烷基， 被C 1-3烷基和羟基取代，C 3-7亚烷基羰基或被哌嗪中断的C 3-7亚烷基; Q是CH或羰基; n为0〜6的整数。

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