公开(公告)号：KR1020070081294A

公开(公告)日：2007-08-16

申请号：KR1020060013167

申请日：2006-02-10

Applicant: 동화약품주식회사

Inventor： 유제만 ,  임문정 ,  노양국 ,  오성준 ,  이현용 ,  장환봉 ,  황연하 ,  이정욱

IPC: A61K31/341 ,  A61K31/56 ,  A61K36/47 ,  A61P19/10

Abstract: A composition for preventing and treating osteoporosis comprising terpenoids isolated from Euphorbia kansui or the extracts thereof is provided to inhibit bone absorption of osteoclasts without side effects. The composition for preventing and treating osteoporosis comprises kansuinine A represented by the formula(1) and gamma-euphorbol represented by the formula(2) or the extracts thereof. The kansuinine A represented by the formula(1) and gamma-euphorbol represented by the formula(2) are isolated by extracting and concentrating Euphorbia kansui with methanol, suspending the concentrated extract of Euphorbia kansui in water, and adding nucleic acid into the suspension to separate a nucleic acid layer, adding methylene chloride into a water layer obtained by separating the nucleic acid layer to obtain a methylene chloride fraction, and subjecting the methylene chloride fraction to chromatography.

Abstract translation: 提供了用于预防和治疗包括从大戟属分离的萜类化合物或其提取物的骨质疏松症的组合物，以抑制破骨细胞的骨吸收而没有副作用。 用于预防和治疗骨质疏松症的组合物包括由式（1）表示的苦参碱A和由式（2）表示的γ-高效药或其提取物。 由式（1）表示的甘露宁A和由式（2）表示的γ-高效酚通过用甲醇萃取浓缩大戟甘油，将浓缩的大戟属浓缩提取物悬浮于水中，并将核酸加入到悬浮液中 分离核酸层，将二氯甲烷加入到通过分离核酸层获得的水层中，得到二氯甲烷部分，并将二氯甲烷部分进行色谱分离。

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。

公开(公告)号：KR1020030008654A

公开(公告)日：2003-01-29

申请号：KR1020010043490

申请日：2001-07-19

Applicant: 동화약품주식회사 ,  서홍석

Inventor： 이진수 ,  김판수 ,  황연하 ,  유제만 ,  정용호 ,  서홍석 ,  김은주 ,  김도희 ,  박용엽

IPC: A61K31/426

CPC classification number: A61K31/426 ,  Y10S514/878

Abstract: PURPOSE: Provided are 4-((4-thiazolyl)phenoxy)alkoxy-benzamidine derivatives(DW1350 and DW1352) acting as leukotriene-B4 receptor antagonistic action. The compounds exhibit an excellent inhibition effect on a differentiation, formation, fusion process and bone absorption function of osteoclast cells, therefore they can be effectively used as an prophylaxis and treatment of osteoporosis. CONSTITUTION: The agent for prophylaxis and treatment of osteoporosis contains an effective amount of 4-((4-thiazolyl)phenoxy)alkoxy-benzamidine derivative of formula(1) or a salt thereof. In formula, R is H or OH. The agent is excellent in an inhibition of osteoclast cells as compared to any compound such as DW1349 and DW1351 having structural similarity as well as HS-1141 and CGS-25019C and has increased efficacy in increasing the activity of osteoblast cells.

Abstract translation: 目的：提供作为白三烯-B4受体拮抗作用的4 - （（4-噻唑基）苯氧基）烷氧基 - 苄脒衍生物（DW1350和DW1352）。 该化合物对破骨细胞的分化，形成，融合过程和骨吸收功能具有优异的抑制作用，因此可有效用于预防和治疗骨质疏松症。 构成：用于预防和治疗骨质疏松症的药物含有有效量的式（1）的4​​ - （（4-噻唑基）苯氧基）烷氧基 - 苄脒衍生物或其盐。 在式中，R是H或OH。 与具有结构相似性的DW1349和DW1351以及HS-1141和CGS-25019C的化合物相比，该试剂在破骨细胞抑制方面优异，并且在增加成骨细胞活性方面具有增加的功效。