公开(公告)号：US20080045714A1

公开(公告)日：2008-02-21

申请号：US11631397

申请日：2005-06-30

申请人： Kimiyuki Shibuya ,  Ayako Tosaka

发明人： Kimiyuki Shibuya ,  Ayako Tosaka

IPC分类号： C07D405/14

CPC分类号： C07D213/75 ,  C07D401/12 ,  C07D413/12

摘要： The present invention provides an industrially useful method for synthesizing a cyclic diamine derivative (4) or a salt thereof which serves as an ACAT inhibitor. A 2-hydroxyacetylaminopyridine compound represented by formula (1), and a method for producing a cyclic diamine derivative represented by formula (4) or a salt thereof from compound (1) through 1) Step A-1, 2) Steps B-1 and B-2, or 3) Steps B-1, B-3, and B-4.

摘要翻译： 本发明提供用作合成作为ACAT抑制剂的环状二胺衍生物（4）或其盐的工业上有用的方法。 由式（1）表示的2-羟基乙酰基氨基吡啶化合物和由式（4）表示的环状二胺衍生物或其盐从化合物（1）至1）步骤A-1,2）步骤B-1 和B-2，或3）步骤B-1，B-3和B-4。

公开(公告)号：US20060035906A1

公开(公告)日：2006-02-16

申请号：US10535705

申请日：2003-11-27

申请人： Kimiyuki Shibuya ,  Yukihiro Sato

发明人： Kimiyuki Shibuya ,  Yukihiro Sato

IPC分类号： A61K31/496 ,  C07D403/02

CPC分类号： C07D235/28

摘要： This invention relates to a method for producing 1-[2-(benzimidazol-2-ylthio)ethyl]piperadine (5) or its salt by the following reaction scheme: This invention enables efficient production of 1-[2-(benzimidazol-2-ylthio) ethyl]piperadine or its salt which is an intermediate in the production of a cyclic diamine compound which is useful as a ACAT inhibitor.

摘要翻译： 本发明涉及通过以下反应方案制备1- [2-（苯并咪唑-2-基硫基）乙基]哌嗪（5）或其盐的方法：本发明可有效生产1- [2-（苯并咪唑-2-基） - 硫基）乙基]哌啶或其盐，其是制备可用作ACAT抑制剂的环状二胺化合物的中间体。

公开(公告)号：US20050165026A1

公开(公告)日：2005-07-28

申请号：US10763241

申请日：2004-01-26

申请人： Kimiyuki Shibuya ,  Toru Miura

发明人： Kimiyuki Shibuya ,  Toru Miura

IPC分类号： C07D263/58 ,  A61K31/496 ,  C07D413/02 ,  C07F7/04

CPC分类号： C07D263/58

摘要： The present invention relates to 2-[4-[2-(7-trifluoromethylbenzoxazol-2-ylthio)ethyl]piperazin-1-yl]-N-[4-hydroxy-2,6-bis(trifluoromethyl)phenyl]acetamide or salt thereof, and an intermediate for the preparation thereof. The above-described compound has both an inhibitory action on ACAT in the artery wall and remarkably high metabolic resistance in human liver microsomes, and exhibits excellent effects for suppressing lipids depression in aorta in vivo so that it is useful as a highly effective preventive or remedy for hyperlipidemia and arteriosclerosis with less side effects.

摘要翻译： 本发明涉及2- [4- [2-（7-三氟甲基苯并恶唑-2-基硫基）乙基]哌嗪-1-基] -N- [4-羟基-2,6-双（三氟甲基）苯基]乙酰胺或 其盐及其制备中间体。 上述化合物对动脉壁中的ACAT具有抑制作用，并且在人肝微粒体中具有显着高的代谢阻力，并且在体内显示出优异的抑制主动脉脂质抑制的作用，因此其作为高效预防或治疗有用 用于高脂血症和动脉硬化，副作用较小。

公开(公告)号：US07951822B2

公开(公告)日：2011-05-31

申请号：US12413894

申请日：2009-03-30

申请人： Ayumu Okuda ,  Takayuki Matsuda ,  Toru Miura ,  Koichi Yamazaki ,  Yuki Yamaguchi ,  Minoru Koura ,  Sayaka Kurobuchi ,  Yuichiro Watanabe ,  Kimiyuki Shibuya

发明人： Ayumu Okuda ,  Takayuki Matsuda ,  Toru Miura ,  Koichi Yamazaki ,  Yuki Yamaguchi ,  Minoru Koura ,  Sayaka Kurobuchi ,  Yuichiro Watanabe ,  Kimiyuki Shibuya

IPC分类号： A61K31/4166 ,  A61K31/427 ,  A61K31/422 ,  A61K31/45 ,  A61K31/4525 ,  C07D405/12 ,  C07D417/12 ,  C07D413/12 ,  C07D407/12

CPC分类号： C07D405/12 ,  C07D405/14 ,  C07D417/12 ,  C07D417/14

摘要： The object is to provide a novel LXRβ agonist that is useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease. The solving means is a 1,3-dihydroisobenzofuran derivative represented by the following general formula (1) or salt thereof, or their solvate.

摘要翻译： 目的是提供一种新颖的LXR＆bgr; 可用作动脉粥样硬化的预防和/或治疗剂的激动剂; 动脉硬化，如糖尿病引起的; 血脂异常 高胆固醇血症 脂质相关疾病; 由炎性细胞因子引起的炎性疾病; 皮肤病如过敏性皮肤病; 糖尿病; 或阿尔茨海默病。 解决方法是由以下通式（1）表示的1,3-二氢异苯并呋喃衍生物或其盐或其溶剂合物。

公开(公告)号：US07576203B2

公开(公告)日：2009-08-18

申请号：US11631397

申请日：2005-06-30

申请人： Kimiyuki Shibuya ,  Ayako Tosaka

发明人： Kimiyuki Shibuya ,  Ayako Tosaka

IPC分类号： C07D213/76 ,  C07D401/12

CPC分类号： C07D213/75 ,  C07D401/12 ,  C07D413/12

摘要： The present invention provides an industrially useful method for synthesizing a cyclic diamine derivative (4) or a salt thereof which serves as an ACAT inhibitor.A 2-hydroxyacetylaminopyridine compound represented by formula (1), and a method for producing a cyclic diamine derivative represented by formula (4) or a salt thereof from compound (1) through 1) Step A-1, 2) Steps B-1 and B-2, or 3) Steps B-1, B-3, and B-4.

摘要翻译： 本发明提供用作合成作为ACAT抑制剂的环状二胺衍生物（4）或其盐的工业上有用的方法。 由式（1）表示的2-羟基乙酰基氨基吡啶化合物和由式（4）表示的环状二胺衍生物或其盐从化合物（1）至1）步骤A-1,2）步骤B-1 和B-2，或3）步骤B-1，B-3和B-4。

公开(公告)号：US20070004749A1

公开(公告)日：2007-01-04

申请号：US10569642

申请日：2004-08-19

申请人： Kimiyuki Shibuya ,  Hideyuki Kobayashi ,  Yasunobu Yoshinaka

发明人： Kimiyuki Shibuya ,  Hideyuki Kobayashi ,  Yasunobu Yoshinaka

IPC分类号： A61K31/496

CPC分类号： A61K31/496 ,  A61K31/4439 ,  C07D401/12

摘要： A method of stabilizing lipid-rich plaques and method of preventing the rupture thereof, characterized in that an effective amount of 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4 -bis(methylthio)-6-methyl-3-pyridyl]acetamide, its acid adduct salt or a hydrate thereof is administered to patients with lipid-rich plaques. Prevention of plaque rupture and stabilization of plaques can be attained by reducing the occupancy of macrophages in lipid-rich plaques being unstable and tending to rupture among plaques being a lesion from a seat of atherosclerosis and simultaneously increasing the occupancy of collagen therein.

摘要翻译： 一种稳定富含脂质斑块的方法和防止其破裂的方法，其特征在于有效量的2- [4- [2-（苯并咪唑-2-基硫基）乙基]哌嗪-1-基] -N- [ 将2,4-双（甲硫基）-6-甲基-3-吡啶基]乙酰胺，其酸加成盐或其水合物给予具有富脂质斑块的患者。 防止斑块破裂和斑块稳定可以通过减少富含脂质的斑块中的巨噬细胞的占有而变得不稳定并且趋于在来自动脉粥样硬化部位的病变的斑块之间破裂并同时增加其中的胶原占有量来实现。

公开(公告)号：US06362208B1

公开(公告)日：2002-03-26

申请号：US09381850

申请日：1999-12-06

申请人： Kimiyuki Shibuya ,  Katsumi Kawamine ,  Yukihiro Sato ,  Toshiyuki Edano ,  Mitsuteru Hirata ,  Chiyoka Ozaki

发明人： Kimiyuki Shibuya ,  Katsumi Kawamine ,  Yukihiro Sato ,  Toshiyuki Edano ,  Mitsuteru Hirata ,  Chiyoka Ozaki

IPC分类号： A61K3142

CPC分类号： C07D263/58 ,  C07D233/84 ,  C07D235/28 ,  C07D263/60 ,  C07D277/74 ,  C07D413/04 ,  C07D413/12 ,  C07D471/04

摘要： The invention relates to a novel anilide compound and a pharmaceutical composition comprising the same. The invention relates to a compound represented by the following general formula: represents a divalent residue of benzene with a substituent(s), heterocycle-condensed benzene which may or may not have a substituent, pyridine which may or may not have a substituent, cyclohexane or naphthalene or Ar represents an aryl group which may or may not have a substituent; X represents —NH—, oxygen atom or sulfur atom; Y represents —NR4—, oxygen atom, sulfur atom, sulfoxide or sulfone; Z represents single bond or —NR5—; R4 represents hydrogen atom, a lower alkyl group, an aryl group or a silylated lower alkyl group which may or may not have a substituent; R5 represents hydrogen atom, a lower alkyl group, an aryl group or a silylated lower alkyl group which may or may not have a substituent; and n represents an integer of 0 to 15. The inventive compounds are useful in the form of pharmaceutical composition, specifically as acyl coenzyme A cholesterol acyltransferase (ACAT) inhibitor.

摘要翻译： 本发明涉及一种新的酰苯胺化合物和包含其的药物组合物。 本发明涉及由以下通式表示的化合物：表示具有取代基的苯的二价残基，可以具有也可以不具有取代基的杂环稠合苯，可以具有也可以不具有取代基的吡啶，可以不具有取代基的吡啶，环己烷 或萘或Ar表示可以具有或不具有取代基的芳基; X表示-NH-，氧原子或硫原子; Y表示-NR4-，氧原子，硫原子，亚砜或砜; Z表示单键或 - NR5-; R4代表氢原子，低级烷基，芳基或可以不具有取代基的甲硅烷基化低级烷基; R5表示氢原子，低级烷基，芳基或甲硅烷基化的低级烷基 其可以具有或不具有取代基; andn表示0至15的整数。本发明化合物可以药物组合物的形式使用，特别是作为酰基辅酶A胆固醇酰基转移酶（ACAT）抑制剂。

公开(公告)号：US08551985B2

公开(公告)日：2013-10-08

申请号：US12769104

申请日：2010-04-28

申请人： Minoru Koura ,  Hisashi Sumida ,  Takayuki Matsuda ,  Yuichiro Watanabe ,  Takashi Enomoto ,  Kimiyuki Shibuya ,  Sumiko Kurobuchi

发明人： Minoru Koura ,  Hisashi Sumida ,  Sayaka Kurobuchi ,  Takayuki Matsuda ,  Yuichiro Watanabe ,  Takashi Enomoto ,  Kimiyuki Shibuya

IPC分类号： A61K31/496 ,  A61K31/551 ,  C07D233/72 ,  C07D401/04 ,  C07D401/14 ,  C07D405/04 ,  C07D405/14 ,  C07D491/048 ,  C07D491/056

CPC分类号： C07D233/78 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/06 ,  C07D405/04 ,  C07D405/14 ,  C07D491/04

摘要： [Object]It is to provide a novel LXRβ agonist useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease.[Solving Means]A carbinol compound represented by the following general formula (I) or salt thereof, or their solvate: (wherein, each V and W independently show N or C—R7; each X and Y independently show CH2, C═O, SO2, etc; Z shows CH or N; each R1, R2 and R7 independently show a hydrogen atom, C1-8 alkyl group, etc.; R3 shows C1-8 alkyl group; R4 shows an optionally substituted C6-10 aryl group or an optionally substituted 5- to 11-membered heterocyclic group; R5 and R6 show a hydrogen atom, etc.; L shows a C1-8 alkyl chain optionally substituted with an oxo group, etc.; and n shows any integer of 0 to 2.)

摘要翻译： 本发明提供可用作动脉粥样硬化的预防和/或治疗剂的新型LXRbeta激动剂; 动脉硬化，如糖尿病引起的; 血脂异常 高胆固醇血症 脂质相关疾病; 由炎性细胞因子引起的炎性疾病; 皮肤病如过敏性皮肤病; 糖尿病; 或阿尔茨海默病。 [解决方案]由以下通式（I）表示的甲醇化合物或其盐或其溶剂化物：（其中，V和W各自独立地表示N或C-R7; X和Y各自独立地表示CH 2，C = O ，SO2等; Z表示CH或N;每个R1，R2和R7独立地表示氢原子，C1-8烷基等; R3表示C1-8烷基; R4表示任选取代的C6-10芳基 或任选取代的5至11元杂环基; R 5和R 6表示氢原子等; L表示任选被氧代基等取代的C 1-8烷基链; n表示0〜 2.）

公开(公告)号：US20110015206A1

公开(公告)日：2011-01-20

申请号：US12857671

申请日：2010-08-17

申请人： Kimiyuki Shibuya ,  Hideyuki Kobayashi ,  Yasunobu Yoshinaka

发明人： Kimiyuki Shibuya ,  Hideyuki Kobayashi ,  Yasunobu Yoshinaka

IPC分类号： A61K31/496 ,  A61P9/10

CPC分类号： A61K31/496 ,  A61K31/4439 ,  C07D401/12

摘要： A method of stabilizing lipid-rich plaques and method of preventing the rupture thereof, characterized in that an effective amount of 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide, its acid adduct salt or a hydrate thereof is administered to patients with lipid-rich plaques. Prevention of plaque rupture and stabilization of plaques can be attained by reducing the occupancy of macrophages in lipid-rich plaques being unstable and tending to rupture among plaques being a lesion from a seat of atherosclerosis and simultaneously increasing the occupancy of collagen therein.

摘要翻译： 一种稳定富含脂质斑块的方法和防止其破裂的方法，其特征在于有效量的2- [4- [2-（苯并咪唑-2-基硫基）乙基]哌嗪-1-基] -N- [ 将2,4-二（甲硫基）-6-甲基-3-吡啶基]乙酰胺，其酸加成盐或其水合物给予富脂质斑块的患者。 防止斑块破裂和斑块稳定可以通过减少富含脂质的斑块中的巨噬细胞的占有而变得不稳定并且趋于在来自动脉粥样硬化部位的病变的斑块之间破裂并同时增加其中的胶原占有量来实现。

公开(公告)号：US20100048610A1

公开(公告)日：2010-02-25

申请号：US12474799

申请日：2009-05-29

申请人： Yuki Yamaguchi ,  Minoru Koura ,  Sayaka Kurobuchi ,  Takayuki Matsuda ,  Ayumu Okuda ,  Hisashi Sumida ,  Yuuichirou Watanabe ,  Takashi Enomoto ,  Kimiyuki Shibuya

发明人： Yuki Yamaguchi ,  Minoru Koura ,  Sayaka Kurobuchi ,  Takayuki Matsuda ,  Ayumu Okuda ,  Hisashi Sumida ,  Yuuichirou Watanabe ,  Takashi Enomoto ,  Kimiyuki Shibuya

IPC分类号： A61K31/436 ,  C07D401/06 ,  A61K31/4439 ,  C07D491/056

CPC分类号： C07D233/72 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D491/048

摘要： [Object] To provide a novel LXRβ agonist that is useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease.[Solving Means] A carbinol compound represented by the following general formula (I) or salt thereof, or their solvate.

摘要翻译： [目的]提供一种新型的LXR＆bgr; 可用作动脉粥样硬化的预防和/或治疗剂的激动剂; 动脉硬化，如糖尿病引起的; 血脂异常 高胆固醇血症 脂质相关疾病; 由炎性细胞因子引起的炎性疾病; 皮肤病如过敏性皮肤病; 糖尿病; 或阿尔茨海默病。 [解决方案]由以下通式（I）表示的甲醇化合物或其盐或其溶剂化物。