公开(公告)号：US07393866B2

公开(公告)日：2008-07-01

申请号：US10985938

申请日：2004-11-09

申请人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

发明人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

IPC分类号： A61K31/4436 ,  C07D417/12

CPC分类号： C07D403/12 ,  A61K31/4439 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D513/04

摘要： The present invention provides to a novel compound having an ACAT inhibiting activity.The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group, Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring, X represents —NH—, an oxygen atom or a sulfur atom, Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone, Z represents a single bond or —NR5—, R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, and n is an integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at least one of these compounds.

摘要翻译： 本发明提供具有ACAT抑制活性的新型化合物。 本发明涉及由式（I）表示的化合物，其中表示任选取代的二价残基例如苯，吡啶，环己烷或萘，或者基团，Het表示5至8元，取代或未取代的杂环基， 至少一个选自氮原子，氧原子和硫原子的杂原子，如单环基团，多环基团或稠环基团，X表示-NH-，氧原子或硫原子 原子，Y表示-NR 4 - ，氧原子，硫原子，亚砜或砜，Z表示单键或-NR 5 - ， - R 4表示氢原子，低级烷基，芳基或任选取代的甲硅烷基低级烷基，R 5表示氢原子，低级烷基，芳基 基团或任选取代的甲硅烷基低级烷基，n为1至15的整数，或其盐或溶剂化物， d含有这些化合物中的至少一种的药物组合物。

公开(公告)号：US06969711B2

公开(公告)日：2005-11-29

申请号：US10371234

申请日：2003-02-20

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

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

IPC分类号： C07D235/28 ,  C07D263/58 ,  C07D277/74 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D498/04 ,  C07F9/6509 ,  C07F9/6558 ,  C07D403/12 ,  A61K31/454 ,  A61P9/10

CPC分类号： C07D263/58 ,  C07D235/28 ,  C07D277/74 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07F9/650952 ,  C07F9/65583

摘要： The present invention offers novel cyclic diamine compounds and a pharmaceutical composition containing the same.The present invention relates to a compound represented by the formula (I) or salt(s) or solvate(s) thereof. (In the formula, is an optionally substituted divalent residue of benzene, pyridine, cyclohexane or naphthalene or is a vinylene group where Ar is an optionally substituted aryl group; X is —NH—, oxygen atom or sulfur atom; Y is —NR1—, oxygen atom, sulfur atom, sulfoxide or sulfone; Z is a single bond or —NR2—; R1 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group; R2 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group; l is an integer of from 0 to 15; m is an integer of 2 or 3; and n is an integer of from 0 to 3). The compound of the present invention is useful as a pharmaceutical composition, particuarly as an inhibitor of acyl coenzyme A cholesterol acyltransferase (ACAT).

摘要翻译： 本发明提供新的环状二胺化合物和含有它们的药物组合物。 本发明涉及由式（I）表示的化合物或其盐或溶剂化物。 （式中，是苯，吡啶，环己烷或萘的任选取代的二价残基，或者是亚乙烯基，其中Ar是任意取代的芳基; X是-NH-，氧原子或硫原子; Y是-NR' SO 2， - 氧原子，硫原子，亚砜或砜; Z是单键或-NR 2 - ; R 1是氢原子， 任选取代的低级烷基，任选取代的芳基或任选取代的甲硅烷基低级烷基; R 2是氢原子，任选取代的低级烷基，任选取代的芳基或任选取代的甲硅烷基低级烷基; l 为0〜15的整数，m为2或3的整数，n为0〜3的整数。 本发明的化合物可用作药物组合物，特别是作为酰基辅酶A胆固醇酰基转移酶（ACAT）的抑制剂。

公开(公告)号：US07414066B2

公开(公告)日：2008-08-19

申请号：US10985915

申请日：2004-11-09

申请人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

发明人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

IPC分类号： A61K31/4439 ,  C07D401/12

CPC分类号： C07D403/12 ,  A61K31/4439 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D513/04

摘要： The present invention provides to a novel compound having an ACAT inhibiting activity.The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group, Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring, X represents —NH—, an oxygen atom or a sulfur atom, Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone, Z represents a single bond or —NR5—, R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, and n is an integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at least one of these compounds.

摘要翻译： 本发明提供具有ACAT抑制活性的新型化合物。 本发明涉及由式（I）表示的化合物，其中表示任选取代的二价残基例如苯，吡啶，环己烷或萘，或者基团，Het表示5至8元，取代或未取代的杂环基， 至少一个选自氮原子，氧原子和硫原子的杂原子，如单环基团，多环基团或稠环基团，X表示-NH-，氧原子或硫原子 原子，Y表示-NR 4 - ，氧原子，硫原子，亚砜或砜，Z表示单键或-NR 5 - ， - R 4表示氢原子，低级烷基，芳基或任选取代的甲硅烷基低级烷基，R 5表示氢原子，低级烷基，芳基 基团或任选取代的甲硅烷基低级烷基，n为1至15的整数，或其盐或溶剂化物， d含有这些化合物中的至少一种的药物组合物。

公开(公告)号：US20050131002A1

公开(公告)日：2005-06-16

申请号：US10985938

申请日：2004-11-09

申请人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

发明人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

IPC分类号： A61K31/4439 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D498/04 ,  C07D513/04 ,  A61K31/506 ,  C07D413/02 ,  C07D417/02 ,  C07D43/02

CPC分类号： C07D403/12 ,  A61K31/4439 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D513/04

摘要： The present invention provides to a novel compound having an ACAT inhibiting activity. The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group, Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring, X represents —NH—, an oxygen atom or a sulfur atom, Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone, Z represents a single bond or —NR5—, R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, and n is an integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at least one of these compounds.

摘要翻译： 本发明提供具有ACAT抑制活性的新型化合物。 本发明涉及由式（I）表示的化合物，其中表示任选取代的二价残基例如苯，吡啶，环己烷或萘，或者基团，Het表示5至8元，取代或未取代的杂环基， 至少一个选自氮原子，氧原子和硫原子的杂原子，如单环基团，多环基团或稠环基团，X表示-NH-，氧原子或硫原子 原子，Y表示-NR 4 - ，氧原子，硫原子，亚砜或砜，Z表示单键或-NR 5 - ， - R 4表示氢原子，低级烷基，芳基或任选取代的甲硅烷基低级烷基，R 5表示氢原子，低级烷基，芳基 基团或任选取代的甲硅烷基低级烷基，n为1至15的整数，或其盐或溶剂化物， d含有这些化合物中的至少一种的药物组合物。

公开(公告)号：US06998486B2

公开(公告)日：2006-02-14

申请号：US10498984

申请日：2002-12-27

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Yukihiro Sato ,  Toru Miura

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Yukihiro Sato ,  Toru Miura

IPC分类号： C07D235/28

CPC分类号： C07D401/12 ,  C07D235/28 ,  Y02P20/55 ,  Y02P20/584

摘要： The present invention is directed to a process for producing cyclic diamine compounds (4) or salts or intermediates thereof according to the following reaction scheme: (wherein R is a protective group and Ar is an optionally substituted aryl group). According to the present invention, the cyclic diamine compounds (4) useful as drugs or salts or intermediates thereof can be produced at high levels of yield and purity in terms of industrially advantageous productivity.

摘要翻译： 本发明涉及根据以下反应方案制备环状二胺化合物（4）或其盐或其中间体的方法：

公开(公告)号：US20050131001A1

公开(公告)日：2005-06-16

申请号：US10985915

申请日：2004-11-09

申请人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Kirata

发明人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Kirata

IPC分类号： A61K31/4439 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D498/04 ,  C07D513/04 ,  A61K31/506 ,  C07D413/02 ,  C07D417/02 ,  C07D43/02

CPC分类号： C07D403/12 ,  A61K31/4439 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D513/04

摘要： The present invention provides to a novel compound having an ACAT inhibiting activity. The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group, Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring, X represents —NH—, an oxygen atom or a sulfur atom, Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone, Z represents a single bond or —NR5—, R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, and n is an integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at least one of these compounds.

摘要翻译： 本发明提供具有ACAT抑制活性的新型化合物。 本发明涉及由式（I）表示的化合物，其中表示任选取代的二价残基例如苯，吡啶，环己烷或萘，或者基团，Het表示5至8元，取代或未取代的杂环基， 至少一个选自氮原子，氧原子和硫原子的杂原子，如单环基团，多环基团或稠环基团，X表示-NH-，氧原子或硫原子 原子，Y表示-NR 4 - ，氧原子，硫原子，亚砜或砜，Z表示单键或-NR 5 - ， - R 4表示氢原子，低级烷基，芳基或任选取代的甲硅烷基低级烷基，R 5表示氢原子，低级烷基，芳基 基团或任选取代的甲硅烷基低级烷基，n为1至15的整数，或其盐或溶剂化物， d含有这些化合物中的至少一种的药物组合物。

公开(公告)号：US20050032814A1

公开(公告)日：2005-02-10

申请号：US10498984

申请日：2002-12-27

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Yukihiro Sato ,  Toru Miura

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Yukihiro Sato ,  Toru Miura

IPC分类号： C07D235/28 ,  C07D401/12 ,  A61K31/496 ,  C07D43/02

CPC分类号： C07D401/12 ,  C07D235/28 ,  Y02P20/55 ,  Y02P20/584

摘要： The present invention is directed to a process for producing cyclic diamine compounds (4) or salts or intermediates thereof according to the following reaction scheme: (wherein R is a protective group and Ar is an optionally substituted aryl group). According to the present invention, the cyclic diamine compounds (4) useful as drugs or salts or intermediates thereof can be produced at high levels of yield and purity in terms of industrially advantageous productivity.

摘要翻译： 本发明涉及根据以下反应方案制备环状二胺化合物（4）或其盐或其中间体的方法：（其中R是保护基，Ar是任选取代的芳基）。 根据本发明，在工业上有利的生产率方面，可以以高产率和纯度生产用作药物或其盐或其中间体的环状二胺化合物（4）。

公开(公告)号：US06849647B1

公开(公告)日：2005-02-01

申请号：US09666152

申请日：2000-09-20

申请人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

发明人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

IPC分类号： A61K31/4439 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D498/04 ,  C07D513/04

CPC分类号： C07D403/12 ,  A61K31/4439 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D513/04

摘要： The present invention provides to a novel compound having an ACAT inhibiting activity.The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group, Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring, X represents —NH—, an oxygen atom or a sulfur atom, Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone, Z represents a single bond or —NR5—, R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, and n is integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at one of these compounds.

摘要翻译： 本发明涉及一种具有ACAT抑制活性的新型化合物。本发明涉及式（I）表示的化合物，其中表示任选取代的二价残基如苯，吡啶，环己烷或萘，或基团，Het表示 含有至少一个选自氮原子，氧原子和硫原子的杂原子的5-至8-元，取代或未取代的杂环基，例如单环基团，多环基团或稠合基团 环，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表示氢 原子，低级烷基，芳基或任选取代的甲硅烷基低级烷基，R 5表示氢原子，低级烷基，芳基或任选取代的甲硅烷基低级烷基，n为1至15的整数 ，要么 盐或溶剂合物，以及含有这些化合物之一的药物组合物。

公开(公告)号：US06825223B2

公开(公告)日：2004-11-30

申请号：US09789967

申请日：2001-02-21

申请人： Kimiyuki Shibuya ,  Katsumi Kawamine ,  Yukihiro Sato ,  Toshiyuki Edano ,  Souhei Tanabe ,  Masami Shiratsuchi

发明人： Kimiyuki Shibuya ,  Katsumi Kawamine ,  Yukihiro Sato ,  Toshiyuki Edano ,  Souhei Tanabe ,  Masami Shiratsuchi

IPC分类号： A61K31428

CPC分类号： C07D263/58 ,  C07D235/28 ,  C07D277/70

摘要： The invention provides novel anilide compounds and pharmaceutical compositions comprising them. The invention relates to compounds of a formula: wherein Ar is an optionally-substituted aryl group; R4 and R5 are the same or different, and each is a hydrogen atom, a lower alkyl group, or a lower alkoxy group; and R4 and R5 may together form a lower alkylene group of which one or more methylene moieties may optionally be substituted by oxygen and/or sulfur atoms; X is —NH—, or an oxygen or sulfur atom; Y is —NH—, an oxygen or sulfur atom, or a sulfoxide or sulfone group; Z is a single bond, or —NR6—; R4 represents a hydrogen atom or a lower alkylene group; and n is an integer of from 0 to 15; and their salts and solvates. The compounds of the invention are useful as pharmaceutical compositions, especially as acyl coenzyme A cholesterol acyltransferase (ACAT) inhibitors.

摘要翻译： 本发明提供了新的酰苯胺化合物和包含它们的药物组合物。本发明涉及下式的化合物：其中Ar是任选取代的芳基; R 4和R 5相同或不同，并且各自是氢原子，低级烷基 基团或低级烷氧基; 并且R 4和R 5可以一起形成低级亚烷基，其中一个或多个亚甲基部分可以任选地被氧和/或硫原子取代; X是-NH-或氧或硫原子; Y是-NH-， 氧或硫原子，或亚砜或砜基; Z为单键或-NR 6 - ; R 4表示氢原子或低级亚烷基; 和n为0至15的整数;以及它们的盐和溶剂化物。本发明的化合物可用作药物组合物，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：US06797717B2

公开(公告)日：2004-09-28

申请号：US10034669

申请日：2001-12-19

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： A61K31435

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 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表示氢原子，可以具有或不具有取代基的低级烷基，芳基或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， 可以或可以不具有取代基; 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。