公开(公告)号：US20100022572A1

公开(公告)日：2010-01-28

申请号：US12504075

申请日：2009-07-16

申请人： Hisashi Nakashima ,  Takahisa Ogamino ,  Takaaki Araki ,  Noriaki Gomi ,  Yasushi Kaneko ,  Kazutoyo Abe ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

发明人： Hisashi Nakashima ,  Takahisa Ogamino ,  Takaaki Araki ,  Noriaki Gomi ,  Yasushi Kaneko ,  Kazutoyo Abe ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

IPC分类号： A61K31/438 ,  C07D221/20 ,  A61P3/00 ,  A61P3/04 ,  A61P9/12

CPC分类号： A61K31/438 ,  C07D221/20 ,  C07D471/10

摘要： It is to provide a novel compound useful for preventing and/or treating diabetes, insulin resistance, diabetes complication, obesity, dyslipidemia, hypertension, fatty liver, or metabolic syndrome.A spiro compound represented by the following general formula (1) or salt thereof, or their solvate.

摘要翻译： 提供可用于预防和/或治疗糖尿病，胰岛素抵抗，糖尿病并发症，肥胖症，血脂异常，高血压，脂肪肝或代谢综合征的新型化合物。 由以下通式（1）表示的螺环化合物或其盐或其溶剂化物。

公开(公告)号：US09045460B2

公开(公告)日：2015-06-02

申请号：US13816534

申请日：2011-08-25

申请人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

发明人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

IPC分类号： C07D401/12 ,  C07D243/08

CPC分类号： C07D401/12 ,  C07D243/08

摘要： The present invention provides a method capable of industrially producing a target product, i.e., a compound represented by the aforementioned formula (I) or a salt thereof, which is useful for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral edema, particularly for preventing and treating glaucoma, at high yield even on a large scale without imposing a negative impact on the environment. The present invention provides a method for producing a compound represented by formula (I) or a salt thereof, wherein the method comprises a step of reacting a compound represented by formula (III) or a salt thereof with a compound represented by formula (II) in the presence of at least one solvent selected from the group consisting of a nitrile solvent, an amide solvent, a sulfoxide solvent, and a urea solvent, and a base.

摘要翻译： 本发明提供一种能够工业生产目标产物的方法，即由上述式（I）表示的化合物或其盐，其可用于预防和治疗脑梗塞，脑出血，蛛网膜下腔出血等脑血管疾病 ，脑水肿，特别是预防和治疗青光眼，即使大规模高产，也不会对环境造成负面影响。 本发明提供一种由式（I）表示的化合物或其盐的制备方法，其中所述方法包括使式（III）表示的化合物或其盐与式（II）表示的化合物反应的步骤， 在选自腈溶剂，酰胺溶剂，亚砜溶剂和尿素溶剂中的至少一种溶剂和碱存在下进行。

公开(公告)号：US20130144054A1

公开(公告)日：2013-06-06

申请号：US13816534

申请日：2011-08-25

申请人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

发明人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

IPC分类号： C07D401/12 ,  C07D243/08

CPC分类号： C07D401/12 ,  C07D243/08

摘要： The present invention provides a method capable of industrially producing a target product, i.e., a compound represented by the aforementioned formula (I) or a salt thereof, which is useful for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral edema, particularly for preventing and treating glaucoma, at high yield even on a large scale without imposing a negative impact on the environment. The present invention provides a method for producing a compound represented by formula (I) or a salt thereof, wherein the method comprises a step of reacting a compound represented by formula (III) or a salt thereof with a compound represented by formula (II) in the presence of at least one solvent selected from the group consisting of a nitrile solvent, an amide solvent, a sulfoxide solvent, and a urea solvent, and a base.

公开(公告)号：US20130225618A1

公开(公告)日：2013-08-29

申请号：US13824782

申请日：2011-10-03

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takeshi Murakami

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takeshi Murakami

IPC分类号： A61K31/505

CPC分类号： A61K31/505 ,  C07D239/47

摘要： The present invention is intended to provide a pharmaceutical product for inhibiting expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, the present invention is also intended to provide a preventive and/or therapeutic agent for various diseases based on inhibition of expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, and the present invention relates to an agent for inhibiting expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, and relates also to a preventive and/or therapeutic agent for various diseases based on the inhibition of the expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, the agent comprising a compound represented by Formula (I), its salt, or a solvate of any of them as an active ingredient: wherein the symbols are the same as those given in the description.

公开(公告)号：US08012989B2

公开(公告)日：2011-09-06

申请号：US12815905

申请日：2010-06-15

申请人： Tadaaki Ohgiya ,  Toru Miura ,  Ayumu Okuda ,  Toshiharu Arai ,  Koichi Yamazaki ,  Taro Aoki ,  Katsutoshi Miyosawa ,  Haruki Shibata ,  Kimiyuki Shibuya

发明人： Tadaaki Ohgiya ,  Toru Miura ,  Ayumu Okuda ,  Toshiharu Arai ,  Koichi Yamazaki ,  Taro Aoki ,  Katsutoshi Miyosawa ,  Haruki Shibata ,  Kimiyuki Shibuya

IPC分类号： A61K31/505

CPC分类号： C07D401/12 ,  C07D403/12 ,  C07D471/04

摘要： A compound represented by the following general formula (I), wherein R1, R2, R3, R4 and R5 represent hydrogen atom, a halogen atom, a lower alkyl group and the like, R6 represents an alkyl group, a cycloalkyl group and the like, R7 and R8 represent hydrogen atom, a lower alkyl group, a (lower cycloalkyl)(lower alkyl) group and the like, R9 represents hydrogen atom, a halogen atom, a lower alkoxy group and the like, R10 and R11 represent hydrogen atom, a lower alkyl group, a lower alkoxy group, a halo(lower alkyl) group and the like, and A represents a heterocyclic ring constituted by 6 to 10 atoms, which has potent inhibitory activity on cholesterol ester transfer protein (CETP).

摘要翻译： 由下列通式（I）表示的化合物，其中R 1，R 2，R 3，R 4和R 5表示氢原子，卤原子，低级烷基等，R 6表示烷基，环烷基等 ，R7和R8表示氢原子，低级烷基，（低级环烷基）（低级烷基）等，R9表示氢原子，卤素原子，低级烷氧基等，R10和R11表示氢原子 ，低级烷基，低级烷氧基，卤代（低级烷基）等，A表示6〜10个原子构成的杂环，对胆固醇酯转移蛋白（CETP）具有有效的抑制活性。

公开(公告)号：US07750150B2

公开(公告)日：2010-07-06

申请号：US10545200

申请日：2004-02-27

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda

IPC分类号： C07D243/00 ,  C07D241/04 ,  C07D295/00

CPC分类号： A61K31/496 ,  C07D401/12

摘要： This invention relates to a method for preparing an acid addition salt of a polyacidic basic compound, or a water adduct having basic site(s) stronger than pyridine. The method comprises reacting the polyacidic basic compound with an acid salt of pyridine.By the present invention, the number of moles of an added acid in the acid addition salt of the polyacidic basic compound can be readily changed to a number suited for the polyacidic basic compound as needed.

摘要翻译： 本发明涉及一种制备多酸碱性化合物的酸加成盐的方法或具有比吡啶强的碱性位点的水加合物。 该方法包括使多酸碱性化合物与吡啶的酸式盐反应。 通过本发明，可以根据需要容易地将多酸碱性化合物的酸加成盐中加入的酸的摩尔数变更为适合于多酸碱性化合物的数量。

公开(公告)号：US20130190540A1

公开(公告)日：2013-07-25

申请号：US13811651

申请日：2011-07-21

申请人： Taichi Kusakabe ,  Kennosuke Matsuda ,  Koichi Yamazaki ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

发明人： Taichi Kusakabe ,  Kennosuke Matsuda ,  Koichi Yamazaki ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

IPC分类号： C07C17/04

CPC分类号： C07C17/04 ,  C07B53/00 ,  C07B2200/07 ,  C07C17/16 ,  C07C22/08

摘要： A method for preparing optically active 1-bromo-1-[3,5-bis(trifluoromethyl)-phenyl]ethane having a high optical purity, which comprises the step of brominating optically active 1-[3,5-bis(trifluoromethyl)phenyl]ethanol by using, as a brominating agent, (a) a combination of a phosphorus halide and hydrogen bromide, (b) a combination of 1,2-dibromo-1,1,2,2-tetrachloroethane and an organic phosphorous compound represented by the general formula (I): P(R1)(R2)(R3) (in the formula, R1, R2, and R3 independently represent a C6-10 aryl group, a C6-10 aryloxy group, a C1-10 alkyl group, a C1-10 alkoxyl group, a C3-6 cycloalkyl group, or a C3-6 cycloalkoxy group), or (c) a combination of N-bromosuccinimide and a dialkyl sulfide.

摘要翻译： 一种具有高光学纯度的光学活性1-溴-1- [3,5-双（三氟甲基） - 苯基]乙烷的制备方法，其包括将光学活性的1- [3,5-双（三氟甲基） 苯基]乙醇通过使用溴化剂，（a）卤化磷和溴化氢的组合，（b）1,2-二溴-1,1,2,2-四氯乙烷与有机磷化合物的组合 由通式（I）表示：P（R1）（R2）（R3）（在式中，R1，R2和R3独立地表示C6-10芳基，C6-10芳氧基，C1-10 烷基，C1-10烷氧基，C3-6环烷基或C3-6环烷氧基），或（c）N-溴代琥珀酰亚胺与二烷基硫醚的组合。

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：US07223764B2

公开(公告)日：2007-05-29

申请号：US10883710

申请日：2004-07-06

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Toru Miura

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Toru Miura

IPC分类号： A61K31/496 ,  C07D213/69 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

CPC分类号： C07D401/12

摘要： The present invention is directed to a 2,4-bis(trifluoroethoxy)pyridine compound represented by formula (1): (wherein X1 represents a fluorine atom or a hydrogen atom) or a salt thereof, and to a drug containing the compound or the salt as an active ingredient. The compound has metabolic resistance in human liver microsome, good absorbability upon oral administration, and excellent ACAT inhibitory activity.

摘要翻译： 本发明涉及由式（1）表示的2,4-双（三氟乙氧基）吡啶化合物：其中X 1表示氟原子或氢原子）或其盐，以及 涉及含有化合物或盐作为活性成分的药物。 该化合物在人肝微粒体中具有代谢阻力，口服时具有良好的吸收性和优异的ACAT抑制活性。

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。