公开(公告)号：EP1357104A1

公开(公告)日：2003-10-29

申请号：EP01272512.3

申请日：2001-12-18

申请人： Research Foundation Itsuu Laboratory

发明人： KAGECHIKA, Hiroyuki

IPC分类号： C07C49/747

CPC分类号： C07D333/74 ,  C07C17/266 ,  C07C45/62 ,  C07C45/63 ,  C07C45/64 ,  C07C45/65 ,  C07C45/673 ,  C07C45/68 ,  C07C45/71 ,  C07C49/683 ,  C07C49/747 ,  C07C49/753 ,  C07C225/20 ,  C07C225/22 ,  C07C233/32 ,  C07C233/76 ,  C07C245/10 ,  C07C275/28 ,  C07C275/38 ,  C07C311/20 ,  C07C2601/18 ,  C07C2602/10 ,  C07D307/46 ,  C07D333/22 ,  C07C25/22 ,  C07C49/717

摘要： Tropolone derivatives represented by the formula (I), which have retinoid actions and are useful as active ingredients of medicaments [R 1 to R 4 represent hydrogen atom, an alkyl group, or an alkoxyl group; the ring represented by Ar represents an aryl ring or a heteroaryl ring; X represents a single bond, -N=N-,-CON(R 5 )-, -(C=C) n CON(R 6 )-, -N(R 7 )CON(R 8 )-, -SO 2 N(R 9 )-, -N(R 10 )- (R 5 to R 9 represent hydrogen atom or an alkyl group, n represents 1 to 3, R 10 represents hydrogen atom, an alkyl group, or an acyl group), an alkylene group, an aryldiyl group, or a heterocyclic diyl group; Y represents hydrogen atom, -OR 11 (R 11 represents hydrogen atom, an alkyl group, or an acyl group), -NHR 12 (R 12 represents hydrogen atom, an alkyl group, an acyl group, or amino group), or a halogen atom.

摘要翻译： 具有类视黄醇作用并且可用作药物活性成分的式（I）的托洛酮衍生物代表氢原子，烷基或烷氧基; 由Ar表示的环表示芳基环或杂芳基环; X表示单键-N = N - ， - CON（R 5） - ， - （C = C）nCON（R 6） - ， - N（R 7）CON（R 8） - ） - ， - SO 2 N（R 9） - ， - N（R 10） - （R 5至R 9）表示氢原子或烷基，n表示1至3，R 10 >表示氢原子，烷基或酰基），亚烷基，芳基二基或杂环二基; Y表示氢原子，-OR 11（R 11表示氢原子，烷基或酰基），-NHR 12（R 12表示氢原子，烷基，酰基） ，或氨基）或卤素原子。

公开(公告)号：EP1500401A1

公开(公告)日：2005-01-26

申请号：EP03717687.2

申请日：2003-04-22

申请人： Research Foundation Itsuu Laboratory

发明人： NAGAI, Ryozo ,  SHINDO, Takayuki ,  MANABE, Ichiro ,  SHUDO, Koichi ,  KAGECHIKA, Hiroyuki

IPC分类号： A61K45/00 ,  A61K31/27 ,  A61K31/695 ,  A61P9/00 ,  A61P9/10 ,  A61P9/14 ,  A61P43/00

CPC分类号： A61K31/27 ,  A61K31/695 ,  A61L31/16

摘要： A medicament for prophylactic and/or therapeutic treatment of a vascular disease such as vascular restenosis and/or reocclusion after percutaneous transluminal coronary angioplasty using an intravascular stent, which comprises as an active ingredient a substance selected from the group consisting of retinoids and agents for controlling actions of retinoids such as 4-[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid or a salt thereof, or 4-[[[3,5-bis-(trimethylsilyl)phenyl]carbonyl]amino]benzoic acid or a salt thereof, wherein said substance has substantially no antiproliferative action on vascular endothelial cells, but substantially has antiproliferative action on vascular smooth muscle cells.

摘要翻译： 一种用于在使用血管内支架的经皮腔内冠状动脉血管成形术之后进行血管疾病如血管再狭窄和/或再闭塞的预防和/或治疗性治疗药物，其包含选自维甲酸类和控制剂的活性成分 类维生素A 4,6,7,8-四氢-5,5,8,8-四甲基-2-萘基）氨基甲酰基苯甲酸或其盐或4-哒嗪-3,5-双（三甲基甲硅烷基） 苯基羰基氨基苯甲酸或其盐，其中所述物质对血管内皮细胞基本上没有抗增殖作用，但对血管平滑肌细胞基本具有抗增殖作用。

公开(公告)号：EP1612264A1

公开(公告)日：2006-01-04

申请号：EP04721319.4

申请日：2004-03-17

申请人： Research Foundation Itsuu Laboratory

发明人： ASASHIMA, Makoto ,  HAMAZAKI, Tatsuo ,  KAGECHIKA, Hiroyuki ,  SHUDO, Koichi

IPC分类号： C12N5/06

CPC分类号： C12N5/0062 ,  C12N2501/385 ,  C12N2501/999 ,  C12N2506/00

摘要： A method for forming an organ and/or tissue from undifferentiated cells derived from a vertebrate animal in vitro, which comprises the step of culturing the undifferentiated cells derived from a vertebrate animal in the presence of a retinoic acid X receptor ligand (e.g., a retinoic acid X receptor agonist or antagonist), and a method for forming a pancreas from undifferentiated cells derived from a vertebrate animal in vitro or a method for forming a tissue having morphology and function of a pancreas from undifferentiated cells derived from a vertebrate in vitro, which comprises the step of culturing the undifferentiated cells derived from a vertebrate animal in the presence of a retinoic acid receptor ligand, together with activin, that does not substantially bind to the retinoic acid receptor subtype γ.

摘要翻译： 一种由体外来源于脊椎动物的未分化细胞形成器官和/或组织的方法，该方法包括以下步骤：在视黄酸X受体配体（例如，视黄酸）存在下培养源自脊椎动物的未分化细胞 酸X受体激动剂或拮抗剂）以及由体外来源于脊椎动物的未分化细胞形成胰腺的方法，或体外来源于脊椎动物的未分化细胞形成具有胰腺形态和功能的组织的方法， 包括在视黄酸受体配体存在的情况下培养源自脊椎动物的未分化细胞以及基本上不与视黄酸受体亚型γ结合的活化素的步骤。

公开(公告)号：EP1314720A1

公开(公告)日：2003-05-28

申请号：EP01963406.2

申请日：2001-08-31

申请人： Toko Pharmaceutical Ind. Co. Ltd ,  Research Foundation Itsuu Laboratory

发明人： KAGECHIKA, Hiroyuki ,  NAGANO, Hiroo

IPC分类号： C07C233/65 ,  C07C231/24

CPC分类号： C07C233/65 ,  C07C231/24 ,  C07C2602/10 ,  C07C235/84

摘要： A method for preparing a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid having a single endothermic peak approximately at 233°C in differential scanning calorimetry, which comprises the step of recrystallizing a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid from a mixture of water and ethanol. The method enables selective preparation of type-II crystals which are stable against physical impact. The resulting crystals are free from highly toxic hexane as a residual solvent, and preferably used as an active ingredient of pharmaceuticals.

公开(公告)号：EP1314720B1

公开(公告)日：2010-09-29

申请号：EP01963406.2

申请日：2001-08-31

申请人： Toko Pharmaceutical Ind. Co. Ltd ,  Research Foundation Itsuu Laboratory

发明人： KAGECHIKA, Hiroyuki ,  NAGANO, Hiroo

IPC分类号： C07C233/65 ,  C07C231/24

CPC分类号： C07C233/65 ,  C07C231/24 ,  C07C2602/10 ,  C07C235/84

摘要： A process for producing crystals of 4-[(5,6,7,8-tetra- hydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid exhibiting a single endothermic peak near 233°C in differential scanning calorimetry, which comprises the step of recrystallizing crystals of 4-[(5,6,7,8-tetrahydro-5,5,8,8 -tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid from a water-ethanol mixture. This process enables selective production of type II crystals stable to physical impact, and the obtained crystals are free from highly toxic hexane as the residual solvent, thus being suitably usable as an active ingredient in medicines.

摘要翻译： 一种制备4-Ä（5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基）氨基甲酰基的重结晶的方法，其具有大约在233℃的单一吸热峰 扫描量热法，其包括从水和乙醇的混合物中重结晶4-Ä（5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基）氨基甲酰基的重氮的步骤 。 该方法能够选择性制备对物理冲击稳定的II型晶体。 所得结晶不含作为残留溶剂的高毒性己烷，优选用作药物的有效成分。

公开(公告)号：EP1733722A1

公开(公告)日：2006-12-20

申请号：EP05720323.4

申请日：2005-03-09

申请人： Research Foundation Itsuu Laboratory ,  R & R Inc.

发明人： SHUDO, Koichi ,  KAGECHIKA, Hiroyuki

IPC分类号： A61K31/192 ,  A61K31/695 ,  A61K45/00 ,  A61P25/16 ,  A61P25/28

CPC分类号： A61K31/192 ,  A61K31/695

摘要： A medicament for promoting memory consolidation, which comprises, as an active ingredient, a non-natural retinoid, preferably a retinoid having a basic skeleton comprising an aromatic ring bound with an aromatic carboxylic acid or tropolone by means of a bridging group, more preferably 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid or 4-[(3,5-bis-trimethylsilylphenyl)-carboxamido]benzoic acid.

摘要翻译： 一种促进记忆巩固的药物，其包含作为活性成分的非天然类视黄醇，优选具有包含芳香族羧酸或托酚酮与桥连基团结合的芳香环的基本骨架的类维生素A，更优选4 - [（5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基）氨基甲酰基]苯甲酸或4 - [（3,5-双 - 三甲基甲硅烷基苯基） - 氨基甲酰基]苯甲酸。