公开(公告)号：US20180042948A1

公开(公告)日：2018-02-15

申请号：US15555721

申请日：2016-03-04

Applicant: JAPAN SCIENCE AND TECHNOLOGY AGENCY

Inventor： Motomu KANAI ,  Yohei SOMA ,  Yusuke SHIMIZU ,  Atsuhiko TANIGUCHI ,  Kounosuke OISAKI ,  Yoichiro KUNINOBU

IPC: A61K31/69 ,  A61K31/4725 ,  C07F5/02 ,  C07D215/06 ,  C07D207/46 ,  C07D207/456 ,  A61K31/4025 ,  C07D401/14

CPC classification number: A61K31/69 ,  A61K31/4025 ,  A61K31/4725 ,  A61K41/00 ,  C07D207/44 ,  C07D207/456 ,  C07D207/46 ,  C07D215/06 ,  C07D401/14 ,  C07D455/04 ,  C07F5/02

Abstract: Provided are a compound which is useful as an in vivo applicable, amyloid-oxygenating catalyst selective for amyloid and applicable not only to an Aβ peptide but also to other amyloids and a drug containing the compound for preventing and/or treating amyloid-related-diseases.Disclosed is a boron-dipyrrin complex represented by the following formula (1) wherein X1 and X2 are the same or different and each represent a halogenoalkyl group or a halogen atom; R1 represents a hydrogen atom, an alkyl group, or a group represented by formula (b); R2 and R6 are the same or different and each represent a hydrogen atom or a halogen atom; R3, R4, R5, and R7 are the same or different and each represent a hydrogen atom, a halogen atom, or an alkyl group; R8 represents a hydrogen atom or —(CH2)l—(Y)m—(CH2)n—Z wherein Y represents —CO—, —CONH—, or a triazole ring, Z represents a carboxyl group, a sulfonic acid group, or a —CO-peptide residue, l and n each represent an integer of 1 to 6, and m represents 0 or 1; R9 and R10 are the same or different and each represent a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, an amino group, a nitro group, or a cyano group; and R8 and R10 together optionally form an alkylene group.

公开(公告)号：US20160297764A1

公开(公告)日：2016-10-13

申请号：US15100866

申请日：2014-12-09

Applicant: JAPAN SCIENCE AND TECHNOLOGY AGENCY

Inventor： Motomu KANAI ,  Yohei SOMA ,  Tadamasa ARAI ,  Takushi ARAYA

IPC: C07D213/81

CPC classification number: C07D213/81 ,  C07D239/30

Abstract: Provided is a novel compound which has an excellent Aβ aggregation inhibitory effect and is useful as a pharmaceutical. An amide compound represented by the formula (1) or a salt thereof, wherein Z represents CH or N; A and B are the same or different and each represents —CH2—, —O—, —S—, or —NH—; R1 and R2 are the same or different and each represents a branched alkyl group, a branched alkenyl group, an optionally substituted aromatic hydrocarbon group, an optionally substituted aralkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aromatic heterocyclic group; and R3 represents a branched alkyl group, a branched alkenyl group, an optionally substituted cycloalkyl group, or an optionally substituted aralkyl group.

Abstract translation: 提供具有优异的A 2聚集抑制作用的新型化合物，可用作药物。 由式（1）表示的酰胺化合物或其盐，其中Z表示CH或N; A和B相同或不同，各自表示-CH 2 - ， - O - ， - S-或-NH-。 R 1和R 2相同或不同，各自表示支链烷基，支链烯基，任选取代的芳族烃基，任选取代的芳烷基，任选取代的环烷基或任选取代的芳族杂环基; 并且R 3表示支链烷基，支链烯基，任选取代的环烷基或任选取代的芳烷基。

公开(公告)号：US20190100537A1

公开(公告)日：2019-04-04

申请号：US16087017

申请日：2017-03-21

Applicant: JAPAN SCIENCE AND TECHNOLOGY AGENCY

Inventor： Motomu KANAI ,  Yohei SOMA ,  Jizhi NI ,  Atsuhiko TANIGUCHI

IPC: C07F5/02 ,  A61P25/16 ,  A61P25/28 ,  A61P3/10

Abstract: Provided is a compound which is bioapplicable and amyloid-selective, and is useful as an amyloid oxygenation catalyst applicable not only to Aβ peptides but also to other amyloids, and a preventive/therapeutic drug for an amyloid-related disease using the same. A curcumin-boron complex represented by the following formula (1): wherein X1 and X2 are identical or different, and each represent a halogenoalkyl group or a halogen atom; X3 represents a bromine atom, an iodine atom, or a selenium atom; R1 and R2 are identical or different, and each represent a hydrogen atom or an optionally substituted alkyl group; R3 and R4 are identical or different, and each represent a hydrogen atom, a halogen atom, an alkoxy group, or an optionally substituted alkyl group, or R1 and R3 or R2 and R4 are optionally taken together to form an optionally substituted alkylene group or alkenylene group; R5 and R6 are identical or different, and each represent a hydrogen atom or an optionally substituted alkyl group; R7 and R8 are identical or different, and each represent a hydrogen atom, a halogen atom, an alkoxy group, or an optionally substituted alkyl group, or R5 and R7 or R6 and R8 are optionally taken together to form an optionally substituted alkylene group or alkenylene group; and m and n each represent an integer of 1 to 3, or a salt thereof.

公开(公告)号：US20160137706A1

公开(公告)日：2016-05-19

申请号：US14898409

申请日：2014-06-13

Applicant: JAPAN SCIENCE AND TECHNOLOGY AGENCY

Inventor： Motomu KANAI ,  Yohei SOMA ,  Atsuhiko TANIGUCHI ,  Daisuke SASAKI

IPC: C07K14/47 ,  C07K1/113

CPC classification number: C07K14/4711 ,  A61K38/00 ,  C07K1/113

Abstract: The invention provides an Aβ peptide aggregation inhibitor, an Aβ peptide toxicity reducing agent, and a preventive and/or therapeutic agent for Alzheimer's disease. The oxidized Aβ peptide in which one or more amino acid residues of Aβ peptide have been oxidized (excluding an oxidized Aβ peptide in which only Met has been oxidized).

Abstract translation: 本发明提供了一种A＆bgr; 肽聚集抑制剂，A＆bgr; 肽毒性还原剂，以及阿尔茨海默病的预防和/或治疗剂。 氧化的A＆bgr 肽，其中A和Bgr的一个或多个氨基酸残基; 肽已被氧化（不包括氧化的A＆bgr肽，其中仅Met被氧化）。

公开(公告)号：US20170197956A1

公开(公告)日：2017-07-13

申请号：US15326320

申请日：2015-07-15

Applicant: JAPAN SCIENCE AND TECHNOLOGY AGENCY

Inventor： Motomu KANAI ,  Yohei SOMA ,  Atsuhiko TANIGUCHI ,  Yusuke SHIMIZU

IPC: C07D455/04 ,  C07D417/04

CPC classification number: C07D455/04 ,  A61K31/4725 ,  A61K31/4745 ,  A61K38/00 ,  C07D417/04 ,  C07K7/06 ,  C07K14/47

Abstract: It is intended to provide: a compound useful as an amyloid oxidation catalyst which is applicable in vivo and is applicable not only to Aβ peptides but to other amyloids; and a prophylactic or therapeutic drug for an amyloid-related disease, comprising the same. The present invention provides a benzothiazole compound represented by the following formula (1) wherein X represents a halogen atom; R1 represents an optionally substituted hydrocarbon group; R2 represents a hydrogen atom or an optionally substituted hydrocarbon group; R3 and R4 are the same or different and each represent a hydrogen atom, an optionally substituted hydrocarbon group, an alkoxy group, a halogen atom, an amino group, a nitro group, or a cyano group; R2 and R4 optionally together form an alkylene group; and R5 represents an anion.

公开(公告)号：US20150299262A1

公开(公告)日：2015-10-22

申请号：US14648834

申请日：2013-10-18

Applicant: JAPAN SCIENCE AND TECHNOLOGY AGENCY

Inventor： Motomu KANAI ,  Yohei SOMA ,  Tadamasa ARAI ,  Daisuke SASAKI ,  Yuki KOBAYASHI

IPC: C07K7/64

CPC classification number: C07K7/64 ,  A61K38/00 ,  C07K7/06

Abstract: Provided is a novel compound which has excellent inhibitory activity for Aβ aggregation, and which is useful as a drug.A cyclic peptide or a salt thereof, the cyclic peptide having an amino acid sequence represented by the following formula (1): X-Leu-Val-Y1—Y2  (1) (wherein X is Lys, Arg, His, Ala, Gly, Ser, or Thr; and Y1 and Y2, which are identical to or different from each other, each represent a group represented by the following formula (2): (wherein Ar1 represents an aromatic hydrocarbon group or an aromatic heterocyclic group (the aromatic hydrocarbon group or the aromatic heterocyclic group may have 1 to 5 substituents selected from the group consisting of an alkyl group, a cycloalkyl group, a haloalkyl group, a halogen atom, a hydroxy group, an alkoxy group, an aromatic hydrocarbon group, an aromatic heterocyclic group, and an amino group); R1 represents a hydrogen atom, an alkyl group, a cycloalkyl group, a haloalkyl group, an aromatic hydrocarbon group, or an aromatic heterocyclic group (the aromatic hydrocarbon group or the aromatic heterocyclic group may have 1 to 5 substituents selected from the group consisting of an alkyl group, a cycloalkyl group, a haloalkyl group, a halogen atom, a hydroxy group, an alkoxy group, an aromatic hydrocarbon group, an aromatic heterocyclic group, and an amino group); and n is an integer from 0 to 2)), wherein the α-amino group at the amino terminus of the amino acid sequence is linked, via a peptide bond, to the carboxyl group at the carboxyl terminus of the amino acid sequence.

Abstract translation: 提供了对A＆Bgr具有优异抑制活性的新型化合物。 聚集，并且其作为药物是有用的。 环状肽或其盐具有下述式（1）表示的氨基酸序列的环状肽：X-Leu-Val-Y1-Y2（1）（式中，X为Lys，Arg，His，Ala，Gly ，Ser或Thr; Y1和Y2彼此相同或不同，分别表示由下式（2）表示的基团：（其中Ar1表示芳香族烃基或芳香族杂环基（芳香族） 烃基或芳族杂环基可以具有1〜5个选自烷基，环烷基，卤代烷基，卤素原子，羟基，烷氧基，芳香族烃基，芳香族烃基 杂环基和氨基）; R 1表示氢原子，烷基，环烷基，卤代烷基，芳香族烃基或芳香族杂环基（芳香族烃基或芳香族杂环基可以具有1个 至5个取代基 由烷基，环烷基，卤代烷基，卤素原子，羟基，烷氧基，芳香族烃基，芳香族杂环基和氨基组成的组构成）。 且n为0至2的整数）），其中氨基酸序列的氨基末端的α-氨基通过肽键连接到氨基酸序列的羧基末端的羧基。