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NOVEL THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE

外国特許コード F160008797
整理番号 (S2015-0060-N0)
掲載日 2016年8月4日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2015JP081417
国際公開番号 WO 2016072522
国際出願日 平成27年11月6日(2015.11.6)
国際公開日 平成28年5月12日(2016.5.12)
優先権データ
  • 特願2014-226236 (2014.11.6) JP
  • 特願2015-196282 (2015.10.1) JP
発明の名称 (英語) NOVEL THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE
発明の概要(英語) The purpose of the present invention is to provide an agent for the prevention and/or treatment of Alzheimer's disease, the agent having a novel mechanism of action and reduced side effects. A polyphenol derivative having heightened liposolubility due to the introduction of at least one liposoluble group selected from the group consisting of linear saturated hydrocarbon groups, linear unsaturated hydrocarbon groups, cyclic saturated hydrocarbon groups, cyclic unsaturated hydrocarbon groups, aromatic hydrocarbon groups, liposoluble vitamin residues, and stearoyl residues exhibits an effect for potentiating the activity of neprilysin and is useful as an agent for the prevention and/or treatment of Alzheimer's disease.
特許請求の範囲(英語) [claim1]
1.  Containing a polyphenol derivative as an active ingredient, Alzheimer's disease prevention and / or therapeutic agent.
[2]
[claim2]
2.  Polyphenol derivative is lipophilic polyphenol derivative of claim 1, wherein the drug.
[3]
[claim3]
3.  Lipophilic polyphenol derivative is a lipid soluble catechin derivatives, according to claim 2 wherein the drug.
[4]
[claim4]
4.  Lipophilic catechin derivatives, represented by formula (the I) (-) - epigallocatechin -3-O-gallate derivative or (-) - lipophilic group is introduced into epicatechin -3-O-gallate derivative a compound, according to claim 3 wherein the drug. [Image] (wherein, n1 represents the number of hydroxyl groups bonded to the A ring, is 0 to 4 integer; n2 represents the number of hydroxyl groups bonded to the G ring is an integer of 0 ~ 5; n3 in n1 + n2 + n3 + n4 is 2 or more; represents the number of hydroxyl groups bonded to the B ring is an integer of 0 ~ 5 of 5; n4 represents the number of hydroxyl groups bonded to a ring C is 0 or 1 is there. )
[5]
[claim5]
5.  Lipophilic catechin derivatives, represented by Formula (II) (-) - epigallocatechin derivative or (-) - a compound lipophilic group is introduced into epicatechin derivatives, according to claim 3 wherein the drug. [Image] (wherein, m1 is 'indicates the number of hydroxyl groups bonded to the ring, an integer from 0 to 4; m2 is Bs' the A indicates the number of hydroxyl groups bonded to the ring, an integer from 0 to 5 ; m3 represents the number of hydroxyl groups bonded to the C 'ring, 0-2 integer; m1 + m2 + m3 is 2 or more. )
[6]
[claim6]
6.  Lipophilic groups, each of which may have a substituent, selected from the group consisting of linear hydrocarbon groups, cyclic hydrocarbon groups, aromatic hydrocarbon groups, fat-soluble vitamins residues and sterol residues the agent of claim 4 or 5.
[7]
[claim7]
7.  Lipophilic group is a good chain hydrocarbon group which may have a substituent group, the agent of claim 4 or 5.
[8]
[claim8]
8.  Lipophilic group is introduced directly by C-C bond in the A ring or A 'ring, the agent according to any one of claims 4-7.
[9]
[claim9]
9.  Do not use introduced into S- ester bond or O- ester bond lipophilic group, a drug according to any one of claims 4-7.
[10]
[claim10]
10.  Carbonyl groups are present at the 4-position of ring C or C 'ring, the agent according to any one of claims 4-9.
[11]
[claim11]
11.  The partition coefficient of lipophilic polyphenol derivative (log P) is, as a control (-) - When using epicatechin -3-O-gallate, is characterized in that its 1.8 times or more, according to claim 2, wherein drug.
[12]
[claim12]
12.  Polyphenol derivative is at least one selected from the following group of compounds according to claim 1, wherein the drug. [Image] [image]
[13]
[claim13]
13.  Polyphenol derivative is at least one selected from the following group of compounds according to claim 1, wherein the drug. [Image]
[14]
[claim14]
14.  Polyphenol derivatives, (i) and catechin or proanthocyanidins, (ii) the following formula [Image] (in the formula, R <1> represents a hydrocarbon group; R <2> represents a hydrogen or a hydrocarbon group; R <3> represents a hydrogen or a hydrocarbon group; R <4> represents a hydroxyl group, or R <3> and R <4> represents a keto group together) In catechin derivatives or proanthocyanidins derivative prepared by reacting a compound represented claim 1 wherein the drug.
[15]
[claim15]
15.  Polyphenol derivatives, and (i) catechin or proanthocyanidins, (ii) 2- hexenal, 2-nonenal, cinnamaldehyde, ferulic aldehyde, p- coumaric aldehyde, citral, citronellal, geranial, geraniol, farnesal, farnesol, 3,7 , 11,15- tetramethyl hexadecenal, phytol, 3-nonene-2 ​​and on or perillaldehyde, a catechin derivative or proanthocyanidins derivative prepared by reacting the addition of acid, according to claim 1, wherein the drug .
[16]
[claim16]
16.  Characterized by enhancing the neprilysin activity, agent according to any one of claims 1 to 15.
[17]
[claim17]
17.  Neprilysin enhanced activity is by promoting the manifestation of the cell surface of Neprilysin, agent of claim 16.
[claim18]
18.

Characterized by enhancing the α-secretase activity, the agents according to any one of claims 1 to 17.
[claim19]
19.

Characterized by inhibiting β-secretase activity, the agents according to any one of claims 1 to 18.
[20]
[claim20]
20.  Effect of enhancing neprilysin activity, characterized by having at least one effect selected from the group consisting of the effect of inhibiting the effect and β-secretase activity enhances the α-secretase activity, any one of claims 1 to 15 agents described in item 1.
[21]
[claim21]
21.  Containing a polyphenol derivative as an active ingredient, enhancer of Neprilysin activity and / or α-secretase activity.
[claim22]
22.

It has the effect of inhibiting β-secretase activity, agent of claim 21.
[23]
[claim23]
23.  Containing a polyphenol derivative as an active ingredient, an inhibitor of β-secretase activity.
[claim24]
24.

It has the effect of inhibiting the effect and / or β-secretase activity enhances the α-secretase activity, agent of claim 23.
[25]
[claim25]
25.  Polyphenol derivative is lipophilic polyphenol derivative, agent according to any one of claims 21 to 24.
[26]
[claim26]
26.  Lipophilic polyphenol derivative is a lipid soluble catechin derivatives, claim 25 agent according.
[27]
[claim27]
27.  Lipophilic catechin derivatives, represented by formula (the I) (-) - epigallocatechin -3-O-gallate derivative or (-) - lipophilic group is introduced into epicatechin -3-O-gallate derivative a compound, agent of claim 26. [Image] (wherein, n1 represents the number of hydroxyl groups bonded to the A ring, is 0 to 4 integer; n2 represents the number of hydroxyl groups bonded to the G ring is an integer of 0 ~ 5; n3 in n1 + n2 + n3 + n4 is 2 or more; represents the number of hydroxyl groups bonded to the B ring is an integer of 0 ~ 5 of 5; n4 represents the number of hydroxyl groups bonded to a ring C is 0 or 1 is there. )
[28]
[claim28]
28.  Lipophilic catechin derivatives, represented by Formula (II) (-) - epigallocatechin derivative or (-) - a compound lipophilic group is introduced into epicatechin derivatives, agents of claim 26. [Image] (wherein, m1 is 'indicates the number of hydroxyl groups bonded to the ring, an integer from 0 to 4; m2 is Bs' the A indicates the number of hydroxyl groups bonded to the ring, an integer from 0 to 5 ; m3 represents the number of hydroxyl groups bonded to the C 'ring, 0-2 integer; m1 + m2 + m3 is 2 or more. )
[29]
[claim29]
29.  Lipophilic groups, each of which may have a substituent, selected from the group consisting of linear hydrocarbon groups, cyclic hydrocarbon groups, aromatic hydrocarbon groups, fat-soluble vitamins residues and sterol residues , agent according to claim 27 or 28.
[30]
[claim30]
30.  Agent according to lipophilic groups have a substituent is also optionally chain hydrocarbon group, according to claim 27 or 28.
[31]
[claim31]
31.  Lipophilic group is introduced directly by C-C bond in the A ring or A 'ring, agent according to any one of claims 27-30.
[32]
[claim32]
32.  Do not use introduced into S- ester bond or O- ester bond lipophilic group, agent according to any one of claims 27-30.
[33]
[claim33]
33.  Carbonyl groups are present at the 4-position of ring C or C 'ring, agent according to any one of claims 27-32.
[34]
[claim34]
34.  The partition coefficient of lipophilic polyphenol derivative (log P) is, as a control (-) - When using epicatechin -3-O-gallate, is characterized in that its 1.8 times or more, according to claim 25, wherein agent.
[35]
[claim35]
35.  Polyphenol derivative is at least one selected from the following compound group, agent according to any one of claims 21 to 24. [Image] [image]
[36]
[claim36]
36.  Polyphenol derivative is at least one selected from the following compound group, agent according to any one of claims 21 to 24. [Image]
[37]
[claim37]
37.  Polyphenol derivatives, (i) and catechin or proanthocyanidins, (ii) the following formula [Image] (in the formula, R <1> represents a hydrocarbon group; R <2> represents a hydrogen or a hydrocarbon group; R <3> represents a hydrogen or a hydrocarbon group; R <4> represents a hydroxyl group, or R <3> and R <4> represents a keto group together) In catechin derivatives or proanthocyanidins derivative prepared by reacting a compound represented, agent according to any one of claims 21 to 24.
[38]
[claim38]
38.  Polyphenol derivatives, and (i) catechin or proanthocyanidins, (ii) 2- hexenal, 2-nonenal, cinnamaldehyde, ferulic aldehyde, p- coumaric aldehyde, citral, citronellal, geranial, geraniol, farnesal, farnesol, 3,7 , 11,15- tetramethyl hexadecenal, phytol, 3-nonene-2-one or a perillaldehyde, a catechin derivative or proanthocyanidins derivative prepared by reacting the addition of acid, according to claim 21 to 24 agent according to any one.1.  Containing a polyphenol derivative as an active ingredient, Alzheimer's disease prevention and / or therapeutic agent.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NAGASAKI UNIVERSITY
  • 発明者(英語)
  • IWATA NOBUHISA
  • SHIROTANI KEIRO
  • ASAI MASASHI
  • TANAKA TAKASHI
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
上記の特許・技術に関心のある方は、下記問い合わせ先にご相談下さい。

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