JP4845332B2 - 抗炎症性及び免疫調整アミノ酸誘導体、その調製及び使用 - Google Patents
抗炎症性及び免疫調整アミノ酸誘導体、その調製及び使用 Download PDFInfo
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- JP4845332B2 JP4845332B2 JP2002591439A JP2002591439A JP4845332B2 JP 4845332 B2 JP4845332 B2 JP 4845332B2 JP 2002591439 A JP2002591439 A JP 2002591439A JP 2002591439 A JP2002591439 A JP 2002591439A JP 4845332 B2 JP4845332 B2 JP 4845332B2
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- 0 CCOCC(CCCCN)**C* Chemical compound CCOCC(CCCCN)**C* 0.000 description 3
- ROPCOGGYRSGBFR-UHFFFAOYSA-N CC1=C2C3=CCCCC23C1 Chemical compound CC1=C2C3=CCCCC23C1 ROPCOGGYRSGBFR-UHFFFAOYSA-N 0.000 description 1
- WNTCPVJEEXOWBN-KTKRTIGZSA-N CCCCCCCC/C=C\CCCCCCCCCCCCCC(NCCCCC(C(O)=O)N)=O Chemical compound CCCCCCCC/C=C\CCCCCCCCCCCCCC(NCCCCC(C(O)=O)N)=O WNTCPVJEEXOWBN-KTKRTIGZSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/49—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a carbon atom of an acyclic unsaturated carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
- C07C323/59—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton with acylated amino groups bound to the carbon skeleton
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
(a)ネルボン酸の反応性誘導体をNH 2 −R1−CH(Y)−COOR又はその塩と反応させる工程と、所望ならばその後、
(b)そのように調製した式(I)の化合物を、反応物質との反応によって式(I)の別の化合物に変換し、その誘導体を形成させる工程
とを含む。
Nε−(z−15−テトラコセノイル)−L−リジン:
(a)その誘導体(例えば、生体前駆体またはプロドラッグ)、溶媒和物、または塩を含む式(I)の新規の化合物;
(b)式(I)の別の化合物を調製するための化合物(I)のエステル化または脱エステル化、またはPaquet(前出)に記載の条件などの適切な条件下でのネルボン酸などの脂肪酸とアミノ酸との反応などによる式(I)の化合物の調製方法;
(c)無毒で有効量の式(I)の化合物または薬学的に許容可能なその塩および薬学的に許容可能なそのキャリアを含む薬学的処方物;
(d)このような処方物の調製方法;
(e)哺乳動物への無毒で有効な抗炎症量の式(I)の化合物の投与を含む、ヒトを含む哺乳動物の炎症の予防または治療の方法;
(f)哺乳動物への無毒で有効な免役調整量の式(I)の化合物の投与を含む、ヒトを含む哺乳動物の免役調整病態の予防または治療の方法;
(g)炎症の阻害及び/又は免役調整系の調整などの薬物または治療用の式(I)の化合物;
(h)炎症及び/又は免疫系の過剰刺激もしくは低刺激に関連する病態の治療もしくは予防などのための薬物の調製における式(I)の化合物の使用;
(i)別の化合物(I)の調製における式(IA)の化合物の使用。
ネルボノイルクロリド(26mmol、10.0g)を含むジクロロメタン溶液(50mL)を、N−ヒドロキシスクシニミド(26mmol、3.0g)およびトリエチルアミン(52mmol、5.2g)を含むジクロロメタン(200mL)の冷却溶液(0℃)に滴下した。添加後1時間撹拌して、反応を完了した。TLC分析(80:18:2ヘキサン−ジエチルエーテル−酢酸)により反応の完了が示された。反応混合物を、ヘキサンに注ぎ、濾過し、濃縮乾燥させた。エタノールからの再結晶により、白色固体としてスクシニミジルネルボネートを得た。
激しく撹拌したL−リジン一塩酸塩(13mmol、2.4g、市販)およびトリエチルアミン(39mmol、3.9g)の50mLの水−アセトン(1:1)溶液に、スクシニミジルネルボネート(13mmol、6.0g、実施例1Aのように調製)の一部を0.5時間添加した。添加中、より大量の水−アセトンートリエチルアミン(10:10:2)を添加して、高濃度で大量の生成物の沈殿を防止した。さらに1時間継続して撹拌した。次いで、混合物を、塩酸水溶液(1:1、v/v)で酸性化して、pHを4にし、冷却した。わずかな泡状の生成物は濾過によって分離され、水および加熱ジオキサンで洗浄して、表題化合物を得た。
2片のハードゼラチンカプセルに、50mgの有効成分、110mgのラクトース、32mgのタルク、および8mgのステアリン酸マグネシウムを充填して、カプセルを調製する。
容量15〜20mlのエアロゾル用コンテナ:有効成分(10mg)を、フレオン(Freon)(商標)などの推進剤(好ましくは、1,2−ジクロロエテンとジフルオロクロロメタンとの組み合わせ)中で0.2〜0.2%のポリソルベート(Polysorbate85)(商標)、オレイン酸又はその混合物などの潤滑剤と混合し、この混合物を吸入投与に適した適切なエアロゾル用コンテナに入れる。
容量15〜20mlのエアロゾル容器:有効成分(10mg)を、エタノール(6〜8ml)に溶解し、0.1〜2.0%のポリソルベート(Polysorbate)85(商標)などの潤滑剤を添加し、フレオン(Freon)(商標)などの推進剤(好ましくは、1,2−ジクロロエテンとジフルオロクロロメタンとの組み合わせ)の中に分散させ、この混合物を鼻腔または経口吸入投与に適した適切なエアロゾル容器に入れる。
プロピレングリコールおよび水中で1.5重量%の有効成分を撹拌して、注射用組成物を調製する。溶液を濾過滅菌する。
10重量部の有効成分(NA:NA及び/又はNA:GLA)と90重量部のオレイン酸エチルとを混合し、オレイン酸エチルの10%脂質希釈物を得て、経口組成物が調整される。
DehouckらによってJ Cont Rel、81〜91、1992に記載された方法に従って、実施例2の化合物の血液脳関門を介した輸送を研究するための実験が行われた。これらの結果は、5μm/lの濃度で使用した場合、化合物に毒性はないことを示している。
Claims (7)
- Rがエチルである請求項1に記載の化合物。
- R2はH、又はネルボン酸(24:1(n−9))、またはドコサヘキサエン酸(22:6(n−3))の残基(ここで、(n−x)中のxは前記脂肪酸の末端メチル基に対する第1の二重結合の位置を示す)である、請求項1又は請求項2に記載の化合物。
- (a)ネルボン酸の反応性誘導体をNH2−R1−CH(Y)−COORまたはその塩と反応させる工程と、所望ならばその後、
(b)そのように調製した式(I)の化合物を、反応物質との反応によって式(I)の別の化合物に変換し、その誘導体を形成させる工程
とを含む、前記請求項のいずれか1項に記載の化合物の調製方法。 - 前記式(I)の化合物を、塩基の存在下でのネルボン酸のスクシニミジル誘導体とNH2−R1−CH(Y)−COORとまたはその塩との反応によって調製する、請求項5に記載の方法。
- 前記反応(b)の条件が加水分解または更なるアミン基置換に適切である、請求項5又は請求項6のいずれかに記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0112324.9A GB0112324D0 (en) | 2001-05-21 | 2001-05-21 | Compounds |
GB0112324.9 | 2001-05-21 | ||
PCT/GB2002/002375 WO2002094764A1 (en) | 2001-05-21 | 2002-05-20 | Anti-inflammatory and immunomodulatory amino acid derivatives, their preparation and use |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2004528387A JP2004528387A (ja) | 2004-09-16 |
JP4845332B2 true JP4845332B2 (ja) | 2011-12-28 |
Family
ID=9914995
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002591439A Expired - Fee Related JP4845332B2 (ja) | 2001-05-21 | 2002-05-20 | 抗炎症性及び免疫調整アミノ酸誘導体、その調製及び使用 |
Country Status (9)
Country | Link |
---|---|
US (1) | US6956059B2 (ja) |
EP (2) | EP1389180A1 (ja) |
JP (1) | JP4845332B2 (ja) |
CN (1) | CN1514822A (ja) |
AU (1) | AU2002256799B2 (ja) |
CA (1) | CA2446944C (ja) |
GB (2) | GB0112324D0 (ja) |
NZ (1) | NZ529023A (ja) |
WO (1) | WO2002094764A1 (ja) |
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EP1618150B1 (en) * | 2003-04-24 | 2008-02-13 | National Research Council Of Canada | Low loss foam composition and cable having low loss foam layer |
AU2005209331A1 (en) * | 2004-01-30 | 2005-08-11 | Peplin Biolipids Pty Ltd | Therapeutic and carrier molecules |
US8852638B2 (en) | 2005-09-30 | 2014-10-07 | Durect Corporation | Sustained release small molecule drug formulation |
JP5599705B2 (ja) | 2007-05-18 | 2014-10-01 | デュレクト コーポレーション | 改良されたデポー製剤 |
ES2562878T3 (es) | 2007-05-25 | 2016-03-08 | Indivior Uk Limited | Formulaciones de liberación sostenida de compuestos de risperidona |
US9085527B2 (en) | 2008-07-08 | 2015-07-21 | Catabasis Pharmaceuticals, Inc. | Fatty acid acylated salicylates and their uses |
US20110172240A1 (en) * | 2010-01-08 | 2011-07-14 | Milne Jill C | Fatty acid fumarate derivatives and their uses |
AU2011230619C1 (en) | 2010-03-25 | 2016-06-23 | Oregon Health & Science University | CMV glycoproteins and recombinant vectors |
LT2691530T (lt) | 2011-06-10 | 2018-08-10 | Oregon Health & Science University | Cmv glikoproteinai ir rekombinantiniai vektoriai |
US20130189754A1 (en) | 2011-09-12 | 2013-07-25 | International Aids Vaccine Initiative | Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies |
US9402894B2 (en) | 2011-10-27 | 2016-08-02 | International Aids Vaccine Initiative | Viral particles derived from an enveloped virus |
CN104219964B (zh) | 2012-03-30 | 2016-09-21 | 奇华顿股份有限公司 | 作为食品加香化合物的n-酰基脯氨酸衍生物 |
KR102125587B1 (ko) | 2012-03-30 | 2020-06-23 | 지보당 에스아 | 식품 향미 화합물인 n-아실-아미노산 유도체, 이를 함유하는 분말 조성물 |
KR102045589B1 (ko) | 2012-03-30 | 2019-11-15 | 지보당 에스아 | 식품 향미 화합물로서의 n-아실-아미노산 유도체 |
EP2830439B1 (en) | 2012-03-30 | 2020-11-04 | Givaudan SA | N-acyl-gaba derivatives for the improvement of the flavour profile of edible compositions |
KR102045591B1 (ko) | 2012-03-30 | 2019-12-02 | 지보당 에스아 | 식품 향미 화합물로서의 감마 아미노-부티르산 및 베타 알라닌의 n-아실 유도체 |
CA2867329C (en) | 2012-03-30 | 2020-03-10 | Givaudan S.A. | N-acylated 1 - aminocycloalkyl carboxylic acids as food flavouring compounds |
SG11201405340XA (en) * | 2012-03-30 | 2014-10-30 | Givaudan Sa | N-acylated methionine derivatives as food flavouring compounds |
EP2679596B1 (en) | 2012-06-27 | 2017-04-12 | International Aids Vaccine Initiative | HIV-1 env glycoprotein variant |
CA2903769A1 (en) | 2013-03-11 | 2014-10-09 | Durect Corporation | Injectable controlled release composition comprising high viscosity liquid carrier |
US20140308352A1 (en) | 2013-03-11 | 2014-10-16 | Zogenix Inc. | Compositions and methods involving polymer, solvent, and high viscosity liquid carrier material |
RU2683651C2 (ru) * | 2013-06-18 | 2019-04-01 | Иван Дмитриевич Захаров | Лекарственное средство для лечения кератоконуса и других дегенеративных заболеваний роговицы и фармацевтические препараты на его основе |
US20150065381A1 (en) | 2013-09-05 | 2015-03-05 | International Aids Vaccine Initiative | Methods of identifying novel hiv-1 immunogens |
WO2015050537A1 (en) | 2013-10-02 | 2015-04-09 | Givaudan S.A. | Organic compounds |
EP3057445B1 (en) | 2013-10-02 | 2018-07-04 | Givaudan SA | Organic compounds having taste-modifying properties |
WO2015050535A1 (en) | 2013-10-02 | 2015-04-09 | Givaudan S.A. | Organic compounds |
WO2015050536A1 (en) | 2013-10-02 | 2015-04-09 | Givaudan S.A. | N-acylated 2-aminoisobutyric acid compounds and flavour compositions containing them |
EP3057444B1 (en) | 2013-10-02 | 2017-12-06 | Givaudan SA | Organic compounds having taste-modifying properties |
WO2015050538A1 (en) | 2013-10-02 | 2015-04-09 | Givaudan S.A. | Organic compounds |
CN105636459A (zh) | 2013-10-02 | 2016-06-01 | 奇华顿股份有限公司 | 有机化合物 |
GB201317424D0 (en) | 2013-10-02 | 2013-11-13 | Givaudan Sa | Improvements in or relating to organic compounds |
US10058604B2 (en) | 2013-10-07 | 2018-08-28 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
KR20160147960A (ko) | 2014-04-25 | 2016-12-23 | 아지노모토 가부시키가이샤 | 면역자극제 |
US10174292B2 (en) | 2015-03-20 | 2019-01-08 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
EP3072901A1 (en) | 2015-03-23 | 2016-09-28 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
US10385015B2 (en) * | 2015-09-30 | 2019-08-20 | Givaudan S.A. | N-acylated methionine sulfoxides as food flavouring compounds |
WO2017073797A1 (en) | 2015-10-28 | 2017-05-04 | Ajinomoto Co., Inc. | Immunostimulating agent |
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JPH02115036A (ja) * | 1988-10-21 | 1990-04-27 | Nippon Oil & Fats Co Ltd | リポソーム形成剤 |
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EP0455783B1 (en) * | 1989-11-30 | 1996-03-13 | CRODA INTERNATIONAL plc | Use of nervonic acid and long chain fatty acids for the treatment of demyelinating disorders |
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GB9416846D0 (en) * | 1994-08-19 | 1994-10-12 | Croda Int Plc | Lipid supplementation |
-
2001
- 2001-05-21 GB GBGB0112324.9A patent/GB0112324D0/en not_active Ceased
-
2002
- 2002-05-20 WO PCT/GB2002/002375 patent/WO2002094764A1/en active IP Right Grant
- 2002-05-20 EP EP02726315A patent/EP1389180A1/en not_active Ceased
- 2002-05-20 US US10/478,819 patent/US6956059B2/en not_active Expired - Fee Related
- 2002-05-20 JP JP2002591439A patent/JP4845332B2/ja not_active Expired - Fee Related
- 2002-05-20 NZ NZ529023A patent/NZ529023A/en not_active IP Right Cessation
- 2002-05-20 CN CNA028104404A patent/CN1514822A/zh active Pending
- 2002-05-20 AU AU2002256799A patent/AU2002256799B2/en not_active Ceased
- 2002-05-20 GB GB0211558A patent/GB2376685B/en not_active Expired - Fee Related
- 2002-05-20 CA CA002446944A patent/CA2446944C/en not_active Expired - Fee Related
- 2002-05-20 EP EP08075033A patent/EP1914223A1/en not_active Ceased
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JPH02124815A (ja) * | 1987-10-29 | 1990-05-14 | Takeda Chem Ind Ltd | 血管形成促進剤 |
JPH02115036A (ja) * | 1988-10-21 | 1990-04-27 | Nippon Oil & Fats Co Ltd | リポソーム形成剤 |
JPH0848660A (ja) * | 1994-05-02 | 1996-02-20 | Hoechst Ag | N− アシル− α− アミノ酸誘導体の製造方法 |
JP2003514886A (ja) * | 1999-11-24 | 2003-04-22 | クロダ・インターナショナル・パブリック・リミテッド・カンパニー | ネルボン酸誘導体、これらの調製、および使用 |
Also Published As
Publication number | Publication date |
---|---|
GB2376685A (en) | 2002-12-24 |
JP2004528387A (ja) | 2004-09-16 |
GB0112324D0 (en) | 2001-07-11 |
CN1514822A (zh) | 2004-07-21 |
NZ529023A (en) | 2004-06-25 |
EP1389180A1 (en) | 2004-02-18 |
AU2002256799B2 (en) | 2006-11-16 |
CA2446944C (en) | 2009-04-28 |
GB2376685B (en) | 2003-07-30 |
CA2446944A1 (en) | 2002-11-28 |
WO2002094764A1 (en) | 2002-11-28 |
US6956059B2 (en) | 2005-10-18 |
US20040242663A1 (en) | 2004-12-02 |
EP1914223A1 (en) | 2008-04-23 |
GB0211558D0 (en) | 2002-06-26 |
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