JPH10500111A - アテローム硬化症及び他の心・血管疾患及び炎症性疾患のための治療 - Google Patents
アテローム硬化症及び他の心・血管疾患及び炎症性疾患のための治療Info
- Publication number
- JPH10500111A JPH10500111A JP7529200A JP52920095A JPH10500111A JP H10500111 A JPH10500111 A JP H10500111A JP 7529200 A JP7529200 A JP 7529200A JP 52920095 A JP52920095 A JP 52920095A JP H10500111 A JPH10500111 A JP H10500111A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- vcam
- alkyl
- dithiocarbamate
- expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/21—Radicals derived from sulfur analogues of carbonic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/145—Amines having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. VCAM−1の発現を抑制するための方法であって、ポリ不飽和脂肪酸の 酸化を防止し又は最少にする物質の有効量を投与することを含む方法。 2. 酸化還元感受性遺伝子の発現を抑制するための方法であって、ポリ不飽和 脂肪酸の酸化を防止し又は最少にする物質の有効量を投与することを含む方法。 3. ポリ不飽和脂肪酸の酸化によって抑制されている遺伝子を活性化するため の方法であって、ポリ不飽和脂肪酸の酸化を防止し又は最少にする物質の有効量 を投与することを含む方法。 4. VCAM−1の発現を抑制するための方法であって、ポリ不飽和脂肪酸と 、VCAM−1の発現を媒介する蛋白質との間の相互作用を防止する物質の有効 量を投与することを含む方法。 5. 該ポリ不飽和酸が、酸化されたリノール酸(C18Δ9,12)、リノレン酸(C18 Δ6,9,12)、アラキドン酸(C20Δ5,8、11、14)及びエイコサトリエン酸(C20Δ8,11, 14 )よりなる群より選ばれるものである、請求項1乃至4のいずれかに記載の方 法。 6. 該酸化還元感受性遺伝子が、免疫応答の開始に関与するサイトカイン(例 えば、IL−1β)、損傷部位への炎症性細胞の移動を促進する化学誘導物質( 例えば、MCP−1)、増殖因子(例えば、IL−6及びトロンビン受容体)、 及び接着分子(例えば、VCAM−1及びE−セレクチン)を発現するものより なる群より選ばれるものである、請求項2又は3に記載の方法。 7. 該物質がピロリジンジチオカルバメート又はその薬剤学的に 許容しうる塩である、請求項1乃至4のいずれかに記載の方法。 8. 生体内においてVCAM−1によって媒介される疾病を予測又は評価する ための方法であって、組織中又は血液中の酸化されたポリ不飽和脂肪酸のレベル を定量することを含む方法。 9. 生体内において酸化還元感受性遺伝子によって媒介される疾病を予測又 は評価するための方法であって、組織中又は血液中の酸化されたポリ不飽和脂肪 酸のレベルを定量することを含む方法。 11. 生体内においてVCAM−1によって媒介される疾病を予測又は評価す るための方法であって、組織中又は血液中の酸化されたポリ不飽和脂肪酸のレベ ルについての代理マーカーを定量することを含む方法。 12. 生体内において酸化還元感受性遺伝子によって媒介される疾病を予測又 は評価するための方法であって、組織中又は血液中の酸化されたポリ不飽和脂肪 酸のレベルに関する代理マーカーを定量することを含む方法。 13. 該代理マーカーが循環中又は細胞表面のVCAM−1である、請求項1 1に記載の方法。 14. ポリ不飽和脂肪酸又はそれらの酸化されたものに対する宿主の血管内皮 細胞の感作の評価のための方法であって、PUFA又はox−PUFAによって 宿主をチャレンジしそして得られた細胞表面又は循環中のVCAM−1又は他の 代理マーカーの濃度を標準集団と比較することを含む方法。 15. VCAM−1によって媒介される疾病を治療する能力について化合物を スクリーニングする方法であって、ポリ不飽和脂肪酸 の酸化を阻害する該化合物の能力を評価することを含む方法。 16. VCAM−1によって媒介される疾病を治療する能力について化合物を スクリーニングする方法であって、蛋白質標的とのPUFA又はox−PUFA の相互作用を阻害する該化合物の能力を評価することを含む方法。 17. ヒトにおける心・血管疾病の治療のための方法であって、 式A−SC(S)−B〔式中、Aは、水素、薬剤学的に許容しうる陽イオン 、及び生理学的に切断可能な脱離基よりなる群より選はれるものであり、そして Bはアルキル、アルケニル、アルキニル、アルカリル、アラルキル、ハロアルキ ル、ハロアルケニル、ハロアルキニル、アリール、アルカリール、水素、C1-6 アルコキシ−C1-10アルキル、C1-6アルキルチオ−C1-10アルキル、NR2R3 、−(CHOH)nCH2OH、(ここにnは0、1、2、3、4、5、又は6で ある)、−(CH2)nCO2R1(アルキルアセチル、アルキルプロピオニル、及 びアルキルブチリルを含む。)、及びHOC1-6アルキル−よりなる群より選ば れるものである。〕のジチオカルバメートの有効量を投与することを含む方法。 18. Aが、水素又は、ナトリウム、カリウム、カルシウム、マグネシウム、 アルミニウム、亜鉛、ビスマス、バリウム、銅、コバルト、ニッケル、又はカド ミウムよりなる群より選ばれる薬剤学的に許容しうる陽イオンである、請求項1 7に記載の方法。 19. Aが塩形成性有機酸である、請求項17に記載の方法。 20. Aがコリン、酢酸、シュウ酸、酒石酸、コハク酸、リンゴ酸、アスコル ビン酸、安息香酸、タンニン酸、パモイン酸、アルギン酸、ポリグルタミン酸、 ナフタレンスルホン酸、ナフタレンジス ルホン酸、又はポリガラクツロン酸よりなる群より選ばれるものである、請求項 19に記載の方法。 21. Aが、アンモニア又は他の窒素原子を含む塩基から形成された陽イオン である、請求項17に記載の方法。 22. Aが、窒素原子を含むヘテロ環であるか、又は式NR4R5R6R7〔式中 、R4、R5、R6、及びR7は独立して水素、C1-6アルキル、ヒドロキシ(C1-6 )アルキル、アリールである。〕、N,N−ジベンジルエチレンジアミン、D− グルコサミン、テトラエチルアンモニウム、又はエチレンジアミンである、請求 項21に記載の方法。 23. Aが生理学的に切断可能な脱離基である、請求項17に記載の方法。 24. Aがアシル基である、請求項17に記載の方法。 25. BがNR2R3〔ここにR2及びR3は、アルキル、−(CHOH)n(C H2)nOH(ここにnは0、1、2、3、4、5、又は6である)、−(CH2 )nCO2R1、−(CH2)nCO2R4、HO(C1-6)アルキル−、アルケニル、 アルキル(CO2H)、アルケニル(CO2H)、アルキニル(CO2H)、又は アリールである。〕よりなる群より選ばれるものであるか、又は、R2及びR3は 一緒になって式−(CH2)n−(ここにmは3、4、5、又は6であり、そして R4は、アセチル、プロピオニル、及びブチリルを含むアリール、アルカリル、 又はアラルキルよりなる群より選ばれるものである。)の架橋を構成することが できるものである、請求項17に記載の方法。 26. Bはヘテロ環又はアルキルヘテロ環基である、請求項17 に記載の方法。 27. 該ヘテロ環が部分的に又は完全に水素添加されたものである、請求項2 6に記載の方法。 28. Bが、A−SC(S)−に直接に結合されているか又は2価の結合部分 を通じて結合されている薬学的に活性な化合物又は薬物の残基である、請求項1 7に記載の方法。 29. Bが、プロブコール、ニコチン酸、アスピリン、クマジン、バラパミル 、ジルチアゼム、ニフェジピン、カプトプリル、エナロプリル、プロパナロール 、テルブタロール、ラベタロール、イブプロフェン、インドメタシン、フェノプ ロフェン、メフェナム酸、フルフェナム酸、スリンダック、及び皮質ステロイド よりなる群より選ばれるものである、請求項17に記載の方法。 30. 該ジチオカルバメートが、構造AO2C−R9−NR10−C(S)SA( 式中、R9はBであるか又はアミノ酸の内部残基であり、R10は水素又は低級ア ルキルである)のアミノ酸誘導体である、請求項17に記載の方法。 31. Bが、1は2以上のジチオカルバメート基が直接に又は任意の適した結 合部分を介して取り付けられているポリマーである、請求項17に記載の方法。 32. 該ポリマーが生分解性である、請求項17に記載の方法。 33. 該ポリマーがペプチド、蛋白質、核蛋白質、リポ蛋白質、糖蛋白質、合 成の及び天然のポリペプチド及びポリアミノ酸、ポリオルトエステル、ポリ(α −ヒドロキシ酸)、ポリ酸無水物、多糖類、及びポリカプロラクトンよりなる群 より選ばれるものである、 請求項32に記載の方法。 34. B−C(S)S−が、ピロリジン−N−カルボジチオエートである、請 求項1に記載の方法。 35. 該心・血管疾病がアテローム硬化症である、請求項17に記載の方法。 36. 該心・血管疾病が血管形成術再狭窄である、請求項17に記載の方法。 37. 該心・血管疾病が冠状動脈疾病である、請求項17に記載の方法。 38. 該心・血管疾病が狭心症である、請求項17に記載の方法。 39. 該心臓血管疾病が小血管疾病である、請求項17に記載の方法。 40. 該ジチオカルバメートが0.5乃至500mg/kg体重の投与量で投 与されるものである、請求項17に記載の方法。 41. 該ジチオカルバメートが灌流バルーンカテーテルによって投与されるも のである、請求項17に記載の方法。 42. 該ジチオカルバメートが、脂質低下剤、血小板凝集阻害剤、抗トロンビ ン剤、カルシウムチャンネル遮断剤、アンギオテンシン変換酵素(ACE)阻害 剤、β遮断剤、非ステロイド性抗炎症剤、及び皮質ステロイドよりなる群より選 ばれる薬剤と組み合わせて投与されるものである、請求項17に記載の方法。 43. ヒト細胞中のVCAM−1発現の抑制のための方法であって、請求項1 7に記載のジチオカルバメートの有効量を投与することを含む方法。 44. VCAM−1によって媒介される炎症性皮膚疾病の治療のための方法で あって、請求項17に記載のジチオカルバメートの有効量を投与することを含む 方法。 45. VCAM−1によって媒介されるヒト内皮疾病の治療のための方法であ って、請求項17に記載のジチオカルバメートの有効量を投与することを含む方 法。 46. 該疾病が、喘息、乾癬、湿疹様皮膚炎、カポシ肉腫、多発性硬化症、及 び平滑筋細胞の増殖性疾病よりなる群より選ばれるものである、請求項45に記 載の方法。 47. 単核白血球によって媒介される炎症性状態の治療のための方法であって 、請求項17に記載のジチオカルバメートの有効量を投与することを含む方法。 48. 請求項17乃至34のいずれかに記載のジチオカルバメート。 49. 心・血管疾病の治療に有効な量の請求項17乃至34のいずれかに記載 の化合物を含む薬剤組成物。 50. VCAM−1によって媒介される疾病の治療に有効な量の請求項17乃 至34のいずれかに記載の化合物を含む薬剤組成物。
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- 1995-05-10 SK SK1364-96A patent/SK136496A3/sk unknown
- 1995-05-10 PL PL95342067A patent/PL184466B1/pl not_active IP Right Cessation
- 1995-05-10 MX MX9605450A patent/MX9605450A/es unknown
- 1995-05-10 CZ CZ963308A patent/CZ330896A3/cs unknown
- 1995-05-10 HU HU9603041A patent/HUT76728A/hu unknown
- 1995-05-10 EP EP95920396A patent/EP0759752A4/en not_active Withdrawn
- 1995-05-10 WO PCT/US1995/005880 patent/WO1995030415A1/en not_active Application Discontinuation
- 1995-05-10 GE GEAP19953488A patent/GEP20012409B/en unknown
- 1995-05-10 KR KR1019960706348A patent/KR100394157B1/ko not_active IP Right Cessation
- 1995-05-10 CN CN95194077A patent/CN1152869A/zh active Pending
- 1995-05-10 NZ NZ287214A patent/NZ287214A/en not_active IP Right Cessation
- 1995-05-10 PL PL95317193A patent/PL180874B1/pl not_active IP Right Cessation
- 1995-05-10 BR BR9507716A patent/BR9507716A/pt not_active Application Discontinuation
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1996
- 1996-11-08 NO NO964742A patent/NO964742L/no not_active Application Discontinuation
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2010001312A (ja) * | 1998-07-06 | 2010-01-07 | Eisai Corp Of North America | 医薬化合物及び組成物として有用なNAALADase阻害剤 |
JP2017142266A (ja) * | 2013-08-07 | 2017-08-17 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | 非典型溶血性尿毒症症候群のバイオマーカータンパク質 |
JP2021009162A (ja) * | 2013-08-07 | 2021-01-28 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | 非典型溶血性尿毒症症候群のバイオマーカータンパク質 |
JP2016538288A (ja) * | 2013-11-15 | 2016-12-08 | ディグニティ サイエンシス リミテッド | 多価不飽和ヒドロキシ脂肪酸の薬学的に許容される塩 |
US10544088B2 (en) | 2013-11-15 | 2020-01-28 | Ds Biopharma Limited | Pharmaceutically acceptable salts of fatty acids |
JP2020055825A (ja) * | 2013-11-15 | 2020-04-09 | ディーエス バイオファーマ リミテッド | 多価不飽和ヒドロキシ脂肪酸の薬学的に許容される塩 |
Also Published As
Publication number | Publication date |
---|---|
US5773231A (en) | 1998-06-30 |
NO964742D0 (no) | 1996-11-08 |
MX9605450A (es) | 1997-12-31 |
CN1152869A (zh) | 1997-06-25 |
PL184466B1 (pl) | 2002-11-29 |
CZ330896A3 (cs) | 1998-07-15 |
CA2189336A1 (en) | 1995-11-16 |
US5846959A (en) | 1998-12-08 |
GEP20012409B (en) | 2001-04-25 |
PL317193A1 (en) | 1997-03-17 |
SK136496A3 (en) | 1999-01-11 |
HUT76728A (en) | 1997-11-28 |
EP0759752A1 (en) | 1997-03-05 |
BR9507716A (pt) | 1997-09-23 |
US5811449A (en) | 1998-09-22 |
NO964742L (no) | 1996-11-08 |
PL180874B1 (pl) | 2001-04-30 |
JP3120091B2 (ja) | 2000-12-25 |
WO1995030415A1 (en) | 1995-11-16 |
KR100394157B1 (ko) | 2004-02-11 |
BG101030A (en) | 1997-09-30 |
HU9603041D0 (en) | 1997-01-28 |
US5750351A (en) | 1998-05-12 |
US5773209A (en) | 1998-06-30 |
US5807884A (en) | 1998-09-15 |
EP0759752A4 (en) | 2001-08-08 |
NZ287214A (en) | 2001-05-25 |
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