JP2008535871A - 器官又は組織における線維症を処置するための医薬の製造における5−メチル−1−(置換されたフェニル)−2−(1h)−ピリドン - Google Patents
器官又は組織における線維症を処置するための医薬の製造における5−メチル−1−(置換されたフェニル)−2−(1h)−ピリドン Download PDFInfo
- Publication number
- JP2008535871A JP2008535871A JP2008505716A JP2008505716A JP2008535871A JP 2008535871 A JP2008535871 A JP 2008535871A JP 2008505716 A JP2008505716 A JP 2008505716A JP 2008505716 A JP2008505716 A JP 2008505716A JP 2008535871 A JP2008535871 A JP 2008535871A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- pyridone
- fibrosis
- compound
- akf
- 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.)
- Pending
Links
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
を備えた合計で29個の化合物を公表したが、そこでは、Aは、芳香族の基である。これらの化合物は、良好な抗炎症及び鎮痛性の活性を有すると共に、尿酸及びブドウ糖の血清のレベルを低減することができる。一つの化合物、特に5−メチル−1−フェニル−2(1H)−ピリドンは、最良の活性及び低い毒性を有する。
1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン及びピルフェニドンによるマウスの糸球体間質の細胞の増殖の抑制
マウスの糸球体間質の細胞におけるAKF−PD及びPEDの効果
*p<0.05 対 対照;**p<0.01 対 対照;***p<0.001対 対照
+p<0.05 対 AKF−PD;++p<0.01 対 AKF−PD;+++p<0.001 対 AKF−PD
例2
−1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン及びピルフェニドンによるラットの心筋の繊維芽細胞の増殖の抑制
ラットの心筋の繊維芽細胞におけるAKF−PD及びPEDの効果
*p<0.05 対 対照;**p<0.01 対 対照;***p<0.001 対 対照
+p<0.05 対 AKF−PD;++p<0.01 対 AKF−PD;+++p<0.001 対 AKF−PD
例3
1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン及びピルフェニドンによる人間の星状細胞の増殖の抑制
細胞の増殖は、MTT分析によって測定された。10%の胎児の血清を備えたDMEMは、細胞の培養物の媒質として使用された。細胞は、懸濁液において調製され(1×105/ml)、且つ、懸濁液の100μLが、96個のウェルのプレートの各々のウェルへ移された。一度細胞が、プラスチックへ付着させられると、培養物は、血清の無い媒質に変化させられ、且つ、別の24時間の間に温置させられた。そして、血清の無い媒質は、吸引され、且つ、10%の血清の媒体における様々な濃度の1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン(AKD−PD)又はピルフェニドン(PFD)は、各々の濃度について5個の複製を備えた各々のウェルの中へ追加された。細胞は、12、24、又は48時間の後の薬物の処置においてMTT(ウェル当たり10μL)で染色された。4時間の温置の後に、MTTを備えた媒質は、各々のウェルから吸引された。一百μLのMTTの溶媒が、15分の間に各々のウェルへ追加され、且つ、そして、溶解させられたMTTは、570nmにおけるプレートの読取装置で測定された。
人間の星状細胞におけるAKF−PD及びPEDの効果
*p<0.05 対 対照; **p<0.01 対 対照; ***p<0.001 対 対照
+p<0.05 対 AKF−PD; ++p<0.01 対 AKF−PD; +++p<0.001 対 AKF−PD
例4
1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン及びピルフェニドンによるラットの肺の繊維芽細胞の増殖の抑制
ラットの肺の繊維芽細胞におけるAKF−PD及びPEDの効果
+p<0.05 対 AKF−PD; ++p<0.01 対 AKF−PD; +++p<0.001 対 AKF−PD
例5
1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン及びピルフェニドンによる人間の皮膚の傷を形成する繊維芽細胞の増殖の抑制
細胞の増殖は、MTT分析によって測定された。10%の胎児の血清を備えたDMEMは、細胞の培養物の媒質として使用された。細胞は、懸濁液において調製され(1×105/ml)、且つ、懸濁液の100μLが、96個のウェルのプレートの各々のウェルへ移された。一度細胞が、プラスチックへ付着させられると、培養物は、血清の無い媒質に変化させられ、且つ、別の24時間の間に温置させられた。そして、血清の無い媒質は、吸引され、且つ、10%の血清の媒体における様々な濃度の1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン(AKD−PD)又はピルフェニドン(PFD)は、各々の濃度について5個の複製を備えた各々のウェルの中へ追加された。細胞は、12、24、又は48時間の後の薬物の処置においてMTT(ウェル当たり10μL)で染色された。4時間の温置の後に、MTTを備えた媒質は、各々のウェルから吸引された。一百μLのMTTの溶媒が、15分の間に各々のウェルへ追加させられ、且つ、溶解させられたMTTは、570nmにおけるプレートの読取装置で測定された。
人間の皮膚の傷を形成する繊維芽細胞におけるAKF−PD及びPEDの効果
*p<0.05 対 対照;**p<0.01 対 対照;***p<0.001 対 対照
+p<0.05 対 AKF−PD;++p<0.01 対 AKF−PD;+++p<0.001 対 AKF−PD
例6
1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン及びピルフェニドンによる人間の腹膜の中皮の細胞の増殖の抑制
人間の腹膜の中皮の細胞においてAKF−PD及びPFDの効果
*p<0.05 対 対照; **p<0.01 対 対照; ***p<0.001 対 対照
+p<0.05 対 AKF−PD; ++p<0.01 対 AKF−PD; +++p<0.001 対 AKF−PD
例7
糸球体硬化症及び間質性の腎性の線維症における1−(3’−フルオロフェニル)−5−メチル−2−(1H)−ピリドン(AKF−PD)の効果
異なる処置の群からの組織病理学的なスコア
繊維化の病変の頻度及び重症度の比較
間質性の区画についての組織学的なスコアの比較
5−メチル−1−(3−フルオロフェニル)−2(1H)−ピリドンのLD50
Claims (10)
- n=1である場合には、Rは、F又はBr又はIであることができる;nが2であるとすれば、Rは、F又はCl又はBr又はI又は飽和の直鎖のアルキル基、又は飽和の直鎖のアルコキシ基、又は飽和の直鎖のハロゲン化されたアルキル基であることができると共に、R基についての相対的な位置は、オルト又はメタ又はパラであることができる、請求項1に記載の使用。
- 前記化合物、5−メチル−1−(置換されたフェニル)−2(1H)−ピリドン類(一般的な構造式I)は、後に続く特徴:
n=1,R=Brのとき、前記化合物は、1−(2−ブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(3−ブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(4−ブロモフェニル)−5−メチル−2−(1H)−ピリドンである:
n=1、R=Fのとき、前記化合物は、1−(2−フルオロフェニル)−5−メチル−2−(1H)−ピリドン、1−(3−フルオロフェニル)−5−メチル−2−(1H)−ピリドン、1−(4−フルオロフェニル)−5−メチル−2−(1H)−ピリドンである:
n=1、R=Iのとき、前記化合物は、1−(2−ヨードフェニル)−5−メチル−2−(1H)−ピリドン、1−(3−ヨードフェニル)−5−メチル−2−(1H)−ピリドン、1−(4−ヨードフェニル)−5−メチル−2−(1H)−ピリドンである:
n=2、R=F又はBr又はClのとき、前記化合物は、1−(2,3−ジブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,4−ジブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,5−ジブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,6−ジブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(3,4−ジブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(3,5−ジブロモフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,3−ジクロロフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,4−ジクロロフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,5−ジクロロフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,6−ジクロロフェニル)−5−メチル−2−(1H)−ピリドン、1−(3,5−ジクロロフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,3−ジフルオロフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,4−ジフルオロフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,5−ジフルオロフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,6−ジフルオロフェニル)−5−メチル−2−(1H)−ピリドン、1−(3,5−ジフルオロフェニル)−5−メチル−2−(1H)−ピリドンである:
n=1又は2、R=トリフルオロメチルのとき、前記化合物は、5−メチル−1−(2−トリフルオロメチルフェニル)−2−(1H)−ピリドン、5−メチル−1−(4−トリフルオロメチルフェニル)−2−(1H)−ピリドン、5−メチル−1−(2,3−ビス−トリフルオロメチルフェニル)−2−(1H)−ピリドン、5−メチル−1−(2,4−ビス−トリフルオロメチルフェニル)−2−(1H)−ピリドン、5−メチル−1−(2,5−ビス−トリフルオロメチルフェニル)−2−(1H)−ピリドン、5−メチル−1−(2,6−ビス−トリフルオロメチルフェニル)−2−(1H)−ピリドン、5−メチル−1−(3,4−ビス−トリフルオロメチルフェニル)−2−(1H)−ピリドン、及び5−メチル−1−(3,5−ビス−トリフルオロメチルフェニル)−2−(1H)−ピリドンである:
n=1又は2及びR=メチルのとき、前記化合物は、5−メチル−1−(2−メチルフェニル)−2−(1H)−ピリドン、5−メチル−1−(3−メチルフェニル)−2−(1H)−ピリドン、1−(2,3−ジメチルフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,4−ジメチルフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,5−ジメチルフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,6−ジメチルフェニル)−5−メチル−2−(1H)−ピリドン、1−(3,4−ジメチルフェニル)−5−メチル−2−(1H)−ピリドン、及び1−(3,5−ジメチルフェニル)−5−メチル−2−(1H)−ピリドンである:
n=1又は2、R=メトキシのとき、前記化合物は、5−メチル−1−(2−メトキシフェニル)−2−(1H)−ピリドン、5−メチル−1−(3−メトキシフェニル)−2−(1H)−ピリドン、1−(2,3−ジメトキシフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,4−ジメトキシフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,5−ジメトキシフェニル)−5−メチル−2−(1H)−ピリドン、1−(2,6−ジメトキシフェニル)−5−メチル−2−(1H)−ピリドン、1−(3,4−ジメトキシフェニル)−5−メチル−2−(1H)−ピリドン、及び1−(3,5−ジメトキシフェニル)−5−メチル−2−(1H)−ピリドンである:
を有する、請求項2に記載の使用。 - 好適な置換Rは、3の位置におけるフルオロである、請求項3に記載の使用。
- 前記飽和の直鎖のアルキル基又は前記飽和の分岐鎖のアルキル基は、1−4個の炭素の好適なものと共に、1−6個の炭素を有する、請求項1又は2に記載の使用。
- 前記線維症は、糸球体の硬化症、腎性の間質性の線維症、肝臓の線維症、肺の線維症、腓骨の線維症、心筋の線維症、及び皮膚の線維症、外科手術後の付着、良性の前立腺の肥大、筋骨格の線維症、強皮症、アルツハイマー病、線維化の血管の疾患、並びに緑内障を含む、請求項1乃至5のいずれかに記載の使用。
- 前記糸球体の硬化症は、糖尿病性の健康状態によって引き起こされる、請求項6に記載の使用。
- 前記腎性の間質性の線維症は、尿管の封鎖又は糖尿病のいずれかによるものである、請求項6に記載の使用。
- 前記肝臓の線維症は、住血吸虫の感染に由来するものである、請求項6に記載の使用。
- 前記化合物の投与は、経口的な、注射の、又は局所的な適用によるものであり;前記化合物を、適合性の製薬の担体及び/又は他の薬物と共に処方することができる、請求項1乃至9のいずれかに記載の使用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNA2005100314457A CN1846699A (zh) | 2005-04-13 | 2005-04-13 | 1-(取代苯基)-5-甲基-2-(1h) 吡啶酮(i)化合物用于制备抗除肾间质纤维化外其他器官纤维化或组织纤维化药物的应用 |
PCT/CN2006/000651 WO2006108354A1 (fr) | 2005-04-13 | 2006-04-11 | 5-méthyl-2-(1h)-pyridone substituée en 1 par un groupement phényle dans la fabrication de médicaments pour le traitement de la fibrose d'organes ou de tissus |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008535871A true JP2008535871A (ja) | 2008-09-04 |
JP2008535871A5 JP2008535871A5 (ja) | 2009-06-18 |
Family
ID=37076581
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008505716A Pending JP2008535871A (ja) | 2005-04-13 | 2006-04-11 | 器官又は組織における線維症を処置するための医薬の製造における5−メチル−1−(置換されたフェニル)−2−(1h)−ピリドン |
Country Status (10)
Country | Link |
---|---|
US (3) | US20090005424A9 (ja) |
EP (1) | EP1878428A4 (ja) |
JP (1) | JP2008535871A (ja) |
KR (1) | KR20080018857A (ja) |
CN (2) | CN1846699A (ja) |
AU (1) | AU2006233433A1 (ja) |
CA (1) | CA2603763A1 (ja) |
RU (1) | RU2007141892A (ja) |
TW (1) | TW200808315A (ja) |
WO (1) | WO2006108354A1 (ja) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8725326B2 (en) | 2006-03-20 | 2014-05-13 | General Electric Company | System and method for predicting a vehicle route using a route network database |
US8751073B2 (en) | 2006-03-20 | 2014-06-10 | General Electric Company | Method and apparatus for optimizing a train trip using signal information |
US8903573B2 (en) | 2006-03-20 | 2014-12-02 | General Electric Company | Method and computer software code for determining a mission plan for a powered system when a desired mission parameter appears unobtainable |
US8924049B2 (en) | 2003-01-06 | 2014-12-30 | General Electric Company | System and method for controlling movement of vehicles |
US9156477B2 (en) | 2006-03-20 | 2015-10-13 | General Electric Company | Control system and method for remotely isolating powered units in a vehicle system |
JP2016540800A (ja) * | 2013-12-19 | 2016-12-28 | サンシャイン・レイク・ファーマ・カンパニー・リミテッドSunshine Lake Pharma Co.,Ltd. | 窒素複素環誘導体およびその医薬品への応用 |
US9669851B2 (en) | 2012-11-21 | 2017-06-06 | General Electric Company | Route examination system and method |
US9733625B2 (en) | 2006-03-20 | 2017-08-15 | General Electric Company | Trip optimization system and method for a train |
US9834237B2 (en) | 2012-11-21 | 2017-12-05 | General Electric Company | Route examining system and method |
US10308265B2 (en) | 2006-03-20 | 2019-06-04 | Ge Global Sourcing Llc | Vehicle control system and method |
US10569792B2 (en) | 2006-03-20 | 2020-02-25 | General Electric Company | Vehicle control system and method |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7825133B2 (en) | 2003-11-14 | 2010-11-02 | Shanghai Genomics, Inc. | Derivatives of pyridone and the use of them |
CN1846699A (zh) * | 2005-04-13 | 2006-10-18 | 中南大学湘雅医院 | 1-(取代苯基)-5-甲基-2-(1h) 吡啶酮(i)化合物用于制备抗除肾间质纤维化外其他器官纤维化或组织纤维化药物的应用 |
DK1928454T3 (da) | 2005-05-10 | 2014-11-03 | Intermune Inc | Pyridonderivater til modulering af stress-aktiveret proteinkinasesystem |
US9689681B2 (en) | 2014-08-12 | 2017-06-27 | General Electric Company | System and method for vehicle operation |
CN101652138B (zh) * | 2007-09-19 | 2011-07-06 | 中南大学 | 1-取代芳基-2(1h)-吡啶酮化合物的新医药用途 |
CN101235013A (zh) | 2008-03-10 | 2008-08-06 | 广东东阳光药业有限公司 | 结晶型1-(3-氟苯基)-5-甲基-2-(1h)吡啶酮、其制备方法、及其组合物和应用 |
ES2567283T3 (es) | 2008-06-03 | 2016-04-21 | Intermune, Inc. | Compuestos y métodos para tratar trastornos inflamatorios y fibróticos |
CN101918364B (zh) * | 2008-10-21 | 2013-02-13 | 史跃年 | 用于治疗高蛋白尿的药物组合物 |
US7566729B1 (en) | 2008-11-10 | 2009-07-28 | Intermune, Inc. | Modifying pirfenidone treatment for patients with atypical liver function |
US7635707B1 (en) | 2008-11-10 | 2009-12-22 | Intermune, Inc. | Pirfenidone treatment for patients with atypical liver function |
US8016980B2 (en) | 2008-11-25 | 2011-09-13 | Dixie Consumer Products Llc | Paper products |
CN101921225B (zh) * | 2009-06-11 | 2013-04-03 | 北京凯得尔森生物技术有限公司 | 吡啡尼酮类化合物、其制备方法和应用 |
US7816383B1 (en) | 2009-12-04 | 2010-10-19 | Intermune, Inc. | Methods of administering pirfenidone therapy |
US8084475B2 (en) * | 2009-12-04 | 2011-12-27 | Intermune, Inc. | Pirfenidone therapy and inducers of cytochrome P450 |
US10105356B2 (en) | 2011-01-31 | 2018-10-23 | Avalyn Pharma Inc. | Aerosol pirfenidone and pyridone analog compounds and uses thereof |
EP4059499A1 (en) | 2011-01-31 | 2022-09-21 | Avalyn Pharma Inc. | Aerosol pirfenidone and pyridone analog compounds and uses thereof |
CA2872110C (en) * | 2012-07-18 | 2019-08-06 | Sunshine Lake Pharma Co., Ltd. | Nitrogenous heterocyclic derivatives and their application in drugs |
CA2819967C (en) | 2012-08-31 | 2016-03-22 | Intermune, Inc. | Use of pirfenidone concomitantly with ciprofloxacin |
AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
US9682716B2 (en) | 2012-11-21 | 2017-06-20 | General Electric Company | Route examining system and method |
WO2015106150A1 (en) | 2014-01-10 | 2015-07-16 | Genoa Pharmaceuticals Inc. | Aerosol pirfenidone and pyridone analog compounds and uses thereof |
ES2824108T3 (es) | 2014-03-12 | 2021-05-11 | Icahn School Med Mount Sinai | Método para identificar receptores de aloinjertos de riñón en riesgo de lesión crónica |
KR102373700B1 (ko) | 2014-04-02 | 2022-03-11 | 인터뮨, 인크. | 항섬유성 피리디논 |
EP3161165B1 (en) | 2014-06-26 | 2020-11-18 | Icahn School of Medicine at Mount Sinai | Method for diagnosing subclinical and clinical acute rejection by analysis of predictive gene sets, therapeutic agent for use in the treatment and kits for determining the expression |
US20170266168A1 (en) * | 2014-09-18 | 2017-09-21 | Rush University Medical Center | Methods for preventing or treating osteoarthritis |
DE102015217418A1 (de) | 2015-09-11 | 2017-03-16 | Mühlbauer Technology Gmbh | Radikalisch polymerisierbares Dentalmaterial |
EP3308765B1 (de) | 2016-10-17 | 2022-07-13 | Mühlbauer Technology GmbH | Radikalisch polymerisierbare verbindung |
US10851068B2 (en) | 2017-07-14 | 2020-12-01 | Sunshine Lake Pharma Co., Ltd. | Method for preparing pyrimidone compound |
JP7464279B2 (ja) | 2018-04-16 | 2024-04-09 | アイカーン スクール オブ メディスン アット マウント シナイ | レシピエント血液における移植前トランスクリプトームシグネチャーを使用した急性拒絶反応および腎臓同種異系移植喪失の予測のための方法およびキット |
CN113456636A (zh) * | 2021-07-09 | 2021-10-01 | 中南大学 | 一种氟非尼酮在制备急性肝损伤药物中的应用 |
CN113274389B (zh) * | 2021-07-09 | 2022-11-08 | 中南大学 | 氟非尼酮在制备治疗急性肺损伤药物中的应用 |
CN114716365B (zh) * | 2022-01-04 | 2024-03-01 | 大连理工大学 | 一类n-取代苯基-2-吡啶酮化合物或其可药用盐在治疗肺纤维化中的应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000051467A (ja) * | 1998-08-07 | 2000-02-22 | Takao:Kk | 弾球遊技機 |
EP1138329A2 (en) * | 1989-02-15 | 2001-10-04 | Yamauchi, Shitotomo | Composition containing 5-Methyl-1-phenyl-2-(1 H)-pyridone for reparation and prevention of fibrotic lesions |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4052509A (en) | 1972-12-18 | 1977-10-04 | Affiliated Medical Research, Inc. | Method for reducing serum uric acid levels |
US4042699A (en) | 1972-12-18 | 1977-08-16 | Affiliated Medical Research, Inc. | Method for reducing serum glucose levels |
CA1049411A (en) | 1972-12-18 | 1979-02-27 | Affiliated Medical Research | N-substituted pyridone and general method for preparing pyridones |
US3839346A (en) | 1972-12-18 | 1974-10-01 | Affiliated Med Res | N-substituted pyridone and general method for preparing pyridones |
US5716632A (en) * | 1989-11-22 | 1998-02-10 | Margolin; Solomon B. | Compositions and methods for reparation and prevention of fibrotic lesions |
US5310562A (en) * | 1989-11-22 | 1994-05-10 | Margolin Solomon B | Composition and method for reparation and prevention of fibrotic lesions |
US5518729A (en) | 1989-11-22 | 1996-05-21 | Margolin; Solomon B. | Compositions and methods for reparation and prevention of fibrotic lesions |
CN2114190U (zh) | 1992-01-09 | 1992-08-26 | 王刚 | 恒流一体化集成电源器件 |
US5716623A (en) * | 1994-12-07 | 1998-02-10 | Immunex Corporation | Isolated Herpesvirus saimiri proteins that bind MHC Class II molecules |
CN1218942C (zh) * | 2002-06-11 | 2005-09-14 | 中南大学湘雅医学院 | 抗纤维化吡啶酮化合物及其生产工艺方法 |
CN1846699A (zh) * | 2005-04-13 | 2006-10-18 | 中南大学湘雅医院 | 1-(取代苯基)-5-甲基-2-(1h) 吡啶酮(i)化合物用于制备抗除肾间质纤维化外其他器官纤维化或组织纤维化药物的应用 |
-
2005
- 2005-04-13 CN CNA2005100314457A patent/CN1846699A/zh active Pending
-
2006
- 2006-04-11 KR KR1020077018590A patent/KR20080018857A/ko not_active Application Discontinuation
- 2006-04-11 EP EP06722303A patent/EP1878428A4/en not_active Withdrawn
- 2006-04-11 CN CN2006800002161A patent/CN1953749B/zh active Active
- 2006-04-11 RU RU2007141892/15A patent/RU2007141892A/ru not_active Application Discontinuation
- 2006-04-11 CA CA002603763A patent/CA2603763A1/en not_active Abandoned
- 2006-04-11 JP JP2008505716A patent/JP2008535871A/ja active Pending
- 2006-04-11 WO PCT/CN2006/000651 patent/WO2006108354A1/zh active Application Filing
- 2006-04-11 AU AU2006233433A patent/AU2006233433A1/en not_active Abandoned
- 2006-08-04 TW TW095128659A patent/TW200808315A/zh unknown
-
2007
- 2007-05-01 US US11/742,664 patent/US20090005424A9/en not_active Abandoned
-
2008
- 2008-09-04 US US12/204,629 patent/US20080319027A1/en not_active Abandoned
-
2009
- 2009-06-25 US US12/491,506 patent/US20090258911A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1138329A2 (en) * | 1989-02-15 | 2001-10-04 | Yamauchi, Shitotomo | Composition containing 5-Methyl-1-phenyl-2-(1 H)-pyridone for reparation and prevention of fibrotic lesions |
JP2000051467A (ja) * | 1998-08-07 | 2000-02-22 | Takao:Kk | 弾球遊技機 |
Non-Patent Citations (1)
Title |
---|
JPN6012014338; J.Cent. South Uni. (Med.Sci.) Vol.29,No.2, 2004 * |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8924049B2 (en) | 2003-01-06 | 2014-12-30 | General Electric Company | System and method for controlling movement of vehicles |
US8725326B2 (en) | 2006-03-20 | 2014-05-13 | General Electric Company | System and method for predicting a vehicle route using a route network database |
US8751073B2 (en) | 2006-03-20 | 2014-06-10 | General Electric Company | Method and apparatus for optimizing a train trip using signal information |
US8903573B2 (en) | 2006-03-20 | 2014-12-02 | General Electric Company | Method and computer software code for determining a mission plan for a powered system when a desired mission parameter appears unobtainable |
US9156477B2 (en) | 2006-03-20 | 2015-10-13 | General Electric Company | Control system and method for remotely isolating powered units in a vehicle system |
US9733625B2 (en) | 2006-03-20 | 2017-08-15 | General Electric Company | Trip optimization system and method for a train |
US10308265B2 (en) | 2006-03-20 | 2019-06-04 | Ge Global Sourcing Llc | Vehicle control system and method |
US10569792B2 (en) | 2006-03-20 | 2020-02-25 | General Electric Company | Vehicle control system and method |
US9669851B2 (en) | 2012-11-21 | 2017-06-06 | General Electric Company | Route examination system and method |
US9834237B2 (en) | 2012-11-21 | 2017-12-05 | General Electric Company | Route examining system and method |
JP2016540800A (ja) * | 2013-12-19 | 2016-12-28 | サンシャイン・レイク・ファーマ・カンパニー・リミテッドSunshine Lake Pharma Co.,Ltd. | 窒素複素環誘導体およびその医薬品への応用 |
Also Published As
Publication number | Publication date |
---|---|
US20090258911A1 (en) | 2009-10-15 |
RU2007141892A (ru) | 2009-05-20 |
TW200808315A (en) | 2008-02-16 |
WO2006108354A1 (fr) | 2006-10-19 |
EP1878428A1 (en) | 2008-01-16 |
EP1878428A4 (en) | 2008-09-03 |
CN1846699A (zh) | 2006-10-18 |
US20080319027A1 (en) | 2008-12-25 |
CA2603763A1 (en) | 2006-10-19 |
AU2006233433A1 (en) | 2006-10-19 |
US20090005424A9 (en) | 2009-01-01 |
CN1953749B (zh) | 2010-04-14 |
KR20080018857A (ko) | 2008-02-28 |
CN1953749A (zh) | 2007-04-25 |
US20070203203A1 (en) | 2007-08-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2008535871A (ja) | 器官又は組織における線維症を処置するための医薬の製造における5−メチル−1−(置換されたフェニル)−2−(1h)−ピリドン | |
EP1364659B1 (en) | Remedies for urinary diseases comprising lpa receptor controlling agents | |
JP5820813B2 (ja) | インドール化合物を含む医薬組成物 | |
JP6557684B2 (ja) | 線維性疾患の治療に用いられるppar化合物 | |
JP7457360B2 (ja) | 線維症の処置 | |
KR20080027191A (ko) | 신규한 벤즈옥사졸 유도체, 이의 제조방법 및 이를포함하는 약학 조성물 | |
KR20140129030A (ko) | 캔디다증 및 아스퍼질러스 감염을 치료하기 위한 화합물 및 방법 | |
TW201026684A (en) | Phosphodiesterase type III (PDE III) inhibitors or Ca2+ -sensitizing agents for the treatment of hypertrophic cardiomyopathy | |
JP2008514636A (ja) | サイトカイン活性の低分子モジュレーター | |
EP3132803B1 (en) | Preventive or therapeutic agent for pain associated with herpes zoster in acute phase | |
Shao et al. | Stachydrine ameliorates the progression of intervertebral disc degeneration via the PI3K/Akt/NF-κB signaling pathway: in vitro and in vivo studies | |
JPH07500811A (ja) | アミノ置換ピリミジン、その誘導体及びその使用方法 | |
KR101199730B1 (ko) | 병리학적 맥락막 혈관신생과 관련된 질환을 치료하기 위한1,2,3-치환된 인돌리진 유도체의 용도 | |
TWI769325B (zh) | 糖尿病性腎病之預防藥及/或治療藥 | |
US20230190754A1 (en) | Therapeutic combinations for the treatment of Progressive Fibrosing interstitial lung diseases | |
US20080287509A1 (en) | Pharmaceutical Composition for the Treatment of Bone Fracture | |
JP2004534760A (ja) | 腎線維症の治療 | |
JP2022504184A (ja) | ブドウ膜黒色腫の治療のための併用療法 | |
JP7453724B2 (ja) | ベンズブロマロンを含む傷または瘢痕の予防または治療用薬学組成物 | |
KR20220046505A (ko) | 과민성 방광의 예방 또는 치료용 약학적 조성물 | |
JPH07145129A (ja) | β−ナフトキノン誘導体及びそれらの塩類の新規な用途 | |
JP4235000B2 (ja) | 糸球体疾患治療剤 | |
HUT72297A (en) | Pharmaceutical compositions for inhibiting the effects of amyloidogenic proteins containing benzotiophene derivatives and process for their preparation | |
WO2017216579A1 (en) | Autophagy inducer compounds | |
JP2004323414A (ja) | 14員環マクロライド化合物を利用した、血管平滑筋の増殖に起因する疾患治療剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090402 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090402 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120321 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120621 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120628 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120723 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120730 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120820 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120827 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130115 |