AU729423B2 - Antithrombotic organic nitrates - Google Patents
Antithrombotic organic nitrates Download PDFInfo
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- AU729423B2 AU729423B2 AU55519/98A AU5551998A AU729423B2 AU 729423 B2 AU729423 B2 AU 729423B2 AU 55519/98 A AU55519/98 A AU 55519/98A AU 5551998 A AU5551998 A AU 5551998A AU 729423 B2 AU729423 B2 AU 729423B2
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 229910004679 ONO2 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003257 anti-anginal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000005792 cardiovascular activity Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 125000002993 cycloalkylene group Chemical group 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- HZUMMZVMNQSPFF-UHFFFAOYSA-N nitro butaneperoxoate Chemical compound CCCC(=O)OO[N+]([O-])=O HZUMMZVMNQSPFF-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000000079 pharmacotherapeutic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C203/00—Esters of nitric or nitrous acid
- C07C203/02—Esters of nitric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Medical Uses (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT96MI002368A IT1295694B1 (it) | 1996-11-14 | 1996-11-14 | Nitrossi derivati per la preparazione di medicamenti ad attivita antitrombinica |
| ITMI96A002368 | 1996-11-14 | ||
| PCT/EP1997/006311 WO1998021193A1 (en) | 1996-11-14 | 1997-11-12 | Antithrombotic organic nitrates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU5551998A AU5551998A (en) | 1998-06-03 |
| AU729423B2 true AU729423B2 (en) | 2001-02-01 |
Family
ID=11375213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU55519/98A Ceased AU729423B2 (en) | 1996-11-14 | 1997-11-12 | Antithrombotic organic nitrates |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6242432B1 (enExample) |
| EP (1) | EP0941218B1 (enExample) |
| JP (1) | JP4264137B2 (enExample) |
| KR (1) | KR100504122B1 (enExample) |
| CN (1) | CN1094931C (enExample) |
| AT (1) | ATE226199T1 (enExample) |
| AU (1) | AU729423B2 (enExample) |
| BR (1) | BR9712959B1 (enExample) |
| CA (1) | CA2272063C (enExample) |
| DE (1) | DE69716461T2 (enExample) |
| DK (1) | DK0941218T3 (enExample) |
| ES (1) | ES2186013T3 (enExample) |
| HU (1) | HUP0000667A3 (enExample) |
| IL (1) | IL129768A (enExample) |
| IT (1) | IT1295694B1 (enExample) |
| PT (1) | PT941218E (enExample) |
| RU (1) | RU2190594C2 (enExample) |
| WO (1) | WO1998021193A1 (enExample) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9801398D0 (en) | 1998-01-22 | 1998-03-18 | Anggard Erik E | Chemical compounds |
| IT1301759B1 (it) * | 1998-06-19 | 2000-07-07 | Nicox Sa | Sali nitrati di farmaci antiipertensivi |
| IT1311923B1 (it) | 1999-04-13 | 2002-03-20 | Nicox Sa | Composti farmaceutici. |
| IE20000052A1 (en) * | 1999-04-29 | 2000-11-29 | Russinsky Ltd | Nitric acid salts of B-blockers |
| IT1314184B1 (it) * | 1999-08-12 | 2002-12-06 | Nicox Sa | Composizioni farmaceutiche per la terapia di condizioni di stressossidativo |
| AU7365900A (en) | 1999-09-08 | 2001-04-10 | Nitromed, Inc. | Methods of treating and preventing congestive heart failure with hydralazine compounds and isosorbide dinitrate or isosorbide mononitrate |
| US7708989B2 (en) * | 1999-10-29 | 2010-05-04 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| US7235237B2 (en) | 1999-10-29 | 2007-06-26 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| CA2386954C (en) | 1999-10-29 | 2011-12-13 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| US7537785B2 (en) * | 1999-10-29 | 2009-05-26 | Nitromed, Inc. | Composition for treating vascular diseases characterized by nitric oxide insufficiency |
| CA2393724A1 (en) * | 1999-12-23 | 2001-06-28 | Nitromed, Inc. | Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use |
| EP1967595A3 (en) | 2000-02-16 | 2008-12-03 | Illumina, Inc. | Parallel genotyping of multiple patient samples |
| CA2410632A1 (en) | 2000-06-22 | 2001-12-27 | David S. Garvey | Nitrosated and nitrosylated taxanes, compositions and methods of use |
| AU2001259399B2 (en) * | 2000-10-27 | 2006-08-17 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| EP1219306A1 (en) * | 2000-12-29 | 2002-07-03 | Nicox S.A. | Compositions comprising cyclodextrins and NO- releasing drugs |
| CA2446064A1 (en) | 2001-05-02 | 2002-11-07 | Nitromed, Inc. | Nitrosated and nitrosylated nebivolol and its metabolites, compositions and methods of use |
| GB0111872D0 (en) * | 2001-05-15 | 2001-07-04 | Northwick Park Inst For Medica | Therapeutic agents and methods |
| US20080026984A1 (en) * | 2002-02-04 | 2008-01-31 | Alfama - Investigacao E Desenvolvimento De Productos Farmaceuticos Lda | Methods for treating inflammatory disease by administering aldehydes and derivatives thereof |
| US7968605B2 (en) * | 2002-02-04 | 2011-06-28 | ALFAMA—Investigação e Desenvolvimento de Produtos Farmacêuticos, Lda. | Methods for treating inflammatory disease by administering aldehydes and derivatives thereof |
| EP2042181A1 (en) * | 2002-02-04 | 2009-04-01 | ALFAMA-Investigacao e Desenvolvimento de Produtos Farmaceuticos Lda. | Use of co-releasing compounds for the manufacture of a medicament for the treatment of inflammatory diseases |
| US7499806B2 (en) | 2002-02-14 | 2009-03-03 | Illumina, Inc. | Image processing in microsphere arrays |
| US7220749B2 (en) * | 2002-06-11 | 2007-05-22 | Nitromed, Inc. | Nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| US20060247216A1 (en) * | 2002-10-25 | 2006-11-02 | Haj-Yehia Abdullah I | Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments |
| GB2395432B (en) * | 2002-11-20 | 2005-09-14 | Northwick Park Inst For Medica | Therapeutic delivery of carbon monoxide to extracorporeal and isolated organs |
| AU2003283789A1 (en) * | 2002-11-22 | 2004-06-18 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Beta-blockers having antioxidant and nitric oxide-donor activity |
| AU2003286389A1 (en) * | 2002-11-29 | 2004-06-23 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Ace-inhibitors having antioxidant and nitricoxid-donor activity |
| US20070207217A1 (en) * | 2003-02-03 | 2007-09-06 | Alfama - Investigacao E Desenvolvimento De Productos Farmaceuticos Lda | Method for treating a mammal by administration of a compound having the ability to release CO |
| US7166638B2 (en) | 2003-05-27 | 2007-01-23 | Nicox S.A. | Statin derivatives |
| US7169805B2 (en) | 2003-05-28 | 2007-01-30 | Nicox S.A. | Captopril derivatives |
| PL379197A1 (pl) * | 2003-06-19 | 2006-07-24 | Nicox S.A. | Nitroksylowe pochodne enalaprilu i pokrewne związki jako inhibitory ACE do leczenia chorób sercowo-naczyniowych |
| CA2536173A1 (en) * | 2003-08-20 | 2005-03-03 | Nitromed, Inc. | Nitrosated and nitrosylated cardiovascular compounds, compositions and methods of use |
| ATE358478T1 (de) * | 2003-12-02 | 2007-04-15 | Nicox Sa | Nitrooxy-derivate von carvedilol und anderen betablockern als antihypertensiva |
| DE602004019579D1 (de) * | 2003-12-02 | 2009-04-02 | Nicox Sa | Nitrooxyderivate von blutdrucksenkenden arzneimitteln |
| GEP20094780B (en) | 2004-01-05 | 2009-09-25 | Nicox Sa | Prostaglandin nitrooxyderivatives |
| JP2008506716A (ja) * | 2004-07-16 | 2008-03-06 | ニトロメッド インコーポレーティッド | 心不全に関連する組成物および方法 |
| JP2008510755A (ja) * | 2004-08-25 | 2008-04-10 | アクテリオン ファーマシューティカルズ リミテッド | ビシクロノネン誘導体 |
| CA2576279A1 (en) * | 2004-11-08 | 2006-05-18 | Nitromed, Inc. | Nitrosated and nitrosylated compounds, compositions and methods for the treatment of ophthalmic disorders |
| CA2595579A1 (en) * | 2005-01-21 | 2006-07-27 | Nitromed, Inc. | Cardiovascular compounds comprising heterocyclic nitric oxide donor group compositions and methods of use |
| US20100028439A1 (en) * | 2005-05-23 | 2010-02-04 | Elan Pharma International Limited | Nanoparticulate stabilized anti-hypertensive compositions |
| AU2006253805A1 (en) * | 2005-05-27 | 2006-12-07 | Actelion Pharmaceuticals Ltd. | Novel piperidine carboxylic acid amide derivatives |
| EP1899295A2 (en) * | 2005-06-29 | 2008-03-19 | Pfizer, Inc. | Prostaglandin derivatives |
| JP2009514809A (ja) * | 2005-10-18 | 2009-04-09 | ニコックス エス エイ | レニン阻害剤のニトロ誘導体 |
| GB0601394D0 (en) | 2006-01-24 | 2006-03-01 | Hemocorm Ltd | Therapeutic delivery of carbon monoxide |
| RU2425032C2 (ru) | 2006-02-02 | 2011-07-27 | Актелион Фармасьютикалз Лтд | Вторичные амины в качестве ингибиторов ренина |
| AU2007217980A1 (en) * | 2006-02-17 | 2007-08-30 | Nitromed, Inc. | Methods using hydralazine compounds and isosorbide dinitrate or isosorbide mononitrate |
| WO2007102127A2 (en) * | 2006-03-08 | 2007-09-13 | Actelion Pharmaceuticals Ltd | New amines |
| JP2007275193A (ja) * | 2006-04-04 | 2007-10-25 | Fujifilm Corp | 光プローブおよび光断層画像化装置 |
| US20090306081A1 (en) * | 2006-05-16 | 2009-12-10 | Letts L Gordon | Solid Dosage Formulations of Hydralazine Compounds and Nitric Oxide Donor Compounds |
| RU2322972C1 (ru) * | 2006-09-12 | 2008-04-27 | Илья Николаевич Медведев | Способ профилактики тромбозов у больных артериальной гипертонией с метаболическим синдромом |
| TW200831079A (en) * | 2006-12-13 | 2008-08-01 | Merck & Co Inc | Angiotensin II receptor antagonists |
| FR2921365B1 (fr) * | 2007-09-21 | 2012-10-12 | Servier Lab | Nouveaux sels d'addition d'inhibiteurs d'enzyme de conversion de l'angiotensine a des acides donneurs de no, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP4790871B2 (ja) * | 2008-05-05 | 2011-10-12 | メルク フロスト カナダ リミテツド | レニン阻害剤としての３，４−置換ピペリジン誘導体 |
| WO2010116270A1 (en) | 2009-04-10 | 2010-10-14 | Pfizer Inc. | Ep2/4 agonists |
| WO2011160974A2 (en) | 2010-06-21 | 2011-12-29 | Nicox S.A. | Statin derivatives |
| US9163044B2 (en) | 2011-04-19 | 2015-10-20 | Alfama, Inc. | Carbon monoxide releasing molecules and uses thereof |
| EP2734235B1 (en) | 2011-07-21 | 2017-03-22 | Alfama, Inc. | Ruthenium carbon monoxide releasing molecules and uses thereof |
| CA2897571C (en) | 2013-01-21 | 2018-12-18 | Apparao Satyam | Nitric oxide releasing prodrugs of therapeutic agents containing at least one carboxylic acid group |
| WO2018087092A1 (en) | 2016-11-08 | 2018-05-17 | Bausch & Lomb Incorporated | Nitric oxide releasing prostaglandin derivatives for treating normal tension glaucoma |
| SMT202400527T1 (it) | 2019-07-01 | 2025-01-14 | Tonix Pharma Ltd | Anticorpi anti-cd154 e loro usi |
| EP4274587A1 (en) | 2021-01-06 | 2023-11-15 | Tonix Pharma Limited | Methods of inducing immune tolerance with modified anti-cd154 antibodies |
| WO2025248134A1 (en) | 2024-05-31 | 2025-12-04 | Tonix Pharma Limited | Treatment methods comprising administration of modified cd154 antibodies |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0637583A1 (en) * | 1993-07-30 | 1995-02-08 | Prodesfarma, S.A. | 1-Aryloxy-3-alkylamino-2-propanol nitrate esters, the use thereof and corresponding pharmaceutical composition |
| WO1995030641A1 (en) * | 1994-05-10 | 1995-11-16 | Nicox S.A. | Nitro compounds and their compositions having anti-inflammatory, analgesic and anti-thrombotic acitivities |
| AU2230897A (en) * | 1996-03-01 | 1997-09-16 | Sankyo Company Limited | Thiazolidine derivatives |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1256345B (it) | 1992-08-20 | 1995-12-01 | Esteri nitrici di derivati dell'acido 2-(2,6-di-alo-fenilammino) fenilacetico e procedimento per la loro preparazione | |
| IT1256450B (it) | 1992-11-26 | 1995-12-05 | Soldato Piero Del | Esteri nitrici con attivita' farmacologica e procedimento per la loro preparazione |
| SI0722434T1 (en) | 1993-10-06 | 1998-12-31 | Nicox S.A. | Nitric esters having anti-inflammatory and/or analgesic activity and process for their preparation |
-
1996
- 1996-11-14 IT IT96MI002368A patent/IT1295694B1/it active IP Right Grant
-
1997
- 1997-11-12 JP JP52217998A patent/JP4264137B2/ja not_active Expired - Fee Related
- 1997-11-12 EP EP97951890A patent/EP0941218B1/en not_active Expired - Lifetime
- 1997-11-12 AU AU55519/98A patent/AU729423B2/en not_active Ceased
- 1997-11-12 DK DK97951890T patent/DK0941218T3/da active
- 1997-11-12 IL IL12976897A patent/IL129768A/en not_active IP Right Cessation
- 1997-11-12 HU HU0000667A patent/HUP0000667A3/hu unknown
- 1997-11-12 CA CA002272063A patent/CA2272063C/en not_active Expired - Fee Related
- 1997-11-12 BR BRPI9712959-3A patent/BR9712959B1/pt not_active IP Right Cessation
- 1997-11-12 RU RU99112517/04A patent/RU2190594C2/ru not_active IP Right Cessation
- 1997-11-12 PT PT97951890T patent/PT941218E/pt unknown
- 1997-11-12 US US09/297,933 patent/US6242432B1/en not_active Expired - Fee Related
- 1997-11-12 KR KR10-1999-7004229A patent/KR100504122B1/ko not_active Expired - Fee Related
- 1997-11-12 AT AT97951890T patent/ATE226199T1/de active
- 1997-11-12 ES ES97951890T patent/ES2186013T3/es not_active Expired - Lifetime
- 1997-11-12 DE DE69716461T patent/DE69716461T2/de not_active Expired - Lifetime
- 1997-11-12 WO PCT/EP1997/006311 patent/WO1998021193A1/en not_active Ceased
- 1997-11-12 CN CN97181245A patent/CN1094931C/zh not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0637583A1 (en) * | 1993-07-30 | 1995-02-08 | Prodesfarma, S.A. | 1-Aryloxy-3-alkylamino-2-propanol nitrate esters, the use thereof and corresponding pharmaceutical composition |
| WO1995030641A1 (en) * | 1994-05-10 | 1995-11-16 | Nicox S.A. | Nitro compounds and their compositions having anti-inflammatory, analgesic and anti-thrombotic acitivities |
| AU2230897A (en) * | 1996-03-01 | 1997-09-16 | Sankyo Company Limited | Thiazolidine derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| DE69716461T2 (de) | 2003-06-26 |
| RU2190594C2 (ru) | 2002-10-10 |
| HUP0000667A2 (en) | 2000-07-28 |
| KR20000053251A (ko) | 2000-08-25 |
| IL129768A0 (en) | 2000-02-29 |
| WO1998021193A1 (en) | 1998-05-22 |
| KR100504122B1 (ko) | 2005-07-27 |
| ITMI962368A0 (it) | 1996-11-14 |
| DK0941218T3 (da) | 2003-02-17 |
| ES2186013T3 (es) | 2003-05-01 |
| PT941218E (pt) | 2003-03-31 |
| EP0941218A1 (en) | 1999-09-15 |
| JP2001507676A (ja) | 2001-06-12 |
| ATE226199T1 (de) | 2002-11-15 |
| CA2272063C (en) | 2008-05-27 |
| IT1295694B1 (it) | 1999-05-27 |
| HUP0000667A3 (en) | 2000-08-28 |
| BR9712959B1 (pt) | 2010-06-01 |
| CN1094931C (zh) | 2002-11-27 |
| AU5551998A (en) | 1998-06-03 |
| CA2272063A1 (en) | 1998-05-22 |
| ITMI962368A1 (it) | 1998-05-14 |
| IL129768A (en) | 2004-02-19 |
| BR9712959A (pt) | 2000-02-01 |
| CN1242768A (zh) | 2000-01-26 |
| JP4264137B2 (ja) | 2009-05-13 |
| DE69716461D1 (de) | 2002-11-21 |
| EP0941218B1 (en) | 2002-10-16 |
| US6242432B1 (en) | 2001-06-05 |
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