AP1127A - Substituted 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators. - Google Patents
Substituted 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators. Download PDFInfo
- Publication number
- AP1127A AP1127A APAP/P/1998/001407A AP9801407A AP1127A AP 1127 A AP1127 A AP 1127A AP 9801407 A AP9801407 A AP 9801407A AP 1127 A AP1127 A AP 1127A
- Authority
- AP
- ARIPO
- Prior art keywords
- lower alkyl
- bis
- hydroxyphenyl
- hydrogen
- alkyl
- Prior art date
Links
- 229910052751 metal Inorganic materials 0.000 title claims description 10
- 239000002184 metal Substances 0.000 title claims description 10
- 239000002738 chelating agent Substances 0.000 title abstract description 4
- KPKQWXGFEKRQQA-UHFFFAOYSA-N 3,5-diphenyl-1h-1,2,4-triazole Chemical class C1=CC=CC=C1C1=NNC(C=2C=CC=CC=2)=N1 KPKQWXGFEKRQQA-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 36
- 229910052742 iron Inorganic materials 0.000 claims abstract description 18
- 241001465754 Metazoa Species 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 229
- 150000003839 salts Chemical class 0.000 claims description 75
- 239000001257 hydrogen Substances 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 150000002431 hydrogen Chemical class 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- 125000003282 alkyl amino group Chemical group 0.000 claims description 24
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 18
- 150000003254 radicals Chemical class 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 150000002825 nitriles Chemical class 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 230000004962 physiological condition Effects 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 125000003435 aroyl group Chemical group 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- BOFQWVMAQOTZIW-UHFFFAOYSA-N deferasirox Chemical group C1=CC(C(=O)O)=CC=C1N1C(C=2C(=CC=CC=2)O)=NC(C=2C(=CC=CC=2)O)=N1 BOFQWVMAQOTZIW-UHFFFAOYSA-N 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 150000001450 anions Chemical group 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- NGJKKFWOJDDGJI-UHFFFAOYSA-N 2-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-N-[2-(2-hydroxyethoxy)ethyl]acetamide Chemical compound OCCOCCNC(=O)CN1N=C(C=2C(=CC=CC=2)O)N=C1C1=CC=CC=C1O NGJKKFWOJDDGJI-UHFFFAOYSA-N 0.000 claims description 2
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
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- OHUIBHVOJJTMNX-UHFFFAOYSA-N pyridin-2-ylmethylhydrazine;hydrochloride Chemical compound Cl.NNCC1=CC=CC=N1 OHUIBHVOJJTMNX-UHFFFAOYSA-N 0.000 description 1
- MNRWHUKMYOKCMQ-UHFFFAOYSA-N pyridin-4-ylmethylhydrazine;hydrochloride Chemical compound Cl.NNCC1=CC=NC=C1 MNRWHUKMYOKCMQ-UHFFFAOYSA-N 0.000 description 1
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- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/04—Chelating agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH159396 | 1996-06-25 | ||
| PCT/EP1997/003315 WO1997049395A1 (en) | 1996-06-25 | 1997-06-24 | Substituted 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9801407A0 AP9801407A0 (en) | 1998-12-31 |
| AP1127A true AP1127A (en) | 2002-12-06 |
Family
ID=4214048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1998/001407A AP1127A (en) | 1996-06-25 | 1997-06-24 | Substituted 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators. |
Country Status (36)
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| US6677487B2 (en) | 2001-08-30 | 2004-01-13 | Pharmacia Corporation | α-haloenamine reagents |
| GB0126618D0 (en) * | 2001-11-06 | 2002-01-02 | Novartis Ag | Organic compounds |
| ES2192494B1 (es) * | 2002-03-27 | 2005-02-16 | Consejo Superior De Investigaciones Cientificas | Derivados de 1,2,4-triazol con propiedades cannabinoides. |
| US8829198B2 (en) | 2007-10-31 | 2014-09-09 | Proteotech Inc | Compounds, compositions and methods for the treatment of beta-amyloid diseases and synucleinopathies |
| GB0223978D0 (en) * | 2002-10-15 | 2002-11-20 | Novartis Ag | Organic compound |
| AR044503A1 (es) * | 2003-03-18 | 2005-09-14 | Merck & Co Inc | Triazoles sustituidos con biarilo como bloqueantes del canal de sodio |
| US20050008699A1 (en) * | 2003-07-11 | 2005-01-13 | Fred Wehling | Effervescent glucosamine composition |
| BRPI0416319A (pt) * | 2003-11-10 | 2007-01-09 | Merck & Co Inc | composto, composição farmacêutica, métodos de tratamento ou prevenção da dor, das sìndromes, e de doença, e, métodos de administrar anestesia local, e para a neuroproteção sob condições isquêmicas |
| RU2006125741A (ru) * | 2003-12-19 | 2008-01-27 | Новартис АГ (CH) | Комбинация (а) n-{5-[4-(4-метилпиперазинометил)бензоиламило]-2-метилфенил}-4-(3-пиридил)-2-пиримидинамина и (б) по меньшей мере одного ингибитора гипузинации и ее применение |
| GB0408078D0 (en) * | 2004-04-08 | 2004-05-12 | Novartis Ag | Organic compounds |
| CA2568134A1 (en) * | 2004-05-24 | 2005-12-08 | New York University | Method of treating or preventing pathologic effects of acute increases in hyperglycemia and/or acute increases of free fatty acid flux |
| US9737511B2 (en) * | 2004-05-24 | 2017-08-22 | Geoffrey C. GURTNER | Method of treating or preventing pathologic effects of acute increases in hyperglycemia and/or acute increases of free fatty acid flux |
| KR101325424B1 (ko) * | 2005-01-28 | 2013-11-04 | 노파르티스 아게 | Ｔｉｅ-2 키나제 활성의 조절에 반응하는 질환의 치료를위한 피리미딜아미노벤즈아미드의 용도 |
| JP2008530043A (ja) * | 2005-02-10 | 2008-08-07 | ノバルティス アクチエンゲゼルシャフト | 薬剤処分の改善法 |
| EP1893198A2 (en) * | 2005-05-31 | 2008-03-05 | Novartis AG | Treatment of liver diseases in which iron plays a role in pathogenesis |
| NZ567155A (en) * | 2005-10-19 | 2010-06-25 | Novartis Ag | Dispersible tablets comprising deferasirox |
| JP5322651B2 (ja) * | 2005-11-01 | 2013-10-23 | ノバルティス アーゲー | シンチグラフィー法 |
| PL1988083T3 (pl) * | 2006-02-03 | 2014-08-29 | Taisho Pharmaceutical Co Ltd | Pochodna triazolowa |
| BRPI0711385A2 (pt) * | 2006-05-09 | 2011-11-08 | Novartis Ag | combinação compreendendo um quelante de ferro e um agente anti-neoplástico e seu uso |
| WO2008005624A2 (en) | 2006-05-23 | 2008-01-10 | Novartis Ag | Method of treatment of hereditary hemochromatosis |
| CL2007002026A1 (es) | 2006-07-13 | 2008-06-06 | Los Angeles Biomed Res Inst | Composicion que comprende al menos un compuesto quelante de hierro y al menos un agente antifungico; y metodo para el tratamiento o prevencion de una condicion fungica. |
| RU2009107487A (ru) * | 2006-08-04 | 2010-09-10 | Новартис АГ (CH) | Лечение эндокринной дисфункции с использованием комплексонов железа |
| RU2339625C2 (ru) * | 2006-11-02 | 2008-11-27 | Российский химико-технологический университет (РХТУ им. Д.И. Менделеева) | ЗАМЕЩЕННЫЕ N-[ω-АЗОЛ-1-ИЛ)АЛКИЛ]БЕНЗОЛСУЛЬФАМИДЫ В КАЧЕСТВЕ СРЕДСТВ С АНТИАГРЕГАЦИОННОЙ АКТИВНОСТЬЮ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ |
| KR20090085081A (ko) | 2006-11-29 | 2009-08-06 | 노파르티스 아게 | 데페라시록스 (ｉｃｌ６７０ａ)의 다형체 형태 |
| EP1927591A1 (en) * | 2006-11-29 | 2008-06-04 | Novartis AG | Polymorphic Forms of Deferasirox (ICL670) |
| WO2008094617A2 (en) * | 2007-01-29 | 2008-08-07 | Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság | Crystalline forms of deferasirox |
| BRPI0811585A2 (pt) * | 2007-05-14 | 2014-12-09 | Novartis Ag | Uso de quelante de ferro para o tratamento de infarto do miocárdio |
| EP1994930A1 (en) | 2007-05-22 | 2008-11-26 | Novartis AG | Triazol compounds for treating biofilm formation |
| WO2009016359A1 (en) * | 2007-07-27 | 2009-02-05 | Pliva Hrvatska D.O.O. | New forms of deferasirox |
| US20090082412A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched deferasirox |
| WO2009067557A1 (en) | 2007-11-19 | 2009-05-28 | Teva Pharmaceutical Industries Ltd. | Deferasirox pharmaceutical compositions |
| CZ301873B6 (cs) * | 2008-01-30 | 2010-07-14 | Farmak, A. S. | Zpusob prípravy kyseliny 4-[3,5-bis(2-hydroxyfenyl)-[1,2,4]triazol-1-yl]benzoové |
| WO2009106824A2 (en) * | 2008-02-25 | 2009-09-03 | Cipla Limited | Pharmaceutical formulations |
| WO2009111611A2 (en) | 2008-03-05 | 2009-09-11 | Proteotech Inc. | Compounds, compositions and methods for the treatment of islet amyloid polypeptide (iapp) accumulation in diabetes |
| US20110097413A1 (en) * | 2008-04-21 | 2011-04-28 | Actavis Group Ptc Ehf | Solid state forms of deferasirox salts and process for the preparation thereof |
| WO2009147529A1 (en) * | 2008-06-02 | 2009-12-10 | Actavis Group Ptc Ehf | Substantially pure deferasirox and processes for the preparation thereof |
| WO2010032489A1 (ja) | 2008-09-22 | 2010-03-25 | 国立大学法人旭川医科大学 | 鉄キレート剤及びその製造方法、並びに鉄イオンの定量・捕捉方法 |
| US10098857B2 (en) | 2008-10-10 | 2018-10-16 | The Board Of Trustees Of The Leland Stanford Junior University | Topical and transdermal delivery of HIF-1 modulators to prevent and treat chronic wounds |
| WO2010092419A1 (en) | 2009-02-12 | 2010-08-19 | Assistance Publique - Hopitaux De Paris | Combined treatment of multiple sclerosis |
| JP2012520878A (ja) | 2009-03-19 | 2012-09-10 | ロサンゼルス ビオメドイカル リサーチ インストイトウテ アト ハルボル‐ユーシーエルエー メドイカル センテル | ムコール菌症、及びその他の真菌疾患の治療のためのワクチン組成物、及び方法 |
| IT1398770B1 (it) * | 2009-07-22 | 2013-03-18 | Bellacchio | Oligonucleotidi attivabili mediante l'appaiamento con sequenze di acidi nucleici e loro uso |
| WO2011021218A2 (en) * | 2009-08-12 | 2011-02-24 | Msn Laboratories Limited | Process for the preparation of 4-[3,5-bis(2-hydroxyphenyl)-1h-1,2,4-triazol-1-yl]-benzoic acid and its amine salts |
| CN102638985A (zh) | 2009-12-07 | 2012-08-15 | Mapi医药公司 | 地拉罗司的制备方法和地拉罗司多晶型物 |
| KR20130041144A (ko) | 2010-07-08 | 2013-04-24 | 라티오팜 게엠베하 | 데페라시록스의 경구투여용 제제 |
| EP2632907B1 (en) * | 2010-08-25 | 2015-10-14 | Davuluri, Ramamohan Rao | Process for preparing 2-(2-hydroxyphenyl)-benz[1,3]oxazin-4-one and its use for preparing deferasirox |
| AU2011309872B2 (en) * | 2010-10-01 | 2014-09-04 | Cipla Limited | Pharmaceutical composition comprising deferasirox |
| EP2643306B1 (en) * | 2010-11-24 | 2015-09-23 | Alembic Pharmaceuticals Limited | Process for the preparation of deferasirox |
| JP5900968B2 (ja) | 2011-01-14 | 2016-04-06 | 株式会社ダステック | 高分子鉄キレート剤 |
| US20140276107A1 (en) | 2011-10-14 | 2014-09-18 | Photocure Asa | Photodynamic diagnosis |
| US20140316534A1 (en) | 2011-10-14 | 2014-10-23 | Photocure Asa | Stent |
| US8822464B2 (en) | 2011-11-28 | 2014-09-02 | Boehringer Ingelheim International Gmbh | N-aryl-piperazine derivatives and their use as positive allosteric modulators of mGluR5 receptors |
| US8741892B2 (en) | 2011-12-05 | 2014-06-03 | Boehringer Ingelheim International Gmbh | Compounds |
| US8642774B2 (en) | 2011-12-08 | 2014-02-04 | Boehringer Ingelheim International Gmbh | Compounds |
| US8846948B2 (en) | 2011-12-13 | 2014-09-30 | Boehringer Ingelheim International Gmbh | Compounds |
| US8796467B2 (en) | 2011-12-13 | 2014-08-05 | Boehringer Ingelheim International Gmbh | Compounds |
| US8883789B2 (en) | 2011-12-14 | 2014-11-11 | Boehringer Ingelheim International Gmbh | Piperazine derivatives and their use as positive allosteric modulators of mGluR5 receptors |
| US8937176B2 (en) | 2011-12-14 | 2015-01-20 | Boehringer Ingelheim International Gmbh | Compounds |
| US8716277B2 (en) | 2011-12-14 | 2014-05-06 | Boehringer Ingelheim International Gmbh | Substituted imidazole compounds useful as positive allosteric modulators of mGlu5 receptor activity |
| US8889677B2 (en) * | 2012-01-17 | 2014-11-18 | Boehringer Ingellheim International GmbH | Substituted triazoles useful as mGlu5 receptor modulators |
| EP2964659B1 (en) * | 2013-03-06 | 2017-08-09 | Biocon Limited | Process for the preparation of deferasirox |
| PL2964202T3 (pl) | 2013-03-08 | 2019-04-30 | Novartis Ag | Doustne formulacje deferazyroksu |
| BR112015028257A2 (pt) * | 2013-05-10 | 2017-07-25 | Cipla Ltd | composição farmacêutica de baixa dose, método para tratar sobrecarga de ferro crônica, método para tratar toxicidade por chumbo, processo para preparar uma composição farmacêutica de baixa dose e processo |
| DE102013217390A1 (de) | 2013-09-02 | 2015-03-05 | Henkel Ag & Co. Kgaa | Wasch- und Reinigungsmittel mit verbesserter Leistung |
| CN103454370B (zh) * | 2013-09-11 | 2014-12-24 | 中美华世通生物医药科技（武汉）有限公司 | 一种利用hplc测定原料药中苯肼类化合物残留的方法 |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
| PH12016501545B1 (en) | 2014-03-14 | 2023-12-06 | Immutep Sas | Antibody molecules to lag-3 and uses thereof |
| TR201909052T4 (tr) | 2014-05-20 | 2019-07-22 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Deferasiroks içeren suda dağılabilen tablet formülasyonu. |
| EP2987482A1 (en) | 2014-08-22 | 2016-02-24 | Santa Farma Ilaç Sanayi A.S. | Soluble and dispersible pharamaceutical deferasirox formulation |
| MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
| CA2964367C (en) | 2014-10-14 | 2024-01-30 | Novartis Ag | Antibody molecules to pd-l1 and uses thereof |
| WO2016100882A1 (en) | 2014-12-19 | 2016-06-23 | Novartis Ag | Combination therapies |
| KR20160088965A (ko) | 2015-01-16 | 2016-07-27 | 대원제약주식회사 | 데페라시록스를 함유하는 현탁제 |
| HK1248603A1 (zh) | 2015-03-10 | 2018-10-19 | Aduro Biotech, Inc. | 用於活化"干扰素基因的刺激剂"依懒性信号传导的组合物和方法 |
| CN104817538A (zh) * | 2015-03-13 | 2015-08-05 | 东南大学 | 去铁斯诺-他克林金属离子鳌合剂及其药物用途 |
| WO2016167729A1 (en) | 2015-04-16 | 2016-10-20 | Öğün Yusuf Toktamiş | Dispersible tablets comprising deferasirox |
| EP3095443A1 (en) | 2015-05-21 | 2016-11-23 | Abdi Ibrahim Ilac Sanayi ve Ticaret A.S. | Pharmaceutical composition comprising deferasirox |
| WO2016203488A1 (en) * | 2015-06-16 | 2016-12-22 | Havaldar Freddy H | Preparation of novel deferasirox analogues for antimalarial activity |
| WO2017019897A1 (en) | 2015-07-29 | 2017-02-02 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
| EP4378957A3 (en) | 2015-07-29 | 2024-08-07 | Novartis AG | Combination therapies comprising antibody molecules to pd-1 |
| DK3317301T3 (da) | 2015-07-29 | 2021-06-28 | Immutep Sas | Kombinationsterapier omfattende antistofmolekyler mod lag-3 |
| KR101695970B1 (ko) * | 2015-07-31 | 2017-01-13 | 건일제약 주식회사 | 데페라시록스 함유 산제 및 그 제조방법 |
| CN106554770B (zh) * | 2015-09-29 | 2018-10-19 | 杭州杜易科技有限公司 | 一种三唑衍生物金属离子荧光探针及其制备方法和应用 |
| US10738041B2 (en) | 2015-10-23 | 2020-08-11 | Vifor (International) Ag | Ferroportin inhibitors |
| KR102833068B1 (ko) | 2015-12-17 | 2025-07-14 | 노파르티스 아게 | Pd-1에 대한 항체 분자 및 그의 용도 |
| EP3429562A1 (en) | 2016-03-17 | 2019-01-23 | Lupin Limited | Compositions of deferasirox |
| EP3507367A4 (en) | 2016-07-05 | 2020-03-25 | Aduro BioTech, Inc. | CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF |
| WO2018059922A1 (en) | 2016-09-30 | 2018-04-05 | Synthon B.V. | Pharmaceutical composition comprising deferasirox |
| JOP20180036A1 (ar) | 2017-04-18 | 2019-01-30 | Vifor Int Ag | أملاح لمثبطات فروبورتين جديدة |
| UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
| CZ2017255A3 (cs) | 2017-05-04 | 2018-11-14 | Zentiva, K.S. | Filmem potažené tablety Deferasiroxu |
| WO2018208242A1 (en) | 2017-05-10 | 2018-11-15 | İlko Ilaç Sanayi Ve Ticaret Anonim Şirketi | Formulation of deferasirox tablet for oral suspension composition with better processability |
| WO2018237173A1 (en) | 2017-06-22 | 2018-12-27 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| US11331288B2 (en) | 2017-09-14 | 2022-05-17 | The Board Of Trustees Of The Leland Stanford Junior University | Conditioning irradiated tissue for increasing vascularity |
| EP3489692A1 (de) | 2017-11-28 | 2019-05-29 | Siemens Healthcare Diagnostics Products GmbH | Prothrombinzeit-reagenz enthaltend einen eisenchelator |
| TR201722910A2 (tr) | 2017-12-29 | 2019-07-22 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Deferasi̇roks i̇çeren suda dağilabi̇len tablet formülasyonlari |
| KR20190110771A (ko) | 2018-03-21 | 2019-10-01 | 주식회사 한국팜비오 | 데페라시록스를 함유하는 소형 분산성 정제 |
| CN108727287B (zh) * | 2018-05-10 | 2020-10-27 | 东南大学 | 1,2,4-三唑类化合物及其盐和应用 |
| AR126019A1 (es) | 2018-05-30 | 2023-09-06 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
| GR1009592B (el) * | 2018-07-03 | 2019-09-11 | Φαρματεν Α.Β.Ε.Ε. | Φαρμακευτικο σκευασμα που περιλαμβανει εναν χηλικο παραγοντα συμπλεκτικο του σιδηρου και μεθοδος για την παρασκευη αυτου |
| KR20200113116A (ko) | 2019-03-22 | 2020-10-06 | 주식회사 한국팜비오 | 데페라시록스를 포함하는 필름코팅정제 |
| TW202102478A (zh) | 2019-04-01 | 2021-01-16 | 瑞士商威佛（國際）股份有限公司 | 新穎的鐵螯合物 |
| CN114502590A (zh) | 2019-09-18 | 2022-05-13 | 诺华股份有限公司 | Entpd2抗体、组合疗法、以及使用这些抗体和组合疗法的方法 |
| IT202000000922A1 (it) | 2020-01-20 | 2021-07-20 | Cage Chemicals S R L | Complessi di ferro e relativi sali come agenti di contrasto per MRI |
| US11155547B1 (en) * | 2020-06-18 | 2021-10-26 | Alterity Therapeutics Limited | Compounds for and methods of treating diseases |
| WO2022186809A1 (en) | 2021-03-05 | 2022-09-09 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | The film coated tablet comprising deferasirox |
| CN114276305B (zh) * | 2021-12-28 | 2023-11-17 | 中山大学 | 一种三取代苯基-1,2,4-三氮唑衍生物及其制备和治疗神经元损伤的应用 |
| CN114591254B (zh) * | 2022-03-31 | 2023-10-13 | 中山大学 | 一种3,5-二取代苯基-1,2,4-三氮唑衍生物及其制备方法和应用 |
| CN114478410B (zh) * | 2022-03-31 | 2022-11-29 | 中山大学 | 一种二取代苯基-1,2,4-三氮唑衍生物及其制备和应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4528196A (en) * | 1981-02-23 | 1985-07-09 | The United States Of America As Represented By The Department Of Health And Human Services | Chelating agents for the treatment of iron overload |
| EP0315434A2 (en) * | 1987-11-02 | 1989-05-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Pyridoxal hydrazone derivatives their production and use and pharmaceutical compositions containing the same |
| DE4320801A1 (de) * | 1993-06-23 | 1995-01-05 | Fahlberg List Pharma Gmbh | 2-Hydroxyphenylsubstituierte 1,2,4-Triazole und 1,2,4-Oxadiazole, ihre Verwendung als pharmazeutische Wirkstoffe und sie enthaltende Arzneimittel |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH84663A4 (en:Method) | 1963-01-24 | 1964-11-14 | ||
| DE2628152C2 (de) | 1976-06-23 | 1985-03-28 | Bayer Ag, 5090 Leverkusen | Fungizide und nematizide Mittel |
| SU1280851A1 (ru) * | 1983-07-08 | 1996-05-27 | Ростовский государственный университет | 1-фенил-3-алкил-5-(o-оксифенил)-1,2,4-триазолы, обладающие транквилизирующим и антигипоксическим действием, и 1-фенил-3-н-бутил-5-(о-оксифенил)-1,2,4-триазол, обладающий транквилизирующим, антигипоксическим и анальгетическим действием |
| GB8429307D0 (en) | 1984-11-20 | 1984-12-27 | Shell Int Research | Heterocyclic herbicides |
| US5260322A (en) | 1990-10-08 | 1993-11-09 | Merck & Co., Inc. | Angiotension II antagonists in the treatment of hyperuricemia |
-
1997
- 1997-06-23 MY MYPI97002822A patent/MY129541A/en unknown
- 1997-06-23 TW TW086108750A patent/TW533205B/zh not_active IP Right Cessation
- 1997-06-24 KR KR1020057017800A patent/KR100616378B1/ko not_active Expired - Lifetime
- 1997-06-24 IL IL12721297A patent/IL127212A0/xx active Protection Beyond IP Right Term
- 1997-06-24 DK DK97928269T patent/DK0914118T3/da active
- 1997-06-24 AU AU32629/97A patent/AU718037B2/en not_active Expired
- 1997-06-24 DE DE122007000020C patent/DE122007000020I2/de active Active
- 1997-06-24 AT AT97928269T patent/ATE226435T1/de active
- 1997-06-24 CZ CZ19984272A patent/CZ291470B6/cs not_active IP Right Cessation
- 1997-06-24 TR TR1998/02693T patent/TR199802693T2/xx unknown
- 1997-06-24 CA CA002255951A patent/CA2255951C/en not_active Expired - Lifetime
- 1997-06-24 HU HU9903111A patent/HU226232B1/hu active Protection Beyond IP Right Term
- 1997-06-24 NZ NZ333308A patent/NZ333308A/xx not_active IP Right Cessation
- 1997-06-24 EP EP97928269A patent/EP0914118B1/en not_active Expired - Lifetime
- 1997-06-24 BR BR9709973A patent/BR9709973A/pt not_active IP Right Cessation
- 1997-06-24 WO PCT/EP1997/003315 patent/WO1997049395A1/en not_active Ceased
- 1997-06-24 PT PT97928269T patent/PT914118E/pt unknown
- 1997-06-24 ES ES97928269T patent/ES2187785T3/es not_active Expired - Lifetime
- 1997-06-24 DE DE1997616602 patent/DE122007000020I1/de active Pending
- 1997-06-24 DE DE69716602T patent/DE69716602T2/de not_active Expired - Lifetime
- 1997-06-24 JP JP50234898A patent/JP3541042B2/ja not_active Expired - Lifetime
- 1997-06-24 AP APAP/P/1998/001407A patent/AP1127A/en active
- 1997-06-24 RU RU99101050/04A patent/RU2208010C2/ru active Protection Beyond IP Right Term
- 1997-06-24 SI SI9730462T patent/SI0914118T1/xx unknown
- 1997-06-24 PL PL330119A patent/PL194758B1/pl unknown
- 1997-06-24 CN CNB971958319A patent/CN1146415C/zh not_active Expired - Lifetime
- 1997-06-24 SK SK1785-98A patent/SK284319B6/sk active Protection Beyond IP Right Term
- 1997-06-25 AR ARP970102792A patent/AR007479A1/es active IP Right Grant
-
1998
- 1998-12-08 BG BG103003A patent/BG64248B1/bg unknown
- 1998-12-21 NO NO19986024A patent/NO317180B1/no not_active IP Right Cessation
- 1998-12-24 OA OA9800247A patent/OA10946A/en unknown
-
2000
- 2000-10-30 US US09/699,765 patent/US6465504B1/en not_active Expired - Lifetime
-
2002
- 2002-09-23 US US10/252,899 patent/US6596750B2/en not_active Expired - Lifetime
-
2003
- 2003-05-29 US US10/447,922 patent/US6723742B2/en not_active Expired - Lifetime
-
2004
- 2004-02-27 CY CY0400016A patent/CY2429B1/xx unknown
-
2006
- 2006-11-27 NL NL300248C patent/NL300248I2/nl unknown
- 2006-11-29 LU LU91291C patent/LU91291I2/fr unknown
- 2006-11-30 NO NO2006017C patent/NO2006017I2/no unknown
- 2006-12-26 FR FR06C0049C patent/FR06C0049I2/fr active Active
-
2007
- 2007-01-16 LT LTPA2007001C patent/LTC0914118I2/lt unknown
- 2007-02-09 CY CY2007005C patent/CY2007005I2/el unknown
- 2007-09-14 GE GEAP200710266A patent/GEP20084355B/en unknown
-
2018
- 2018-04-17 NO NO2018014C patent/NO2018014I2/no unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4528196A (en) * | 1981-02-23 | 1985-07-09 | The United States Of America As Represented By The Department Of Health And Human Services | Chelating agents for the treatment of iron overload |
| EP0315434A2 (en) * | 1987-11-02 | 1989-05-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Pyridoxal hydrazone derivatives their production and use and pharmaceutical compositions containing the same |
| DE4320801A1 (de) * | 1993-06-23 | 1995-01-05 | Fahlberg List Pharma Gmbh | 2-Hydroxyphenylsubstituierte 1,2,4-Triazole und 1,2,4-Oxadiazole, ihre Verwendung als pharmazeutische Wirkstoffe und sie enthaltende Arzneimittel |
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