CA3167093A1 - Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride - Google Patents
Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochlorideInfo
- Publication number
- CA3167093A1 CA3167093A1 CA3167093A CA3167093A CA3167093A1 CA 3167093 A1 CA3167093 A1 CA 3167093A1 CA 3167093 A CA3167093 A CA 3167093A CA 3167093 A CA3167093 A CA 3167093A CA 3167093 A1 CA3167093 A1 CA 3167093A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- ponatinib
- crystalline form
- solvent
- xrpd
- 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
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 150
- BWTNNZPNKQIADY-UHFFFAOYSA-N ponatinib hydrochloride Chemical compound Cl.C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 BWTNNZPNKQIADY-UHFFFAOYSA-N 0.000 claims description 143
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000003981 vehicle Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 abstract description 38
- 238000002360 preparation method Methods 0.000 abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 135
- 229960002183 ponatinib hydrochloride Drugs 0.000 description 129
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- 238000002474 experimental method Methods 0.000 description 113
- 239000002904 solvent Substances 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
- 229960001131 ponatinib Drugs 0.000 description 73
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 71
- 239000013078 crystal Substances 0.000 description 69
- 239000002137 L01XE24 - Ponatinib Substances 0.000 description 63
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- 238000002425 crystallisation Methods 0.000 description 52
- 230000008025 crystallization Effects 0.000 description 48
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- 239000012296 anti-solvent Substances 0.000 description 44
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 38
- 239000007858 starting material Substances 0.000 description 38
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
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- 238000009792 diffusion process Methods 0.000 description 34
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 34
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000000523 sample Substances 0.000 description 27
- 238000000113 differential scanning calorimetry Methods 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
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- 101100450563 Mus musculus Serpind1 gene Proteins 0.000 description 22
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- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 22
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- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 16
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
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- 239000000047 product Substances 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- 238000003860 storage Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
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- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 13
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- 238000001757 thermogravimetry curve Methods 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 12
- 239000007789 gas Substances 0.000 description 12
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 11
- 239000012458 free base Substances 0.000 description 11
- -1 4-METHYLPIPERAZIN-1-YL Chemical class 0.000 description 10
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 10
- 238000004108 freeze drying Methods 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 238000010926 purge Methods 0.000 description 10
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- 239000008096 xylene Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 9
- 101100408036 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PGU1 gene Proteins 0.000 description 9
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
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- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 6
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 6
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- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011027 product recovery Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- AQRYNYUOKMNDDV-UHFFFAOYSA-M silver behenate Chemical compound [Ag+].CCCCCCCCCCCCCCCCCCCCCC([O-])=O AQRYNYUOKMNDDV-UHFFFAOYSA-M 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229940068117 sprycel Drugs 0.000 description 1
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- 239000000829 suppository Substances 0.000 description 1
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 238000001107 thermogravimetry coupled to mass spectrometry Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
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- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US201261736543P | 2012-12-12 | 2012-12-12 | |
| US61/736,543 | 2012-12-12 | ||
| US201261737007P | 2012-12-13 | 2012-12-13 | |
| US61/737,007 | 2012-12-13 | ||
| US201361788208P | 2013-03-15 | 2013-03-15 | |
| US61/788,208 | 2013-03-15 | ||
| CA3022250A CA3022250A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3022250A Division CA3022250A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Publications (1)
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| CA3167093A1 true CA3167093A1 (en) | 2014-06-12 |
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| CA2815506A Active CA2815506C (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| CA3022250A Abandoned CA3022250A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Family Applications After (2)
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| CA2815506A Active CA2815506C (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| CA3022250A Abandoned CA3022250A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Country Status (9)
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| US (9) | US9493470B2 (cg-RX-API-DMAC7.html) |
| JP (4) | JP6447508B2 (cg-RX-API-DMAC7.html) |
| CN (2) | CN105188701A (cg-RX-API-DMAC7.html) |
| CA (3) | CA3167093A1 (cg-RX-API-DMAC7.html) |
| CL (1) | CL2015001643A1 (cg-RX-API-DMAC7.html) |
| HK (1) | HK1218878A1 (cg-RX-API-DMAC7.html) |
| MX (11) | MX391445B (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ709648A (cg-RX-API-DMAC7.html) |
| WO (2) | WO2014093583A2 (cg-RX-API-DMAC7.html) |
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| DK2495016T3 (da) | 2005-12-23 | 2019-12-16 | Ariad Pharma Inc | Bicykliske heteroarylforbindelser |
| TWI568722B (zh) | 2012-06-15 | 2017-02-01 | 葛蘭馬克製藥公司 | 作爲ｍＰＧＥＳ－１抑制劑之三唑酮化合物 |
| CA3167093A1 (en) | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| AU2014286047B2 (en) | 2013-07-04 | 2018-02-08 | Sandoz Ag | Crystalline forms of ponatinib hydrochloride |
| CN104496940B (zh) * | 2014-01-06 | 2017-03-15 | 广东东阳光药业有限公司 | 一种制备bcr‑abl抑制剂中间体的方法 |
| CA3047107A1 (en) * | 2016-12-15 | 2018-06-21 | Ariad Pharmaceuticals, Inc. | Benzimidazole compounds as c-kit inhibitors |
| US10221184B2 (en) | 2017-01-20 | 2019-03-05 | Apicore Us Llc | Polymorphs of ponatinib hydrochloride |
| WO2018232501A1 (en) * | 2017-06-20 | 2018-12-27 | Apotex Inc. | Crystalline forms of ponatinib hydrochloride |
| KR20250010134A (ko) * | 2018-04-02 | 2025-01-20 | 스텔스 바이오테라퓨틱스 인코포레이티드 | 엘라미프레티드의 합성에 유용한 결정질 디펩티드 |
| WO2019246479A1 (en) * | 2018-06-22 | 2019-12-26 | Johnson Matthey Public Limited Company | Form of ponatinib |
| CA3118330A1 (en) | 2018-11-01 | 2020-05-07 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
| WO2020223235A1 (en) | 2019-04-29 | 2020-11-05 | Incyte Corporation | Mini-tablet dosage forms of ponatinib |
| CN111004240B (zh) * | 2019-12-13 | 2020-12-01 | 山东铂源药业有限公司 | 一种泊那替尼中间体3-乙炔基咪唑并[1,2-b]哒嗪的合成方法 |
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| US5099067A (en) | 1988-08-05 | 1992-03-24 | Northwestern University | Use of ammonium formate as a hydrogen transfer reagent for reduction of chiral nitro compounds with retention of configuration |
| EP1230231B1 (en) | 1999-11-08 | 2005-06-22 | Schering Corporation | Process for preparing n-(4-hydroxyphenyl)-n'-(4'-aminophenyl)-piperazine |
| HN2001000008A (es) | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
| DE10021246A1 (de) | 2000-04-25 | 2001-10-31 | Schering Ag | Substituierte Benzoesäureamide und deren Verwendung als Arzneimittel |
| IL159811A0 (en) | 2001-07-13 | 2004-06-20 | Neurogen Corp | Heteroaryl substituted fused bicyclic heteroaryl compounds as gabaa receptor ligands |
| AR041992A1 (es) | 2002-11-06 | 2005-06-08 | Smithkline Beecham Corp | Compuesto de piridinil benzoheterociclico, composicion farmaceutica que lo comprende y su uso para prepararla |
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| ES2317079T3 (es) | 2003-12-24 | 2009-04-16 | Astrazeneca Ab | Pirimidinas con actividad tie2 (tek). |
| EA011930B1 (ru) | 2004-04-07 | 2009-06-30 | Лаборатуар Сероно Са | Карбоновые кислоты |
| JP2008506702A (ja) | 2004-07-14 | 2008-03-06 | ピーティーシー セラピューティクス，インコーポレーテッド | Ｃ型肝炎を治療するための方法 |
| US7776869B2 (en) | 2004-10-18 | 2010-08-17 | Amgen Inc. | Heteroaryl-substituted alkyne compounds and method of use |
| GB0502418D0 (en) | 2005-02-05 | 2005-03-16 | Astrazeneca Ab | Compounds |
| JP2008534565A (ja) | 2005-03-31 | 2008-08-28 | アストラゼネカ アクチボラグ | Ｔｉｅ２阻害活性のあるアミノピリミジン誘導体 |
| JP2009502734A (ja) | 2005-07-29 | 2009-01-29 | アステラス製薬株式会社 | Ｌｃｋ阻害剤としての縮合複素環 |
| JP5321061B2 (ja) | 2005-08-11 | 2013-10-23 | アリアド・ファーマシューティカルズ・インコーポレイテッド | 不飽和複素環誘導体 |
| DK2495016T3 (da) | 2005-12-23 | 2019-12-16 | Ariad Pharma Inc | Bicykliske heteroarylforbindelser |
| SI1973545T1 (sl) * | 2005-12-23 | 2013-04-30 | Ariad Pharmaceuticals, Inc. | Spojine bicikličnega heteroarila |
| MX2008014290A (es) | 2006-05-08 | 2008-11-26 | Ariad Pharma Inc | Compuestos heteroarilicos monociclicos. |
| BRPI0710328A2 (pt) | 2006-05-08 | 2011-08-09 | Ariad Pharma Inc | composto da fórmula i, um tautomer da mesma, ou um sal farmaceuticamente aceitável, hidrato ou outro solvato do mesmo e método para o tratamento de cáncer em um mamìfero necessitado do mesmo e composição |
| EP2107054A1 (en) | 2008-04-01 | 2009-10-07 | Università Degli Studi Di Milano - Bicocca | Antiproliferative compounds and therapeutic uses thereof |
| US20100273772A1 (en) * | 2009-04-23 | 2010-10-28 | Wyeth Llc | Bisaryl Alkynylamides as Negative Allosteric Modulators of Metabotropic Glutamate Receptor 5 (MGLUR5) |
| US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| EA201290255A1 (ru) * | 2009-10-30 | 2013-04-30 | Ариад Фармасьютикалз, Инк. | Способы и композиции для лечения рака |
| EP2694064A1 (en) * | 2011-04-07 | 2014-02-12 | Ariad Pharmaceuticals, Incorporated | Methods and compositions for treating neurodegenerative diseases |
| KR20140022062A (ko) | 2011-04-07 | 2014-02-21 | 어리어드 파마슈티칼스, 인코포레이티드 | 파킨슨병을 치료하기 위한 방법 및 조성물 |
| US20150105377A1 (en) | 2012-04-25 | 2015-04-16 | Ariad Pharmaceuticals, Inc. | Methods and Compositions for RAF Kinase Mediated Diseases |
| CA3167093A1 (en) * | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
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