IL155189A - CRYSTALLINE FORMS OF A FACTOR Xa INHIBITOR - Google Patents
CRYSTALLINE FORMS OF A FACTOR Xa INHIBITORInfo
- Publication number
- IL155189A IL155189A IL155189A IL15518903A IL155189A IL 155189 A IL155189 A IL 155189A IL 155189 A IL155189 A IL 155189A IL 15518903 A IL15518903 A IL 15518903A IL 155189 A IL155189 A IL 155189A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- solvent
- butanol
- factor
- acid
- Prior art date
Links
- 229940123583 Factor Xa inhibitor Drugs 0.000 title description 7
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 85
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 8
- BTANRVKWQNVYAZ-SCSAIBSYSA-N (2R)-butan-2-ol Chemical compound CC[C@@H](C)O BTANRVKWQNVYAZ-SCSAIBSYSA-N 0.000 claims description 2
- BTANRVKWQNVYAZ-BYPYZUCNSA-N (2S)-butan-2-ol Chemical compound CC[C@H](C)O BTANRVKWQNVYAZ-BYPYZUCNSA-N 0.000 claims description 2
- MPRHTQKVOLVEQZ-CQWFHMBZSA-N (2r,3r)-2-[(3-carbamimidoylphenyl)methyl]-3-[[4-(1-oxidopyridin-1-ium-4-yl)benzoyl]amino]butanoic acid;hydrochloride Chemical compound Cl.N([C@H](C)[C@@H](CC=1C=C(C=CC=1)C(N)=N)C(O)=O)C(=O)C(C=C1)=CC=C1C1=CC=[N+]([O-])C=C1 MPRHTQKVOLVEQZ-CQWFHMBZSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 39
- 238000000034 method Methods 0.000 abstract description 31
- 108010074860 Factor Xa Proteins 0.000 abstract description 21
- 238000002360 preparation method Methods 0.000 abstract description 18
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 description 126
- 239000002904 solvent Substances 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 32
- 150000003839 salts Chemical class 0.000 description 26
- 239000012453 solvate Substances 0.000 description 24
- 239000013078 crystal Substances 0.000 description 21
- 239000002253 acid Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 235000019441 ethanol Nutrition 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 238000002425 crystallisation Methods 0.000 description 14
- -1 propyl amide compound Chemical class 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 13
- 239000003146 anticoagulant agent Substances 0.000 description 13
- 230000008025 crystallization Effects 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000001953 recrystallisation Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
- 108090000190 Thrombin Proteins 0.000 description 7
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- 239000008101 lactose Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 150000001793 charged compounds Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000000113 differential scanning calorimetry Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
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- 230000008901 benefit Effects 0.000 description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
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- 235000003599 food sweetener Nutrition 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 5
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
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- 235000019270 ammonium chloride Nutrition 0.000 description 4
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- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
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- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
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- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
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- 230000000699 topical effect Effects 0.000 description 1
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- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- A61P9/10—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Liquid Crystal Substances (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicinal Preparation (AREA)
- Pyridine Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23831600P | 2000-10-05 | 2000-10-05 | |
| GBGB0108903.6A GB0108903D0 (en) | 2000-10-05 | 2001-04-10 | Novel crystalline forms of a factor Xa inhibitor |
| PCT/US2001/031087 WO2002028836A1 (en) | 2000-10-05 | 2001-10-04 | Novel crystalline forms of a factor xa inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL155189A true IL155189A (en) | 2011-11-30 |
Family
ID=22897372
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL155189A IL155189A (en) | 2000-10-05 | 2003-04-01 | CRYSTALLINE FORMS OF A FACTOR Xa INHIBITOR |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7034160B2 (de) |
| EP (1) | EP1326838B1 (de) |
| JP (1) | JP4177663B2 (de) |
| AT (1) | ATE396177T1 (de) |
| AU (2) | AU1142502A (de) |
| CA (1) | CA2424565C (de) |
| CY (1) | CY1108224T1 (de) |
| DK (1) | DK1326838T3 (de) |
| ES (1) | ES2304396T3 (de) |
| GB (1) | GB0108903D0 (de) |
| IL (1) | IL155189A (de) |
| MX (1) | MXPA03002067A (de) |
| PT (1) | PT1326838E (de) |
| WO (1) | WO2002028836A1 (de) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6964784B2 (en) * | 2002-03-07 | 2005-11-15 | Optigenex, Inc. | Method of preparation and composition of a water soluble extract of the bioactive component of the plant species uncaria for enhancing immune, anti-inflammatory, anti-tumor and dna repair processes of warm blooded animals |
| SG193612A1 (en) * | 2011-03-29 | 2013-11-29 | Sanofi Sa | Benzoic acid salt of otamixaban |
| TWI551289B (zh) * | 2011-03-29 | 2016-10-01 | 賽諾菲公司 | 具有改良之安定性之奧米沙班調配物 |
| EA025572B1 (ru) * | 2011-03-29 | 2017-01-30 | Санофи | Лекарственные формы отамиксабана с улучшенной стабильностью |
| CA3218491A1 (en) | 2012-06-04 | 2013-12-12 | Pharmacyclics Llc | Crystalline forms of a bruton's tyrosine kinase inhibitor |
| MX2017001671A (es) | 2014-08-07 | 2017-07-04 | Pharmacyclics Llc | Formulaciones novedosas de un inhibidor de la tirosina cinasa de bruton. |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| MA41827A (fr) * | 2015-03-27 | 2018-01-30 | Pharmacyclics Llc | Formes solvatées d'un inhibiteur de la tyrosine kinase de bruton |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ297544B6 (cs) * | 1996-01-02 | 2007-02-07 | Aventis Pharmaceuticals Inc. | Substituované N-[(aminoiminomethyl)-fenyl]propylamidy nebo N-[(aminomethyl)fenyl]propylamidy |
| US6080767A (en) * | 1996-01-02 | 2000-06-27 | Aventis Pharmaceuticals Products Inc. | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
-
2001
- 2001-04-10 GB GBGB0108903.6A patent/GB0108903D0/en not_active Ceased
- 2001-10-04 AU AU1142502A patent/AU1142502A/xx active Pending
- 2001-10-04 CA CA2424565A patent/CA2424565C/en not_active Expired - Fee Related
- 2001-10-04 MX MXPA03002067A patent/MXPA03002067A/es active IP Right Grant
- 2001-10-04 ES ES01979459T patent/ES2304396T3/es not_active Expired - Lifetime
- 2001-10-04 AU AU2002211425A patent/AU2002211425B2/en not_active Ceased
- 2001-10-04 DK DK01979459T patent/DK1326838T3/da active
- 2001-10-04 PT PT01979459T patent/PT1326838E/pt unknown
- 2001-10-04 JP JP2002532422A patent/JP4177663B2/ja not_active Expired - Fee Related
- 2001-10-04 AT AT01979459T patent/ATE396177T1/de active
- 2001-10-04 EP EP01979459A patent/EP1326838B1/de not_active Expired - Lifetime
- 2001-10-04 WO PCT/US2001/031087 patent/WO2002028836A1/en not_active Ceased
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2003
- 2003-04-01 IL IL155189A patent/IL155189A/en not_active IP Right Cessation
- 2003-04-01 US US10/404,678 patent/US7034160B2/en not_active Expired - Lifetime
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2008
- 2008-07-29 CY CY20081100790T patent/CY1108224T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT1326838E (pt) | 2008-07-08 |
| US20030225144A1 (en) | 2003-12-04 |
| US7034160B2 (en) | 2006-04-25 |
| JP2004521082A (ja) | 2004-07-15 |
| ES2304396T3 (es) | 2008-10-16 |
| ATE396177T1 (de) | 2008-06-15 |
| AU2002211425B2 (en) | 2006-03-02 |
| JP4177663B2 (ja) | 2008-11-05 |
| CA2424565C (en) | 2011-04-26 |
| EP1326838B1 (de) | 2008-05-21 |
| AU1142502A (en) | 2002-04-15 |
| WO2002028836A1 (en) | 2002-04-11 |
| MXPA03002067A (es) | 2003-06-24 |
| WO2002028836A9 (en) | 2003-11-20 |
| GB0108903D0 (en) | 2001-05-30 |
| DK1326838T3 (da) | 2008-09-22 |
| CY1108224T1 (el) | 2014-02-12 |
| EP1326838A1 (de) | 2003-07-16 |
| CA2424565A1 (en) | 2002-04-11 |
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