CA2711043A1 - Method of synthesis of bosentan, its polymorphic forms and its salts - Google Patents
Method of synthesis of bosentan, its polymorphic forms and its salts Download PDFInfo
- Publication number
- CA2711043A1 CA2711043A1 CA2711043A CA2711043A CA2711043A1 CA 2711043 A1 CA2711043 A1 CA 2711043A1 CA 2711043 A CA2711043 A CA 2711043A CA 2711043 A CA2711043 A CA 2711043A CA 2711043 A1 CA2711043 A1 CA 2711043A1
- Authority
- CA
- Canada
- Prior art keywords
- bosentan
- anhydrous
- process according
- salt
- solvent
- 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.)
- Abandoned
Links
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 title claims abstract description 224
- 229960003065 bosentan Drugs 0.000 title claims abstract description 114
- 238000000034 method Methods 0.000 title claims abstract description 76
- 150000003839 salts Chemical class 0.000 title claims abstract description 36
- 230000015572 biosynthetic process Effects 0.000 title description 9
- 238000003786 synthesis reaction Methods 0.000 title description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims abstract description 15
- -1 alkaline earth metal salts Chemical class 0.000 claims abstract description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 107
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 68
- 238000006243 chemical reaction Methods 0.000 claims description 67
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 48
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 46
- 239000002904 solvent Substances 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 38
- 239000000243 solution Substances 0.000 claims description 37
- 239000012296 anti-solvent Substances 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 21
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical group [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 16
- 229910001863 barium hydroxide Inorganic materials 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 238000005859 coupling reaction Methods 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 230000008878 coupling Effects 0.000 claims description 13
- 238000010168 coupling process Methods 0.000 claims description 13
- 238000010438 heat treatment Methods 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 12
- 239000002244 precipitate Substances 0.000 claims description 11
- 159000000009 barium salts Chemical class 0.000 claims description 10
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical group [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 8
- 239000000920 calcium hydroxide Substances 0.000 claims description 8
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 159000000007 calcium salts Chemical class 0.000 claims description 7
- XKISWHVJIZSPSC-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2N=CC=CN=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XKISWHVJIZSPSC-UHFFFAOYSA-N 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 150000002430 hydrocarbons Chemical class 0.000 claims description 6
- 239000011877 solvent mixture Substances 0.000 claims description 6
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 5
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 5
- 239000008096 xylene Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000001938 differential scanning calorimetry curve Methods 0.000 claims description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical group COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 238000002329 infrared spectrum Methods 0.000 claims description 4
- 239000012454 non-polar solvent Substances 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- 229960004132 diethyl ether Drugs 0.000 claims 2
- 238000002360 preparation method Methods 0.000 abstract description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000002585 base Substances 0.000 description 29
- 239000007787 solid Substances 0.000 description 29
- 239000012535 impurity Substances 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- 150000005325 alkali earth metal hydroxides Chemical class 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- OGFSLMSWJVQVQU-UHFFFAOYSA-N potassium;benzenesulfonylazanide Chemical compound [K+].[NH-]S(=O)(=O)C1=CC=CC=C1 OGFSLMSWJVQVQU-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 229910052788 barium Inorganic materials 0.000 description 5
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 5
- 229940036810 bosentan monohydrate Drugs 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003230 pyrimidines Chemical class 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- NIKHCURLTIQUJY-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide;potassium Chemical compound [K].COC1=CC=CC=C1OC1=C(Cl)N=C(C=2N=CC=CN=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NIKHCURLTIQUJY-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
- 229940011051 isopropyl acetate Drugs 0.000 description 3
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical group [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 3
- 239000000347 magnesium hydroxide Substances 0.000 description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- UUCCCPNEFXQJEL-UHFFFAOYSA-L strontium dihydroxide Chemical compound [OH-].[OH-].[Sr+2] UUCCCPNEFXQJEL-UHFFFAOYSA-L 0.000 description 3
- 229910001866 strontium hydroxide Inorganic materials 0.000 description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000013341 scale-up Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- 238000001757 thermogravimetry curve Methods 0.000 description 2
- 229940118436 tracleer Drugs 0.000 description 2
- BIIBYWQGRFWQKM-JVVROLKMSA-N (2S)-N-[4-(cyclopropylamino)-3,4-dioxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl]-2-[[(E)-3-(2,4-dichlorophenyl)prop-2-enoyl]amino]-4,4-dimethylpentanamide Chemical compound CC(C)(C)C[C@@H](C(NC(C[C@H](CCN1)C1=O)C(C(NC1CC1)=O)=O)=O)NC(/C=C/C(C=CC(Cl)=C1)=C1Cl)=O BIIBYWQGRFWQKM-JVVROLKMSA-N 0.000 description 1
- BDLXTDLGTWNUFM-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]ethanol Chemical compound CC(C)(C)OCCO BDLXTDLGTWNUFM-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical class CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- FNJVDWXUKLTFFL-UHFFFAOYSA-N diethyl 2-bromopropanedioate Chemical compound CCOC(=O)C(Br)C(=O)OCC FNJVDWXUKLTFFL-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- BCUMPULZWNQMKD-UHFFFAOYSA-N methanol;propan-2-yl acetate Chemical compound OC.CC(C)OC(C)=O BCUMPULZWNQMKD-UHFFFAOYSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/69—Benzenesulfonamido-pyrimidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN12/MUM/2008 | 2008-01-01 | ||
| IN12MU2008 | 2008-01-01 | ||
| IN836/MUM/2008 | 2008-04-09 | ||
| IN836MU2008 | 2008-04-09 | ||
| PCT/GB2009/000009 WO2009083739A1 (en) | 2008-01-01 | 2009-01-02 | Method of synthesis of bosentan, its polymorphic forms and its salts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2711043A1 true CA2711043A1 (en) | 2009-07-09 |
Family
ID=40424567
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2711043A Abandoned CA2711043A1 (en) | 2008-01-01 | 2009-01-02 | Method of synthesis of bosentan, its polymorphic forms and its salts |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8481730B2 (enExample) |
| EP (2) | EP2238118A1 (enExample) |
| JP (1) | JP5535082B2 (enExample) |
| KR (1) | KR20100113542A (enExample) |
| AU (1) | AU2009203174B2 (enExample) |
| CA (1) | CA2711043A1 (enExample) |
| NZ (1) | NZ586900A (enExample) |
| WO (1) | WO2009083739A1 (enExample) |
| ZA (1) | ZA201005014B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE551339T1 (de) | 2003-11-05 | 2012-04-15 | Sarcode Bioscience Inc | Modulatoren der zellulären adhäsion |
| JP5535082B2 (ja) | 2008-01-01 | 2014-07-02 | シプラ・リミテッド | ボセンタン、その多形形態及びその塩の合成方法 |
| CA2781541A1 (en) | 2009-11-12 | 2011-05-19 | Ranbaxy Laboratories Limited | Crystalline forms of bosentan salt and processes for their preparation |
| JP5356323B2 (ja) * | 2010-07-01 | 2013-12-04 | 富士化学工業株式会社 | 新規な非晶質ボセンタン及びその製造方法 |
| WO2012002547A1 (ja) * | 2010-07-02 | 2012-01-05 | 富士化学工業株式会社 | ボセンタン固体分散体 |
| JP5850576B2 (ja) * | 2010-07-06 | 2016-02-03 | 富士化学工業株式会社 | ボセンタン固体分散体 |
| US20130245259A1 (en) | 2012-03-16 | 2013-09-19 | Natco Pharma Limited | Process for the preparation of bosentan monohydrate |
| ITMI20120701A1 (it) | 2012-04-27 | 2013-10-28 | Dipharma Francis Srl | Procedimento per la purificazione di un composto benzensolfonammidico |
| WO2014018748A1 (en) * | 2012-07-25 | 2014-01-30 | Sarcode Bioscience Inc. | Lfa-1 inhibitor and polymorph thereof |
| WO2014033758A1 (en) * | 2012-08-31 | 2014-03-06 | Rao Davuluri Ramamohan | 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium |
| KR102004422B1 (ko) | 2012-12-20 | 2019-07-26 | 제일약품주식회사 | 보센탄 일수화물의 제조방법, 이에 사용되는 신규 중간체 및 이의 제조방법 |
| HK1217488A1 (zh) * | 2013-02-21 | 2017-01-13 | Adverio Pharma Gmbh | {4,6-二氨基-2-[1-(2-氟苄基)-1h-吡唑并[3,4-b]吡啶-3-基]嘧啶-5-基}甲基氨基甲酸甲酯的形式 |
| KR102259824B1 (ko) * | 2018-07-24 | 2021-06-02 | 주식회사 마더스제약 | 보센탄을 함유한 약학 제제 |
| WO2023150702A2 (en) * | 2022-02-03 | 2023-08-10 | The Johns Hopkins University | Compositions and methods for treatment of connective tissue disorders |
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| RU2086544C1 (ru) * | 1991-06-13 | 1997-08-10 | Хоффманн-Ля Рош АГ | Бензолсульфонамидные производные пиримидина или их соли, фармацевтическая композиция для лечения заболеваний, связанных с активностью эндотелина |
| US6136971A (en) | 1998-07-17 | 2000-10-24 | Roche Colorado Corporation | Preparation of sulfonamides |
| SK9742002A3 (en) * | 2000-01-07 | 2003-02-04 | Transform Pharmaceuticals Inc | High-throughput formation, identification, and analysis of diverse solid-forms |
| ES2255973T3 (es) * | 2000-01-25 | 2006-07-16 | F. Hoffmann-La Roche Ag | Preparacion de sulfonamidas. |
| CA2686457A1 (en) * | 2007-05-08 | 2008-11-13 | Generics [Uk] Limited | Novel polymorphic forms |
| CA2694242C (en) * | 2007-06-29 | 2013-10-01 | Generics [Uk] Limited | Process for introduction of hydroxyethoxy side chain in bosentan |
| WO2009047637A1 (en) * | 2007-10-11 | 2009-04-16 | Actavis Group Ptc Ehf | Novel polymorphs of bosentan |
| US8530488B2 (en) * | 2007-10-24 | 2013-09-10 | Generics [Uk] Limited | Crystalline forms of bosentan |
| JP5535082B2 (ja) | 2008-01-01 | 2014-07-02 | シプラ・リミテッド | ボセンタン、その多形形態及びその塩の合成方法 |
| WO2009093127A2 (en) * | 2008-01-24 | 2009-07-30 | Actavis Group Ptc Ehf | Substantially pure and a stable crystalline form of bosentan |
| EP2294056A1 (en) * | 2008-05-23 | 2011-03-16 | Synthon B.V. | Bosentan salts |
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2009
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- 2009-01-02 AU AU2009203174A patent/AU2009203174B2/en not_active Ceased
- 2009-01-02 US US12/811,279 patent/US8481730B2/en not_active Expired - Fee Related
- 2009-01-02 KR KR1020107017092A patent/KR20100113542A/ko not_active Abandoned
- 2009-01-02 NZ NZ586900A patent/NZ586900A/xx not_active IP Right Cessation
- 2009-01-02 CA CA2711043A patent/CA2711043A1/en not_active Abandoned
- 2009-01-02 WO PCT/GB2009/000009 patent/WO2009083739A1/en not_active Ceased
- 2009-01-02 EP EP09700123A patent/EP2238118A1/en not_active Withdrawn
- 2009-01-02 EP EP10172685A patent/EP2248805A3/en not_active Withdrawn
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| EP2248805A3 (en) | 2011-02-23 |
| NZ586900A (en) | 2012-10-26 |
| JP5535082B2 (ja) | 2014-07-02 |
| EP2238118A1 (en) | 2010-10-13 |
| WO2009083739A1 (en) | 2009-07-09 |
| KR20100113542A (ko) | 2010-10-21 |
| AU2009203174B2 (en) | 2014-01-30 |
| US8481730B2 (en) | 2013-07-09 |
| JP2011508767A (ja) | 2011-03-17 |
| ZA201005014B (en) | 2011-03-30 |
| US20110015394A1 (en) | 2011-01-20 |
| AU2009203174A1 (en) | 2009-07-09 |
| EP2248805A2 (en) | 2010-11-10 |
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