EA025438B1 - КРИСТАЛЛИЧЕСКИЙ КОМПЛЕКС 1-ЦИАНО-2-(4-ЦИКЛОПРОПИЛБЕНЗИЛ)-4-(β-D-ГЛЮКОПИРАНОЗ-1-ИЛ)БЕНЗОЛА, СПОСОБЫ ЕГО ПОЛУЧЕНИЯ И ЕГО ПРИМЕНЕНИЕ ДЛЯ ПРИГОТОВЛЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВ - Google Patents
КРИСТАЛЛИЧЕСКИЙ КОМПЛЕКС 1-ЦИАНО-2-(4-ЦИКЛОПРОПИЛБЕНЗИЛ)-4-(β-D-ГЛЮКОПИРАНОЗ-1-ИЛ)БЕНЗОЛА, СПОСОБЫ ЕГО ПОЛУЧЕНИЯ И ЕГО ПРИМЕНЕНИЕ ДЛЯ ПРИГОТОВЛЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВ Download PDFInfo
- Publication number
- EA025438B1 EA025438B1 EA201500038A EA201500038A EA025438B1 EA 025438 B1 EA025438 B1 EA 025438B1 EA 201500038 A EA201500038 A EA 201500038A EA 201500038 A EA201500038 A EA 201500038A EA 025438 B1 EA025438 B1 EA 025438B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- crystalline complex
- solution
- crystalline
- benzene
- glucopyranos
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title abstract description 15
- PESZPPAQWQMZAM-XNBWIAOKSA-N 2-[(4-cyclopropylphenyl)methyl]-4-[(2r,3r,4s,5s,6r)-2,3,4,5-tetrahydroxy-6-(hydroxymethyl)oxan-2-yl]benzonitrile Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@]1(O)C1=CC=C(C#N)C(CC=2C=CC(=CC=2)C2CC2)=C1 PESZPPAQWQMZAM-XNBWIAOKSA-N 0.000 title abstract 3
- 150000001413 amino acids Chemical class 0.000 claims abstract description 23
- 239000002904 solvent Substances 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 37
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 16
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 239000002244 precipitate Substances 0.000 claims description 10
- 230000005855 radiation Effects 0.000 claims description 10
- -1 4-cyclopropylbenzyl Chemical group 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 7
- 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 claims description 7
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 7
- 239000008103 glucose Substances 0.000 claims description 7
- 230000001575 pathological effect Effects 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 230000006806 disease prevention Effects 0.000 claims 3
- 239000000243 solution Substances 0.000 description 55
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 229940126062 Compound A Drugs 0.000 description 37
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 21
- 239000013543 active substance Substances 0.000 description 19
- 229960002429 proline Drugs 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 229940079593 drug Drugs 0.000 description 13
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 229930182821 L-proline Natural products 0.000 description 8
- 238000000113 differential scanning calorimetry Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000000227 grinding Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000825 pharmaceutical preparation Substances 0.000 description 7
- 238000002411 thermogravimetry Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 239000012296 anti-solvent Substances 0.000 description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
- 229940088679 drug related substance Drugs 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- WDXHGFYJUQMFDV-UHFFFAOYSA-N (2-bromo-5-iodophenyl)methanol Chemical compound OCC1=CC(I)=CC=C1Br WDXHGFYJUQMFDV-UHFFFAOYSA-N 0.000 description 2
- YNLGFXOBRXSMJZ-UHFFFAOYSA-N (4-cyclopropylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1CC1 YNLGFXOBRXSMJZ-UHFFFAOYSA-N 0.000 description 2
- IPTYFZLHONGTGW-UHFFFAOYSA-N 1-bromo-2-(chloromethyl)-4-iodobenzene Chemical compound ClCC1=CC(I)=CC=C1Br IPTYFZLHONGTGW-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000006748 scratching Methods 0.000 description 2
- 230000002393 scratching effect Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 238000009827 uniform distribution Methods 0.000 description 2
- JRDNBWVMEFUNCQ-UHFFFAOYSA-N 1-bromo-4-cyclopropylbenzene Chemical compound C1=CC(Br)=CC=C1C1CC1 JRDNBWVMEFUNCQ-UHFFFAOYSA-N 0.000 description 1
- GCQNURAETVDXDM-UHFFFAOYSA-N 1-bromo-4-iodo-2-(phenoxymethyl)benzene Chemical compound BrC1=CC=C(I)C=C1COC1=CC=CC=C1 GCQNURAETVDXDM-UHFFFAOYSA-N 0.000 description 1
- QPKKBDSNZFSSOD-UHFFFAOYSA-N 2-bromo-5-iodobenzoic acid Chemical compound OC(=O)C1=CC(I)=CC=C1Br QPKKBDSNZFSSOD-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- 101000606741 Homo sapiens Phosphoribosylglycinamide formyltransferase Proteins 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 229910013470 LiC1 Inorganic materials 0.000 description 1
- 102100039654 Phosphoribosylglycinamide formyltransferase Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H7/00—Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
- C07H7/04—Carbocyclic radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Pyrane Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12177944 | 2012-07-26 | ||
| PCT/EP2013/065736 WO2014016381A1 (en) | 2012-07-26 | 2013-07-25 | CRYSTALLINE COMPLEX OF 1-CYANO-2-(4-CYCLOPROPYL-BENZYL)-4-(ß- D-GLUCOPYRANOS-1-YL)-BENZENE, METHODS FOR ITS PREPARATION AND THE USE THEREOF FOR PREPARING MEDICAMENTS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201500038A1 EA201500038A1 (ru) | 2015-07-30 |
| EA025438B1 true EA025438B1 (ru) | 2016-12-30 |
Family
ID=48874313
Family Applications (2)
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| US9145434B2 (en) | 2012-07-26 | 2015-09-29 | Boehringer Ingelheim International Gmbh | Crystalline complex of 1-cyano-2-(4-cyclopropyl-benzyl)-4-(ss-d-glucopyranos-1-yl)-benzene, methods for its preparation and the use thereof for preparing medicaments |
| PT2981269T (pt) | 2013-04-04 | 2023-10-10 | Boehringer Ingelheim Vetmedica Gmbh | Tratamento de distúrbios metabólicos em animais equinos |
| KR20240017116A (ko) | 2013-12-17 | 2024-02-06 | 베링거잉겔하임베트메디카게엠베하 | 고양이과 동물에서 대사 장애의 치료 |
| KR102414283B1 (ko) | 2014-01-23 | 2022-06-29 | 베링거잉겔하임베트메디카게엠베하 | 개과 동물에서 대사 장애의 치료 |
| ES2811261T3 (es) | 2014-04-01 | 2021-03-11 | Boehringer Ingelheim Vetmedica Gmbh | Tratamiento de trastornos metabólicos en animales equinos |
| CN103965020B (zh) * | 2014-05-06 | 2015-09-09 | 启东东岳药业有限公司 | 制备5-碘-2-溴苄醇的方法 |
| WO2016046150A1 (en) | 2014-09-25 | 2016-03-31 | Boehringer Ingelheim Vetmedica Gmbh | Combination treatment of sglt2 inhibitors and dopamine agonists for preventing metabolic disorders in equine animals |
| WO2016050134A1 (zh) * | 2014-09-30 | 2016-04-07 | 江苏恒瑞医药股份有限公司 | 一种钠-葡萄糖协同转运蛋白2抑制剂的l-脯氨酸复合物、其一水合物及晶体 |
| CZ2015110A3 (cs) * | 2015-02-18 | 2016-08-31 | Zentiva, K.S. | Pevné formy empagliflozinu |
| BR112018003749B1 (pt) | 2015-08-27 | 2023-10-31 | Boehringer Ingelheim Vetmedica Gmbh | Composições farmacêuticas líquidas compreendendo inibidores sglt-2, kit de peças e processo para a produção da composição farmacêutica líquida |
| WO2017203457A1 (en) * | 2016-05-26 | 2017-11-30 | Dr. Reddy's Laboratories Limited | Solid state forms of empagliflozin |
| CN109476624B (zh) | 2016-05-28 | 2021-07-09 | 吉林惠升生物制药有限公司 | 钠-葡萄糖协同转运蛋白2抑制剂的晶型 |
| MX2023004791A (es) * | 2017-12-19 | 2023-12-07 | Boehringer Ingelheim Vetmedica Gmbh | Sintesis del cocristal 1:1:1 de 1-ciano-2-(4-ciclopropil-bencil)-4 -(beta-d-glucopiranos-1-il)-benceno, l-prolina y agua. |
| BR112022010385A2 (pt) | 2019-11-28 | 2022-08-23 | Boehringer Ingelheim Vetmedica Gmbh | Uso de inibidores de sglt-2 na secagem de mamíferos não humanos |
| JP7423800B2 (ja) | 2020-02-17 | 2024-01-29 | ベーリンガー インゲルハイム フェトメディカ ゲーエムベーハー | ネコにおける心臓疾患の予防および／または治療のためのｓｇｌｔ－２阻害剤の使用 |
| US20240269105A1 (en) | 2021-07-28 | 2024-08-15 | Boehringer Ingelheim Vetmedica Gmbh | Use of sglt-2 inhibitors for the prevention and/or treatment of hypertension in non-human mammals |
| JP2024525981A (ja) | 2021-07-28 | 2024-07-12 | ベーリンガー インゲルハイム フェトメディカ ゲーエムベーハー | ヒト以外の哺乳動物における腎疾患の予防及び／又は治療のためのｓｇｌｔ－２阻害剤の使用 |
| KR20240041966A (ko) | 2021-07-28 | 2024-04-01 | 베링거잉겔하임베트메디카게엠베하 | 고양이를 제외한 비인간 포유류, 특히 개에서 심장 질환의 예방 및/또는 치료를 위한 sglt-2 억제제의 용도 |
| CA3256728A1 (en) | 2022-05-25 | 2023-11-30 | Boehringer Ingelheim Vetmedica Gmbh | AQUEOUS PHARMACEUTICAL COMPOSITIONS CONTAINING SGLT-2 INHIBITORS |
| AR132054A1 (es) | 2023-03-06 | 2025-05-21 | Boehringer Ingelheim Vetmedica Gmbh | Sistemas y métodos para la administración de composiciones farmacéuticas líquidas, en particular que comprenden uno o más inhibidores de sglt-2 |
| CN121039113A (zh) | 2023-04-24 | 2025-11-28 | 勃林格殷格翰动物保健有限公司 | 维格列净与所选共晶形成剂的结晶复合物、其制备方法及其在制备药物中的用途 |
| CN121175053A (zh) | 2023-05-24 | 2025-12-19 | 勃林格殷格翰动物保健有限公司 | 包含一或多种sglt-2抑制剂及替米沙坦的非人类哺乳动物中肾脏疾病和/或高血压的组合治疗和/或预防 |
| CN121218995A (zh) | 2023-05-24 | 2025-12-26 | 勃林格殷格翰动物保健有限公司 | 包含一或多种sglt-2抑制剂及匹莫苯丹和/或替米沙坦的非人类哺乳动物中心脏疾病的组合治疗和/或预防 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007093610A1 (en) * | 2006-02-15 | 2007-08-23 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
| WO2007128749A1 (en) * | 2006-05-03 | 2007-11-15 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2258141T3 (es) | 2001-04-11 | 2006-08-16 | Bristol-Myers Squibb Company | Complejos de aminoacidos de glucosidos c-arilo para el tratamiento de la diabetes y procedimiento. |
| US7927613B2 (en) * | 2002-02-15 | 2011-04-19 | University Of South Florida | Pharmaceutical co-crystal compositions |
| BR0317929A (pt) * | 2003-01-03 | 2006-04-11 | Bristol Myers Squibb Co | métodos de produzir inibidores de sglt2 de glicosìdeo de c-arila |
| EA011158B1 (ru) * | 2004-03-16 | 2009-02-27 | Бёрингер Ингельхайм Интернациональ Гмбх | Замещённые глюкопиранозилом бензольные производные, содержащие эти соединения лекарственные средства, их применение и способ их получения |
| BRPI0615882A2 (pt) * | 2005-09-08 | 2011-05-31 | Boehringer Ingelheim Int | formas cristalinas de 1-cloro-4-(beta-d-glicopiranos-1-il)-2-(4-etinil-benzil)- benzeno, métodos para sua preparação e o uso para preparar medicamentos do mesmo |
| TWI370818B (en) * | 2006-04-05 | 2012-08-21 | Astellas Pharma Inc | Cocrystal of c-glycoside derivative and l-proline |
| US7919598B2 (en) | 2006-06-28 | 2011-04-05 | Bristol-Myers Squibb Company | Crystal structures of SGLT2 inhibitors and processes for preparing same |
| TW200817424A (en) | 2006-08-04 | 2008-04-16 | Daiichi Sankyo Co Ltd | Benzylphenyl glucopyranoside derivatives |
| TW200904405A (en) | 2007-03-22 | 2009-02-01 | Bristol Myers Squibb Co | Pharmaceutical formulations containing an SGLT2 inhibitor |
| US20080287529A1 (en) * | 2007-05-18 | 2008-11-20 | Bristol-Myers Squibb Company | Crystal structures of sglt2 inhibitors and processes for preparing same |
| CN101468976B (zh) * | 2007-12-27 | 2013-11-20 | 百时美施贵宝公司 | Sglt2抑制剂的晶体结构及其制备方法 |
| HRP20161648T1 (hr) * | 2008-08-22 | 2017-02-10 | Theracos Sub, Llc | Postupak za pripravu sglt2 inhibitora |
| AU2009286380B2 (en) | 2008-08-28 | 2011-09-15 | Pfizer Inc. | Dioxa-bicyclo[3.2.1.]octane-2,3,4-triol derivatives |
| WO2010048358A2 (en) | 2008-10-22 | 2010-04-29 | Auspex Pharmaceutical, Inc. | Ethoxyphenylmethyl inhibitors of sglt2 |
| WO2011153712A1 (en) * | 2010-06-12 | 2011-12-15 | Theracos, Inc. | Crystalline form of benzylbenzene sglt2 inhibitor |
| US9145434B2 (en) | 2012-07-26 | 2015-09-29 | Boehringer Ingelheim International Gmbh | Crystalline complex of 1-cyano-2-(4-cyclopropyl-benzyl)-4-(ss-d-glucopyranos-1-yl)-benzene, methods for its preparation and the use thereof for preparing medicaments |
| PT2981269T (pt) | 2013-04-04 | 2023-10-10 | Boehringer Ingelheim Vetmedica Gmbh | Tratamento de distúrbios metabólicos em animais equinos |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007093610A1 (en) * | 2006-02-15 | 2007-08-23 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
| WO2007128749A1 (en) * | 2006-05-03 | 2007-11-15 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
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