CA2635838A1 - Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture - Google Patents
Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture Download PDFInfo
- Publication number
- CA2635838A1 CA2635838A1 CA002635838A CA2635838A CA2635838A1 CA 2635838 A1 CA2635838 A1 CA 2635838A1 CA 002635838 A CA002635838 A CA 002635838A CA 2635838 A CA2635838 A CA 2635838A CA 2635838 A1 CA2635838 A1 CA 2635838A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- group
- ethyl
- hydroxy
- benzyl
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 119
- 150000008359 benzonitriles Chemical class 0.000 title claims abstract description 13
- 239000008194 pharmaceutical composition Chemical class 0.000 title claims description 24
- 238000000034 method Methods 0.000 title description 27
- 230000008569 process Effects 0.000 title description 9
- 238000004519 manufacturing process Methods 0.000 title description 4
- -1 2-hydroxyl-ethyl Chemical group 0.000 claims abstract description 69
- 239000000203 mixture Substances 0.000 claims abstract description 68
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 22
- 239000000460 chlorine Substances 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 9
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims abstract description 9
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 7
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims abstract description 3
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims abstract description 3
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims abstract description 3
- 239000011737 fluorine Substances 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 3
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims abstract description 3
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims abstract description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 3
- 125000006702 (C1-C18) alkyl group Chemical group 0.000 claims abstract 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 229910052740 iodine Inorganic materials 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 claims description 11
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 claims description 11
- 102100037202 Sodium/myo-inositol cotransporter 2 Human genes 0.000 claims description 11
- 101710090560 Sodium/myo-inositol cotransporter 2 Proteins 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 11
- 229910052796 boron Inorganic materials 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 108091006269 SLC5A2 Proteins 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 8
- 150000003857 carboxamides Chemical class 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 6
- 125000004036 acetal group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 210000004185 liver Anatomy 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 5
- 230000002159 abnormal effect Effects 0.000 claims description 5
- 238000009825 accumulation Methods 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 150000003214 pyranose derivatives Chemical group 0.000 claims description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
- 239000002934 diuretic Substances 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- 229940030600 antihypertensive agent Drugs 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 230000007850 degeneration Effects 0.000 claims description 3
- 150000002012 dioxanes Chemical group 0.000 claims description 3
- 230000006806 disease prevention Effects 0.000 claims description 3
- 229940030606 diuretics Drugs 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 208000010444 Acidosis Diseases 0.000 claims description 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 2
- 201000001431 Hyperuricemia Diseases 0.000 claims description 2
- 208000013016 Hypoglycemia Diseases 0.000 claims description 2
- 206010022489 Insulin Resistance Diseases 0.000 claims description 2
- 208000007976 Ketosis Diseases 0.000 claims description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
- 206010027417 Metabolic acidosis Diseases 0.000 claims description 2
- 206010030113 Oedema Diseases 0.000 claims description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 208000018914 glucose metabolism disease Diseases 0.000 claims description 2
- 230000035879 hyperinsulinaemia Effects 0.000 claims description 2
- 230000004140 ketosis Effects 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- 102000058081 Sodium-Glucose Transporter 2 Human genes 0.000 claims 1
- 125000003172 aldehyde group Chemical group 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 132
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 109
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 239000000243 solution Substances 0.000 description 94
- 238000001819 mass spectrum Methods 0.000 description 62
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 47
- 239000002904 solvent Substances 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 45
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 37
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- 229940093499 ethyl acetate Drugs 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 36
- 235000002639 sodium chloride Nutrition 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 239000013543 active substance Substances 0.000 description 33
- 229910052938 sodium sulfate Inorganic materials 0.000 description 30
- 235000011152 sodium sulphate Nutrition 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 239000012074 organic phase Substances 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- 229910052751 metal Inorganic materials 0.000 description 16
- 239000002184 metal Substances 0.000 description 16
- 125000006239 protecting group Chemical group 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 230000000875 corresponding effect Effects 0.000 description 14
- 229910052723 transition metal Inorganic materials 0.000 description 14
- 150000003624 transition metals Chemical class 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- 150000001299 aldehydes Chemical group 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 102100020888 Sodium/glucose cotransporter 2 Human genes 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 229960004132 diethyl ether Drugs 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 239000012039 electrophile Substances 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 229910052744 lithium Inorganic materials 0.000 description 7
- 239000011777 magnesium Substances 0.000 description 7
- 229910052749 magnesium Inorganic materials 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 239000011369 resultant mixture Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052725 zinc Inorganic materials 0.000 description 7
- 239000011701 zinc Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 6
- 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 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 150000001241 acetals Chemical class 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 239000003638 chemical reducing agent Substances 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
- 238000001816 cooling Methods 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
- 239000007848 Bronsted acid Substances 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- 239000002841 Lewis acid Substances 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 235000012209 glucono delta-lactone Nutrition 0.000 description 5
- 229960003681 gluconolactone Drugs 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
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- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 150000003752 zinc compounds Chemical class 0.000 description 1
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Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
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- 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
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Medicinal Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
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- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06101711.7 | 2006-02-15 | ||
| EP06101711 | 2006-02-15 | ||
| EP06113412 | 2006-05-03 | ||
| EP06113412.8 | 2006-05-03 | ||
| EP06124833 | 2006-11-27 | ||
| EP06124833.2 | 2006-11-27 | ||
| PCT/EP2007/051411 WO2007093610A1 (en) | 2006-02-15 | 2007-02-14 | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2635838A1 true CA2635838A1 (en) | 2007-08-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002635838A Abandoned CA2635838A1 (en) | 2006-02-15 | 2007-02-14 | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7745414B2 (enExample) |
| EP (1) | EP1989191B1 (enExample) |
| JP (1) | JP2009531291A (enExample) |
| KR (1) | KR20080102395A (enExample) |
| AR (1) | AR059489A1 (enExample) |
| AT (1) | ATE517099T1 (enExample) |
| AU (1) | AU2007216452A1 (enExample) |
| BR (1) | BRPI0707849A2 (enExample) |
| CA (1) | CA2635838A1 (enExample) |
| EA (1) | EA200801773A1 (enExample) |
| EC (1) | ECSP088605A (enExample) |
| IL (1) | IL193385A0 (enExample) |
| NO (1) | NO20082649L (enExample) |
| TW (1) | TW200801029A (enExample) |
| WO (1) | WO2007093610A1 (enExample) |
Families Citing this family (145)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| ME01422B (me) * | 2004-03-16 | 2013-12-20 | Boehringer Ingelheim Int | Derivati benzola supstituisani glukopiranozilom, ljekovi koji sadrže navedena jedinjenja, njihova primjena i njihov postupak proizvodnje |
| DE102004048388A1 (de) * | 2004-10-01 | 2006-04-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | D-Pyranosyl-substituierte Phenyle, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| JP2008524162A (ja) * | 2004-12-16 | 2008-07-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | グルコピラノシル置換ベンゼン誘導体、該化合物を含む薬物、その使用及びその製造方法 |
| WO2006089872A1 (en) * | 2005-02-23 | 2006-08-31 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted ( (hetero)arylethynyl-benzyd-benzene derivatives and use thereof as sodium-dependent glucose cotransporter 2 (sglt2) inhibitors |
| WO2006108842A1 (en) * | 2005-04-15 | 2006-10-19 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted (heteroaryloxy-benzyl)-benzene derivatives as sglt inhibitors |
| UA91546C2 (uk) | 2005-05-03 | 2010-08-10 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ |
| US7723309B2 (en) * | 2005-05-03 | 2010-05-25 | Boehringer Ingelheim International Gmbh | Crystalline forms of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene, a method for its preparation and the use thereof for preparing medicaments |
| US7772191B2 (en) | 2005-05-10 | 2010-08-10 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein |
| TW200726755A (en) * | 2005-07-07 | 2007-07-16 | Astellas Pharma Inc | A crystalline choline salt of an azulene derivative |
| DE602006014411D1 (de) * | 2005-07-27 | 2010-07-01 | Boehringer Ingelheim Pharma | Glucopyranosyl-substituierte ((hetero)cycloalyklethynyl-benzyl)-benzenderivative und deren verwendung als inhibitoren des natriumabhängigen glucose-cotransporters (sglt) |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| CA2620566A1 (en) * | 2005-08-30 | 2007-03-08 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| TW200745075A (en) * | 2005-09-08 | 2007-12-16 | Boehringer Ingelheim Int | Crystalline forms of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-(4-ethynyl-benzyl)-benzene, methods for its preparation and the use thereof for preparing medicaments |
| AR056195A1 (es) * | 2005-09-15 | 2007-09-26 | Boehringer Ingelheim Int | Procedimientos para preparar derivados de (etinil-bencil)-benceno sustituidos de glucopiranosilo y compuestos intermedios de los mismos |
| PE20080697A1 (es) * | 2006-05-03 | 2008-08-05 | Boehringer Ingelheim Int | Derivados de benzonitrilo sustituidos con glucopiranosilo, composiciones farmaceuticas que contienen compuestos de este tipo, su uso y procedimiento para su fabricacion |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
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| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| WO2008020011A1 (en) * | 2006-08-15 | 2008-02-21 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted cyclopropylbenzene derivatives, pharmaceutical compositions containing such compounds, their use as sglt inhibitors and process for their manufacture |
| CA2664095A1 (en) * | 2006-09-21 | 2008-03-27 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted difluorobenzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| JP2010507629A (ja) * | 2006-10-27 | 2010-03-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ４−（β−Ｄ−グルコピラノス−１−イル）−１−メチル−２−［４−（（Ｓ）−テトラヒドロフラン−３−イルオキシ）−ベンジル］−ベンゼンの結晶形、その製造方法及び医薬品を製造するための使用 |
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| JPWO2008075736A1 (ja) * | 2006-12-21 | 2010-04-15 | アステラス製薬株式会社 | Ｃ−グリコシド誘導体の製造方法及びその合成中間体 |
| JP2010519273A (ja) | 2007-02-21 | 2010-06-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 四置換グルコピラノシル化ベンゼン誘導体、このような化合物を含む薬物、それらの使用及びそれらの製造方法 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| CL2008002427A1 (es) | 2007-08-16 | 2009-09-11 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende 1-cloro-4-(b-d-glucopiranos-1-il)-2-[4-((s)-tetrahidrofurano-3-iloxi)bencil]-benceno combinado con 1-[(4-metilquinazolin-2-il)metil]-3-metil-7-(2-butin-1-il)-8-(3-(r)-aminopiperidin-1-il)xantina; y su uso para tratar diabetes mellitus tipo 2. |
| EP2217602B1 (en) | 2007-11-30 | 2018-08-29 | Boehringer Ingelheim International GmbH | 1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one derivatives and their use as pde9a modulators for the treatment of cns disorders |
| EP2236137B1 (en) * | 2008-01-31 | 2015-06-24 | Astellas Pharma Inc. | Pharmaceutical composition for treatment of fatty liver diseases |
| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
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| US8603989B2 (en) * | 2008-05-22 | 2013-12-10 | Bristol-Myers Squibb Company | Method for treating and preventing kidney stones employing an SGLT2 inhibitor and composition containing same |
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| BRPI0916769A2 (pt) | 2008-07-15 | 2017-09-26 | Theracos Inc | derivados de benzilbenzeno deuterados e métodos de uso |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| KR20190016601A (ko) | 2008-08-06 | 2019-02-18 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
| US9079905B2 (en) | 2008-09-08 | 2015-07-14 | Boehringer Ingelheim International Gmbh | Compounds for the treatment of CNS disorders |
| MX2011002558A (es) | 2008-09-10 | 2011-04-26 | Boehringer Ingelheim Int | Terapia de combinacion para el tratamiento de diabetes y estados relacionados. |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| CA2745037C (en) | 2008-12-23 | 2020-06-23 | Boehringer Ingelheim International Gmbh | Salt forms of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8(3-(r)-amino-piperidin-1-yl)-xanthine |
| AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
| KR101921934B1 (ko) | 2009-02-13 | 2018-11-26 | 베링거 인겔하임 인터내셔날 게엠베하 | 글루코피라노실 디페닐메탄 유도체를 포함하는 약제학적 조성물, 이들의 약제학적 용량형, 이들의 제조방법 및 환자에서의 개선된 당 조절을 위한 이들의 용도 |
| UY32427A (es) | 2009-02-13 | 2010-09-30 | Boheringer Ingelheim Internat Gmbh | Composicion farmaceutica, forma farmaceutica, procedimiento para su preparacion, metodos de tratamiento y usos de la misma |
| AU2010212867B2 (en) * | 2009-02-13 | 2013-05-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition comprising a SGLT2 inhibitor, a DPP-IV inhibitor and optionally a further antidiabetic agent and uses thereof |
| AU2016213789B2 (en) * | 2009-02-13 | 2018-01-18 | Boehringer Ingelheim International Gmbh | SGLT-2 inhibitor for treating type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance or hyperglycemia |
| EA021796B1 (ru) * | 2009-02-13 | 2015-09-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Способы улучшения гликемического контроля и снижения жира в организме, или профилактики увеличения жира в организме, или ускорения снижения жира в организме путем применения ингибитора sglt-2 |
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| CN102753161A (zh) | 2009-11-27 | 2012-10-24 | 贝林格尔.英格海姆国际有限公司 | 基因型糖尿病患者利用dpp-iv抑制剂例如利拉利汀的治疗 |
| AR079438A1 (es) | 2009-12-09 | 2012-01-25 | Panacea Biotec Ltd | Derivados de azucar, composiciones farmaceuticas y sus usos |
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| DE102004048388A1 (de) * | 2004-10-01 | 2006-04-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | D-Pyranosyl-substituierte Phenyle, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| JP2008524162A (ja) * | 2004-12-16 | 2008-07-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | グルコピラノシル置換ベンゼン誘導体、該化合物を含む薬物、その使用及びその製造方法 |
| WO2006089872A1 (en) | 2005-02-23 | 2006-08-31 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted ( (hetero)arylethynyl-benzyd-benzene derivatives and use thereof as sodium-dependent glucose cotransporter 2 (sglt2) inhibitors |
| WO2006108842A1 (en) | 2005-04-15 | 2006-10-19 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted (heteroaryloxy-benzyl)-benzene derivatives as sglt inhibitors |
| US7723309B2 (en) | 2005-05-03 | 2010-05-25 | Boehringer Ingelheim International Gmbh | Crystalline forms of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene, a method for its preparation and the use thereof for preparing medicaments |
| UA91546C2 (uk) * | 2005-05-03 | 2010-08-10 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ |
| US7772191B2 (en) | 2005-05-10 | 2010-08-10 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein |
| WO2007000445A1 (en) * | 2005-06-29 | 2007-01-04 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| DE602006014411D1 (de) * | 2005-07-27 | 2010-07-01 | Boehringer Ingelheim Pharma | Glucopyranosyl-substituierte ((hetero)cycloalyklethynyl-benzyl)-benzenderivative und deren verwendung als inhibitoren des natriumabhängigen glucose-cotransporters (sglt) |
| CA2620566A1 (en) | 2005-08-30 | 2007-03-08 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| TW200745075A (en) * | 2005-09-08 | 2007-12-16 | Boehringer Ingelheim Int | Crystalline forms of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-(4-ethynyl-benzyl)-benzene, methods for its preparation and the use thereof for preparing medicaments |
| AR056195A1 (es) | 2005-09-15 | 2007-09-26 | Boehringer Ingelheim Int | Procedimientos para preparar derivados de (etinil-bencil)-benceno sustituidos de glucopiranosilo y compuestos intermedios de los mismos |
| PE20080697A1 (es) * | 2006-05-03 | 2008-08-05 | Boehringer Ingelheim Int | Derivados de benzonitrilo sustituidos con glucopiranosilo, composiciones farmaceuticas que contienen compuestos de este tipo, su uso y procedimiento para su fabricacion |
-
2007
- 2007-02-14 US US11/674,839 patent/US7745414B2/en active Active
- 2007-02-14 EA EA200801773A patent/EA200801773A1/ru unknown
- 2007-02-14 WO PCT/EP2007/051411 patent/WO2007093610A1/en not_active Ceased
- 2007-02-14 CA CA002635838A patent/CA2635838A1/en not_active Abandoned
- 2007-02-14 JP JP2008554770A patent/JP2009531291A/ja active Pending
- 2007-02-14 EP EP07726367A patent/EP1989191B1/en active Active
- 2007-02-14 TW TW096105389A patent/TW200801029A/zh unknown
- 2007-02-14 AU AU2007216452A patent/AU2007216452A1/en not_active Abandoned
- 2007-02-14 AR ARP070100615A patent/AR059489A1/es unknown
- 2007-02-14 KR KR1020087022537A patent/KR20080102395A/ko not_active Withdrawn
- 2007-02-14 BR BRPI0707849-8A patent/BRPI0707849A2/pt not_active IP Right Cessation
- 2007-02-14 AT AT07726367T patent/ATE517099T1/de active
-
2008
- 2008-06-05 NO NO20082649A patent/NO20082649L/no not_active Application Discontinuation
- 2008-07-04 EC EC2008008605A patent/ECSP088605A/es unknown
- 2008-08-12 IL IL193385A patent/IL193385A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EA200801773A1 (ru) | 2009-02-27 |
| EP1989191B1 (en) | 2011-07-20 |
| JP2009531291A (ja) | 2009-09-03 |
| US20080058379A1 (en) | 2008-03-06 |
| NO20082649L (no) | 2008-09-09 |
| BRPI0707849A2 (pt) | 2011-05-10 |
| US7745414B2 (en) | 2010-06-29 |
| KR20080102395A (ko) | 2008-11-25 |
| TW200801029A (en) | 2008-01-01 |
| AU2007216452A1 (en) | 2007-08-23 |
| AR059489A1 (es) | 2008-04-09 |
| ECSP088605A (es) | 2008-08-29 |
| EP1989191A1 (en) | 2008-11-12 |
| WO2007093610A1 (en) | 2007-08-23 |
| ATE517099T1 (de) | 2011-08-15 |
| IL193385A0 (en) | 2009-05-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20150721 |