BR112012009053B1 - Derivados de glicosídeos, seus usos, e composições farmacêuticas - Google Patents
Derivados de glicosídeos, seus usos, e composições farmacêuticas Download PDFInfo
- Publication number
- BR112012009053B1 BR112012009053B1 BR112012009053-4A BR112012009053A BR112012009053B1 BR 112012009053 B1 BR112012009053 B1 BR 112012009053B1 BR 112012009053 A BR112012009053 A BR 112012009053A BR 112012009053 B1 BR112012009053 B1 BR 112012009053B1
- Authority
- BR
- Brazil
- Prior art keywords
- phenyl
- tetrahydro
- triol
- hydroxymethyl
- pyran
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 229930182470 glycoside Natural products 0.000 title abstract description 5
- 150000002338 glycosides Chemical class 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 47
- 201000010099 disease Diseases 0.000 claims abstract description 40
- 238000011282 treatment Methods 0.000 claims abstract description 31
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 24
- 239000011734 sodium Substances 0.000 claims abstract description 19
- 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 abstract description 18
- 230000001404 mediated effect Effects 0.000 claims abstract description 17
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 17
- 102000034534 Cotransporters Human genes 0.000 claims abstract description 15
- 108020003264 Cotransporters Proteins 0.000 claims abstract description 15
- 125000001424 substituent group Chemical group 0.000 claims description 84
- 239000001257 hydrogen Substances 0.000 claims description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims description 73
- 150000003839 salts Chemical class 0.000 claims description 63
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 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 40
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 37
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 26
- 239000003112 inhibitor Substances 0.000 claims description 24
- 102000004877 Insulin Human genes 0.000 claims description 18
- 108090001061 Insulin Proteins 0.000 claims description 18
- 229940125396 insulin Drugs 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 16
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims description 15
- 206010022489 Insulin Resistance Diseases 0.000 claims description 15
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 14
- 208000008589 Obesity Diseases 0.000 claims description 12
- 235000020824 obesity Nutrition 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 229940123208 Biguanide Drugs 0.000 claims description 8
- 229920001268 Cholestyramine Polymers 0.000 claims description 8
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims description 8
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 8
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 claims description 8
- 229940122199 Insulin secretagogue Drugs 0.000 claims description 8
- 239000011230 binding agent Substances 0.000 claims description 8
- 229940125753 fibrate Drugs 0.000 claims description 8
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 7
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 229940122355 Insulin sensitizer Drugs 0.000 claims description 7
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 7
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 7
- 102000018692 Sulfonylurea Receptors Human genes 0.000 claims description 7
- 108010091821 Sulfonylurea Receptors Proteins 0.000 claims description 7
- 230000002473 insulinotropic effect Effects 0.000 claims description 7
- 239000003446 ligand Substances 0.000 claims description 7
- 229960003512 nicotinic acid Drugs 0.000 claims description 7
- 235000001968 nicotinic acid Nutrition 0.000 claims description 7
- 239000011664 nicotinic acid Substances 0.000 claims description 7
- 239000004059 squalene synthase inhibitor Substances 0.000 claims description 7
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 6
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 6
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 6
- 201000001421 hyperglycemia Diseases 0.000 claims description 6
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 239000004026 insulin derivative Substances 0.000 claims description 4
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 claims 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 118
- 238000000034 method Methods 0.000 abstract description 71
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 218
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 171
- -1 biguanides) Chemical compound 0.000 description 162
- 239000000243 solution Substances 0.000 description 149
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 112
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 125000005843 halogen group Chemical group 0.000 description 98
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
- 239000011541 reaction mixture Substances 0.000 description 88
- 238000005481 NMR spectroscopy Methods 0.000 description 84
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 79
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 78
- 235000019439 ethyl acetate Nutrition 0.000 description 74
- 125000000623 heterocyclic group Chemical group 0.000 description 74
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 71
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 70
- 229960002429 proline Drugs 0.000 description 70
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 69
- 238000006243 chemical reaction Methods 0.000 description 64
- 239000012267 brine Substances 0.000 description 63
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 63
- 229910052938 sodium sulfate Inorganic materials 0.000 description 61
- 235000011152 sodium sulphate Nutrition 0.000 description 61
- 239000000543 intermediate Substances 0.000 description 59
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 56
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 56
- 125000000217 alkyl group Chemical group 0.000 description 50
- 239000012044 organic layer Substances 0.000 description 50
- 238000000634 powder X-ray diffraction Methods 0.000 description 50
- 125000001072 heteroaryl group Chemical group 0.000 description 49
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 48
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 239000000460 chlorine Substances 0.000 description 42
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 42
- 238000003756 stirring Methods 0.000 description 41
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- 238000010898 silica gel chromatography Methods 0.000 description 40
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 38
- 150000002431 hydrogen Chemical group 0.000 description 38
- 125000003118 aryl group Chemical group 0.000 description 37
- 230000002829 reductive effect Effects 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- 239000012043 crude product Substances 0.000 description 33
- 229910052757 nitrogen Inorganic materials 0.000 description 33
- 235000017557 sodium bicarbonate Nutrition 0.000 description 33
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 33
- 239000002253 acid Substances 0.000 description 32
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 31
- 229920006395 saturated elastomer Polymers 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
- 125000004093 cyano group Chemical group *C#N 0.000 description 28
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 28
- 239000008103 glucose Substances 0.000 description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 26
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 24
- 229930182821 L-proline Natural products 0.000 description 24
- 229910052799 carbon Inorganic materials 0.000 description 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 21
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 21
- 125000004429 atom Chemical group 0.000 description 21
- 239000013078 crystal Substances 0.000 description 21
- 239000003039 volatile agent Substances 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 229910052801 chlorine Inorganic materials 0.000 description 19
- 238000004440 column chromatography Methods 0.000 description 19
- 125000003003 spiro group Chemical group 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- 125000003545 alkoxy group Chemical group 0.000 description 18
- 125000004104 aryloxy group Chemical group 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 125000000000 cycloalkoxy group Chemical group 0.000 description 18
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 125000005553 heteroaryloxy group Chemical group 0.000 description 17
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 17
- 125000004043 oxo group Chemical group O=* 0.000 description 17
- 238000002953 preparative HPLC Methods 0.000 description 17
- 125000000753 cycloalkyl group Chemical group 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- YNCHESVKDKRUDJ-SJSRKZJXSA-N (2s,3r,4r,5s,6r)-2-[4-cyclopropyl-3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C(C=C1CC=2C=C3OCCOC3=CC=2)=CC=C1C1CC1 YNCHESVKDKRUDJ-SJSRKZJXSA-N 0.000 description 15
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
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- XFJAMQQAAMJFGB-ZQGJOIPISA-N (2s,3r,4r,5s,6r)-2-[3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-ethylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound C1=C(CC=2C=C3OCCOC3=CC=2)C(CC)=CC=C1[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O XFJAMQQAAMJFGB-ZQGJOIPISA-N 0.000 description 14
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- 125000002950 monocyclic group Chemical group 0.000 description 14
- OXMCCMNQOLPNQU-RXFVIIJJSA-N (2r,3s,4r,5r,6s)-2-(hydroxymethyl)-6-[4-propan-2-yl-3-(1,2,3,4-tetrahydroquinolin-7-ylmethyl)phenyl]oxane-3,4,5-triol Chemical compound C1=C(CC=2C=C3NCCCC3=CC=2)C(C(C)C)=CC=C1[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O OXMCCMNQOLPNQU-RXFVIIJJSA-N 0.000 description 13
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- MPCAJMNYNOGXPB-UHFFFAOYSA-N 1,5-anhydrohexitol Chemical compound OCC1OCC(O)C(O)C1O MPCAJMNYNOGXPB-UHFFFAOYSA-N 0.000 description 12
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 12
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
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- 238000001228 spectrum Methods 0.000 description 11
- FTNIERGYEVLCRV-ADAARDCZSA-N (2s,3r,4r,5s,6r)-2-[4-chloro-3-(3,4-dihydro-2h-1,4-benzoxazin-6-ylmethyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=C3NCCOC3=CC=2)=C1 FTNIERGYEVLCRV-ADAARDCZSA-N 0.000 description 10
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- 230000003595 spectral effect Effects 0.000 description 9
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 125000002947 alkylene group Chemical group 0.000 description 8
- 125000002619 bicyclic group Chemical group 0.000 description 8
- 125000001309 chloro group Chemical group Cl* 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
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- 229910052744 lithium Inorganic materials 0.000 description 8
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- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
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- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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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
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Landscapes
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- Child & Adolescent Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2173/DEL/2009 | 2009-10-20 | ||
| IN2173DE2009 | 2009-10-20 | ||
| IN2689DE2009 | 2009-12-23 | ||
| IN2689/DEL/2009 | 2009-12-23 | ||
| PCT/EP2010/065747 WO2011048112A1 (en) | 2009-10-20 | 2010-10-19 | Glycoside derivatives and uses thereof |
Publications (2)
| Publication Number | Publication Date |
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| BR112012009053A2 BR112012009053A2 (pt) | 2016-04-19 |
| BR112012009053B1 true BR112012009053B1 (pt) | 2020-03-03 |
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| Application Number | Title | Priority Date | Filing Date |
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| BR112012009053-4A BR112012009053B1 (pt) | 2009-10-20 | 2010-10-19 | Derivados de glicosídeos, seus usos, e composições farmacêuticas |
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| SG174402A1 (en) | 2009-03-23 | 2011-10-28 | Glenmark Pharmaceuticals Sa | Fused pyrimidine-dione derivatives as trpa1 modulators |
| US20110009347A1 (en) | 2009-07-08 | 2011-01-13 | Yin Liang | Combination therapy for the treatment of diabetes |
| US8163704B2 (en) * | 2009-10-20 | 2012-04-24 | Novartis Ag | Glycoside derivatives and uses thereof |
| CN102134226B (zh) * | 2010-01-26 | 2013-06-12 | 天津药物研究院 | 一类苯基c-葡萄糖苷衍生物、其制备方法和用途 |
| SG185525A1 (en) | 2010-05-11 | 2012-12-28 | Janssen Pharmaceutica Nv | Pharmaceutical formulations comprising 1 - (beta-d-glucopyranosyl) - 2 -thienylmethylbenzene derivatives as inhibitors of sglt |
| AU2012241897C1 (en) | 2011-04-13 | 2017-05-11 | Janssen Pharmaceutica Nv | Process for the preparation of compounds useful as inhibitors of SGLT2 |
| US8614195B2 (en) * | 2011-04-14 | 2013-12-24 | Novartis Ag | Glycoside derivatives and uses thereof |
| JP2014510782A (ja) | 2011-04-14 | 2014-05-01 | ノバルティス アーゲー | グリコシド誘導体およびその使用 |
| US9035044B2 (en) * | 2011-05-09 | 2015-05-19 | Janssen Pharmaceutica Nv | L-proline and citric acid co-crystals of (2S, 3R, 4R, 5S,6R)-2-(3-((5-(4-fluorophenyl)thiopen-2-yl)methyl)4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol |
| ES2719656T3 (es) * | 2011-06-01 | 2019-07-11 | Green Cross Corp | Derivados de difenilmetano novedosos como inhibidores del SGLT2 |
| CN102827122B (zh) * | 2011-06-17 | 2015-01-14 | 山东轩竹医药科技有限公司 | 糖苷衍生物 |
| CN102863417B (zh) * | 2011-07-09 | 2015-01-14 | 山东轩竹医药科技有限公司 | C-糖苷衍生物 |
| WO2013010679A1 (en) | 2011-07-15 | 2013-01-24 | Novartis Ag | Salts of aza-bicyclic di-aryl ethers and methods to make them or their precursors |
| AR087701A1 (es) * | 2011-08-31 | 2014-04-09 | Japan Tobacco Inc | Derivados de pirazol con actividad inhibidora de sglt1 |
| UA113086C2 (xx) | 2012-05-10 | 2016-12-12 | Піразольні сполуки як інгібітори sglt1 | |
| AU2014249535B2 (en) * | 2013-03-11 | 2018-03-22 | Janssen Pharmaceutica Nv | Dual SGLT1/SGLT2 inhibitors |
| WO2014203217A1 (en) | 2013-06-21 | 2014-12-24 | Lupin Limited | Substituted heterocyclic compounds as crac modulators |
| EP3013810A1 (en) | 2013-06-24 | 2016-05-04 | Lupin Limited | Chromane and chromene derivatives and their use as crac modulators |
| CN104250272B (zh) * | 2013-06-27 | 2018-10-09 | 上海方楠生物科技有限公司 | 一种利用微反应器制备列净类药物中间体的方法 |
| US10011627B2 (en) | 2013-09-09 | 2018-07-03 | Youngene Therapeutics Co., Ltd | C-aryl glucoside derivative, preparation methods thereof, and medical applications thereof |
| AR098670A1 (es) | 2013-11-08 | 2016-06-08 | Lilly Co Eli | Inhibidor de sglt1 |
| CN104017031A (zh) * | 2014-06-21 | 2014-09-03 | 李友香 | 降血糖药物和组合物 |
| CN104031098A (zh) * | 2014-06-21 | 2014-09-10 | 李友香 | 降糖药物 |
| CN105294624B (zh) * | 2015-11-16 | 2018-01-12 | 山东罗欣药业集团股份有限公司 | 一种达格列净的制备方法 |
| HRP20211670T8 (hr) | 2016-06-17 | 2022-03-18 | Daewoong Pharmaceutical Co., Ltd. | Derivat difenilmetana u kristalnom obliku |
| WO2018089449A1 (en) * | 2016-11-10 | 2018-05-17 | Janssen Pharmaceutica Nv | Benzocyclobutane derivatives useful as dual sglt1/sglt2 modulators |
| CN108203432B (zh) * | 2016-12-20 | 2021-03-02 | 宜昌东阳光长江药业股份有限公司 | 吡喃葡萄糖基衍生物及其在医药上的应用 |
| AR111161A1 (es) | 2017-03-03 | 2019-06-12 | Novartis Ag | Régimen de dosificación para el inhibidor sglt1/2 (licogliflozin) |
| JP2019517459A (ja) * | 2017-04-12 | 2019-06-24 | ノバルティス アーゲー | 心不全患者におけるｌｉｋ０６６の使用 |
| JP2020524684A (ja) * | 2017-06-21 | 2020-08-20 | ノバルティス アーゲー | 非アルコール性脂肪性肝炎の治療のためのリコフリゴジン |
| US10696662B2 (en) | 2017-08-21 | 2020-06-30 | Janssen Pharmaceutica Nv | 5-fluoro-C-(aryl or heterocyclyl)-glycoside derivatives useful as dual SGLT1 / SGLT2 modulators |
| GB201721960D0 (en) | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
| GB201721961D0 (en) | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
| GB201721964D0 (en) | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
| GB201721957D0 (en) | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
| GB201721967D0 (en) | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
| BR112021000964A2 (pt) | 2018-07-25 | 2021-04-20 | Novartis Ag | inibidores do inflamassoma de nlrp3 |
| CN108863736A (zh) * | 2018-07-27 | 2018-11-23 | 福州大学 | 一种羰基功能化的芳香羧酸的制备方法 |
| WO2020039394A1 (en) | 2018-08-24 | 2020-02-27 | Novartis Ag | New drug combinations |
| WO2020151623A1 (zh) * | 2019-01-24 | 2020-07-30 | 北京盈科瑞创新药物研究有限公司 | 化合物、其制备方法及其作为药物中间体的应用 |
| WO2020151620A1 (zh) * | 2019-01-24 | 2020-07-30 | 北京盈科瑞创新药物研究有限公司 | 化合物、其制备方法及其作为药物中间体的应用 |
| AR119731A1 (es) | 2019-05-17 | 2022-01-05 | Novartis Ag | Inhibidores del inflamasoma nlrp3 |
| JP2022541503A (ja) | 2019-07-23 | 2022-09-26 | ノバルティス アーゲー | Ｆｘｒアゴニストを使用した肝疾患の組み合わせ処置 |
| CN111099975A (zh) * | 2019-12-23 | 2020-05-05 | 河北合佳医药科技集团股份有限公司 | 一种5-溴-2-氯-4’-乙氧基二苯甲酮的制备方法 |
| JP2023551441A (ja) * | 2020-11-19 | 2023-12-08 | ベイジン・インクリーズ・イノベーティブ・ドラッグ・カンパニー，リミテッド | グリコシド系誘導体及びその製造方法と応用 |
| KR20220080880A (ko) * | 2020-12-08 | 2022-06-15 | 주식회사 종근당 | 엠파글리플로진 공결정을 함유하는 약제학적 조성물 |
| UY40374A (es) | 2022-08-03 | 2024-02-15 | Novartis Ag | Inhibidores de inflamasoma nlrp3 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1020944C (zh) | 1990-01-30 | 1993-05-26 | 阿图尔-费希尔股份公司费希尔厂 | 紧固件 |
| US5410031A (en) | 1992-02-24 | 1995-04-25 | The Regents Of The University Of California Office Of Technology Transfer | Nucleoside cotransporter protein cDNA |
| US5410054A (en) | 1993-07-20 | 1995-04-25 | Merck Frosst Canada, Inc. | Heteroaryl quinolines as inhibitors of leukotriene biosynthesis |
| WO1998031697A1 (en) | 1997-01-15 | 1998-07-23 | Sankyo Company, Limited | Aryl c-glycoside compounds and sulfated esters thereof |
| HU229581B1 (en) | 1999-08-31 | 2014-02-28 | Kissei Pharmaceutical | Glucopyranosyloxypyrazole derivatives, medicinal compositions containing the same and intermediates in the production thereof |
| PH12000002657B1 (en) | 1999-10-12 | 2006-02-21 | Bristol Myers Squibb Co | C-aryl glucoside SGLT2 inhibitors |
| US6515117B2 (en) * | 1999-10-12 | 2003-02-04 | Bristol-Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
| JP4272319B2 (ja) * | 1999-11-30 | 2009-06-03 | アイシン精機株式会社 | ヘッドレスト装置 |
| US6627611B2 (en) * | 2000-02-02 | 2003-09-30 | Kotobuki Pharmaceutical Co Ltd | C-glycosides and preparation of thereof as antidiabetic agents |
| JP4456768B2 (ja) | 2000-02-02 | 2010-04-28 | 壽製薬株式会社 | Ｃ−配糖体を含有する薬剤 |
| WO2001068660A1 (en) | 2000-03-17 | 2001-09-20 | Kissei Pharmaceutical Co., Ltd. | Glucopyranosyloxy benzylbenzene derivatives, medicinal compositions containing the same and intermediates for the preparation of the derivatives |
| US6683056B2 (en) | 2000-03-30 | 2004-01-27 | Bristol-Myers Squibb Company | O-aryl glucoside SGLT2 inhibitors and method |
| BR0114310A (pt) | 2000-09-29 | 2003-10-14 | Kissei Pharmaceutical | Derivados do glicopiranosiloxibenzilbenzeno e composições medicinais contendo os mesmos |
| US6936590B2 (en) | 2001-03-13 | 2005-08-30 | Bristol Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
| ATE442148T1 (de) | 2001-04-04 | 2009-09-15 | Ortho Mcneil Janssen Pharm | Kombinationstherapie durch glukoseresorptionshemmer und retinoid x rezeptorenmodulatoren |
| JP4590159B2 (ja) | 2001-04-04 | 2010-12-01 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | グルコース再吸収阻害剤およびｐｐａｒモジュレーターを含んで成る併用療法 |
| WO2003020737A1 (en) | 2001-09-05 | 2003-03-13 | Bristol-Myers Squibb Company | O-pyrazole glucoside sglt2 inhibitors and method of use |
| DE10231370B4 (de) | 2002-07-11 | 2006-04-06 | Sanofi-Aventis Deutschland Gmbh | Thiophenglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
| JP2004137245A (ja) | 2002-08-23 | 2004-05-13 | Kissei Pharmaceut Co Ltd | ピラゾール誘導体、それを含有する医薬組成物、その医薬用途及びその製造中間体 |
| JPWO2004050122A1 (ja) | 2002-12-04 | 2006-03-30 | キッセイ薬品工業株式会社 | 高血糖症に起因する疾患の予防又は治療剤 |
| DE10258008B4 (de) | 2002-12-12 | 2006-02-02 | Sanofi-Aventis Deutschland Gmbh | Heterocyclische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
| DE10258007B4 (de) | 2002-12-12 | 2006-02-09 | Sanofi-Aventis Deutschland Gmbh | Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
| ATE419747T1 (de) | 2003-02-05 | 2009-01-15 | Hermann Koepsell | Rs1 defizientes transgenes tier und dessen verwendungen |
| ES2363941T3 (es) | 2003-03-14 | 2011-08-19 | Astellas Pharma Inc. | Derivados de c-glucósido para el tratamiento de diabetes. |
| AU2003902263A0 (en) | 2003-05-12 | 2003-05-29 | Fujisawa Pharmaceutical Co., Ltd. | Monosaccharide compounds |
| EA010655B1 (ru) | 2003-08-01 | 2008-10-30 | Янссен Фармацевтика Н.В. | Замещенные индазол-о-глюкозиды |
| ES2649737T5 (es) * | 2003-08-01 | 2021-07-07 | Mitsubishi Tanabe Pharma Corp | Compuestos novedosos que tienen actividad inhibidora frente a transportador de glucosa dependiente de sodio |
| EP1660509B1 (de) | 2003-08-26 | 2009-02-04 | Boehringer Ingelheim International GmbH | Glucopyranosyloxy-pyrazole, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| EP1724277A4 (en) | 2004-03-04 | 2012-05-02 | Kissei Pharmaceutical | ACCOLE HETEROCYCLIC DERIVATIVE, DRUG-CONTAINING COMPOSITION THEREOF, AND THE USE THEREOF |
| CA2557269C (en) | 2004-03-04 | 2012-12-04 | Kissei Pharmaceutical Co., Ltd. | Fused heterocycle derivative, medicinal composition containing the same, and medicinal use thereof |
| DE102004028241B4 (de) | 2004-06-11 | 2007-09-13 | Sanofi-Aventis Deutschland Gmbh | Neue Fluorglykosidderivate von Pyrazolen, diese Verbindungen enthaltende Arzneimittel und Herstellung dieser Arzneimittel |
| US7393836B2 (en) | 2004-07-06 | 2008-07-01 | Boehringer Ingelheim International Gmbh | D-xylopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture |
| DE102004034690A1 (de) | 2004-07-17 | 2006-02-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Methyliden-D-xylopyranosyl-und Oxo-D-xylopyranosyl-substituierte Phenyle, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| EP1773800A1 (de) | 2004-07-27 | 2007-04-18 | Boehringer Ingelheim International GmbH | D-glucopyranosyl-phenyl-substituierte cyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| WO2006018150A1 (de) | 2004-08-11 | 2006-02-23 | Boehringer Ingelheim International Gmbh | D-xylopyranosyl-phenyl-substituierte cyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| US20090196878A1 (en) | 2004-09-22 | 2009-08-06 | Soraya Shirazi-Beechey | Intestinal epithelial glucose sensor |
| 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 |
| JP5086643B2 (ja) | 2004-11-18 | 2012-11-28 | キッセイ薬品工業株式会社 | １−置換−３−（β−Ｄ−グリコピラノシル）含窒素ヘテロ環化合物、及びそれを含有する医薬 |
| 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 |
| TWI370818B (en) * | 2006-04-05 | 2012-08-21 | Astellas Pharma Inc | Cocrystal of c-glycoside derivative and l-proline |
| WO2007140191A2 (en) | 2006-05-23 | 2007-12-06 | Theracos, Inc. | Glucose transport inhibitors and methods of use |
| US20080027014A1 (en) | 2006-07-28 | 2008-01-31 | Tanabe Seiyaku Co., Ltd. | Novel SGLT inhibitors |
| TW200817424A (en) | 2006-08-04 | 2008-04-16 | Daiichi Sankyo Co Ltd | Benzylphenyl glucopyranoside derivatives |
| WO2008115574A1 (en) | 2007-03-21 | 2008-09-25 | Reliant Pharmaceuticals, Inc. | Cb1 antagonist and a dyslipidemic agent and/or metabolic regulator, and methods of making and using same |
| TW200904454A (en) | 2007-03-22 | 2009-02-01 | Bristol Myers Squibb Co | Methods for treating obesity employing an SGLT2 inhibitor and compositions thereof |
| DK2147315T3 (da) | 2007-04-18 | 2013-09-23 | Tethys Bioscience Inc | Diabetesrelaterede biomarkører og fremgangsmåder til anvendelse deraf |
| EP2197433A4 (en) | 2007-08-20 | 2010-09-08 | Sinai School Medicine | REGULATION OF GLP-1 AND SGLT-1 IN GASTROINTESTINAL CELLS |
| JP4809931B2 (ja) | 2007-08-23 | 2011-11-09 | セラコス・インコーポレイテッド | ベンジルベンゼン誘導体およびその使用方法 |
| CL2008003653A1 (es) | 2008-01-17 | 2010-03-05 | Mitsubishi Tanabe Pharma Corp | Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica. |
| CA2711673A1 (en) * | 2008-01-31 | 2009-08-06 | Astellas Pharma Inc. | Pharmaceutical compositions for treating fatty liver disease |
| WO2009143021A1 (en) | 2008-05-22 | 2009-11-26 | Bristol-Myers Squibb Company | Method for treating and preventing kidney stones employing an sglt2 inhibitor and composition containing same |
| CA2725047A1 (en) | 2008-05-22 | 2009-11-26 | Bristol-Myers Squibb Company | Method for treating hyperuricemia employing an sglt2 inhibitor and composition containing same |
| WO2009143010A1 (en) | 2008-05-22 | 2009-11-26 | Bristol-Myers Squibb Company | Method for treating hyponatremia employing an sglt2 inhibitor and composition containing same |
| JP2012502953A (ja) | 2008-09-19 | 2012-02-02 | ノバルティス アーゲー | グルコシド誘導体およびｓｇｌｔ阻害剤としてのその使用 |
| EA201100502A1 (ru) | 2008-09-19 | 2011-10-31 | Новартис Аг | Гликозидные производные и их применения |
| US9056850B2 (en) | 2008-10-17 | 2015-06-16 | Janssen Pharmaceutica N.V. | Process for the preparation of compounds useful as inhibitors of SGLT |
| WO2010045656A2 (en) | 2008-10-17 | 2010-04-22 | Nectid, Inc. | Novel sglt2 inhibitor dosage forms |
| US20100167988A1 (en) | 2008-10-22 | 2010-07-01 | Auspex Pharmaceuticals, Inc. | Ethoxyphenylmethyl inhibitors of sglt2 |
| WO2010074219A1 (ja) | 2008-12-26 | 2010-07-01 | アステラス製薬株式会社 | ベンゾチオフェン化合物 |
| US20120035105A1 (en) | 2009-01-09 | 2012-02-09 | Sdg, Inc. | Insulin Therapies for the Treatment of Diabetes, Diabetes Related Ailments, and/or Diseases or Conditions Other Than Diabetes or Diabetes Related Ailments |
| KR20110118668A (ko) | 2009-02-13 | 2011-10-31 | 베링거 인겔하임 인터내셔날 게엠베하 | １형 당뇨병, ２형 당뇨병, 내당능 장애 또는 고혈당증을 치료하기 위한 ｓｇｌｔ２ 억제제 |
| EP2395983B1 (en) | 2009-02-13 | 2020-04-08 | Boehringer Ingelheim International GmbH | Pharmaceutical composition comprisng a sglt2 inhibitor, a dpp-iv inhibitor and optionally a further antidiabetic agent and uses thereof |
| WO2010128152A1 (en) * | 2009-05-07 | 2010-11-11 | Novartis Ag | Fused heterocyclic c-glycosides for the treatment of diabetes |
| US8163704B2 (en) * | 2009-10-20 | 2012-04-24 | Novartis Ag | Glycoside derivatives and uses thereof |
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