CA2569915A1 - D-xylopyranosyl-substituted phenyls, medicaments containing said compounds, the use thereof, and methods for producing the same - Google Patents
D-xylopyranosyl-substituted phenyls, medicaments containing said compounds, the use thereof, and methods for producing the same Download PDFInfo
- Publication number
- CA2569915A1 CA2569915A1 CA002569915A CA2569915A CA2569915A1 CA 2569915 A1 CA2569915 A1 CA 2569915A1 CA 002569915 A CA002569915 A CA 002569915A CA 2569915 A CA2569915 A CA 2569915A CA 2569915 A1 CA2569915 A1 CA 2569915A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- groups
- group
- aryl
- cycloalkyl
- 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.)
- Withdrawn
Links
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 52
- 150000001875 compounds Chemical class 0.000 title claims description 105
- 238000000034 method Methods 0.000 title claims description 21
- 239000003814 drug Chemical class 0.000 title abstract description 5
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 claims abstract description 13
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 claims abstract description 13
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 102100037202 Sodium/myo-inositol cotransporter 2 Human genes 0.000 claims abstract description 12
- 101710090560 Sodium/myo-inositol cotransporter 2 Proteins 0.000 claims abstract description 12
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 8
- -1 C1-4-alkylcarbonyl Chemical group 0.000 claims description 137
- 239000000460 chlorine Substances 0.000 claims description 90
- 229910052801 chlorine Inorganic materials 0.000 claims description 86
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 80
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 69
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 65
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 44
- 229910052731 fluorine Inorganic materials 0.000 claims description 42
- 239000011737 fluorine Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 150000002431 hydrogen Chemical class 0.000 claims description 39
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 38
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 229910052794 bromium Inorganic materials 0.000 claims description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 31
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 30
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 17
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 9
- 125000004036 acetal group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical group 0.000 claims description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 9
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 9
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 6
- 125000005997 bromomethyl group Chemical group 0.000 claims description 6
- 239000000969 carrier Substances 0.000 claims description 6
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000006702 (C1-C18) alkyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000002934 diuretic Substances 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 4
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 125000001118 alkylidene group Chemical group 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- 229940030600 antihypertensive agent Drugs 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000004122 cyclic group Chemical group 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
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 150000003214 pyranose derivatives Chemical group 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 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
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 2
- 230000007850 degeneration Effects 0.000 claims description 2
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 claims description 2
- 208000018914 glucose metabolism disease Diseases 0.000 claims description 2
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 2
- 230000035879 hyperinsulinaemia Effects 0.000 claims description 2
- 230000004140 ketosis Effects 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 4
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- 239000000243 solution Substances 0.000 description 148
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 56
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- 235000002639 sodium chloride Nutrition 0.000 description 38
- 239000002904 solvent Substances 0.000 description 38
- 238000001819 mass spectrum Methods 0.000 description 35
- 239000013543 active substance Substances 0.000 description 34
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 28
- 235000011152 sodium sulphate Nutrition 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 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
- 238000002360 preparation method Methods 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 108091006269 SLC5A2 Proteins 0.000 description 8
- 102100020888 Sodium/glucose cotransporter 2 Human genes 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-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
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 235000011089 carbon dioxide Nutrition 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
- 230000000694 effects Effects 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000000556 agonist Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 4
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QBMACPLNLMUFGJ-UHFFFAOYSA-N 4-bromo-1-chloro-2-[(4-methoxyphenyl)methyl]benzene Chemical compound C1=CC(OC)=CC=C1CC1=CC(Br)=CC=C1Cl QBMACPLNLMUFGJ-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 208000002249 Diabetes Complications Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000005708 Sodium hypochlorite Substances 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 125000000532 dioxanyl group Chemical group 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 3
- VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 3
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- 125000002873 tetrahydrofuranonyl group Chemical group 0.000 description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 3
- 125000002673 tetrahydropyranonyl group Chemical group O1C(C(CCC1)*)=O 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
- NIEQZZXEZYUFMQ-UHFFFAOYSA-N (5-bromo-2-chlorophenyl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC(Br)=CC=C1Cl NIEQZZXEZYUFMQ-UHFFFAOYSA-N 0.000 description 2
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- YMMHAIJRFWRDMG-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-1h-quinolin-2-one Chemical compound C1C=CC=C2NC(=O)CCC21 YMMHAIJRFWRDMG-UHFFFAOYSA-N 0.000 description 2
- NTNKZGHUNBWBBV-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-isoquinolin-1-one Chemical compound C1C=CC=C2C(=O)NCCC21 NTNKZGHUNBWBBV-UHFFFAOYSA-N 0.000 description 2
- CSQCYSDEAYXXTN-UHFFFAOYSA-N 4-[(5-bromo-2-chlorophenyl)methyl]phenol Chemical compound C1=CC(O)=CC=C1CC1=CC(Br)=CC=C1Cl CSQCYSDEAYXXTN-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- 206010012655 Diabetic complications Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 108091006277 SLC5A1 Proteins 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 102000058090 Sodium-Glucose Transporter 1 Human genes 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108010084455 Zeocin Proteins 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 2
- 239000012154 double-distilled water Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940121377 sodium-glucose co-transporter inhibitor Drugs 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- 229940075966 (+)- menthol Drugs 0.000 description 1
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 1
- NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- LNSCNEJNLACZPA-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylphenyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=CC=C1C LNSCNEJNLACZPA-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 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
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 239000003148 4 aminobutyric acid receptor blocking agent Substances 0.000 description 1
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
- NFFXEUUOMTXWCX-UHFFFAOYSA-N 5-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-methoxy-n-[[4-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C(F)(F)F)C(OC)=CC=C1CC1SC(=O)NC1=O NFFXEUUOMTXWCX-UHFFFAOYSA-N 0.000 description 1
- FGERXQWKKIVFQG-UHFFFAOYSA-N 5-bromo-2-chlorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC=C1Cl FGERXQWKKIVFQG-UHFFFAOYSA-N 0.000 description 1
- IMVDZFOSXJSXFP-UHFFFAOYSA-N 5-chloro-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carbaldehyde Chemical compound CCCC1=NC(Cl)=C(C=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 IMVDZFOSXJSXFP-UHFFFAOYSA-N 0.000 description 1
- CCIQPVZNSKMTKM-UHFFFAOYSA-N 6-[4-chloro-3-[(4-methoxyphenyl)methyl]phenyl]-3,4,5-trihydroxy-n-methyloxane-2-carboxamide Chemical compound OC1C(O)C(O)C(C(=O)NC)OC1C1=CC=C(Cl)C(CC=2C=CC(OC)=CC=2)=C1 CCIQPVZNSKMTKM-UHFFFAOYSA-N 0.000 description 1
- QNCOMAHAZYTICJ-UHFFFAOYSA-N 6-[4-chloro-3-[(4-methoxyphenyl)methyl]phenyl]-3,4,5-trihydroxyoxane-2-carboxamide Chemical compound C1=CC(OC)=CC=C1CC1=CC(C2C(C(O)C(O)C(O2)C(N)=O)O)=CC=C1Cl QNCOMAHAZYTICJ-UHFFFAOYSA-N 0.000 description 1
- DJRZPSZSVLRVJZ-UHFFFAOYSA-N 6-[4-chloro-3-[(4-methoxyphenyl)methyl]phenyl]-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CC1=CC(C2C(C(O)C(O)C(O2)C(O)=O)O)=CC=C1Cl DJRZPSZSVLRVJZ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101100460776 Arabidopsis thaliana NPY2 gene Proteins 0.000 description 1
- 101100460788 Arabidopsis thaliana NPY5 gene Proteins 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- PTQXTEKSNBVPQJ-UHFFFAOYSA-N Avasimibe Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1CC(=O)NS(=O)(=O)OC1=C(C(C)C)C=CC=C1C(C)C PTQXTEKSNBVPQJ-UHFFFAOYSA-N 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002081 C09CA05 - Tasosartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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 1
- 150000000901 D-xylose derivatives Chemical class 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
- 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 1
- 229940098788 GABA receptor antagonist Drugs 0.000 description 1
- 108091007911 GSKs Proteins 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 229940122904 Glucagon receptor antagonist Drugs 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class 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 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 102000003638 Glucose-6-Phosphatase Human genes 0.000 description 1
- 108010086800 Glucose-6-Phosphatase Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
- 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
- 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 102100030488 HEAT repeat-containing protein 6 Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 101000990566 Homo sapiens HEAT repeat-containing protein 6 Proteins 0.000 description 1
- 101000801684 Homo sapiens Phospholipid-transporting ATPase ABCA1 Proteins 0.000 description 1
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
- 101000716688 Homo sapiens Sodium/glucose cotransporter 1 Proteins 0.000 description 1
- 101000716682 Homo sapiens Sodium/glucose cotransporter 2 Proteins 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- 206010054805 Macroangiopathy Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101000822667 Mus musculus Something about silencing protein 10 Proteins 0.000 description 1
- 101150111774 NPY5R gene Proteins 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 239000005480 Olmesartan Substances 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 102000008316 Type 4 Melanocortin Receptor Human genes 0.000 description 1
- 108010021436 Type 4 Melanocortin Receptor Proteins 0.000 description 1
- 101710204865 Tyrosine-protein phosphatase 1 Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 229940116731 Uricosuric agent Drugs 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- FDKIDFYIEWFERB-UHFFFAOYSA-N [2-butyl-5-chloro-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol;potassium Chemical compound [K].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 FDKIDFYIEWFERB-UHFFFAOYSA-N 0.000 description 1
- DGZRKOVWOYLOAW-UHFFFAOYSA-N [4-[(5-bromo-2-chlorophenyl)methyl]phenoxy]-tert-butyl-dimethylsilane Chemical compound C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1CC1=CC(Br)=CC=C1Cl DGZRKOVWOYLOAW-UHFFFAOYSA-N 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
- 229940127252 advanced glycation end product inhibitor Drugs 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000003705 antithrombocytic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005002 aryl methyl group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 229950010046 avasimibe Drugs 0.000 description 1
- 108010014210 axokine Proteins 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229960004349 candesartan cilexetil Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 229960004597 dexfenfluramine Drugs 0.000 description 1
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000674 effect on sodium Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229960000573 eprosartan mesylate Drugs 0.000 description 1
- DJSLTDBPKHORNY-XMMWENQYSA-N eprosartan methanesulfonate Chemical compound CS(O)(=O)=O.C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 DJSLTDBPKHORNY-XMMWENQYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 229960000815 ezetimibe Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- 235000012209 glucono delta-lactone Nutrition 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 102000052194 human SLC5A1 Human genes 0.000 description 1
- 102000052543 human SLC5A2 Human genes 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 125000006328 iso-butylcarbonyl group Chemical group [H]C([H])([H])C([H])(C(*)=O)C([H])([H])[H] 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- ZEUXAIYYDDCIRX-UHFFFAOYSA-N losartan carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 ZEUXAIYYDDCIRX-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002779 membrane potential assay Methods 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- WHTLZJHQWPPTRF-UHFFFAOYSA-N methylsilyl trifluoromethanesulfonate Chemical compound C[SiH2]OS(=O)(=O)C(F)(F)F WHTLZJHQWPPTRF-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- SPIFDSWFDKNERT-UHFFFAOYSA-N nickel;hydrate Chemical compound O.[Ni] SPIFDSWFDKNERT-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000005482 norpinyl group Chemical group 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 1
- 229960005117 olmesartan Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 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
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 1
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003881 protein kinase C inhibitor Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000651 tasosartan Drugs 0.000 description 1
- ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical group CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CEAWWDXUKYZTJL-UHFFFAOYSA-N triethyl(phenyl)silane Chemical group CC[Si](CC)(CC)C1=CC=CC=C1 CEAWWDXUKYZTJL-UHFFFAOYSA-N 0.000 description 1
- XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 1
- MMYRBBZVCDXGHG-UHFFFAOYSA-N tripropylsilicon Chemical group CCC[Si](CCC)CCC MMYRBBZVCDXGHG-UHFFFAOYSA-N 0.000 description 1
- SCHZCUMIENIQMY-UHFFFAOYSA-N tris(trimethylsilyl)silicon Chemical compound C[Si](C)(C)[Si]([Si](C)(C)C)[Si](C)(C)C SCHZCUMIENIQMY-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 230000003424 uricosuric effect Effects 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 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
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Obesity (AREA)
- Biotechnology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004032823A DE102004032823A1 (de) | 2004-07-06 | 2004-07-06 | D-Xylopyranosyl-substituierte Phenyle, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE102004032823.4 | 2004-07-06 | ||
| DE102004054603.7 | 2004-11-11 | ||
| DE102004054603A DE102004054603A1 (de) | 2004-11-11 | 2004-11-11 | D-Xylopyranosyl-substituierte Phenyle, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| PCT/EP2005/007042 WO2006002912A1 (de) | 2004-07-06 | 2005-06-30 | D-xylopyranosyl-substituierte phenyle, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2569915A1 true CA2569915A1 (en) | 2006-01-12 |
Family
ID=34982318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002569915A Withdrawn CA2569915A1 (en) | 2004-07-06 | 2005-06-30 | D-xylopyranosyl-substituted phenyls, medicaments containing said compounds, the use thereof, and methods for producing the same |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7393836B2 (https=) |
| EP (1) | EP1765842B1 (https=) |
| JP (1) | JP5164568B2 (https=) |
| AT (1) | ATE383366T1 (https=) |
| CA (1) | CA2569915A1 (https=) |
| DE (1) | DE502005002516D1 (https=) |
| ES (1) | ES2299047T3 (https=) |
| WO (1) | WO2006002912A1 (https=) |
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8283326B2 (en) | 2006-10-27 | 2012-10-09 | Boehringer Ingelheim International Gmbh | Crystalline form of 4-(beta-D-glucopyranos-1-yl)-1-methyl-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene, a method for its preparation and the use thereof for preparing medicaments |
| US8551957B2 (en) | 2007-08-16 | 2013-10-08 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition comprising a glucopyranosyl-substituted benzene derivate |
| US8557782B2 (en) | 2006-05-03 | 2013-10-15 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
| US8802842B2 (en) | 2009-09-30 | 2014-08-12 | Boehringer Ingelheim International Gmbh | Method for the preparation of a crystalline form |
| US9024010B2 (en) | 2009-09-30 | 2015-05-05 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives |
| US9127034B2 (en) | 2005-05-10 | 2015-09-08 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivates and intermediates therein |
| US9192617B2 (en) | 2012-03-20 | 2015-11-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| US9949997B2 (en) | 2013-04-05 | 2018-04-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US9949998B2 (en) | 2013-04-05 | 2018-04-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US20180185291A1 (en) | 2011-03-07 | 2018-07-05 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions |
| US10406172B2 (en) | 2009-02-13 | 2019-09-10 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US10610489B2 (en) | 2009-10-02 | 2020-04-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, pharmaceutical dosage form, process for their preparation, methods for treating and uses thereof |
| US11666590B2 (en) | 2013-04-18 | 2023-06-06 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US11813275B2 (en) | 2013-04-05 | 2023-11-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US12263153B2 (en) | 2016-11-10 | 2025-04-01 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US12433906B2 (en) | 2013-04-05 | 2025-10-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US12527810B2 (en) | 2009-02-13 | 2026-01-20 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
Families Citing this family (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103030617A (zh) * | 2004-03-16 | 2013-04-10 | 贝林格尔.英格海姆国际有限公司 | 吡喃葡萄糖基取代的苯基衍生物、含该化合物的药物、其用途及其制造方法 |
| 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 |
| AR051446A1 (es) * | 2004-09-23 | 2007-01-17 | Bristol Myers Squibb Co | Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2) |
| DE602005009745D1 (de) * | 2004-12-16 | 2008-10-23 | Boehringer Ingelheim Pharma | Glucopyranosyl-substituierte benzen-derivate, medikamente mit solchen verbindungen, ihre verwendung und herstellungsverfahren dafür |
| TW200637869A (en) | 2005-01-28 | 2006-11-01 | Chugai Pharmaceutical Co Ltd | The spiroketal derivatives and the use as therapeutical agent for diabetes of the same |
| JP5264183B2 (ja) * | 2005-02-23 | 2013-08-14 | 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（（ヘテロ）アリールエチニル−ベンジル）−ベンゼン誘導体及びナトリウム依存性グルコース共輸送体２（ｓｇｌｔ２）インヒビターとしてのそれらの使用 |
| ATE453656T1 (de) * | 2005-04-15 | 2010-01-15 | Boehringer Ingelheim Int | Glucopyranosyl-substituierte (heteroaryloxy- benzyl)-benzen-derivate als sglt-inhibitoren |
| 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 |
| TW200726755A (en) * | 2005-07-07 | 2007-07-16 | Astellas Pharma Inc | A crystalline choline salt of an azulene derivative |
| AR054871A1 (es) * | 2005-07-27 | 2007-07-25 | Boehringer Ingelheim Int | Derivados de (hetero)cicloalquiletinil-bencil)-benceno sustituidos con glucopiranosilo, medicamentos que contienen dichos compuestos, sus uso y proceso para su fabricacion |
| WO2007025943A2 (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 |
| AU2006289093A1 (en) * | 2005-09-08 | 2007-03-15 | Boehringer Ingelheim International Gmbh | Crystalline forms of 1-chloro-4-(beta-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 |
| AR059489A1 (es) * | 2006-02-15 | 2008-04-09 | Boehringer Ingelheim Vetmed | Derivados de benzonitrilo sustituidos con glucopiranosilo, composiciones farmaceuticas que contienen compuestos de este tipo, su uso y procedimiento para su fabricacion |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| US7803778B2 (en) * | 2006-05-23 | 2010-09-28 | Theracos, Inc. | Glucose transport inhibitors and methods of use |
| TWI403516B (zh) | 2006-07-27 | 2013-08-01 | Chugai Pharmaceutical Co Ltd | To replace spirocyclic alcohol derivatives, and its use as a therapeutic agent for diabetes |
| TWI432446B (zh) | 2006-07-27 | 2014-04-01 | Chugai Pharmaceutical Co Ltd | 稠環螺酮縮醇衍生物、及其做為糖尿病治療藥之使用 |
| US20080027014A1 (en) * | 2006-07-28 | 2008-01-31 | Tanabe Seiyaku Co., Ltd. | Novel SGLT inhibitors |
| 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 |
| WO2008034859A1 (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 |
| TWI499414B (zh) * | 2006-09-29 | 2015-09-11 | Lexicon Pharmaceuticals Inc | 鈉與葡萄糖第２型共同運輸體（ｃｏ-ｔｒａｎｓｐｏｒｔｅｒ ２）的抑制物與其應用方法 |
| AU2007307544A1 (en) | 2006-10-13 | 2008-04-17 | Chugai Seiyaku Kabushiki Kaisha | Thioglucose spiroketal derivative and use thereof as therapeutic agent for diabetes |
| CA2668623A1 (en) | 2006-11-06 | 2008-05-15 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzyl-benzonitrile derivatives, medicaments containing such compounds, their use and process for their manufacture |
| NZ577391A (en) * | 2006-12-04 | 2011-11-25 | Janssen Pharmaceutica Nv | Thienyl-containing glycopyranosyl derivatives as antidiabetics |
| WO2008075736A1 (ja) | 2006-12-21 | 2008-06-26 | Astellas Pharma Inc. | Ｃ－グリコシド誘導体の製造方法及びその合成中間体 |
| US7795228B2 (en) * | 2006-12-28 | 2010-09-14 | Theracos, Inc. | Spiroheterocyclic glycosides and methods of use |
| WO2008101939A1 (en) | 2007-02-21 | 2008-08-28 | Boehringer Ingelheim International Gmbh | Tetrasubstituted glucopyranosylated benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| US7846945B2 (en) * | 2007-03-08 | 2010-12-07 | Lexicon Pharmaceuticals, Inc. | Piperdine-based inhibitors of sodium glucose co-transporter 2 and methods of their use |
| NZ583369A (en) | 2007-08-23 | 2011-08-26 | Theracos Inc | Benzylbenzene derivatives and methods of use |
| RS56990B1 (sr) * | 2007-09-10 | 2018-05-31 | Janssen Pharmaceutica Nv | Postupak za dobijanje jedinjenja koja su korisna kao inhibitori sglt |
| JP5498392B2 (ja) * | 2007-11-30 | 2014-05-21 | 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 | １，５−ジヒドロ−ピラゾロ［３，４−ｄ］ピリミジン−４−オン誘導体及びｃｎｓ障害の治療のためのｐｄｅ９ａモジュレーターとしてのそれらの使用 |
| UA101004C2 (en) * | 2007-12-13 | 2013-02-25 | Теракос, Инк. | Derivatives of benzylphenylcyclohexane and use thereof |
| ES2541141T3 (es) * | 2008-01-31 | 2015-07-16 | Astellas Pharma Inc. | Composición farmacéutica para el tratamiento de las enfermedades del hígado graso |
| 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 |
| WO2009135181A2 (en) | 2008-05-02 | 2009-11-05 | Seattle Genetics, Inc. | Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation |
| US8791077B2 (en) | 2008-05-22 | 2014-07-29 | Astrazeneca Ab | Method for treating hyperuricemia employing an SGLT2 inhibitor and composition containing same |
| AU2009270936B2 (en) | 2008-07-15 | 2014-12-18 | Theracos, Inc. | Deuterated benzylbenzene derivatives and methods of use |
| CN103910702A (zh) | 2008-08-22 | 2014-07-09 | 泰拉科斯有限公司 | 制备sglt2抑制剂的方法 |
| AU2009286380B2 (en) * | 2008-08-28 | 2011-09-15 | Pfizer Inc. | Dioxa-bicyclo[3.2.1.]octane-2,3,4-triol derivatives |
| KR20110063447A (ko) | 2008-09-08 | 2011-06-10 | 베링거 인겔하임 인터내셔날 게엠베하 | 피라졸로피리미딘 및 ｃｎｓ 장애의 치료를 위한 이들의 용도 |
| US20110230403A1 (en) * | 2008-09-19 | 2011-09-22 | Novartis Ag | Glycoside derivatives and uses thereof |
| MX2011002990A (es) * | 2008-09-19 | 2011-04-11 | Novartis Ag | Derivados de glucosido y usos de los mismos como inhibidores de sglt. |
| US9056850B2 (en) * | 2008-10-17 | 2015-06-16 | Janssen Pharmaceutica N.V. | Process for the preparation of compounds useful as inhibitors of SGLT |
| US20110014284A1 (en) * | 2009-02-13 | 2011-01-20 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, pharmaceutical dosage form, process for their preparation, methods for treating and uses thereof |
| PT2414363E (pt) | 2009-03-31 | 2014-02-26 | Boehringer Ingelheim Int | Derivados de 1-heterociclil-1,5-di-hidro-pirazolo[3,4- d]pirimidin-4-ona e sua utilização como moduladores de pde9a |
| US20110009347A1 (en) | 2009-07-08 | 2011-01-13 | Yin Liang | Combination therapy for the treatment of diabetes |
| EP2451797B1 (en) | 2009-07-10 | 2013-04-03 | Janssen Pharmaceutica, N.V. | CRYSTALLISATION PROCESS FOR 1-(ß-D-GLUCOPYRANOSYL)-4-METHYL-3-[5-(4-FLUOROPHENYL)-2-THIENYLMETHYL]BENZENE |
| TW201118099A (en) * | 2009-08-12 | 2011-06-01 | Boehringer Ingelheim Int | New compounds for the treatment of CNS disorders |
| HUE031375T2 (en) * | 2009-10-14 | 2017-07-28 | Janssen Pharmaceutica Nv | Process for the preparation of compounds useful as inhibitors of sglt2 |
| CN101693730B (zh) * | 2009-10-16 | 2012-07-18 | 天津中医药大学 | 芒果叶苷及其制备方法与应用 |
| US8163704B2 (en) | 2009-10-20 | 2012-04-24 | Novartis Ag | Glycoside derivatives and uses thereof |
| BR112012008924A2 (pt) | 2009-10-20 | 2019-09-24 | Novartis Ag | derivado de glicosídeo e usos do mesmo |
| RS53827B1 (sr) | 2009-11-02 | 2015-06-30 | Pfizer Inc. | Derivati dioksa-biciklo[3.2.1]oktan-2,3,4-triola |
| AR079438A1 (es) | 2009-12-09 | 2012-01-25 | Panacea Biotec Ltd | Derivados de azucar, composiciones farmaceuticas y sus usos |
| TWI562775B (en) | 2010-03-02 | 2016-12-21 | Lexicon Pharmaceuticals Inc | Methods of using inhibitors of sodium-glucose cotransporters 1 and 2 |
| SG10201506114UA (en) | 2010-05-11 | 2015-09-29 | Janssen Pharmaceutica Nv | Pharmaceutical formulations comprising 1 - (beta-d-glucopyranosyl) - 2 -thienylmethylbenzene derivatives as inhibitors of sglt |
| WO2011153712A1 (en) | 2010-06-12 | 2011-12-15 | Theracos, Inc. | Crystalline form of benzylbenzene sglt2 inhibitor |
| RU2625768C2 (ru) | 2010-08-05 | 2017-07-18 | Сиэтл Дженетикс, Инк. | Способы ингибирования фукозилирования белков in vivo с использованием аналогов фукозы |
| EP2603511B1 (en) | 2010-08-12 | 2017-03-15 | Boehringer Ingelheim International GmbH | 6-cycloalkyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a inhibitors |
| WO2012025857A1 (en) | 2010-08-23 | 2012-03-01 | Hetero Research Foundation | Cycloalkyl methoxybenzyl phenyl pyran derivatives as sodium dependent glucose co transporter (sglt2) inhibitors |
| TWI631963B (zh) * | 2011-01-05 | 2018-08-11 | 雷西肯製藥股份有限公司 | 包含鈉－葡萄糖共同輸送體１與２之抑制劑的組合物與應用方法 |
| US8809345B2 (en) | 2011-02-15 | 2014-08-19 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders |
| EP2697218B1 (en) | 2011-04-13 | 2016-05-25 | 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 |
| TWI542596B (zh) | 2011-05-09 | 2016-07-21 | 健生藥品公司 | （２ｓ,３ｒ,４ｒ,５ｓ,６ｒ）－２－（３－（（５－（４－氟苯基）噻吩－２－基）甲基）－４－甲基苯基）－６－（羥甲基）四氫－２ｈ－哌喃－３,４,５－三醇之ｌ－脯胺酸及檸檬酸共晶體 |
| EP2717689A4 (en) * | 2011-06-13 | 2014-11-05 | Panacea Biotec Ltd | NEW SGLT HEMMER |
| US9018249B2 (en) | 2011-09-13 | 2015-04-28 | Panacea Biotec Limited | SGLT inhibitors |
| US8697658B2 (en) | 2011-12-15 | 2014-04-15 | National Health Research Institutes | Glycoside compounds |
| WO2013152476A1 (en) | 2012-04-10 | 2013-10-17 | Theracos, Inc. | Process for the preparation of benzylbenzene sglt2 inhibitors |
| US10350228B2 (en) | 2012-08-23 | 2019-07-16 | Seattle Genetics, Inc. | Treatment of sickle cell disease and inflammatory conditions |
| CN103864737B (zh) * | 2012-12-17 | 2016-08-17 | 天津药物研究院 | 含脱氧葡萄糖结构的苯基c-葡萄糖苷衍生物及其制备方法和用途 |
| EP2933250B1 (en) * | 2012-12-17 | 2017-08-09 | Tianjin Institute Of Pharmaceutical Research | Phenyl c-glucoside derivative containing deoxyglucose structure, preparation method and use thereof |
| CN104045613B (zh) * | 2013-03-15 | 2016-02-10 | 天津药物研究院 | (1s)-1-[4-氯-3-(4-乙氧基苄基)苯基]-1,6-二脱氧-d-葡萄糖和l-脯氨酸的共结晶i及其制备方法和应用 |
| US9783490B2 (en) | 2012-12-18 | 2017-10-10 | The Secretary Of State For Health | Antimicrobial compounds, their synthesis and applications thereof |
| EP3466431B1 (en) | 2013-03-14 | 2023-11-15 | MSD International GmbH | Crystalline forms and methods for preparing sglt2 inhibitors |
| CN104045614B (zh) * | 2013-03-15 | 2016-02-10 | 天津药物研究院 | (1s)-1-[4-氯-3-(4-乙氧基苄基)苯基]-1,6-二脱氧-d-葡萄糖的晶型c及其制备方法和应用 |
| CN104098536B (zh) * | 2013-04-01 | 2016-06-01 | 天津药物研究院 | 一种脱氧c-糖苷类sglt2抑制剂的合成方法及其中间产物 |
| PT2981269T (pt) | 2013-04-04 | 2023-10-10 | Boehringer Ingelheim Vetmedica Gmbh | Tratamento de distúrbios metabólicos em animais equinos |
| CN104418847A (zh) * | 2013-09-10 | 2015-03-18 | 天津药物研究院 | 4-(6-脱氧-β-D-吡喃葡萄糖基)-2-[5-(4-氟苯基)噻吩-2-甲基]-1-甲基苯的制备工艺 |
| ES2605886T3 (es) | 2013-09-27 | 2017-03-16 | Sunshine Lake Pharma Co., Ltd. | Derivados de glucopiranosilo y sus usos en medicina |
| CN105611920B (zh) | 2013-10-12 | 2021-07-16 | 泰拉科斯萨普有限责任公司 | 羟基-二苯甲烷衍生物的制备 |
| CN104693190B (zh) * | 2013-12-09 | 2017-05-17 | 天津药物研究院有限公司 | 一种化合物的晶型b及其制备方法和应用 |
| CN104693191A (zh) * | 2013-12-09 | 2015-06-10 | 天津药物研究院 | 一种共结晶i及其制备方法和应用 |
| CN104693192A (zh) * | 2013-12-09 | 2015-06-10 | 天津药物研究院 | 一种化合物的晶型a及其制备方法和应用 |
| ES2969764T3 (es) | 2013-12-17 | 2024-05-22 | Boehringer Ingelheim Vetmedica Gmbh | Un inhibidor de SGLT-2 para usar en el tratamiento de un trastorno metabólico en animales felinos |
| CN104761523B (zh) * | 2014-01-06 | 2017-03-15 | 天津药物研究院有限公司 | 含3‑氧代葡萄糖结构的苯基c‑葡萄糖苷衍生物、其制备方法和用途 |
| CN115671290A (zh) * | 2014-01-23 | 2023-02-03 | 勃林格殷格翰动物保健有限公司 | 犬科动物中代谢紊乱的治疗 |
| WO2015150299A2 (en) | 2014-04-01 | 2015-10-08 | Boehringer Ingelheim Vetmedica Gmbh | Treatment of metabolic disorders in equine animals |
| 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 |
| KR102659761B1 (ko) | 2015-08-27 | 2024-04-24 | 베링거잉겔하임베트메디카게엠베하 | Sglt-2 억제제를 포함하는 액상 약제학적 조성물 |
| US20170071970A1 (en) | 2015-09-15 | 2017-03-16 | Janssen Pharmaceutica Nv | Co-therapy comprising canagliflozin and phentermine for the treatment of obesity and obesity related disorders |
| WO2017141202A1 (en) | 2016-02-17 | 2017-08-24 | Lupin Limited | Complex of sglt2 inhibitor and process for preparation thereof |
| WO2017221211A1 (en) * | 2016-06-24 | 2017-12-28 | Biocon Limited | Process for the preparation of dapagliflozin and its solvate thereof |
| MA53175A (fr) | 2018-07-19 | 2021-05-26 | Astrazeneca Ab | Méthodes de traitement de hfpef au moyen de dapagliflozine et compositions comprenant celle-ci |
| CN116392472B (zh) | 2020-07-27 | 2025-06-20 | 阿斯利康(瑞典)有限公司 | 用达格列净治疗慢性肾脏病的方法 |
| US12409186B2 (en) | 2020-07-27 | 2025-09-09 | Astrazeneca Ab | Methods of treating chronic kidney disease with dapagliflozin |
| EP4315350A1 (en) | 2021-04-01 | 2024-02-07 | AstraZeneca UK Limited | Systems and methods for managing prediabetes with a gliflozin sodium-glucose cotransport 2 inhibitor pharmaceutical composition |
| CN115991702B (zh) * | 2021-12-09 | 2024-02-02 | 珠海市藤栢医药有限公司 | 芳基c-葡萄糖苷衍生物、其制备方法及其用途 |
| WO2023104201A1 (zh) * | 2021-12-09 | 2023-06-15 | 珠海市藤栢医药有限公司 | 芳基c-葡萄糖苷衍生物、其制备方法及其用途 |
| US20250108065A1 (en) | 2022-01-26 | 2025-04-03 | Astrazeneca Ab | Methods of treating prediabetes or reducing the risk of developing type 2 diabetes with dapagliflozin |
| TW202525278A (zh) | 2023-12-15 | 2025-07-01 | 愛爾蘭商阿斯特捷利康愛爾蘭有限公司 | 治療慢性腎病及高血壓之方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6024998A (en) | 1997-01-15 | 1998-08-07 | Glycomed Incorporated | Aryl c-glycoside compounds and sulfated esters 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 |
| AU2002254567B2 (en) | 2001-04-11 | 2007-10-11 | Bristol-Myers Squibb Company | Amino acid complexes of C-aryl glucosides for treatment of diabetes and method |
| TWI254635B (en) | 2002-08-05 | 2006-05-11 | Yamanouchi Pharma Co Ltd | Azulene derivative and salt thereof |
| DE10258007B4 (de) | 2002-12-12 | 2006-02-09 | Sanofi-Aventis Deutschland Gmbh | Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
| DE10258008B4 (de) | 2002-12-12 | 2006-02-02 | Sanofi-Aventis Deutschland Gmbh | Heterocyclische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
| ES2363941T3 (es) | 2003-03-14 | 2011-08-19 | Astellas Pharma Inc. | Derivados de c-glucósido para el tratamiento de diabetes. |
| JP2004359630A (ja) * | 2003-06-06 | 2004-12-24 | Yamanouchi Pharmaceut Co Ltd | ジフルオロジフェニルメタン誘導体及びその塩 |
| ES2531660T3 (es) | 2003-08-01 | 2015-03-18 | Mitsubishi Tanabe Pharma Corporation | Compuestos novedosos que tienen actividad inhibidora frente a transportador de glucosa dependiente de sodio |
| CN103030617A (zh) * | 2004-03-16 | 2013-04-10 | 贝林格尔.英格海姆国际有限公司 | 吡喃葡萄糖基取代的苯基衍生物、含该化合物的药物、其用途及其制造方法 |
| 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 |
-
2005
- 2005-06-28 US US11/168,905 patent/US7393836B2/en not_active Expired - Lifetime
- 2005-06-30 EP EP05755962A patent/EP1765842B1/de not_active Expired - Lifetime
- 2005-06-30 JP JP2007519682A patent/JP5164568B2/ja not_active Expired - Fee Related
- 2005-06-30 CA CA002569915A patent/CA2569915A1/en not_active Withdrawn
- 2005-06-30 WO PCT/EP2005/007042 patent/WO2006002912A1/de not_active Ceased
- 2005-06-30 ES ES05755962T patent/ES2299047T3/es not_active Expired - Lifetime
- 2005-06-30 AT AT05755962T patent/ATE383366T1/de active
- 2005-06-30 DE DE502005002516T patent/DE502005002516D1/de not_active Expired - Lifetime
Cited By (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9127034B2 (en) | 2005-05-10 | 2015-09-08 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivates and intermediates therein |
| US10442795B2 (en) | 2005-05-10 | 2019-10-15 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein |
| US8557782B2 (en) | 2006-05-03 | 2013-10-15 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
| US8283326B2 (en) | 2006-10-27 | 2012-10-09 | Boehringer Ingelheim International Gmbh | Crystalline form of 4-(beta-D-glucopyranos-1-yl)-1-methyl-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene, a method for its preparation and the use thereof for preparing medicaments |
| US8551957B2 (en) | 2007-08-16 | 2013-10-08 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition comprising a glucopyranosyl-substituted benzene derivate |
| US12115179B2 (en) | 2009-02-13 | 2024-10-15 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US12527810B2 (en) | 2009-02-13 | 2026-01-20 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US10406172B2 (en) | 2009-02-13 | 2019-09-10 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US9024010B2 (en) | 2009-09-30 | 2015-05-05 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives |
| US9873714B2 (en) | 2009-09-30 | 2018-01-23 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives |
| US8802842B2 (en) | 2009-09-30 | 2014-08-12 | Boehringer Ingelheim International Gmbh | Method for the preparation of a crystalline form |
| US10610489B2 (en) | 2009-10-02 | 2020-04-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, pharmaceutical dosage form, process for their preparation, methods for treating and uses thereof |
| US10596120B2 (en) | 2011-03-07 | 2020-03-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions |
| US11564886B2 (en) | 2011-03-07 | 2023-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions |
| US20180185291A1 (en) | 2011-03-07 | 2018-07-05 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| US9192617B2 (en) | 2012-03-20 | 2015-11-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US10258637B2 (en) | 2013-04-05 | 2019-04-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US11090323B2 (en) | 2013-04-05 | 2021-08-17 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US9949998B2 (en) | 2013-04-05 | 2018-04-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US11813275B2 (en) | 2013-04-05 | 2023-11-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US11833166B2 (en) | 2013-04-05 | 2023-12-05 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US11918596B2 (en) | 2013-04-05 | 2024-03-05 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US9949997B2 (en) | 2013-04-05 | 2018-04-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US12433906B2 (en) | 2013-04-05 | 2025-10-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US11666590B2 (en) | 2013-04-18 | 2023-06-06 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US12427162B2 (en) | 2013-04-18 | 2025-09-30 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| US12263153B2 (en) | 2016-11-10 | 2025-04-01 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| DE502005002516D1 (de) | 2008-02-21 |
| EP1765842B1 (de) | 2008-01-09 |
| US7393836B2 (en) | 2008-07-01 |
| JP5164568B2 (ja) | 2013-03-21 |
| EP1765842A1 (de) | 2007-03-28 |
| WO2006002912A1 (de) | 2006-01-12 |
| JP2008505146A (ja) | 2008-02-21 |
| US20060009400A1 (en) | 2006-01-12 |
| ES2299047T3 (es) | 2008-05-16 |
| ATE383366T1 (de) | 2008-01-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7393836B2 (en) | D-xylopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture | |
| US7419959B2 (en) | D-pyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture | |
| US7417032B2 (en) | D-xylopyranosyl-phenyl-substituted cycles, medicaments containing such compounds, their use and process for their manufacture | |
| US7375090B2 (en) | Glucopyranosyloxy-pyrazoles, pharmaceutical compositions containing these compounds, the use thereof and processed for the preparation thereof | |
| US7371732B2 (en) | Glucopyranosyloxy-substituted aromatic compounds, medicaments containing such compounds, their use and process for their manufacture | |
| US7662790B2 (en) | Glucopyranosyl-substituted (heteroaryloxy-benzyl)-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture | |
| CA2557801C (en) | Glucopyranosyl-substituted benzol derivatives, drugs containing said compounds, the use thereof and method for the production thereof | |
| US20060035841A1 (en) | D-xylopyranosyl-phenyl-substituted cycles, medicaments containing such compounds, their use and process for their manufacture | |
| US7858587B2 (en) | Glucopyranosyl-substituted difluorobenzyl-benzene derivates, medicaments containing such compounds, their use and process for their manufacture | |
| US7879807B2 (en) | Tetrasubstituted glucopyranosylated benzene derivatives, medicaments containing such compounds, their use and process for their manufacture | |
| US20060019948A1 (en) | Methylidene-D-xylopyranosyl- and oxo-D-xylopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture | |
| US20070004648A1 (en) | Glucopyranosyl-substituted benzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture | |
| WO2007025943A2 (en) | Glucopyranosyl-substituted benzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture | |
| CA2548353A1 (en) | Glucopyranosyloxy-substituted aromates, medicaments containing said compounds, the use thereof, and methods for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| AZWI | Withdrawn application |
Effective date: 20121017 |