UA71994C2 - Glucopyranosyloxypyrazole derivatives, a pharmaceutical composition containing these derivatives and intermediate compounds for the preparation thereof - Google Patents

Glucopyranosyloxypyrazole derivatives, a pharmaceutical composition containing these derivatives and intermediate compounds for the preparation thereof Download PDF

Info

Publication number: UA71994C2
Authority: UA; Ukraine
Prior art keywords: methyl; glucopyranosyloxy; pyrazole; acetyl; tetra
Prior art date: 1999-08-31

Application number

UA2002032522A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Kissei Pharmaceutical

Priority date (The priority date 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 date listed.)

1999-08-31

Filing date

2000-08-24

Publication date

2005-01-17

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=17153879&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=UA71994(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2000-08-24 Application filed by Kissei Pharmaceutical filed Critical Kissei Pharmaceutical

2005-01-17 Publication of UA71994C2 publication Critical patent/UA71994C2/uk

Links

150000001875 compounds Chemical class 0.000 title description 113
239000008194 pharmaceutical composition Substances 0.000 title description 5
238000002360 preparation method Methods 0.000 title description 4
125000000217 alkyl group Chemical group 0.000 abstract description 34
150000003839 salts Chemical class 0.000 abstract description 19
125000005843 halogen group Chemical group 0.000 abstract description 8
230000002401 inhibitory effect Effects 0.000 abstract description 8
125000003545 alkoxy group Chemical group 0.000 abstract description 7
125000004414 alkyl thio group Chemical group 0.000 abstract description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 7
206010012601 diabetes mellitus Diseases 0.000 abstract description 6
230000000694 effects Effects 0.000 abstract description 6
208000008589 Obesity Diseases 0.000 abstract description 3
235000020824 obesity Nutrition 0.000 abstract description 3
101000716682 Homo sapiens Sodium/glucose cotransporter 2 Proteins 0.000 abstract 1
102000052543 human SLC5A2 Human genes 0.000 abstract 1
229910052739 hydrogen Inorganic materials 0.000 abstract 1
239000001257 hydrogen Substances 0.000 abstract 1
230000003449 preventive effect Effects 0.000 abstract 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 108
238000005481 NMR spectroscopy Methods 0.000 description 71
238000000034 method Methods 0.000 description 63
-1 methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, tertpentyloxy group Chemical group 0.000 description 35
239000002904 solvent Substances 0.000 description 33
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
238000006243 chemical reaction Methods 0.000 description 22
239000008103 glucose Substances 0.000 description 20
239000000243 solution Substances 0.000 description 20
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 17
210000002700 urine Anatomy 0.000 description 17
239000000872 buffer Substances 0.000 description 14
239000000203 mixture Substances 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000012442 inert solvent Substances 0.000 description 10
239000000725 suspension Substances 0.000 description 10
ZNJLQCPPAZECMW-UHFFFAOYSA-N (4-propan-2-yloxyphenyl)methanol Chemical compound CC(C)OC1=CC=C(CO)C=C1 ZNJLQCPPAZECMW-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000007858 starting material Substances 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 8
239000003480 eluent Substances 0.000 description 8
229910052736 halogen Inorganic materials 0.000 description 8
150000002367 halogens Chemical class 0.000 description 8
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 8
230000035484 reaction time Effects 0.000 description 8
239000000126 substance Substances 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
239000002253 acid Substances 0.000 description 7
229940068918 polyethylene glycol 400 Drugs 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
CYAKWEQUWJAHLW-UHFFFAOYSA-N 1-(chloromethyl)-4-propan-2-ylbenzene Chemical compound CC(C)C1=CC=C(CCl)C=C1 CYAKWEQUWJAHLW-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
241000700159 Rattus Species 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
238000010171 animal model Methods 0.000 description 6
239000012634 fragment Substances 0.000 description 6
JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 6
238000011160 research Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
238000005259 measurement Methods 0.000 description 5
239000012046 mixed solvent Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 4
230000037396 body weight Effects 0.000 description 4
238000005858 glycosidation reaction Methods 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
235000019743 Choline chloride Nutrition 0.000 description 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000002835 absorbance Methods 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
239000001110 calcium chloride Substances 0.000 description 3
229910001628 calcium chloride Inorganic materials 0.000 description 3
SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 3
229960003178 choline chloride Drugs 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
230000009982 effect on human Effects 0.000 description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
229910001629 magnesium chloride Inorganic materials 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000013612 plasmid Substances 0.000 description 3
239000001103 potassium chloride Substances 0.000 description 3
235000011164 potassium chloride Nutrition 0.000 description 3
238000012746 preparative thin layer chromatography Methods 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000012266 salt solution Substances 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
239000013598 vector Substances 0.000 description 3
MTXQKSQYMREAGJ-UHFFFAOYSA-N (4-methylsulfanylphenyl)methanol Chemical compound CSC1=CC=C(CO)C=C1 MTXQKSQYMREAGJ-UHFFFAOYSA-N 0.000 description 2
ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 2
125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
244000068988 Glycine max Species 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
108091034117 Oligonucleotide Proteins 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000008272 agar Substances 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
230000003321 amplification Effects 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
229910000024 caesium carbonate Inorganic materials 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
230000029142 excretion Effects 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229940083761 high-ceiling diuretics pyrazolone derivative Drugs 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
238000003199 nucleic acid amplification method Methods 0.000 description 2
239000013600 plasmid vector Substances 0.000 description 2
230000002265 prevention Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
238000005070 sampling Methods 0.000 description 2
229910001958 silver carbonate Inorganic materials 0.000 description 2
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000007929 subcutaneous injection Substances 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
210000003462 vein Anatomy 0.000 description 2
238000005406 washing Methods 0.000 description 2
MGKNBDBZIKPUFM-UHFFFAOYSA-N (4-butoxyphenyl)methanol Chemical compound CCCCOC1=CC=C(CO)C=C1 MGKNBDBZIKPUFM-UHFFFAOYSA-N 0.000 description 1
BUJZENMUXBWWFE-UHFFFAOYSA-N (4-propoxyphenyl)methanol Chemical compound CCCOC1=CC=C(CO)C=C1 BUJZENMUXBWWFE-UHFFFAOYSA-N 0.000 description 1
TZZUWLNIZBCCGL-UHFFFAOYSA-N (4-propylphenyl)methanol Chemical compound CCCC1=CC=C(CO)C=C1 TZZUWLNIZBCCGL-UHFFFAOYSA-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
GIGRWGTZFONRKA-UHFFFAOYSA-N 1-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CBr)C=C1 GIGRWGTZFONRKA-UHFFFAOYSA-N 0.000 description 1
WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical compound CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 1
DUBCVXSYZVTCOC-UHFFFAOYSA-N 1-(chloromethyl)-4-ethylbenzene Chemical compound CCC1=CC=C(CCl)C=C1 DUBCVXSYZVTCOC-UHFFFAOYSA-N 0.000 description 1
MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
UDPHMXUHHUPILH-UHFFFAOYSA-N 2-(4-propan-2-yloxyphenyl)ethanesulfonic acid Chemical compound CC(C)OC1=CC=C(C=C1)CCS(=O)(=O)O UDPHMXUHHUPILH-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
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
FHSUFDYFOHSYHI-UHFFFAOYSA-N 3-oxopentanoic acid Chemical compound CCC(=O)CC(O)=O FHSUFDYFOHSYHI-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
MOOUWXDQAUXZRG-UHFFFAOYSA-N 4-(trifluoromethyl)benzyl alcohol Chemical compound OCC1=CC=C(C(F)(F)F)C=C1 MOOUWXDQAUXZRG-UHFFFAOYSA-N 0.000 description 1
PUTLIQUUCVJLFT-UHFFFAOYSA-N 4-benzyl-5-(trifluoromethyl)-1,2-dihydropyrazol-3-one Chemical compound N1NC(=O)C(CC=2C=CC=CC=2)=C1C(F)(F)F PUTLIQUUCVJLFT-UHFFFAOYSA-N 0.000 description 1
YSHMJUPGPHEDIR-UHFFFAOYSA-N 4-benzyl-5-methyl-1,2-dihydropyrazol-3-one Chemical compound N1NC(=O)C(CC=2C=CC=CC=2)=C1C YSHMJUPGPHEDIR-UHFFFAOYSA-N 0.000 description 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
KTFGWHSLIOZEKH-UHFFFAOYSA-N 5-benzyl-1h-pyrazole Chemical class C=1C=CC=CC=1CC1=CC=NN1 KTFGWHSLIOZEKH-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 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
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
239000004909 Moisturizer Substances 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
244000004005 Nypa fruticans Species 0.000 description 1
235000005305 Nypa fruticans Nutrition 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
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 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
ZOMLPKKJTRFTEU-UHFFFAOYSA-N [4-(2-methylpropyl)phenyl]methanol Chemical compound CC(C)CC1=CC=C(CO)C=C1 ZOMLPKKJTRFTEU-UHFFFAOYSA-N 0.000 description 1
230000009102 absorption Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000002152 alkylating effect Effects 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
229960000723 ampicillin Drugs 0.000 description 1
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
230000002421 anti-septic effect Effects 0.000 description 1
229940064004 antiseptic throat preparations Drugs 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000037429 base substitution Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
239000011230 binding agent Substances 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
239000002775 capsule Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000010367 cloning Methods 0.000 description 1
238000010276 construction Methods 0.000 description 1
239000013068 control sample Substances 0.000 description 1
230000034994 death Effects 0.000 description 1
231100000517 death Toxicity 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000010575 fractional recrystallization Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
230000030279 gene silencing Effects 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000011835 investigation Methods 0.000 description 1
229910052740 iodine Inorganic materials 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
238000002955 isolation Methods 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
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
229930027917 kanamycin Natural products 0.000 description 1
229960000318 kanamycin Drugs 0.000 description 1
SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
229930182823 kanamycin A Natural products 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 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
125000005905 mesyloxy group Chemical group 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000001333 moisturizer Effects 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
150000004682 monohydrates Chemical class 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
229910017604 nitric acid Inorganic materials 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
FVEINXLJOJPHLH-UHFFFAOYSA-N p-tert-Butylbenzyl alcohol Chemical compound CC(C)(C)C1=CC=C(CO)C=C1 FVEINXLJOJPHLH-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000009103 reabsorption Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000010839 reverse transcription Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
229960002385 streptomycin sulfate Drugs 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 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
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
238000012546 transfer Methods 0.000 description 1
239000004474 valine Substances 0.000 description 1
125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
- 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
- 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
- A61P3/08—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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Diabetes (AREA)
Public Health (AREA)
Molecular Biology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Hematology (AREA)
Biotechnology (AREA)
Obesity (AREA)
Biochemistry (AREA)
Genetics & Genomics (AREA)
Endocrinology (AREA)
Child & Adolescent Psychology (AREA)
Emergency Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

UA2002032522A 1999-08-31 2000-08-24 Glucopyranosyloxypyrazole derivatives, a pharmaceutical composition containing these derivatives and intermediate compounds for the preparation thereof UA71994C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP24680099		1999-08-31
PCT/JP2000/005678 WO2001016147A1 (en)	1999-08-31	2000-08-24	Glucopyranosyloxypyrazole derivatives, medicinal compositions containing the same and intermediates in the production thereof

Publications (1)

Publication Number	Publication Date
UA71994C2 true UA71994C2 (en)	2005-01-17

Family

ID=17153879

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2002032522A UA71994C2 (en)	1999-08-31	2000-08-24	Glucopyranosyloxypyrazole derivatives, a pharmaceutical composition containing these derivatives and intermediate compounds for the preparation thereof

Country Status (28)

Country	Link
US (4)	US6972283B2 (de)
EP (1)	EP1213296B1 (de)
JP (1)	JP3989730B2 (de)
KR (1)	KR100591585B1 (de)
CN (1)	CN1145635C (de)
AT (1)	ATE264337T1 (de)
AU (1)	AU782330B2 (de)
BG (1)	BG65388B1 (de)
BR (1)	BRPI0013667B8 (de)
CA (1)	CA2382480C (de)
CZ (1)	CZ303372B6 (de)
DE (1)	DE60009929T2 (de)
DK (1)	DK1213296T3 (de)
ES (1)	ES2216937T3 (de)
HU (1)	HU229581B1 (de)
IL (2)	IL148384A0 (de)
MX (1)	MXPA02002271A (de)
NO (1)	NO322703B1 (de)
NZ (1)	NZ517439A (de)
PL (1)	PL203124B1 (de)
PT (1)	PT1213296E (de)
RU (1)	RU2232767C2 (de)
SK (1)	SK286600B6 (de)
TR (1)	TR200201082T2 (de)
TW (1)	TW579378B (de)
UA (1)	UA71994C2 (de)
WO (1)	WO2001016147A1 (de)
ZA (1)	ZA200201991B (de)

Families Citing this family (127)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN1020944C (zh)	1990-01-30	1993-05-26	阿图尔-费希尔股份公司费希尔厂	紧固件
PH12000002657B1 (en) *	1999-10-12	2006-02-21	Bristol Myers Squibb Co	C-aryl glucoside SGLT2 inhibitors
CZ20023023A3 (cs) *	2000-03-17	2003-04-16	Kissei Pharmaceutical Co., Ltd.	Glukopyranosyloxybenzylbenzenové deriváty, léčivé směsi obsahující tyto látky a meziprodukty pro přípravu derivátů
ES2337127T3 (es)	2000-11-02	2010-04-21	Ajinomoto Co., Inc.	Nuevos derivados de pirazol y remedios contra la diabetes que los contienen.
JP4591781B2 (ja) *	2000-11-02	2010-12-01	味の素株式会社	新規ピラゾール誘導体及びそれらを含有する糖尿病治療薬
CA2429833A1 (en) *	2000-11-30	2002-06-06	Kissei Pharmaceutical Co., Ltd.	Glucopyranosyloxybenzylbenzene derivatives, medicinal compositions containing the same and intermediates in the production thereof
MXPA03005923A (es)	2000-12-28	2004-01-26	Kissei Pharmaceuticals Co Ltd	Derivados de glupopiranosiloxipirazol y su uso en medicinas.
WO2002068439A1 (fr) *	2001-02-26	2002-09-06	Kissei Pharmaceutical Co., Ltd.	Derives de glycopyranosyloxypyrazole et utilisation medicinale de ceux-ci
US7294618B2 (en)	2001-02-27	2007-11-13	Kissei Pharmaceutical Co., Ltd.	Glucopyranosyloxypyrazole derivatives and medicinal use thereof
US6936590B2 (en)	2001-03-13	2005-08-30	Bristol Myers Squibb Company	C-aryl glucoside SGLT2 inhibitors and method
WO2002080935A1 (en)	2001-04-04	2002-10-17	Ortho Mcneil Pharmaceutical, Inc.	Combination therapy comprising glucose reabsorption inhibitors and retinoid-x receptor modulators
US20030045553A1 (en)	2001-04-04	2003-03-06	Bussolari Jacqueline C.	Combination therapy comprising glucose reabsorption inhibitors and PPAR modulators
ATE318272T1 (de) *	2001-04-11	2006-03-15	Bristol Myers Squibb Co	Aminosäurekomplexe von c-arylglycosiden zur behandlung von diabetes und verfahren
JP4292570B2 (ja)	2001-04-27	2009-07-08	味の素株式会社	Ｎ−置換ピラゾール−ｏ−グリコシド誘導体及びそれらを含有する糖尿病治療薬
EP1400529A4 (de) *	2001-05-30	2007-12-19	Kissei Pharmaceutical	Glucopyranosyloxypyrazol derivat, diese enthaltende medizinische zusammensetzung, dessen medizinische verwendung und zwischenprodukt zu dessen herstellung
WO2003000712A1 (en) *	2001-06-20	2003-01-03	Kissei Pharmaceutical Co., Ltd.	Nitrogenous heterocyclic derivative, medicinal composition containing the same, medicinal use thereof, and intermediate therefor
WO2003011880A1 (fr) *	2001-07-31	2003-02-13	Kissei Pharmaceutical Co., Ltd.	Derive de glucopyranosyloxybenzylbenzene, composition medicinale contenant ce derive, usage medicinal de cette composition et produit intermediaire pour produire cette composition
US20030087843A1 (en) *	2001-09-05	2003-05-08	Washburn William N.	O-pyrazole glucoside SGLT2 inhibitors and method of use
CA2484306A1 (en) *	2002-04-26	2003-11-06	Katsumi Maezono	Prophylactic and therapeutic agent of diabetes mellitus
US7956041B2 (en)	2002-04-26	2011-06-07	Ajinomoto Co., Inc.	Prophylactic and therapeutic agent of diabetes mellitus
DE10231370B4 (de) *	2002-07-11	2006-04-06	Sanofi-Aventis Deutschland Gmbh	Thiophenglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
BRPI0313290B1 (pt)	2002-08-08	2016-12-06	Kissei Pharmaceutical	derivados de pirazol, promedicamento, composição farmacêutica, agentes terapêuticos e uso medicinal
ZA200501094B (en) *	2002-08-08	2006-10-25	Kissei Pharmaceutical	Pyrazole derivative, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof
UA77300C2 (en) *	2002-08-09	2006-11-15	Taisho Pharmaceutical Co Ltd	5-thio-?-d-glucopyranoside derivatives and pharmaceutical composition for treating diabetes
CN100413878C (zh) *	2002-08-23	2008-08-27	橘生药品工业株式会社	吡唑衍生物、含该衍生物的医药组合物、其医药用途及用于制备的中间体
JP2004137245A (ja)	2002-08-23	2004-05-13	Kissei Pharmaceut Co Ltd	ピラゾール誘導体、それを含有する医薬組成物、その医薬用途及びその製造中間体
AU2003262262A1 (en) *	2002-08-27	2004-03-19	Kissei Pharmaceutical Co., Ltd.	Pyrazole derivatives, medicinal composition containing the same, and medicinal use thereof
CA2500873C (en)	2002-10-04	2012-01-17	Kissei Pharmaceutical Co., Ltd.	Pyrazole derivative, medicinal composition containing the same, medicinal use thereof and intermediate in producing the same
EP1568380A4 (de) *	2002-12-04	2009-10-21	Kissei Pharmaceutical	Vorbeugende massnahme oder heilmittel für krankheiten aufgrund von blutzuckererhöhung
DE10258008B4 (de) *	2002-12-12	2006-02-02	Sanofi-Aventis Deutschland Gmbh	Heterocyclische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
DE10258007B4 (de) *	2002-12-12	2006-02-09	Sanofi-Aventis Deutschland Gmbh	Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
WO2004058790A1 (ja) *	2002-12-25	2004-07-15	Kissei Pharmaceutical Co., Ltd.	含窒素複素環誘導体、それを含有する医薬組成物およびその医薬用途
CN1761676A (zh)	2003-04-01	2006-04-19	大正制药株式会社	杂芳基5－硫代－β－D－吡喃葡糖苷衍生物及含有该衍生物的糖尿病治疗药
JPWO2004089966A1 (ja) *	2003-04-01	2006-07-06	大正製薬株式会社	選択的なヘテロアリール５−チオ−β−Ｄ−アルドヘキソピラノシドの製造法
US7576064B2 (en) *	2003-06-20	2009-08-18	Kissei Pharmaceutical Co., Ltd.	Pyrazole derivative, drug composition containing the same and production intermediate therefor
US7375090B2 (en)	2003-08-26	2008-05-20	Boehringer Ingelheim International Gmbh	Glucopyranosyloxy-pyrazoles, pharmaceutical compositions containing these compounds, the use thereof and processed for the preparation thereof
JP4520988B2 (ja) *	2003-08-26	2010-08-11	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	グルコピラノシルオキシ−ピラゾール、これらの化合物を含む医薬組成物、これらの使用及びこれらの調製方法
DE102004028241B4 (de) *	2004-06-11	2007-09-13	Sanofi-Aventis Deutschland Gmbh	Neue Fluorglykosidderivate von Pyrazolen, diese Verbindungen enthaltende Arzneimittel und Herstellung dieser Arzneimittel
JP5010918B2 (ja) *	2004-07-21	2012-08-29	キッセイ薬品工業株式会社	肝臓脂肪の異常蓄積に起因する疾患の進展抑制剤
TW200606129A (en) *	2004-07-26	2006-02-16	Chugai Pharmaceutical Co Ltd	Novel cyclohexane derivative, its prodrug, its salt and diabetic therapeutic agent containing the same
EP1813611B1 (de)	2004-11-18	2014-10-01	Kissei Pharmaceutical Co., Ltd.	1-substituierte 3-beta-d-glycopyranosylierte stickstoffhaltige heterocyclische verbindungen und medikamente, die diese enthalten
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
AR053329A1 (es) *	2005-01-31	2007-05-02	Tanabe Seiyaku Co	Derivados de indol utiles como inhibidores de los transportadores de glucosa dependientes del sodio (sglt)
CA2600372C (en) *	2005-03-17	2013-04-02	Kissei Pharmaceutical Co., Ltd.	Process for production of glucopyranosyloxypyrazole derivative
UA91546C2 (uk) *	2005-05-03	2010-08-10	Бьорінгер Інгельхайм Інтернаціональ Гмбх	КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ
US7772191B2 (en)	2005-05-10	2010-08-10	Boehringer Ingelheim International Gmbh	Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein
UY29694A1 (es) *	2005-07-28	2007-02-28	Boehringer Ingelheim Int	Metodos para prevenir y tratar trastornos metabolicos y nuevos derivados de pirazol-o-glucosido
CN101243050B (zh) *	2005-08-31	2012-07-04	霍夫曼-拉罗奇有限公司	吡唑啉酮衍生物
UY30082A1 (es)	2006-01-11	2007-08-31	Boehringer Ingelheim Int	Forma cristalina de 1-(1-metiletil)-4`-((2-fluoro-4-metoxifenil)metil)-5`- metil-1h-pirazol-3`-o-b-d-glucopiranosido, un metodo para su preparacion y el uso de la misma para preparar medicamentos
PE20080697A1 (es)	2006-05-03	2008-08-05	Boehringer Ingelheim Int	Derivados de benzonitrilo sustituidos con glucopiranosilo, composiciones farmaceuticas que contienen compuestos de este tipo, su uso y procedimiento para su fabricacion
PE20110235A1 (es)	2006-05-04	2011-04-14	Boehringer Ingelheim Int	Combinaciones farmaceuticas que comprenden linagliptina y metmorfina
DE102006028862A1 (de)	2006-06-23	2007-12-27	Merck Patent Gmbh	3-Amino-imidazo[1,2-a]pyridinderivate
US20080020987A1 (en) *	2006-07-20	2008-01-24	Waldemar Pfrengle	Processes for preparing pyrazole-O-glycoside derivatives and novel intermediates of said processes
BRPI0719941A2 (pt)	2006-12-06	2014-04-22	Smithkline Beecham Corp	Composto, uso de um composto, método para o tratamento de distúrbios ou condições metabólicos, composição farmacêutica, e, processo para a preparação de uma composição farmacêutica
DE102007008420A1 (de)	2007-02-21	2008-08-28	Merck Patent Gmbh	Benzimidazolderivate
TW200904454A (en)	2007-03-22	2009-02-01	Bristol Myers Squibb Co	Methods for treating obesity employing an SGLT2 inhibitor and compositions thereof
CL2008002427A1 (es)	2007-08-16	2009-09-11	Boehringer Ingelheim Int	Composicion farmaceutica que comprende 1-cloro-4-(b-d-glucopiranos-1-il)-2-[4-((s)-tetrahidrofurano-3-iloxi)bencil]-benceno combinado con 1-[(4-metilquinazolin-2-il)metil]-3-metil-7-(2-butin-1-il)-8-(3-(r)-aminopiperidin-1-il)xantina; y su uso para tratar diabetes mellitus tipo 2.
DE102007048716A1 (de)	2007-10-11	2009-04-23	Merck Patent Gmbh	Imidazo[1,2-a]pyrimidinderivate
CL2008003653A1 (es)	2008-01-17	2010-03-05	Mitsubishi Tanabe Pharma Corp	Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica.
DE102008017590A1 (de)	2008-04-07	2009-10-08	Merck Patent Gmbh	Glucopyranosidderivate
AP2728A (en) *	2008-08-28	2013-08-31	Pfizer	Dioxa-bicyclo[3.2.1.] octane-2,3,4-triol derivatives
EP2349309A4 (de) *	2008-11-20	2014-01-08	Teikoku Pharma Usa Inc	Pyrazolonderivatformulierungen
SG171307A1 (en) *	2008-11-21	2011-07-28	Glaxosmithkline Llc	Chemical process
CN101445528B (zh) *	2008-12-25	2011-06-15	天津药物研究院	硫代葡萄糖衍生物、其制备方法和用途
HUE050287T2 (hu)	2009-02-13	2020-11-30	Boehringer Ingelheim Int	SGLT2-inhibitort, DPP-IV-inhibitort és adott esetben egy további antidiabetikus hatóanyagot tartalmazó gyógyászati készítmény és alkalmazásai
CN102387783A (zh) *	2009-02-13	2012-03-21	贝林格尔.英格海姆国际有限公司	包含吡喃葡萄糖基二苯基甲烷衍生物的药物组合物、其药物剂型、其制备方法及其在患者中改善血糖控制的用途
EP4684831A3 (de)	2009-02-13	2026-03-11	Boehringer Ingelheim International GmbH	Sglt2-inhibitor zur verbesserung der glykämischen kontrolle
BR112012007085B8 (pt)	2009-09-30	2021-05-25	Boehringer Ingelheim Int	processos para a preparação de derivados de benzil-benzeno substituídos com glicopiranosila
NZ598318A (en)	2009-09-30	2014-02-28	Boehringer Ingelheim Int	Method for the preparation of a crystalline form of 1-chloro-4- (beta-d-glucopyranos-1-yl)-2-(4-((s)-tetrahydrofuran-3-yloxy)benzyl)benzene
UY32919A (es)	2009-10-02	2011-04-29	Boehringer Ingelheim Int	Composición farmacéutica, forma de dosificación farmacéutica, procedimiento para su preparación, mé todos para su tratamiento y sus usos
WO2011048148A2 (en)	2009-10-20	2011-04-28	Novartis Ag	Glycoside derivative and uses thereof
US8163704B2 (en)	2009-10-20	2012-04-24	Novartis Ag	Glycoside derivatives and uses thereof
DK2496583T3 (en)	2009-11-02	2015-02-02	Pfizer	Dioxa-bicyclo [3.2.1] octane-2,3,4-triol DERIVATIVES
WO2011070592A2 (en)	2009-12-09	2011-06-16	Panacea Biotec Ltd.	Novel sugar derivatives
WO2011107494A1 (de)	2010-03-03	2011-09-09	Sanofi	Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung
US20140088027A1 (en)	2010-03-30	2014-03-27	Boehringer Ingelheim International Gmbh	Pharmaceutical composition comprising an sglt2 inhibitor and a ppar- gamma agonist and uses thereof
WO2012025857A1 (en)	2010-08-23	2012-03-01	Hetero Research Foundation	Cycloalkyl methoxybenzyl phenyl pyran derivatives as sodium dependent glucose co transporter (sglt2) inhibitors
US20120283169A1 (en)	2010-11-08	2012-11-08	Boehringer Ingelheim International Gmbh	Pharmaceutical composition, methods for treating and uses thereof
US20130035281A1 (en)	2011-02-09	2013-02-07	Boehringer Ingelheim International Gmbh	Pharmaceutical composition, methods for treating and uses thereof
AR085689A1 (es)	2011-03-07	2013-10-23	Boehringer Ingelheim Int	Composiciones farmaceuticas de metformina, linagliptina y un inhibidor de sglt-2
CA2832951A1 (en)	2011-04-14	2012-10-18	Novartis Ag	Glycoside derivatives and uses thereof
US8614195B2 (en)	2011-04-14	2013-12-24	Novartis Ag	Glycoside derivatives and uses thereof
US20130137646A1 (en)	2011-06-03	2013-05-30	Boehringer Ingelheim International Gmbh	Methods of treatment, pharmaceutical compositions and uses thereof
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
UA113086C2 (xx)	2012-05-10	2016-12-12		Піразольні сполуки як інгібітори sglt1
TW201425326A (zh)	2012-10-05	2014-07-01	Lilly Co Eli	新穎脲化合物
EP2774619B1 (de)	2013-03-04	2016-05-18	BioActive Food GmbH	Zusammensetzung zur Behandlung von hyperglykämischen Erkrankungen
PT2981269T (pt)	2013-04-04	2023-10-10	Boehringer Ingelheim Vetmedica Gmbh	Tratamento de distúrbios metabólicos em animais equinos
US20140303097A1 (en)	2013-04-05	2014-10-09	Boehringer Ingelheim International Gmbh	Pharmaceutical composition, methods for treating and uses thereof
CA2812519A1 (en)	2013-04-05	2014-10-05	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
TR201901110T4 (tr)	2013-04-05	2019-02-21	Boehringer Ingelheim Int	Empagliflozinin terapötik kullanımları.
HK1215378A1 (zh)	2013-04-18	2016-08-26	勃林格殷格翰国际有限公司	药物组合物、治疗方法及其用途
AR098670A1 (es)	2013-11-08	2016-06-08	Lilly Co Eli	Inhibidor de sglt1
CN105828815B (zh)	2013-12-17	2020-03-27	勃林格殷格翰动物保健有限公司	猫科动物中代谢紊乱的治疗
PL3485890T3 (pl)	2014-01-23	2023-08-28	Boehringer Ingelheim Vetmedica Gmbh	Inhibitory SGLT2 do leczenia zaburzeń metabolicznych u zwierząt psowatych
KR102662473B1 (ko)	2014-04-01	2024-05-03	베링거잉겔하임베트메디카게엠베하	말과 동물에서 대사 장애의 치료
EP2944311A1 (de)	2014-05-16	2015-11-18	BioActive Food GmbH	Kombination von biologisch aktiven Substanzen zur Behandlung von hyperglykämischen Erkrankungen
DK3197429T3 (da)	2014-09-25	2024-08-26	Boehringer Ingelheim Vetmedica Gmbh	Kombinationsbehandling med sglt2-hæmmere og dopaminagonister til forebyggelse af metaboliske lidelser af dyr i hestefamilien
CN104478967A (zh) *	2015-01-14	2015-04-01	佛山市赛维斯医药科技有限公司	含腈基苯噻唑基的o-半乳糖苷衍生物、其制备方法和用途
CN104447907A (zh) *	2015-01-14	2015-03-25	佛山市赛维斯医药科技有限公司	含硝基联苯双葡萄糖苷结构化合物、其制备方法和用途
CN104478969A (zh) *	2015-01-14	2015-04-01	佛山市赛维斯医药科技有限公司	含烷氧苯基噻唑基的o-半乳糖苷衍生物、其制备方法和用途
CN104447905A (zh) *	2015-01-14	2015-03-25	佛山市赛维斯医药科技有限公司	一种含硝基苯和双o-葡萄糖苷衍生物、其制备方法和用途
CN104478956A (zh) *	2015-01-14	2015-04-01	佛山市赛维斯医药科技有限公司	苯基双o-葡萄糖苷衍生物、其制备方法和用途
CN104497074A (zh) *	2015-01-15	2015-04-08	佛山市赛维斯医药科技有限公司	一种含丙烯腈基和硝基苯o-葡萄糖苷结构化合物及用途
CN104497073A (zh) *	2015-01-15	2015-04-08	佛山市赛维斯医药科技有限公司	含丙烯腈和烷氧苯基o-葡萄糖苷结构的衍生物和用途
CN104497072A (zh) *	2015-01-15	2015-04-08	佛山市赛维斯医药科技有限公司	含丙烯腈和卤代苯o-葡萄糖苷结构衍生物、其制备方法和用途
CN104478962A (zh) *	2015-01-15	2015-04-01	佛山市赛维斯医药科技有限公司	一类卤代苯基s-葡萄糖苷衍生物、其制备方法和用途
CN104478960A (zh) *	2015-01-15	2015-04-01	佛山市赛维斯医药科技有限公司	一种含丙烯腈基和三氟甲苯基o-葡萄糖苷结构化合物和用途
EP3528800A1 (de)	2016-10-19	2019-08-28	Boehringer Ingelheim International GmbH	Kombinationen mit einem ssao/vap-1-hemmer und einem sglt2-hemmer, verwendungen davon
AU2017357589B2 (en)	2016-11-10	2023-05-11	Boehringer Ingelheim International Gmbh	Pharmaceutical composition, methods for treating and uses thereof
AU2019254371A1 (en)	2018-04-17	2020-10-08	Boehringer Ingelheim International Gmbh	Pharmaceutical composition, methods for treating and uses thereof
WO2020039394A1 (en)	2018-08-24	2020-02-27	Novartis Ag	New drug combinations
CN112955214B (zh)	2018-10-29	2024-05-07	勃林格殷格翰国际有限公司	吡啶基磺酰胺衍生物、药物组合物及其用途
CN112955215B (zh)	2018-10-29	2024-05-17	勃林格殷格翰国际有限公司	吡啶基磺酰胺衍生物、药物组合物及其用途
WO2021105152A1 (en)	2019-11-28	2021-06-03	Boehringer Ingelheim Vetmedica Gmbh	Use of sglt-2 inhibitors in the drying-off of non-human mammals
BR112022016360A2 (pt)	2020-02-17	2022-10-04	Boehringer Ingelheim Vetmedica Gmbh	Uso de inibidores de sglt-2 para a prevenção e/ou tratamento de doenças cardíacas em felinos
US20240269105A1 (en)	2021-07-28	2024-08-15	Boehringer Ingelheim Vetmedica Gmbh	Use of sglt-2 inhibitors for the prevention and/or treatment of hypertension in non-human mammals
EP4376829A1 (de)	2021-07-28	2024-06-05	Boehringer Ingelheim Vetmedica GmbH	Verwendung von sglt-2-inhibitoren zur prävention und/oder behandlung von herzerkrankungen bei nichtmenschlichen säugern unter ausschluss von katzen, insbesondere hunden
WO2023006747A1 (en)	2021-07-28	2023-02-02	Boehringer Ingelheim Vetmedica Gmbh	Use of sglt-2 inhibitors for the prevention and/or treatment of renal diseases in non-human mammals
WO2023129595A1 (en)	2021-12-30	2023-07-06	Newamsterdam Pharma B.V.	Obicetrapib and sglt2 inhibitor combination
CA3256728A1 (en)	2022-05-25	2023-11-30	Boehringer Ingelheim Vetmedica Gmbh	AQUEOUS PHARMACEUTICAL COMPOSITIONS CONTAINING SGLT-2 INHIBITORS
TW202500160A (zh)	2023-03-06	2025-01-01	德商百靈佳殷格翰維美迪加股份有限公司	用於遞送特別是包含一或多種ｓｇｌｔ—２抑制劑之液體醫藥組合物之系統及方法
EP4701626A1 (de)	2023-04-24	2026-03-04	NewAmsterdam Pharma B.V.	Kombination aus amorphem obicetrapib und sglt2-inhibitor
WO2024240632A1 (en)	2023-05-24	2024-11-28	Boehringer Ingelheim Vetmedica Gmbh	Combination treatment and/or prevention of cardiac diseases in non-human mammals comprising one or more sglt-2 inhibitors and pimobendan and/or telmisartan
TW202508455A (zh)	2023-05-24	2025-03-01	德商百靈佳殷格翰維美迪加股份有限公司	包含一或多種sglt-2抑制劑及替米沙坦(telmisartan)之非人類哺乳動物之腎臟疾病及/或高血壓之組合治療及/或預防

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5264451A (en) *	1992-04-07	1993-11-23	American Home Products Corporation	Process for treating hyperglycemia using trifluoromethyl substituted 3H-pyrazol-3-ones
US5274111A (en) *	1992-04-07	1993-12-28	American Home Products Corporation	Trifluoromethyl substituted 1H-pyrazoles and derivatives thereof
ES2337127T3 (es)	2000-11-02	2010-04-21	Ajinomoto Co., Inc.	Nuevos derivados de pirazol y remedios contra la diabetes que los contienen.
US20030087843A1 (en)	2001-09-05	2003-05-08	Washburn William N.	O-pyrazole glucoside SGLT2 inhibitors and method of use

2000
- 2000-08-24 BR BRPI0013667A patent/BRPI0013667B8/pt not_active IP Right Cessation
- 2000-08-24 SK SK287-2002A patent/SK286600B6/sk not_active IP Right Cessation
- 2000-08-24 PL PL364800A patent/PL203124B1/pl unknown
- 2000-08-24 DK DK00954963T patent/DK1213296T3/da active
- 2000-08-24 AT AT00954963T patent/ATE264337T1/de active
- 2000-08-24 IL IL14838400A patent/IL148384A0/xx unknown
- 2000-08-24 TR TR2002/01082T patent/TR200201082T2/xx unknown
- 2000-08-24 HU HU0203190A patent/HU229581B1/hu unknown
- 2000-08-24 CA CA002382480A patent/CA2382480C/en not_active Expired - Lifetime
- 2000-08-24 WO PCT/JP2000/005678 patent/WO2001016147A1/ja not_active Ceased
- 2000-08-24 PT PT00954963T patent/PT1213296E/pt unknown
- 2000-08-24 CN CNB008137722A patent/CN1145635C/zh not_active Expired - Lifetime
- 2000-08-24 JP JP2001519711A patent/JP3989730B2/ja not_active Expired - Fee Related
- 2000-08-24 DE DE60009929T patent/DE60009929T2/de not_active Expired - Lifetime
- 2000-08-24 AU AU67275/00A patent/AU782330B2/en not_active Expired
- 2000-08-24 UA UA2002032522A patent/UA71994C2/uk unknown
- 2000-08-24 CZ CZ20020665A patent/CZ303372B6/cs not_active IP Right Cessation
- 2000-08-24 RU RU2002107975/04A patent/RU2232767C2/ru active
- 2000-08-24 EP EP00954963A patent/EP1213296B1/de not_active Expired - Lifetime
- 2000-08-24 MX MXPA02002271A patent/MXPA02002271A/es active IP Right Grant
- 2000-08-24 KR KR1020027002744A patent/KR100591585B1/ko not_active Expired - Lifetime
- 2000-08-24 NZ NZ517439A patent/NZ517439A/xx not_active IP Right Cessation
- 2000-08-24 ES ES00954963T patent/ES2216937T3/es not_active Expired - Lifetime
- 2000-08-31 TW TW089117757A patent/TW579378B/zh not_active IP Right Cessation
2002
- 2002-02-26 IL IL148384A patent/IL148384A/en active IP Right Grant
- 2002-02-27 NO NO20020968A patent/NO322703B1/no not_active IP Right Cessation
- 2002-02-27 BG BG106451A patent/BG65388B1/bg unknown
- 2002-03-11 ZA ZA200201991A patent/ZA200201991B/en unknown
2004
- 2004-01-20 US US10/759,138 patent/US6972283B2/en not_active Expired - Lifetime
- 2004-11-03 US US10/979,154 patent/US20050137143A1/en not_active Abandoned
2005
- 2005-07-27 US US11/189,832 patent/US7056892B2/en not_active Expired - Lifetime
- 2005-07-28 US US11/191,024 patent/US7115575B2/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
IL148384A0 (en)	2002-09-12
NZ517439A (en)	2003-03-28
ZA200201991B (en)	2003-05-28
NO20020968D0 (no)	2002-02-27
BRPI0013667B8 (pt)	2021-05-25
CZ303372B6 (cs)	2012-08-22
CN1145635C (zh)	2004-04-14
NO20020968L (no)	2002-04-26
JP3989730B2 (ja)	2007-10-10
US20050137143A1 (en)	2005-06-23
US7115575B2 (en)	2006-10-03
US20050261206A1 (en)	2005-11-24
SK286600B6 (sk)	2009-02-05
CZ2002665A3 (cs)	2002-06-12
AU6727500A (en)	2001-03-26
PL203124B1 (pl)	2009-08-31
HUP0203190A2 (hu)	2003-01-28
HU229581B1 (en)	2014-02-28
EP1213296A1 (de)	2002-06-12
SK2872002A3 (en)	2003-01-09
IL148384A (en)	2009-06-15
EP1213296A4 (de)	2002-09-04
US20050261205A1 (en)	2005-11-24
AU782330B2 (en)	2005-07-21
BR0013667A (pt)	2002-06-11
RU2232767C2 (ru)	2004-07-20
KR100591585B1 (ko)	2006-06-20
NO322703B1 (no)	2006-11-27
DE60009929D1 (de)	2004-05-19
PL364800A1 (en)	2004-12-13
TR200201082T2 (tr)	2002-07-22
CA2382480A1 (en)	2001-03-08
DK1213296T3 (da)	2004-08-16
MXPA02002271A (es)	2002-10-31
EP1213296B1 (de)	2004-04-14
WO2001016147A1 (en)	2001-03-08
BG106451A (en)	2002-09-30
KR20020033781A (ko)	2002-05-07
CA2382480C (en)	2008-09-30
US20040147729A1 (en)	2004-07-29
PT1213296E (pt)	2004-08-31
BRPI0013667B1 (pt)	2016-06-14
HUP0203190A3 (en)	2003-04-28
HK1050369A1 (en)	2003-06-20
ES2216937T3 (es)	2004-11-01
US7056892B2 (en)	2006-06-06
TW579378B (en)	2004-03-11
ATE264337T1 (de)	2004-04-15
US6972283B2 (en)	2005-12-06
CN1377363A (zh)	2002-10-30
DE60009929T2 (de)	2005-03-31
BG65388B1 (bg)	2008-05-30

Publication	Publication Date	Title
UA71994C2 (en)	2005-01-17	Glucopyranosyloxypyrazole derivatives, a pharmaceutical composition containing these derivatives and intermediate compounds for the preparation thereof
JP4326024B2 (ja)	2009-09-02	新規なＮ―７―ヘテロサイクリル―ピロロ［２，３―ｄ］ピリミジンおよびこれらの使用
JPWO2001016147A1 (ja)	2003-03-25	グルコピラノシルオキシピラゾール誘導体、それを含有する医薬組成物およびその製造中間体
TWI290556B (en)	2007-12-01	Glucopyranosyloxybenzyl benzene derivatives, medicinal compositions containing the same and intermediates in the production thereof
KR20200029509A (ko)	2020-03-18	Fxr 작용제
UA73606C2 (en)	2005-08-15	Glucopyranosyloxybenzylbenzene derivatives and medicinal compositions containing them
US7053114B2 (en)	2006-05-30	Prodrugs of a 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
CN113149968A (zh)	2021-07-23	一种作为己酮糖激酶抑制剂的化合物及其应用
JP4601038B2 (ja)	2010-12-22	インドリルマレイミド類
WO2007034846A1 (ja)	2007-03-29	Grk阻害剤からなる強心薬
CN111718351B (zh)	2021-10-12	含氧取代吡唑并嘧啶化合物和药物组合物及其应用
CN112209896A (zh)	2021-01-12	噻唑烷二酮衍生物以及包含其的药物组合物
WO2025157003A1 (zh)	2025-07-31	作为ripk1抑制剂的杂环化合物
EA019067B1 (ru)	2013-12-30	Соединения 1,5-дифенилпирролидин-2-она как лиганды св-1