JP5225980B2 - １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤としてのピエリジニル置換ピロリジノン - Google Patents
１１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤としてのピエリジニル置換ピロリジノン Download PDFInfo
- Publication number
- JP5225980B2 JP5225980B2 JP2009507978A JP2009507978A JP5225980B2 JP 5225980 B2 JP5225980 B2 JP 5225980B2 JP 2009507978 A JP2009507978 A JP 2009507978A JP 2009507978 A JP2009507978 A JP 2009507978A JP 5225980 B2 JP5225980 B2 JP 5225980B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- dichloro
- pyrrolidin
- ylmethyl
- biphenyl
- 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.)
- Expired - Fee Related
Links
- 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 title description 31
- 102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 title description 30
- 239000003112 inhibitor Substances 0.000 title description 11
- 150000004040 pyrrolidinones Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 182
- 150000002367 halogens Chemical class 0.000 claims description 182
- 239000001257 hydrogen Substances 0.000 claims description 109
- 229910052739 hydrogen Inorganic materials 0.000 claims description 109
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 90
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 70
- 150000002431 hydrogen Chemical class 0.000 claims description 39
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 34
- 239000000460 chlorine Substances 0.000 claims description 31
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- -1 3,5-dichloro-4'-trifluoromethyl-biphenyl-4-ylmethyl Chemical group 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 21
- 239000011737 fluorine Substances 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- GKBQUUWPGKYVCC-INIZCTEOSA-N 4-[(3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(F)=CC=2)Cl)CC1 GKBQUUWPGKYVCC-INIZCTEOSA-N 0.000 claims description 5
- KMLQOMUMWAYYCW-NRFANRHFSA-N methyl 4-[(3r)-3-[[2,6-dichloro-4-[4-[4-(trifluoromethyl)piperidine-1-carbonyl]phenyl]phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(=CC=2)C(=O)N2CCC(CC2)C(F)(F)F)Cl)CC1 KMLQOMUMWAYYCW-NRFANRHFSA-N 0.000 claims description 3
- ZOJLBBQEBUMFCU-INIZCTEOSA-N (3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-1-(1-methylsulfonylpiperidin-4-yl)pyrrolidin-2-one Chemical compound C1CN(S(=O)(=O)C)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(F)=CC=2)Cl)CC1 ZOJLBBQEBUMFCU-INIZCTEOSA-N 0.000 claims description 2
- CNNLTMSBPIKXPM-UHFFFAOYSA-N 3-[[2,6-dichloro-4-[4-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]phenyl]phenyl]methyl]-1-(1-methylsulfonylpiperidin-4-yl)pyrrolidin-2-one Chemical compound C1CN(S(=O)(=O)C)CCC1N1C(=O)C(CC=2C(=CC(=CC=2Cl)C=2C=CC(=CC=2)C(=O)N2CCN(CC(F)(F)F)CC2)Cl)CC1 CNNLTMSBPIKXPM-UHFFFAOYSA-N 0.000 claims description 2
- KZOLFEWPGNJGIJ-INIZCTEOSA-N 4-[(3r)-3-[[2,6-dichloro-4-[4-(trifluoromethoxy)phenyl]phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(OC(F)(F)F)=CC=2)Cl)CC1 KZOLFEWPGNJGIJ-INIZCTEOSA-N 0.000 claims description 2
- XXOCJEDPQIFLAQ-NRFANRHFSA-N 4-[(3r)-3-[[2,6-dichloro-4-[4-[4-(trifluoromethyl)piperidine-1-carbonyl]phenyl]phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(=CC=2)C(=O)N2CCC(CC2)C(F)(F)F)Cl)CC1 XXOCJEDPQIFLAQ-NRFANRHFSA-N 0.000 claims description 2
- RNABFKLYNRWJML-INIZCTEOSA-N methyl 4-[(3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(F)=CC=2)Cl)CC1 RNABFKLYNRWJML-INIZCTEOSA-N 0.000 claims description 2
- WDQVDGUKAPWZNZ-SFHVURJKSA-N 4-[(3r)-3-[[2,6-dichloro-4-(4-cyanophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(=CC=2)C#N)Cl)CC1 WDQVDGUKAPWZNZ-SFHVURJKSA-N 0.000 claims 1
- ILFLDZSMSGFGTJ-FQEVSTJZSA-N 4-[(3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-phenylpiperidine-1-carboxamide Chemical compound C1=CC(F)=CC=C1C(C=C1Cl)=CC(Cl)=C1C[C@H]1C(=O)N(C2CCN(CC2)C(=O)NC=2C=CC=CC=2)CC1 ILFLDZSMSGFGTJ-FQEVSTJZSA-N 0.000 claims 1
- FXCOPNPNUHWSTQ-IBGZPJMESA-N 4-[(3r)-3-[[2,6-dichloro-4-(4-propan-2-yloxyphenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(OC(C)C)=CC=2)Cl)CC1 FXCOPNPNUHWSTQ-IBGZPJMESA-N 0.000 claims 1
- WDRZOMROYRDRKS-INIZCTEOSA-N 4-[(3r)-3-[[2,6-dichloro-4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(=CC=2)C(F)(F)F)Cl)CC1 WDRZOMROYRDRKS-INIZCTEOSA-N 0.000 claims 1
- VFZYXSQMAWPNHV-UHFFFAOYSA-N 4-[3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-ethylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NCC)CCC1N1C(=O)C(CC=2C(=CC(=CC=2Cl)C=2C=CC(F)=CC=2)Cl)CC1 VFZYXSQMAWPNHV-UHFFFAOYSA-N 0.000 claims 1
- KXHWIUXOFOFHOF-UHFFFAOYSA-N 4-[3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxamide Chemical compound C1CN(C(=O)N)CCC1N1C(=O)C(CC=2C(=CC(=CC=2Cl)C=2C=CC(F)=CC=2)Cl)CC1 KXHWIUXOFOFHOF-UHFFFAOYSA-N 0.000 claims 1
- BPGFEKRMECDIQC-UHFFFAOYSA-N 4-[3-[[2,6-dichloro-4-(4-methylphenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)C(CC=2C(=CC(=CC=2Cl)C=2C=CC(C)=CC=2)Cl)CC1 BPGFEKRMECDIQC-UHFFFAOYSA-N 0.000 claims 1
- FXCOPNPNUHWSTQ-UHFFFAOYSA-N 4-[3-[[2,6-dichloro-4-(4-propan-2-yloxyphenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)C(CC=2C(=CC(=CC=2Cl)C=2C=CC(OC(C)C)=CC=2)Cl)CC1 FXCOPNPNUHWSTQ-UHFFFAOYSA-N 0.000 claims 1
- JQRXICJLNSCYTB-UHFFFAOYSA-N 4-[3-[[2,6-dichloro-4-[2-(trifluoromethyl)phenyl]phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)C(CC=2C(=CC(=CC=2Cl)C=2C(=CC=CC=2)C(F)(F)F)Cl)CC1 JQRXICJLNSCYTB-UHFFFAOYSA-N 0.000 claims 1
- PYVLUSPYWYDNQG-UHFFFAOYSA-N 4-[3-[[2,6-dichloro-4-[3-(trifluoromethyl)phenyl]phenyl]methyl]-2-oxopyrrolidin-1-yl]-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1N1C(=O)C(CC=2C(=CC(=CC=2Cl)C=2C=C(C=CC=2)C(F)(F)F)Cl)CC1 PYVLUSPYWYDNQG-UHFFFAOYSA-N 0.000 claims 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims 1
- NPXWHTKMKGVLEG-FQEVSTJZSA-N n-cyclohexyl-4-[(3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxamide Chemical compound C1=CC(F)=CC=C1C(C=C1Cl)=CC(Cl)=C1C[C@H]1C(=O)N(C2CCN(CC2)C(=O)NC2CCCCC2)CC1 NPXWHTKMKGVLEG-FQEVSTJZSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 32
- 239000000203 mixture Substances 0.000 abstract description 27
- 208000001145 Metabolic Syndrome Diseases 0.000 abstract description 24
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 24
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 24
- 230000000694 effects Effects 0.000 abstract description 23
- 208000008589 Obesity Diseases 0.000 abstract description 11
- 235000020824 obesity Nutrition 0.000 abstract description 11
- 206010020772 Hypertension Diseases 0.000 abstract description 8
- 201000001421 hyperglycemia Diseases 0.000 abstract description 8
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 2
- 239000005557 antagonist Substances 0.000 abstract description 2
- 229910052740 iodine Inorganic materials 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 70
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
- 238000002360 preparation method Methods 0.000 description 53
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 39
- 239000000243 solution Substances 0.000 description 34
- 239000000047 product Substances 0.000 description 31
- 208000035475 disorder Diseases 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000011282 treatment Methods 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 20
- 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 20
- 239000002904 solvent Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 17
- 229910052794 bromium Inorganic materials 0.000 description 17
- 125000004093 cyano group Chemical group *C#N 0.000 description 17
- 239000012267 brine Substances 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 229960000890 hydrocortisone Drugs 0.000 description 13
- 241000124008 Mammalia Species 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 238000003556 assay Methods 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 10
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 0 CC1(*)C=C(*)N=CC(C)=C1 Chemical compound CC1(*)C=C(*)N=CC(C)=C1 0.000 description 9
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 9
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 9
- 108090001061 Insulin Proteins 0.000 description 9
- 102000004877 Insulin Human genes 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- 229960004544 cortisone Drugs 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 229940125396 insulin Drugs 0.000 description 9
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 108010004469 allophycocyanin Proteins 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 229960003105 metformin Drugs 0.000 description 8
- 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 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 201000001320 Atherosclerosis Diseases 0.000 description 7
- 229940100389 Sulfonylurea Drugs 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 6
- 206010022489 Insulin Resistance Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 208000006011 Stroke Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- JIWAALDUIFCBLV-UHFFFAOYSA-N oxoosmium Chemical compound [Os]=O JIWAALDUIFCBLV-UHFFFAOYSA-N 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000003472 antidiabetic agent Substances 0.000 description 5
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229910052693 Europium Inorganic materials 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
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000036755 cellular response Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229960004580 glibenclamide Drugs 0.000 description 4
- 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 4
- 210000005119 human aortic smooth muscle cell Anatomy 0.000 description 4
- 244000144972 livestock Species 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 208000031225 myocardial ischemia Diseases 0.000 description 4
- 229960000698 nateglinide Drugs 0.000 description 4
- 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 4
- 230000001575 pathological effect Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 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 3
- GSLGJKVUKATZNM-RSAXXLAASA-N (3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-1-piperidin-4-ylpyrrolidin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(F)=CC=C1C(C=C1Cl)=CC(Cl)=C1C[C@H]1C(=O)N(C2CCNCC2)CC1 GSLGJKVUKATZNM-RSAXXLAASA-N 0.000 description 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
- 208000004611 Abdominal Obesity Diseases 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- BQENDLAVTKRQMS-SBBGFIFASA-L Carbenoxolone sodium Chemical compound [Na+].[Na+].C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C([O-])=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](OC(=O)CCC([O-])=O)C1(C)C BQENDLAVTKRQMS-SBBGFIFASA-L 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 3
- 229960002632 acarbose Drugs 0.000 description 3
- 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 3
- 239000013543 active substance Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 229940125708 antidiabetic agent Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229960000530 carbenoxolone Drugs 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000037356 lipid metabolism Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 229910000487 osmium oxide Inorganic materials 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 229960002354 repaglinide Drugs 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- ZVYAFVOHYMRKHP-UHFFFAOYSA-N tert-butyl-(3,5-dichlorophenoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC1=CC(Cl)=CC(Cl)=C1 ZVYAFVOHYMRKHP-UHFFFAOYSA-N 0.000 description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 3
- 229960001641 troglitazone Drugs 0.000 description 3
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 3
- INRQLTIPUQDPNJ-HNNXBMFYSA-N (3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-1-piperidin-4-ylpyrrolidin-2-one Chemical compound C1=CC(F)=CC=C1C(C=C1Cl)=CC(Cl)=C1C[C@H]1C(=O)N(C2CCNCC2)CC1 INRQLTIPUQDPNJ-HNNXBMFYSA-N 0.000 description 2
- XIZSGAQLLOCNDI-FCHUYYIVSA-N (3r)-4-[(4r)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-[(2,6-dichloro-4-phenylmethoxyphenyl)methyl]-4-oxobutanal Chemical compound C=1C(Cl)=C(C[C@H](CC=O)C(=O)N2C(OC[C@H]2CC=2C=CC=CC=2)=O)C(Cl)=CC=1OCC1=CC=CC=C1 XIZSGAQLLOCNDI-FCHUYYIVSA-N 0.000 description 2
- PQCXFUXRTRESBD-UHFFFAOYSA-N (4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C=C1 PQCXFUXRTRESBD-UHFFFAOYSA-N 0.000 description 2
- OJOFMLDBXPDXLQ-SECBINFHSA-N (4r)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-SECBINFHSA-N 0.000 description 2
- NNBFTSKHXAMHPF-XZOQPEGZSA-N (4r)-4-benzyl-3-[(2s)-2-[(2,6-dichloro-4-phenylmethoxyphenyl)methyl]pent-4-enoyl]-1,3-oxazolidin-2-one Chemical compound C=1C(Cl)=C(C[C@H](CC=C)C(=O)N2C(OC[C@H]2CC=2C=CC=CC=2)=O)C(Cl)=CC=1OCC1=CC=CC=C1 NNBFTSKHXAMHPF-XZOQPEGZSA-N 0.000 description 2
- VKEZZGBUHSYSJM-CYBMUJFWSA-N (4r)-4-benzyl-3-pent-4-enoyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)CCC=C)[C@@H]1CC1=CC=CC=C1 VKEZZGBUHSYSJM-CYBMUJFWSA-N 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- FFEKJBVVAJTQST-WLHGVMLRSA-N (e)-but-2-enedioic acid;1,1-dimethyl-2-(2-morpholin-4-ylphenyl)guanidine Chemical compound OC(=O)\C=C\C(O)=O.CN(C)C(N)=NC1=CC=CC=C1N1CCOCC1 FFEKJBVVAJTQST-WLHGVMLRSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- 102000008645 11-beta-Hydroxysteroid Dehydrogenase Type 1 Human genes 0.000 description 2
- 108010088011 11-beta-Hydroxysteroid Dehydrogenase Type 1 Proteins 0.000 description 2
- KBAGYDQLZMGHMT-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dichloro-5-methoxybenzene Chemical compound COC1=CC(Cl)=C(CBr)C(Cl)=C1 KBAGYDQLZMGHMT-UHFFFAOYSA-N 0.000 description 2
- GUXFHOKKFSZLTH-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dichloro-5-phenylmethoxybenzene Chemical compound ClC1=C(CBr)C(Cl)=CC(OCC=2C=CC=CC=2)=C1 GUXFHOKKFSZLTH-UHFFFAOYSA-N 0.000 description 2
- KMUKXPQVPQUCDB-UHFFFAOYSA-N 4-(trifluoromethyl)piperidine;hydrochloride Chemical compound Cl.FC(F)(F)C1CCNCC1 KMUKXPQVPQUCDB-UHFFFAOYSA-N 0.000 description 2
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 2
- BBJWLPOUOFZPHM-IBGZPJMESA-N 4-[3,5-dichloro-4-[[(3r)-1-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-2-oxopyrrolidin-3-yl]methyl]phenyl]benzoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(=CC=2)C(O)=O)Cl)CC1 BBJWLPOUOFZPHM-IBGZPJMESA-N 0.000 description 2
- 208000011732 Abnormal glucose homeostasis Diseases 0.000 description 2
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 101100451536 Arabidopsis thaliana HSD2 gene Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- HZZCSLKKNXVQSN-UHFFFAOYSA-N CC(N(CC1)CCC1(F)F)=O Chemical compound CC(N(CC1)CCC1(F)F)=O HZZCSLKKNXVQSN-UHFFFAOYSA-N 0.000 description 2
- 206010065941 Central obesity Diseases 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
- 102000001267 GSK3 Human genes 0.000 description 2
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 2
- 102000051325 Glucagon Human genes 0.000 description 2
- 108060003199 Glucagon Proteins 0.000 description 2
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 2
- 102000030595 Glucokinase Human genes 0.000 description 2
- 108010021582 Glucokinase Proteins 0.000 description 2
- 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 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 2
- 108010057186 Insulin Glargine Proteins 0.000 description 2
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 102000034527 Retinoid X Receptors Human genes 0.000 description 2
- 108010038912 Retinoid X Receptors Proteins 0.000 description 2
- 206010038923 Retinopathy Diseases 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000003524 antilipemic agent Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 229960001381 glipizide Drugs 0.000 description 2
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 2
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=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](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)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(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 2
- 229960004666 glucagon Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 2
- 201000008980 hyperinsulinism Diseases 0.000 description 2
- 229940126904 hypoglycaemic agent Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 229940060975 lantus Drugs 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 229950004994 meglitinide Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- JDKQTIKEGOOXTJ-UHFFFAOYSA-N pent-4-enoyl chloride Chemical compound ClC(=O)CCC=C JDKQTIKEGOOXTJ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 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
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 description 2
- MURNECHTHNUQJJ-ZDUSSCGKSA-N tert-butyl 4-[(3r)-3-[(2,6-dichloro-4-hydroxyphenyl)methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)[C@H](CC=2C(=CC(O)=CC=2Cl)Cl)CC1 MURNECHTHNUQJJ-ZDUSSCGKSA-N 0.000 description 2
- NRQWCFKXLIKEQZ-FQEVSTJZSA-N tert-butyl 4-[(3r)-3-[(2,6-dichloro-4-phenylmethoxyphenyl)methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)[C@H](CC=2C(=CC(OCC=3C=CC=CC=3)=CC=2Cl)Cl)CC1 NRQWCFKXLIKEQZ-FQEVSTJZSA-N 0.000 description 2
- RMLXCPREIMCSQS-SFHVURJKSA-N tert-butyl 4-[(3r)-3-[[2,6-dichloro-4-(4-fluorophenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(F)=CC=2)Cl)CC1 RMLXCPREIMCSQS-SFHVURJKSA-N 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
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 229960005371 tolbutamide Drugs 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
- OVPWEQROJNJHAG-UHFFFAOYSA-N (1-naphthalen-1-ylnaphthalen-2-yl)-diphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1)C1=CC=CC=C1 OVPWEQROJNJHAG-UHFFFAOYSA-N 0.000 description 1
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- GZPKMEKJXBJIEZ-UHFFFAOYSA-N (2,6-dichloro-4-methoxyphenyl)methanol Chemical compound COC1=CC(Cl)=C(CO)C(Cl)=C1 GZPKMEKJXBJIEZ-UHFFFAOYSA-N 0.000 description 1
- WTHWVGFNEDOQGB-UHFFFAOYSA-N (2,6-dichloro-4-phenylmethoxyphenyl)methanol Chemical compound C1=C(Cl)C(CO)=C(Cl)C=C1OCC1=CC=CC=C1 WTHWVGFNEDOQGB-UHFFFAOYSA-N 0.000 description 1
- WMUIIGVAWPWQAW-XMMPIXPASA-N (2r)-2-ethoxy-3-[4-(2-phenoxazin-10-ylethoxy)phenyl]propanoic acid Chemical compound C1=CC(C[C@@H](OCC)C(O)=O)=CC=C1OCCN1C2=CC=CC=C2OC2=CC=CC=C21 WMUIIGVAWPWQAW-XMMPIXPASA-N 0.000 description 1
- QNDFBOXBUCDYNZ-NRFANRHFSA-N (2s)-2-ethoxy-3-[4-[2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]ethoxy]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(NC(=O)OC(C)(C)C)C=C1 QNDFBOXBUCDYNZ-NRFANRHFSA-N 0.000 description 1
- OOERCJWCDJJRNT-FQEVSTJZSA-N (3R)-3-[[2,6-dichloro-4-[4-[4-(trifluoromethyl)piperidine-1-carbonyl]phenyl]phenyl]methyl]-1-piperidin-4-ylpyrrolidin-2-one Chemical compound C1CC(C(F)(F)F)CCN1C(=O)C1=CC=C(C=2C=C(Cl)C(C[C@H]3C(N(C4CCNCC4)CC3)=O)=C(Cl)C=2)C=C1 OOERCJWCDJJRNT-FQEVSTJZSA-N 0.000 description 1
- POQXHPHQAKZNSX-HNNXBMFYSA-N (3r)-3-[[2,6-dichloro-4-[4-(trifluoromethoxy)phenyl]phenyl]methyl]-1-piperidin-4-ylpyrrolidin-2-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1C(C=C1Cl)=CC(Cl)=C1C[C@H]1C(=O)N(C2CCNCC2)CC1 POQXHPHQAKZNSX-HNNXBMFYSA-N 0.000 description 1
- XMVSIONTYYRHMA-RSAXXLAASA-N (3r)-3-[[2,6-dichloro-4-[4-(trifluoromethoxy)phenyl]phenyl]methyl]-1-piperidin-4-ylpyrrolidin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(OC(F)(F)F)=CC=C1C(C=C1Cl)=CC(Cl)=C1C[C@H]1C(=O)N(C2CCNCC2)CC1 XMVSIONTYYRHMA-RSAXXLAASA-N 0.000 description 1
- WIZXZSAEGQQEHS-DLBZAZTESA-N (4r)-4-benzyl-3-[(2s)-2-[(2,6-dichloro-4-methoxyphenyl)methyl]pent-4-enoyl]-1,3-oxazolidin-2-one Chemical compound ClC1=CC(OC)=CC(Cl)=C1C[C@H](CC=C)C(=O)N1C(=O)OC[C@H]1CC1=CC=CC=C1 WIZXZSAEGQQEHS-DLBZAZTESA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- 229940124681 11 beta HSD inhibitor Drugs 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- WWFRBIPLCLSKNH-UHFFFAOYSA-N 2,6-dichloro-4-hydroxybenzaldehyde Chemical compound OC1=CC(Cl)=C(C=O)C(Cl)=C1 WWFRBIPLCLSKNH-UHFFFAOYSA-N 0.000 description 1
- FLHXTURECXRMQK-UHFFFAOYSA-N 2,6-dichloro-4-phenylmethoxybenzaldehyde Chemical compound ClC1=C(C=O)C(Cl)=CC(OCC=2C=CC=CC=2)=C1 FLHXTURECXRMQK-UHFFFAOYSA-N 0.000 description 1
- BWHDTKLVHSIHSQ-UHFFFAOYSA-N 2-(1-adamantyl)acetamide Chemical compound C1C(C2)CC3CC2CC1(CC(=O)N)C3 BWHDTKLVHSIHSQ-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- LUACLLSCZRRTIH-UPHRSURJSA-N 2-[[4-[(z)-4-[4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy]but-2-enoxy]phenyl]methyl]-1,2,4-oxadiazolidine-3,5-dione Chemical compound O1C(=O)NC(=O)N1CC(C=C1)=CC=C1OC\C=C/COC(C=C1)=CC=C1CN1C(=O)NC(=O)O1 LUACLLSCZRRTIH-UPHRSURJSA-N 0.000 description 1
- BJBCSGQLZQGGIQ-QGZVFWFLSA-N 2-acetamidoethyl (2r)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetate Chemical compound O([C@@H](C(=O)OCCNC(=O)C)C=1C=CC(Cl)=CC=1)C1=CC=CC(C(F)(F)F)=C1 BJBCSGQLZQGGIQ-QGZVFWFLSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- LGSOKZOQANLOEU-UHFFFAOYSA-N 4-[2-(2,4-dioxo-1,3-thiazolidin-5-yl)ethoxy]benzonitrile Chemical compound S1C(=O)NC(=O)C1CCOC1=CC=C(C#N)C=C1 LGSOKZOQANLOEU-UHFFFAOYSA-N 0.000 description 1
- QBQLYIISSRXYKL-UHFFFAOYSA-N 4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,2-oxazolidine-3,5-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1C(=O)NOC1=O QBQLYIISSRXYKL-UHFFFAOYSA-N 0.000 description 1
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 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
- MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 1
- SLXTWXQUEZSSTJ-UHFFFAOYSA-N 6-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl]pyridine-3-carboxylic acid Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C1(C=2N=CC(=CC=2)C(O)=O)CC1 SLXTWXQUEZSSTJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- UGSHHRVZMJMAEA-UHFFFAOYSA-N B1C(CCC2)CCCC12CC1=CC=CC=C1 Chemical compound B1C(CCC2)CCCC12CC1=CC=CC=C1 UGSHHRVZMJMAEA-UHFFFAOYSA-N 0.000 description 1
- 241000283726 Bison Species 0.000 description 1
- 241000282817 Bovidae Species 0.000 description 1
- ZNRGLCHATGKOEJ-ASNTXRKJSA-N C(C1=CC=CC=C1)[C@H]1N(C(OC1)=O)C([C@@H](CC=C)CC1=C(C=C(C=C1Cl)OC)Cl)=O.C(C1=CC=CC=C1)[C@H]1N(C(OC1)=O)C([C@@H](CC=O)CC1=C(C=C(C=C1Cl)OC)Cl)=O Chemical compound C(C1=CC=CC=C1)[C@H]1N(C(OC1)=O)C([C@@H](CC=C)CC1=C(C=C(C=C1Cl)OC)Cl)=O.C(C1=CC=CC=C1)[C@H]1N(C(OC1)=O)C([C@@H](CC=O)CC1=C(C=C(C=C1Cl)OC)Cl)=O ZNRGLCHATGKOEJ-ASNTXRKJSA-N 0.000 description 1
- GBVXCTIWEVXILG-UHFFFAOYSA-N CC(N(CC1)CCC1C(F)(F)F)=O Chemical compound CC(N(CC1)CCC1C(F)(F)F)=O GBVXCTIWEVXILG-UHFFFAOYSA-N 0.000 description 1
- KYWXRBNOYGGPIZ-UHFFFAOYSA-N CC(N1CCOCC1)=O Chemical compound CC(N1CCOCC1)=O KYWXRBNOYGGPIZ-UHFFFAOYSA-N 0.000 description 1
- GQKZBCPTCWJTAS-UHFFFAOYSA-N COCc1ccccc1 Chemical compound COCc1ccccc1 GQKZBCPTCWJTAS-UHFFFAOYSA-N 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N COc1ccccc1 Chemical compound COc1ccccc1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 101100451537 Caenorhabditis elegans hsd-1 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- YPKBCLZFIYBSHK-UHFFFAOYSA-N Cc(cc1)cc2c1[nH]cc2 Chemical compound Cc(cc1)cc2c1[nH]cc2 YPKBCLZFIYBSHK-UHFFFAOYSA-N 0.000 description 1
- KCZQNAOFWQGLCN-UHFFFAOYSA-N Cc(cc1)cc2c1[o]cc2 Chemical compound Cc(cc1)cc2c1[o]cc2 KCZQNAOFWQGLCN-UHFFFAOYSA-N 0.000 description 1
- DOHZWDWNQFZIKH-UHFFFAOYSA-N Cc(cc1)cc2c1[s]cc2 Chemical compound Cc(cc1)cc2c1[s]cc2 DOHZWDWNQFZIKH-UHFFFAOYSA-N 0.000 description 1
- SEBIXVUYSFOUEL-UHFFFAOYSA-N Cc(cc1)cc2c1[s]cn2 Chemical compound Cc(cc1)cc2c1[s]cn2 SEBIXVUYSFOUEL-UHFFFAOYSA-N 0.000 description 1
- MGHKWBQZEBMFOH-UHFFFAOYSA-N Cc1c(C)[o]nc1C Chemical compound Cc1c(C)[o]nc1C MGHKWBQZEBMFOH-UHFFFAOYSA-N 0.000 description 1
- RRZFDFYIDRCBCQ-UHFFFAOYSA-N Cc1cc2n[o]nc2cc1 Chemical compound Cc1cc2n[o]nc2cc1 RRZFDFYIDRCBCQ-UHFFFAOYSA-N 0.000 description 1
- XQQBUAPQHNYYRS-UHFFFAOYSA-N Cc1ccc[s]1 Chemical compound Cc1ccc[s]1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- YGFLBGPRPVQIDC-UHFFFAOYSA-N ClC1=C(C=O)C(=CC(=C1)O)Cl.ClC1=C(C=O)C(=CC(=C1)OC)Cl Chemical compound ClC1=C(C=O)C(=CC(=C1)O)Cl.ClC1=C(C=O)C(=CC(=C1)OC)Cl YGFLBGPRPVQIDC-UHFFFAOYSA-N 0.000 description 1
- XIUBNWFNLSOOOL-UHFFFAOYSA-N ClC1=C(C=O)C(=CC(=C1)OC)Cl.ClC1=C(C(=CC(=C1)OC)Cl)CO Chemical compound ClC1=C(C=O)C(=CC(=C1)OC)Cl.ClC1=C(C(=CC(=C1)OC)Cl)CO XIUBNWFNLSOOOL-UHFFFAOYSA-N 0.000 description 1
- SRPJWWLDIRJDNR-UHFFFAOYSA-N ClC=1C=C(C=C(C1)Cl)O.ClC1=C(C=O)C(=CC(=C1)O)Cl Chemical compound ClC=1C=C(C=C(C1)Cl)O.ClC1=C(C=O)C(=CC(=C1)O)Cl SRPJWWLDIRJDNR-UHFFFAOYSA-N 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- PSCXEUSWZWRCMQ-UHFFFAOYSA-N F[S](F)F Chemical compound F[S](F)F PSCXEUSWZWRCMQ-UHFFFAOYSA-N 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- GGUVRMBIEPYOKL-WMVCGJOFSA-N GW 409544 Chemical compound C([C@H](NC(/C)=C\C(=O)C=1C=CC=CC=1)C(O)=O)C(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 GGUVRMBIEPYOKL-WMVCGJOFSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010056997 Impaired fasting glucose Diseases 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 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
- 241000286209 Phasianidae Species 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100040918 Pro-glucagon Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000282849 Ruminantia Species 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
- 208000034189 Sclerosis Diseases 0.000 description 1
- 206010049416 Short-bowel syndrome Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 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
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000001837 anti-cortisol effect Effects 0.000 description 1
- 230000002402 anti-lipaemic effect Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-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
- 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 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229950009226 ciglitazone Drugs 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012612 commercial material Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000007821 culture assay Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 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
- 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
- 235000013365 dairy product Nutrition 0.000 description 1
- QQKNSPHAFATFNQ-UHFFFAOYSA-N darglitazone Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=O)C(C=C1)=CC=C1CC1SC(=O)NC1=O QQKNSPHAFATFNQ-UHFFFAOYSA-N 0.000 description 1
- 229950006689 darglitazone Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229950000269 emiglitate Drugs 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 229950002375 englitazone Drugs 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- NWWORXYTJRPSMC-QKPAOTATSA-N ethyl 4-[2-[(2r,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 NWWORXYTJRPSMC-QKPAOTATSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZZCHHVUQYRMYLW-HKBQPEDESA-N farglitazar Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZCHHVUQYRMYLW-HKBQPEDESA-N 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
- 239000012467 final product Substances 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 229960004279 formaldehyde Drugs 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 229960004346 glimepiride 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
- 229940048956 glucagon injection Drugs 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 230000004116 glycogenolysis Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 208000028867 ischemia Diseases 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
- NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 229960003365 mitiglinide Drugs 0.000 description 1
- WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- BFYLULHOYZNWPC-UHFFFAOYSA-N n-[[4,5-dimethyl-1-[(2-methylphenyl)methyl]imidazol-2-yl]methyl]-2,4-dimethoxy-n-(3-methylbutyl)benzamide Chemical compound COC1=CC(OC)=CC=C1C(=O)N(CCC(C)C)CC1=NC(C)=C(C)N1CC1=CC=CC=C1C BFYLULHOYZNWPC-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [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
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- YDCVQGAUCOROHB-UHFFFAOYSA-N oxadiazolidine-4,5-dione Chemical compound O=C1NNOC1=O YDCVQGAUCOROHB-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000018656 positive regulation of gluconeogenesis Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000003450 potassium channel blocker Substances 0.000 description 1
- 229940125422 potassium channel blocker Drugs 0.000 description 1
- 239000004036 potassium channel stimulating agent Substances 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-M pravastatin(1-) Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC([O-])=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-M 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- XMSXOLDPMGMWTH-UHFFFAOYSA-N rivoglitazone Chemical compound CN1C2=CC(OC)=CC=C2N=C1COC(C=C1)=CC=C1CC1SC(=O)NC1=O XMSXOLDPMGMWTH-UHFFFAOYSA-N 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 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
- 230000028327 secretion Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 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
- 235000011888 snacks Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- PFNKDSLKAZAJSO-FQEVSTJZSA-N tert-butyl 4-[(3r)-3-[[2,6-dichloro-4-(4-methoxycarbonylphenyl)phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1C(C=C1Cl)=CC(Cl)=C1C[C@H]1C(=O)N(C2CCN(CC2)C(=O)OC(C)(C)C)CC1 PFNKDSLKAZAJSO-FQEVSTJZSA-N 0.000 description 1
- ZEXGJXKAAZOTLM-QHCPKHFHSA-N tert-butyl 4-[(3r)-3-[[2,6-dichloro-4-[4-[4-(trifluoromethyl)piperidine-1-carbonyl]phenyl]phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)[C@H](CC=2C(=CC(=CC=2Cl)C=2C=CC(=CC=2)C(=O)N2CCC(CC2)C(F)(F)F)Cl)CC1 ZEXGJXKAAZOTLM-QHCPKHFHSA-N 0.000 description 1
- HNRJNPMJFUZXEU-UHFFFAOYSA-N tert-butyl 4-[3-[[2,6-dichloro-4-(trifluoromethylsulfonyloxy)phenyl]methyl]-2-oxopyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)C(CC=2C(=CC(OS(=O)(=O)C(F)(F)F)=CC=2Cl)Cl)CC1 HNRJNPMJFUZXEU-UHFFFAOYSA-N 0.000 description 1
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- ZAADRXMXROEPIU-UHFFFAOYSA-N tert-butyl(2-chloropropan-2-yloxy)silane Chemical compound CC(C)(C)[SiH2]OC(C)(C)Cl ZAADRXMXROEPIU-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61P3/06—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
- 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
- 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
- A61P9/06—Antiarrhythmics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Gynecology & Obstetrics (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79611206P | 2006-04-28 | 2006-04-28 | |
| US60/796,112 | 2006-04-28 | ||
| PCT/US2007/067597 WO2007127901A1 (en) | 2006-04-28 | 2007-04-27 | Pieridinyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2009535362A JP2009535362A (ja) | 2009-10-01 |
| JP2009535362A5 JP2009535362A5 (enExample) | 2010-05-13 |
| JP5225980B2 true JP5225980B2 (ja) | 2013-07-03 |
Family
ID=38421166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009507978A Expired - Fee Related JP5225980B2 (ja) | 2006-04-28 | 2007-04-27 | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤としてのピエリジニル置換ピロリジノン |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7829582B2 (enExample) |
| EP (1) | EP2049513B1 (enExample) |
| JP (1) | JP5225980B2 (enExample) |
| KR (1) | KR101060016B1 (enExample) |
| CN (1) | CN101448816B (enExample) |
| AT (1) | ATE542811T1 (enExample) |
| AU (1) | AU2007244742B2 (enExample) |
| BR (1) | BRPI0710469A2 (enExample) |
| CA (1) | CA2650627C (enExample) |
| CY (1) | CY1112466T1 (enExample) |
| DK (1) | DK2049513T3 (enExample) |
| EA (1) | EA014719B1 (enExample) |
| EC (1) | ECSP088849A (enExample) |
| IL (1) | IL194879A0 (enExample) |
| MA (1) | MA30421B1 (enExample) |
| MX (1) | MX2008013844A (enExample) |
| NO (1) | NO20084874L (enExample) |
| PL (1) | PL2049513T3 (enExample) |
| PT (1) | PT2049513E (enExample) |
| SI (1) | SI2049513T1 (enExample) |
| TN (1) | TNSN08432A1 (enExample) |
| WO (1) | WO2007127901A1 (enExample) |
| ZA (1) | ZA200808816B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ571175A (en) * | 2006-04-21 | 2011-10-28 | Lilly Co Eli | Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| BRPI0710273A2 (pt) | 2006-04-21 | 2011-08-09 | Lilly Co Eli | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, intermediário |
| US8088776B2 (en) * | 2006-04-21 | 2012-01-03 | Eli Lilly And Company | Biphenyl amide lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CA2649650C (en) | 2006-04-24 | 2014-01-14 | Eli Lilly And Company | Substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| ATE543798T1 (de) | 2006-04-24 | 2012-02-15 | Lilly Co Eli | Cyclohexyl-substituierte pyrrolidinone als hemmer von 11-beta-hydroxysteroiddehydrogenase 1 |
| ATE472542T1 (de) | 2006-04-24 | 2010-07-15 | Lilly Co Eli | 11-beta-hydroxysteroid-dehydrogenase-1-hemmer |
| AU2007244863B2 (en) * | 2006-04-25 | 2012-01-19 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EP2021337B1 (en) | 2006-04-25 | 2010-01-13 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US7968585B2 (en) | 2006-04-25 | 2011-06-28 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US8507493B2 (en) | 2009-04-20 | 2013-08-13 | Abbvie Inc. | Amide and amidine derivatives and uses thereof |
| WO2011068927A2 (en) * | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| KR101593493B1 (ko) | 2014-10-28 | 2016-02-18 | 주식회사 아이에스티이 | 대면적 유리기판 열처리 장치 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20050051691A (ko) * | 2002-10-11 | 2005-06-01 | 아스트라제네카 아베 | 1,4-이치환 피페리딘 유도체 및 11-베타ｈｓｄ1억제제로서의 이들의 용도 |
| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| CA2565630C (en) * | 2004-05-07 | 2013-05-28 | Janssen Pharmaceutica N.V. | Pyrrolidin-2-one and piperidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| EP1747198B1 (en) | 2004-05-07 | 2008-06-04 | Janssen Pharmaceutica N.V. | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| EP1802623A1 (en) | 2004-10-12 | 2007-07-04 | Novo Nordisk A/S | 11beta-hydroxysteroid dehydrogenase type 1 active spiro compounds |
| WO2006049952A1 (en) * | 2004-10-29 | 2006-05-11 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| SG161261A1 (en) | 2004-11-10 | 2010-05-27 | Incyte Corp | Lactam compounds and their use as pharmaceuticals |
| ATE399546T1 (de) * | 2004-12-20 | 2008-07-15 | Lilly Co Eli | Cycloalkyl-lactam-derivate als inhibitoren von 11-beta-hydroxysteroiddehydrogenase 1 |
| EP1830840B1 (en) * | 2004-12-21 | 2008-07-16 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EP1864971A4 (en) | 2005-03-31 | 2010-02-10 | Takeda Pharmaceutical | PROPHYLACTIC / THERAPEUTIC AGENT AGAINST DIABETES |
| US7998959B2 (en) | 2006-01-12 | 2011-08-16 | Incyte Corporation | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| BRPI0710273A2 (pt) * | 2006-04-21 | 2011-08-09 | Lilly Co Eli | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, intermediário |
| US8088776B2 (en) * | 2006-04-21 | 2012-01-03 | Eli Lilly And Company | Biphenyl amide lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| NZ571175A (en) * | 2006-04-21 | 2011-10-28 | Lilly Co Eli | Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CA2649650C (en) * | 2006-04-24 | 2014-01-14 | Eli Lilly And Company | Substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| ATE543798T1 (de) | 2006-04-24 | 2012-02-15 | Lilly Co Eli | Cyclohexyl-substituierte pyrrolidinone als hemmer von 11-beta-hydroxysteroiddehydrogenase 1 |
| ATE472542T1 (de) | 2006-04-24 | 2010-07-15 | Lilly Co Eli | 11-beta-hydroxysteroid-dehydrogenase-1-hemmer |
| AU2007244863B2 (en) * | 2006-04-25 | 2012-01-19 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US7968585B2 (en) * | 2006-04-25 | 2011-06-28 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EP2021337B1 (en) | 2006-04-25 | 2010-01-13 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CL2008001839A1 (es) | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
-
2007
- 2007-04-27 MX MX2008013844A patent/MX2008013844A/es active IP Right Grant
- 2007-04-27 US US12/297,951 patent/US7829582B2/en not_active Expired - Fee Related
- 2007-04-27 DK DK07761424.6T patent/DK2049513T3/da active
- 2007-04-27 WO PCT/US2007/067597 patent/WO2007127901A1/en not_active Ceased
- 2007-04-27 BR BRPI0710469-3A patent/BRPI0710469A2/pt not_active IP Right Cessation
- 2007-04-27 AT AT07761424T patent/ATE542811T1/de active
- 2007-04-27 CN CN2007800154205A patent/CN101448816B/zh not_active Expired - Fee Related
- 2007-04-27 CA CA2650627A patent/CA2650627C/en not_active Expired - Fee Related
- 2007-04-27 EP EP07761424A patent/EP2049513B1/en active Active
- 2007-04-27 PT PT07761424T patent/PT2049513E/pt unknown
- 2007-04-27 PL PL07761424T patent/PL2049513T3/pl unknown
- 2007-04-27 EA EA200870489A patent/EA014719B1/ru not_active IP Right Cessation
- 2007-04-27 SI SI200730872T patent/SI2049513T1/sl unknown
- 2007-04-27 AU AU2007244742A patent/AU2007244742B2/en not_active Ceased
- 2007-04-27 JP JP2009507978A patent/JP5225980B2/ja not_active Expired - Fee Related
- 2007-04-27 KR KR1020087026195A patent/KR101060016B1/ko not_active Expired - Fee Related
-
2008
- 2008-10-15 ZA ZA200808816A patent/ZA200808816B/xx unknown
- 2008-10-23 IL IL194879A patent/IL194879A0/en unknown
- 2008-10-24 TN TNP2008000432A patent/TNSN08432A1/en unknown
- 2008-10-27 EC EC2008008849A patent/ECSP088849A/es unknown
- 2008-11-19 NO NO20084874A patent/NO20084874L/no not_active Application Discontinuation
- 2008-11-20 MA MA31397A patent/MA30421B1/fr unknown
-
2012
- 2012-03-08 CY CY20121100235T patent/CY1112466T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN101448816B (zh) | 2013-08-07 |
| TNSN08432A1 (en) | 2010-04-14 |
| EP2049513A1 (en) | 2009-04-22 |
| PT2049513E (pt) | 2012-03-20 |
| ECSP088849A (es) | 2008-11-27 |
| MX2008013844A (es) | 2008-11-10 |
| US20090088430A1 (en) | 2009-04-02 |
| JP2009535362A (ja) | 2009-10-01 |
| ZA200808816B (en) | 2009-12-30 |
| SI2049513T1 (sl) | 2012-04-30 |
| CN101448816A (zh) | 2009-06-03 |
| ATE542811T1 (de) | 2012-02-15 |
| NO20084874L (no) | 2008-11-19 |
| EA014719B1 (ru) | 2011-02-28 |
| PL2049513T3 (pl) | 2012-06-29 |
| KR20090007371A (ko) | 2009-01-16 |
| BRPI0710469A2 (pt) | 2011-08-16 |
| KR101060016B1 (ko) | 2011-08-29 |
| IL194879A0 (en) | 2009-08-03 |
| US7829582B2 (en) | 2010-11-09 |
| AU2007244742B2 (en) | 2012-03-08 |
| EA200870489A1 (ru) | 2009-04-28 |
| MA30421B1 (fr) | 2009-05-04 |
| CY1112466T1 (el) | 2015-12-09 |
| WO2007127901A1 (en) | 2007-11-08 |
| EP2049513B1 (en) | 2012-01-25 |
| CA2650627C (en) | 2013-07-16 |
| DK2049513T3 (da) | 2012-02-27 |
| AU2007244742A1 (en) | 2007-11-08 |
| CA2650627A1 (en) | 2007-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5189078B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| JP5101602B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| EP2049513B1 (en) | Piperidinyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 | |
| JP5236628B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１阻害剤としての、シクロヘキシルイミダゾールラクタム誘導体 | |
| JP5118692B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤としてのシクロヘキシル置換ピロリジノン | |
| JP5265521B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１阻害剤としてのビフェニルアミドラクタム誘導体 | |
| JP5269765B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| JP5189079B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 | |
| JP5324427B2 (ja) | １１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100326 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100326 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121023 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130115 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130212 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130313 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160322 Year of fee payment: 3 |
|
| LAPS | Cancellation because of no payment of annual fees |