WO1997046556A1 - OXADIAZOLE BENZENESULFONAMIDES AS SELECTIVE β3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY - Google Patents
OXADIAZOLE BENZENESULFONAMIDES AS SELECTIVE β3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY Download PDFInfo
- Publication number
- WO1997046556A1 WO1997046556A1 PCT/US1997/009536 US9709536W WO9746556A1 WO 1997046556 A1 WO1997046556 A1 WO 1997046556A1 US 9709536 W US9709536 W US 9709536W WO 9746556 A1 WO9746556 A1 WO 9746556A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ethyl
- hydroxy
- oxadiazol
- phenyl
- amino
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 29
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 17
- 208000008589 Obesity Diseases 0.000 title claims abstract description 11
- 235000020824 obesity Nutrition 0.000 title claims abstract description 11
- -1 OXADIAZOLE BENZENESULFONAMIDES Chemical class 0.000 title claims description 56
- 239000000556 agonist Substances 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 238000000034 method Methods 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 23
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 18
- 102000015779 HDL Lipoproteins Human genes 0.000 claims abstract description 9
- 108010010234 HDL Lipoproteins Proteins 0.000 claims abstract description 9
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 7
- 208000007920 Neurogenic Inflammation Diseases 0.000 claims abstract description 5
- 230000010243 gut motility Effects 0.000 claims abstract 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 411
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 210
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 206
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 166
- 150000002367 halogens Chemical class 0.000 claims description 88
- 229910052736 halogen Inorganic materials 0.000 claims description 80
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 229910052757 nitrogen Chemical group 0.000 claims description 39
- 229910052760 oxygen Inorganic materials 0.000 claims description 39
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 38
- 239000001301 oxygen Substances 0.000 claims description 38
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 36
- 239000011593 sulfur Chemical group 0.000 claims description 36
- 125000005842 heteroatom Chemical group 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 31
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 18
- 125000002947 alkylene group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000002837 carbocyclic group Chemical group 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 235000019256 formaldehyde Nutrition 0.000 claims description 4
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- GWAKLMBIGDXTOM-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1C1=CC=C(F)C=C1 GWAKLMBIGDXTOM-UHFFFAOYSA-N 0.000 claims description 2
- BIUDHHGROGJSHN-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzaldehyde Chemical group FC1=CC=C(C=O)C=C1C(F)(F)F BIUDHHGROGJSHN-UHFFFAOYSA-N 0.000 claims description 2
- 125000006356 alkylene carbonyl group Chemical group 0.000 claims description 2
- NCTSAWXMVCCIFP-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(2-methylphenyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound CC1=CC=CC=C1C1=NC(C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(CCNCC(O)C=3C=NC=CC=3)=CC=2)=NO1 NCTSAWXMVCCIFP-UHFFFAOYSA-N 0.000 claims description 2
- GYWICHDKAKGABO-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(3-nitrophenyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1C1=CC=CC([N+]([O-])=O)=C1 GYWICHDKAKGABO-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 10
- 230000003247 decreasing effect Effects 0.000 claims 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- ZZQJOPOKZTXCKB-UHFFFAOYSA-N 4-[5-(1,3-benzodioxol-5-ylmethyl)-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=CC(=CC=2)C=2N=C(CC=3C=C4OCOC4=CC=3)ON=2)C=CC=1CCNCC(O)C1=CC=CN=C1 ZZQJOPOKZTXCKB-UHFFFAOYSA-N 0.000 claims 1
- AKVOHMWXKCTPRR-UHFFFAOYSA-N 4-[5-(1-benzofuran-2-yl)-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=CC(=CC=2)C=2N=C(ON=2)C=2OC3=CC=CC=C3C=2)C=CC=1CCNCC(O)C1=CC=CN=C1 AKVOHMWXKCTPRR-UHFFFAOYSA-N 0.000 claims 1
- WOLUYNYAJCOOPT-UHFFFAOYSA-N 4-[5-(3-fluorophenyl)-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1C1=CC=CC(F)=C1 WOLUYNYAJCOOPT-UHFFFAOYSA-N 0.000 claims 1
- ZBALLCANCTYRPS-UHFFFAOYSA-N 4-[5-(4-fluorobenzoyl)-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1C(=O)C1=CC=C(F)C=C1 ZBALLCANCTYRPS-UHFFFAOYSA-N 0.000 claims 1
- LJGZBXGXTXKHNC-UHFFFAOYSA-N 4-[5-[(3,4-difluorophenoxy)methyl]-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1COC1=CC=C(F)C(F)=C1 LJGZBXGXTXKHNC-UHFFFAOYSA-N 0.000 claims 1
- VVPOZWCWABYDFK-UHFFFAOYSA-N 4-[5-[(3-chlorophenyl)methyl]-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1CC1=CC=CC(Cl)=C1 VVPOZWCWABYDFK-UHFFFAOYSA-N 0.000 claims 1
- SBACQNMIKWVEKA-UHFFFAOYSA-N 4-[5-[(3-fluorophenyl)methyl]-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1CC1=CC=CC(F)=C1 SBACQNMIKWVEKA-UHFFFAOYSA-N 0.000 claims 1
- MLCHPVHJKNLRMJ-UHFFFAOYSA-N 4-[5-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1CC1=CC=C(F)C=C1 MLCHPVHJKNLRMJ-UHFFFAOYSA-N 0.000 claims 1
- YQJZLWNUAQMPKM-UHFFFAOYSA-N 4-[5-[3-(4-fluorophenyl)-3-oxopropyl]-1,2,4-oxadiazol-3-yl]-n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1CCC(=O)C1=CC=C(F)C=C1 YQJZLWNUAQMPKM-UHFFFAOYSA-N 0.000 claims 1
- ORMYPXNHFOAYRQ-UHFFFAOYSA-N [4-[[3-[4-[[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]sulfamoyl]phenyl]-1,2,4-oxadiazol-5-yl]methoxy]phenyl] acetate Chemical compound C1=CC(OC(=O)C)=CC=C1OCC1=NC(C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(CCNCC(O)C=3C=NC=CC=3)=CC=2)=NO1 ORMYPXNHFOAYRQ-UHFFFAOYSA-N 0.000 claims 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims 1
- 230000000994 depressogenic effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- UCZVAVMAKKOYDR-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(1h-indol-3-ylmethyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=CC(=CC=2)C=2N=C(CC=3C4=CC=CC=C4NC=3)ON=2)C=CC=1CCNCC(O)C1=CC=CN=C1 UCZVAVMAKKOYDR-UHFFFAOYSA-N 0.000 claims 1
- QJNXILTVKUHXOF-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(2-phenoxyethyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1CCOC1=CC=CC=C1 QJNXILTVKUHXOF-UHFFFAOYSA-N 0.000 claims 1
- KMFAUKAYKGTSJZ-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(3-methylsulfanylphenyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound CSC1=CC=CC(C=2ON=C(N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(CCNCC(O)C=3C=NC=CC=3)=CC=2)=C1 KMFAUKAYKGTSJZ-UHFFFAOYSA-N 0.000 claims 1
- OIOGLWJERDKLQQ-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(3-methylsulfonylphenyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound CS(=O)(=O)C1=CC=CC(C=2ON=C(N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(CCNCC(O)C=3C=NC=CC=3)=CC=2)=C1 OIOGLWJERDKLQQ-UHFFFAOYSA-N 0.000 claims 1
- BSSRIZKLUOVTPO-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-[(4-pyridin-3-ylphenyl)methyl]-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1CC(C=C1)=CC=C1C1=CC=CN=C1 BSSRIZKLUOVTPO-UHFFFAOYSA-N 0.000 claims 1
- YFBKYRWCIPHZIS-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1C1=CC=C(C(F)(F)F)C=C1 YFBKYRWCIPHZIS-UHFFFAOYSA-N 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 24
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 abstract description 15
- 230000004130 lipolysis Effects 0.000 abstract description 6
- 229940124530 sulfonamide Drugs 0.000 abstract description 6
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 abstract description 4
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 abstract description 4
- 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 abstract description 4
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 abstract description 4
- 230000008878 coupling Effects 0.000 abstract description 4
- 238000010168 coupling process Methods 0.000 abstract description 4
- 238000005859 coupling reaction Methods 0.000 abstract description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 3
- 239000000935 antidepressant agent Substances 0.000 abstract description 2
- 150000008331 benzenesulfonamides Chemical class 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 239000000048 adrenergic agonist Substances 0.000 abstract 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 abstract 1
- 102000016967 beta-1 Adrenergic Receptors Human genes 0.000 abstract 1
- 108010014494 beta-1 Adrenergic Receptors Proteins 0.000 abstract 1
- 150000002118 epoxides Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 37
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- SBBOPUCCCOEMDA-UHFFFAOYSA-N 5-[4-chloro-3-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound ClC1=C(C=C(C=C1)C1=NN=C(O1)O)C(F)(F)F SBBOPUCCCOEMDA-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
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- 229920005989 resin Polymers 0.000 description 13
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
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- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
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- 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 8
- 238000003556 assay Methods 0.000 description 8
- 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 8
- 150000004866 oxadiazoles Chemical class 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
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- 229910052744 lithium Inorganic materials 0.000 description 1
- 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 1
- 229960004844 lovastatin Drugs 0.000 description 1
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- 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 1
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- 230000000873 masking effect Effects 0.000 description 1
- 229950008446 melinamide Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- BLBFLHCCPUAXDL-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)-2-hydroxyacetate Chemical compound COC(=O)C(O)C1=CC=C(F)C=C1 BLBFLHCCPUAXDL-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- IMIDGDYKUKZXST-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(3-methoxyphenyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound COC1=CC=CC(C=2ON=C(N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(CCNCC(O)C=3C=NC=CC=3)=CC=2)=C1 IMIDGDYKUKZXST-UHFFFAOYSA-N 0.000 description 1
- WLNKOLLTYHYJCC-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-(3-methylphenyl)-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound CC1=CC=CC(C=2ON=C(N=2)C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(CCNCC(O)C=3C=NC=CC=3)=CC=2)=C1 WLNKOLLTYHYJCC-UHFFFAOYSA-N 0.000 description 1
- SLIMEVKNMJKEMU-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-[(4-pyridin-2-ylphenyl)methyl]-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1CC(C=C1)=CC=C1C1=CC=CC=N1 SLIMEVKNMJKEMU-UHFFFAOYSA-N 0.000 description 1
- FYHUILYPFUNCMT-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-2-pyridin-3-ylethyl)amino]ethyl]phenyl]-4-[5-[[3-(trifluoromethyl)phenoxy]methyl]-1,2,4-oxadiazol-3-yl]benzenesulfonamide Chemical compound C=1C=CN=CC=1C(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C(C=C1)=CC=C1C(N=1)=NOC=1COC1=CC=CC(C(F)(F)F)=C1 FYHUILYPFUNCMT-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960004738 nicotinyl alcohol Drugs 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin 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-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 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
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 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
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007886 soft shell capsule Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- 229940125670 thienopyridine Drugs 0.000 description 1
- 239000002175 thienopyridine Substances 0.000 description 1
- 230000000929 thyromimetic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- WILBTFWIBAOWLN-UHFFFAOYSA-N triethyl(triethylsilyloxy)silane Chemical compound CC[Si](CC)(CC)O[Si](CC)(CC)CC WILBTFWIBAOWLN-UHFFFAOYSA-N 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 210000000636 white adipocyte Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- 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
- A61P25/24—Antidepressants
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97929769A EP0906310A4 (en) | 1996-06-07 | 1997-06-03 | OXADIAZOLE BENZENESULFONAMIDES AS SELECTIVE -g(b) 3? AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY |
JP10500782A JP2000511903A (en) | 1996-06-07 | 1997-06-03 | Oxadiazole benzenesulfonamide as a selective beta 3 agonist for the treatment of diabetes and obesity |
AU33748/97A AU712057B2 (en) | 1996-06-07 | 1997-06-03 | Oxadiazole benzenesulfonamides as selective beta3 agonists for the treatment of diabetes and obesity |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1929596P | 1996-06-07 | 1996-06-07 | |
US60/019,295 | 1996-06-07 | ||
GB9614191.6 | 1996-07-05 | ||
GBGB9614191.6A GB9614191D0 (en) | 1996-07-05 | 1996-07-05 | Oxadiazole benzenesulfonamides as selectives B3 agonists for the treatment of diabetes and obesity |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997046556A1 true WO1997046556A1 (en) | 1997-12-11 |
Family
ID=26309646
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1997/009536 WO1997046556A1 (en) | 1996-06-07 | 1997-06-03 | OXADIAZOLE BENZENESULFONAMIDES AS SELECTIVE β3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0906310A4 (en) |
JP (1) | JP2000511903A (en) |
AU (1) | AU712057B2 (en) |
CA (1) | CA2257206A1 (en) |
WO (1) | WO1997046556A1 (en) |
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WO2002006221A2 (en) * | 2000-07-17 | 2002-01-24 | Wyeth | Cyclylamine sulfonamides as beta-3 adrenergic receptor agonists |
WO2002006276A1 (en) * | 2000-07-13 | 2002-01-24 | Eli Lilly And Company | Beta3 adrenergic agonists |
US6537994B2 (en) | 2000-07-17 | 2003-03-25 | Wyeth | Heterocyclic β3 adrenergic receptor agonists |
US6569873B2 (en) | 2000-07-17 | 2003-05-27 | Wyeth | Azolidines as beta-3 adrenergic receptor agonists |
US6583140B2 (en) | 2000-07-17 | 2003-06-24 | Wyeth | 2-substituted thiazolidinones as beta-3 adrenergic receptor agonists |
US6660752B2 (en) | 2001-04-23 | 2003-12-09 | Bayer Pharmaceuticals Corporation | 2,6-Substituted chroman derivatives useful as beta-3 adrenoreceptor agonists |
US6699860B2 (en) | 2000-12-11 | 2004-03-02 | Bayer Pharmaceuticals Corporation | Di-substituted aminomethyl-chroman derivative beta-3 adrenoreceptor agonists |
WO2004043443A2 (en) * | 2002-11-12 | 2004-05-27 | Nicox S.A. | Drugs for sexual dysfunctions |
US6780859B2 (en) | 2001-09-14 | 2004-08-24 | Bayer Pharmaceuticals Corporation | Benzofuran and dihydrobenzofuran derivatives useful as beta-3 adrenoreceptor agonists |
US6825220B2 (en) | 2000-11-10 | 2004-11-30 | Eli Lilly And Company | 3-Substituted oxindole β 3 agonists |
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Also Published As
Publication number | Publication date |
---|---|
AU3374897A (en) | 1998-01-05 |
JP2000511903A (en) | 2000-09-12 |
CA2257206A1 (en) | 1997-12-11 |
AU712057B2 (en) | 1999-10-28 |
EP0906310A4 (en) | 1999-09-01 |
EP0906310A1 (en) | 1999-04-07 |
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