DE60215028T2 - Indol derivate als beta-3-adrenerge agonisten zur behandlung von typ 2 diabetes - Google Patents
Indol derivate als beta-3-adrenerge agonisten zur behandlung von typ 2 diabetes Download PDFInfo
- Publication number
- DE60215028T2 DE60215028T2 DE60215028T DE60215028T DE60215028T2 DE 60215028 T2 DE60215028 T2 DE 60215028T2 DE 60215028 T DE60215028 T DE 60215028T DE 60215028 T DE60215028 T DE 60215028T DE 60215028 T2 DE60215028 T2 DE 60215028T2
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- Prior art keywords
- mmol
- alkyl
- amine
- mixture
- phenyl
- Prior art date
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- 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 16
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title description 14
- 239000000556 agonist Substances 0.000 title description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 208000008589 Obesity Diseases 0.000 claims abstract description 16
- 235000020824 obesity Nutrition 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims description 165
- -1 D is NR 8 Inorganic materials 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 19
- 150000003536 tetrazoles Chemical class 0.000 claims description 16
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims description 10
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 150000003852 triazoles Chemical class 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical group C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 230000004130 lipolysis Effects 0.000 abstract description 2
- 229940126158 β3 adrenergic receptor agonist Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 396
- 150000001412 amines Chemical class 0.000 description 222
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 207
- 239000000203 mixture Substances 0.000 description 181
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 173
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 166
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 151
- 239000000243 solution Substances 0.000 description 133
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- 238000000434 field desorption mass spectrometry Methods 0.000 description 72
- 239000011541 reaction mixture Substances 0.000 description 60
- 150000002924 oxiranes Chemical class 0.000 description 56
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- 238000000034 method Methods 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 50
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 239000012267 brine Substances 0.000 description 46
- 239000012074 organic phase Substances 0.000 description 46
- 239000011734 sodium Substances 0.000 description 46
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 46
- 239000000460 chlorine Substances 0.000 description 37
- 239000012458 free base Substances 0.000 description 37
- 239000000047 product Substances 0.000 description 37
- 238000010992 reflux Methods 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 238000002360 preparation method Methods 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 238000003756 stirring Methods 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 238000003818 flash chromatography Methods 0.000 description 28
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 24
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
- 239000000284 extract Substances 0.000 description 22
- 102000005962 receptors Human genes 0.000 description 21
- 108020003175 receptors Proteins 0.000 description 21
- 229910004298 SiO 2 Inorganic materials 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 239000004593 Epoxy Substances 0.000 description 18
- 239000012071 phase Substances 0.000 description 18
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 17
- AIHIHVZYAAMDPM-QMMMGPOBSA-N [(2s)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@H]2OC2)=C1 AIHIHVZYAAMDPM-QMMMGPOBSA-N 0.000 description 16
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 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 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 13
- 238000010828 elution Methods 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical class C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
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- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 10
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 10
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- ZEMSPQCZQNWQGR-UHFFFAOYSA-N [3-[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]-1h-indol-7-yl] trifluoromethanesulfonate Chemical compound C1=CC=C2C(CC(C)(C)NC(=O)OC(C)(C)C)=CNC2=C1OS(=O)(=O)C(F)(F)F ZEMSPQCZQNWQGR-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
- 150000001502 aryl halides Chemical class 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 7
- 241000282414 Homo sapiens Species 0.000 description 7
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- 229940079593 drug Drugs 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
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- WPZQTEPILMUYQG-GFCCVEGCSA-N tert-butyl n-[(2r)-1-[7-(cyanomethoxy)-1h-indol-3-yl]propan-2-yl]carbamate Chemical compound C1=CC=C2C(C[C@@H](C)NC(=O)OC(C)(C)C)=CNC2=C1OCC#N WPZQTEPILMUYQG-GFCCVEGCSA-N 0.000 description 1
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- OTBJNHHQPWERHY-UHFFFAOYSA-N tert-butyl n-[2-methyl-1-(7-thiophen-2-yl-1h-indol-3-yl)propan-2-yl]carbamate Chemical compound C1=CC=C2C(CC(C)(C)NC(=O)OC(C)(C)C)=CNC2=C1C1=CC=CS1 OTBJNHHQPWERHY-UHFFFAOYSA-N 0.000 description 1
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- SWZHVDPXQFUEAP-UHFFFAOYSA-N tert-butyl n-[2-methyl-1-[7-[2-(1,2,4-triazol-1-yl)ethyl]-1h-indol-3-yl]propan-2-yl]carbamate Chemical compound C1=CC=C2C(CC(C)(C)NC(=O)OC(C)(C)C)=CNC2=C1CCN1C=NC=N1 SWZHVDPXQFUEAP-UHFFFAOYSA-N 0.000 description 1
- YBIBNLIGKLIPNM-UHFFFAOYSA-N tert-butyl n-[2-methyl-1-[7-[2-(methylamino)-2-oxoethoxy]-1h-indol-3-yl]propan-2-yl]carbamate Chemical compound CNC(=O)COC1=CC=CC2=C1NC=C2CC(C)(C)NC(=O)OC(C)(C)C YBIBNLIGKLIPNM-UHFFFAOYSA-N 0.000 description 1
- OJBXLLZQSNDEKV-UHFFFAOYSA-N tert-butyl n-[2-methyl-1-[7-[4-(trifluoromethyl)phenyl]-1h-indol-3-yl]propan-2-yl]carbamate Chemical compound C1=CC=C2C(CC(C)(C)NC(=O)OC(C)(C)C)=CNC2=C1C1=CC=C(C(F)(F)F)C=C1 OJBXLLZQSNDEKV-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
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- 230000035924 thermogenesis Effects 0.000 description 1
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- BRJDXTKDGMMXIH-UHFFFAOYSA-N thieno[2,3-d][1,2]oxazole Chemical compound O1N=CC2=C1C=CS2 BRJDXTKDGMMXIH-UHFFFAOYSA-N 0.000 description 1
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- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
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- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
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- 229940116362 tragacanth Drugs 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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
- C07D413/02—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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31227501P | 2001-08-14 | 2001-08-14 | |
| US312275P | 2001-08-14 | ||
| PCT/US2002/021317 WO2003016307A1 (en) | 2001-08-14 | 2002-08-06 | β3 ADRENERGIC AGONISTS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60215028D1 DE60215028D1 (de) | 2006-11-09 |
| DE60215028T2 true DE60215028T2 (de) | 2007-03-15 |
Family
ID=23210688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60215028T Expired - Fee Related DE60215028T2 (de) | 2001-08-14 | 2002-08-06 | Indol derivate als beta-3-adrenerge agonisten zur behandlung von typ 2 diabetes |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7208505B2 (enExample) |
| EP (1) | EP1421078B1 (enExample) |
| JP (1) | JP2005501856A (enExample) |
| AT (1) | ATE340794T1 (enExample) |
| DE (1) | DE60215028T2 (enExample) |
| ES (1) | ES2272749T3 (enExample) |
| WO (1) | WO2003016307A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1421078B1 (en) | 2001-08-14 | 2006-09-27 | Eli Lilly And Company | Indole derivatives as beta-3 adrenergic agonists for the treatment of type 2 diabetes |
| WO2003044017A1 (en) * | 2001-11-20 | 2003-05-30 | Eli Lilly And Company | Beta 3 adrenergic agonists |
| DE60204718T2 (de) | 2001-11-20 | 2006-05-18 | Eli Lilly And Co., Indianapolis | 3-substituierte oxindol beta 3 agonisten |
| JP2005520805A (ja) | 2002-01-11 | 2005-07-14 | イーライ・リリー・アンド・カンパニー | ２−オキソ−ベンズイミダゾリル置換型エタノールアミン誘導体およびβ３アゴニストとしてのその使用 |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| US7435837B2 (en) | 2003-10-24 | 2008-10-14 | Wyeth | Dihydrobenzofuranyl alkanamine derivatives and methods for using same |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
| US7622491B2 (en) * | 2004-08-13 | 2009-11-24 | Metabolex Inc. | Modulators of PPAR and methods of their preparation |
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-
2002
- 2002-08-06 EP EP02752178A patent/EP1421078B1/en not_active Expired - Lifetime
- 2002-08-06 JP JP2003521230A patent/JP2005501856A/ja active Pending
- 2002-08-06 ES ES02752178T patent/ES2272749T3/es not_active Expired - Lifetime
- 2002-08-06 US US10/486,867 patent/US7208505B2/en not_active Expired - Fee Related
- 2002-08-06 DE DE60215028T patent/DE60215028T2/de not_active Expired - Fee Related
- 2002-08-06 WO PCT/US2002/021317 patent/WO2003016307A1/en not_active Ceased
- 2002-08-06 AT AT02752178T patent/ATE340794T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1421078A1 (en) | 2004-05-26 |
| WO2003016307A1 (en) | 2003-02-27 |
| DE60215028D1 (de) | 2006-11-09 |
| US20050080110A1 (en) | 2005-04-14 |
| JP2005501856A (ja) | 2005-01-20 |
| US7208505B2 (en) | 2007-04-24 |
| ATE340794T1 (de) | 2006-10-15 |
| ES2272749T3 (es) | 2007-05-01 |
| EP1421078B1 (en) | 2006-09-27 |
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