CA2868474A1 - New indanyloxydihydrobenzofuranylacetic acid derivatives and their use as gpr40 receptor agonists - Google Patents
New indanyloxydihydrobenzofuranylacetic acid derivatives and their use as gpr40 receptor agonists Download PDFInfo
- Publication number
- CA2868474A1 CA2868474A1 CA2868474A CA2868474A CA2868474A1 CA 2868474 A1 CA2868474 A1 CA 2868474A1 CA 2868474 A CA2868474 A CA 2868474A CA 2868474 A CA2868474 A CA 2868474A CA 2868474 A1 CA2868474 A1 CA 2868474A1
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- Canada
- Prior art keywords
- group
- alkyl
- cycloalkyl
- heterocyclyl
- replaced
- 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.)
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- RSYYSLLENSVCGM-UHFFFAOYSA-N 2-(2,3-dihydro-1-benzofuran-2-yl)-2-(2,3-dihydro-1h-inden-1-yloxy)acetic acid Chemical class C1C2=CC=CC=C2OC1C(C(=O)O)OC1C2=CC=CC=C2CC1 RSYYSLLENSVCGM-UHFFFAOYSA-N 0.000 title description 5
- 229940044601 receptor agonist Drugs 0.000 title description 2
- 239000000018 receptor agonist Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 394
- 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 claims abstract description 37
- 102100026148 Free fatty acid receptor 1 Human genes 0.000 claims abstract description 36
- 238000011282 treatment Methods 0.000 claims abstract description 36
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 19
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims description 358
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 283
- 125000001072 heteroaryl group Chemical group 0.000 claims description 144
- -1 C2-6-alkinyl Chemical group 0.000 claims description 130
- 229920006395 saturated elastomer Polymers 0.000 claims description 87
- 125000000623 heterocyclic group Chemical group 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000005842 heteroatom Chemical group 0.000 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 36
- 201000010099 disease Diseases 0.000 claims description 35
- 125000001153 fluoro group Chemical group F* 0.000 claims description 35
- 206010012601 diabetes mellitus Diseases 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 26
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 23
- 229940124597 therapeutic agent Drugs 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 17
- 208000008589 Obesity Diseases 0.000 claims description 17
- 235000020824 obesity Nutrition 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 229910052740 iodine Inorganic materials 0.000 claims description 16
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 9
- 206010020772 Hypertension Diseases 0.000 claims description 9
- 206010022489 Insulin Resistance Diseases 0.000 claims description 9
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 125000003566 oxetanyl group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 5
- 206010033307 Overweight Diseases 0.000 claims description 4
- 239000003472 antidiabetic agent Substances 0.000 claims description 4
- 229940125708 antidiabetic agent Drugs 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 102000005962 receptors Human genes 0.000 abstract description 3
- 108020003175 receptors Proteins 0.000 abstract description 3
- 230000006806 disease prevention Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 441
- 239000000543 intermediate Substances 0.000 description 303
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 299
- 239000000203 mixture Substances 0.000 description 256
- 238000001819 mass spectrum Methods 0.000 description 209
- 239000000243 solution Substances 0.000 description 162
- 229940093499 ethyl acetate Drugs 0.000 description 147
- 235000019439 ethyl acetate Nutrition 0.000 description 147
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 144
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 142
- 239000002904 solvent Substances 0.000 description 111
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 111
- 239000012074 organic phase Substances 0.000 description 108
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 99
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 96
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 95
- 239000000741 silica gel Substances 0.000 description 95
- 229910002027 silica gel Inorganic materials 0.000 description 95
- 229960001866 silicon dioxide Drugs 0.000 description 95
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 72
- 235000019341 magnesium sulphate Nutrition 0.000 description 72
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 67
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 47
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 46
- 239000011541 reaction mixture Substances 0.000 description 46
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 44
- 239000012267 brine Substances 0.000 description 44
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- 229960004132 diethyl ether Drugs 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 31
- 238000001816 cooling Methods 0.000 description 31
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 30
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 29
- WMUWDPLTTLJNPE-UHFFFAOYSA-N 4-bromo-3,5-dimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1Br WMUWDPLTTLJNPE-UHFFFAOYSA-N 0.000 description 27
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000012071 phase Substances 0.000 description 24
- 229910052786 argon Inorganic materials 0.000 description 23
- 235000017557 sodium bicarbonate Nutrition 0.000 description 22
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 125000004432 carbon atom Chemical group C* 0.000 description 19
- 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 19
- 239000007864 aqueous solution Substances 0.000 description 18
- 125000004093 cyano group Chemical group *C#N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 150000003254 radicals Chemical class 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 16
- 229910052801 chlorine Inorganic materials 0.000 description 16
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 16
- 235000019798 tripotassium phosphate Nutrition 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000008346 aqueous phase Substances 0.000 description 15
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 239000003643 water by type Substances 0.000 description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- QFHHDLIXCIGLBS-UHFFFAOYSA-N 2-bromo-5-iodo-1,3-dimethylbenzene Chemical compound CC1=CC(I)=CC(C)=C1Br QFHHDLIXCIGLBS-UHFFFAOYSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 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 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 239000008103 glucose Substances 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 12
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 12
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 11
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 239000000556 agonist Substances 0.000 description 11
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 10
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 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 10
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 9
- 102000004877 Insulin Human genes 0.000 description 9
- 108090001061 Insulin Proteins 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 229940125396 insulin Drugs 0.000 description 9
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
- 235000015320 potassium carbonate Nutrition 0.000 description 9
- 239000012453 solvate Substances 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 8
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- 230000003914 insulin secretion Effects 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 7
- 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
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 150000004677 hydrates Chemical class 0.000 description 7
- 239000000859 incretin Substances 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 229910052723 transition metal Inorganic materials 0.000 description 7
- 150000003624 transition metals Chemical class 0.000 description 7
- 238000010792 warming Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- 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
- C07D405/14—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 three or more hetero rings
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- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- A—HUMAN NECESSITIES
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12161240 | 2012-03-26 | ||
| EP12161240.2 | 2012-03-26 | ||
| PCT/EP2013/056312 WO2013144097A1 (en) | 2012-03-26 | 2013-03-25 | New indanyloxydihydrobenzofuranylacetic acid derivatives and their use as gpr40 receptor agonists |
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| CA2868474A1 true CA2868474A1 (en) | 2013-10-03 |
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| CA2868474A Abandoned CA2868474A1 (en) | 2012-03-26 | 2013-03-25 | New indanyloxydihydrobenzofuranylacetic acid derivatives and their use as gpr40 receptor agonists |
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| EP (2) | EP2831064B1 (OSRAM) |
| JP (2) | JP6131492B2 (OSRAM) |
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| AR084050A1 (es) * | 2010-12-01 | 2013-04-17 | Boehringer Ingelheim Int | Acidos indaniloxidihidrobenzofuranilaceticos |
| US8642585B2 (en) * | 2012-03-26 | 2014-02-04 | Boehringer Ingelheim International Gmbh | Indanyloxydihydrobenzofuranylacetic acids |
| EP3036237A4 (en) * | 2013-08-23 | 2017-01-25 | Fujian Haixi Pharmaceuticals Co. Ltd | Carboxylic acid compounds in treatment of diabetes mellitus |
| EA201690888A1 (ru) | 2013-11-14 | 2016-10-31 | Кадила Хелзкэр Лимитед | Новые гетероциклические соединения |
| EP3076959B1 (en) | 2013-12-04 | 2018-07-04 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| US10059667B2 (en) | 2014-02-06 | 2018-08-28 | Merck Sharp & Dohme Corp. | Antidiabetic compounds |
| US10100042B2 (en) | 2014-08-08 | 2018-10-16 | Merck Sharp & Dohme Corp. | [5,6]—fused bicyclic antidiabetic compounds |
| JP2018526405A (ja) * | 2015-09-09 | 2018-09-13 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | [{[2,3−ジヒドロ−1H−インデン−1−イル]アミノ}−2H,3H−フロ[3,2−b]ピリジン−3−イル]酢酸、それらの医薬組成物および使用 |
| EP3544958B1 (en) | 2016-11-28 | 2021-03-24 | Boehringer Ingelheim International GmbH | Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof |
| WO2018138030A1 (en) | 2017-01-26 | 2018-08-02 | Boehringer Ingelheim International Gmbh | Benzyloxypyrazinylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof |
| US10919859B2 (en) | 2017-01-26 | 2021-02-16 | Boehringer Ingelheim International Gmbh | Benzylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof |
| WO2018138029A1 (en) | 2017-01-26 | 2018-08-02 | Boehringer Ingelheim International Gmbh | Benzyloxypyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof |
| EP3573965B1 (en) | 2017-01-26 | 2021-06-23 | Boehringer Ingelheim International GmbH | Indanylaminopyrazinylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof |
| JP7049349B2 (ja) | 2017-01-26 | 2022-04-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンジルアミノピラジニルシクロプロパンカルボン酸、その医薬組成物及び使用 |
| US10550127B1 (en) | 2017-02-08 | 2020-02-04 | Boehringer Ingelheim International Gmbh | Indanylaminoazadihydrobenzofuranylacetic acids, pharmaceutical compositions for the treatment of diabetes |
| EP3604267A4 (en) * | 2017-03-31 | 2020-12-16 | Takeda Pharmaceutical Company Limited | Aromatic compound |
| EP3720835B1 (en) * | 2017-12-04 | 2022-07-13 | Basf Se | Method for preparing ethers of cycloaliphatic or araliphatic diols |
| SG11202006935VA (en) * | 2018-02-05 | 2020-08-28 | Glaxosmithkline Ip Dev Ltd | Ghrelin o-acyltransferase inhibitors |
| KR102708681B1 (ko) | 2018-02-13 | 2024-09-26 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| US12083118B2 (en) | 2018-03-29 | 2024-09-10 | Arbutus Biopharma Corporation | Substituted 1,1′-biphenyl compounds, analogues thereof, and methods using same |
| EP3781556B1 (en) | 2018-04-19 | 2025-06-18 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| CN118221646A (zh) | 2018-07-13 | 2024-06-21 | 吉利德科学公司 | Pd-1/pd-l1抑制剂 |
| US20210236476A1 (en) * | 2018-08-29 | 2021-08-05 | Chemocentryx, Inc. | Methods of treating cancer with small molecule pd-l1 inhibitors |
| TW202028183A (zh) * | 2018-10-10 | 2020-08-01 | 大陸商江蘇豪森藥業集團有限公司 | 含氮雜芳類衍生物調節劑、其製備方法和應用 |
| KR102635333B1 (ko) | 2018-10-24 | 2024-02-15 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| WO2021071837A1 (en) | 2019-10-07 | 2021-04-15 | Kallyope, Inc. | Gpr119 agonists |
| TW202140440A (zh) | 2020-02-28 | 2021-11-01 | 美商克力歐普股份有限公司 | Gpr40激動劑 |
| EP4153589A4 (en) | 2020-05-19 | 2024-06-12 | Kallyope, Inc. | AMPK ACTIVATORS |
| WO2021263039A1 (en) | 2020-06-26 | 2021-12-30 | Kallyope, Inc. | Ampk activators |
Family Cites Families (13)
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|---|---|---|---|---|
| AU2003277576A1 (en) | 2002-11-08 | 2004-06-07 | Takeda Pharmaceutical Company Limited | Receptor function controlling agent |
| JP4594611B2 (ja) * | 2002-11-08 | 2010-12-08 | 武田薬品工業株式会社 | 受容体機能調節剤 |
| CN1735408A (zh) * | 2002-11-08 | 2006-02-15 | 武田药品工业株式会社 | 受体机能调节剂 |
| JP4805552B2 (ja) * | 2003-05-30 | 2011-11-02 | 武田薬品工業株式会社 | 縮合環化合物 |
| WO2004106276A1 (ja) * | 2003-05-30 | 2004-12-09 | Takeda Pharmaceutical Company Limited | 縮合環化合物 |
| WO2007114213A1 (ja) | 2006-03-30 | 2007-10-11 | Asahi Kasei Pharma Corporation | 置換二環式環状誘導体及びその用途 |
| JO2969B1 (en) * | 2006-06-27 | 2016-03-15 | تاكيدا فارماسويتيكال كمبني ليمتد | Welded circular compounds |
| WO2009157418A1 (ja) | 2008-06-25 | 2009-12-30 | 第一三共株式会社 | カルボン酸化合物 |
| EP2358656B1 (en) | 2008-10-15 | 2014-01-01 | Amgen, Inc | Spirocyclic gpr40 modulators |
| US20120172351A1 (en) | 2009-06-09 | 2012-07-05 | Nobuyuki Negoro | Novel fused cyclic compound and use thereof |
| TWI543984B (zh) * | 2010-07-09 | 2016-08-01 | 艾伯維公司 | 作為s1p調節劑的螺-哌啶衍生物 |
| AR084050A1 (es) | 2010-12-01 | 2013-04-17 | Boehringer Ingelheim Int | Acidos indaniloxidihidrobenzofuranilaceticos |
| US8642585B2 (en) * | 2012-03-26 | 2014-02-04 | Boehringer Ingelheim International Gmbh | Indanyloxydihydrobenzofuranylacetic acids |
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| HK1201260A1 (en) | 2015-08-28 |
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| MA20150065A1 (fr) | 2015-02-27 |
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| CN104321319A (zh) | 2015-01-28 |
| WO2013144098A1 (en) | 2013-10-03 |
| SG11201405713UA (en) | 2014-10-30 |
| JP6040486B2 (ja) | 2016-12-07 |
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| AR090493A1 (es) | 2014-11-19 |
| MX2014011465A (es) | 2015-01-12 |
| JP2015511613A (ja) | 2015-04-20 |
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