TW201124415A - Novel spiropiperidine compunds - Google Patents
Novel spiropiperidine compunds Download PDFInfo
- Publication number
- TW201124415A TW201124415A TW099134098A TW99134098A TW201124415A TW 201124415 A TW201124415 A TW 201124415A TW 099134098 A TW099134098 A TW 099134098A TW 99134098 A TW99134098 A TW 99134098A TW 201124415 A TW201124415 A TW 201124415A
- Authority
- TW
- Taiwan
- Prior art keywords
- compound
- group
- salt
- phenyl
- etoac
- Prior art date
Links
- JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical compound C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 221
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 36
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 118
- 239000000126 substance Substances 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 229910052707 ruthenium Inorganic materials 0.000 claims description 14
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000006519 CCH3 Chemical group 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 229910052762 osmium Inorganic materials 0.000 claims 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 claims 1
- 150000002923 oximes Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 143
- 238000002360 preparation method Methods 0.000 description 80
- 235000019439 ethyl acetate Nutrition 0.000 description 72
- 239000011541 reaction mixture Substances 0.000 description 46
- -1 CCH3 compound Chemical class 0.000 description 42
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 34
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 31
- 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 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 28
- 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 27
- 239000008103 glucose Substances 0.000 description 27
- 241000237858 Gastropoda Species 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 22
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 21
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 20
- 125000006612 decyloxy group Chemical group 0.000 description 20
- 125000001041 indolyl group Chemical group 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
- 102100026148 Free fatty acid receptor 1 Human genes 0.000 description 19
- 235000019260 propionic acid Nutrition 0.000 description 19
- 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 description 18
- 239000002253 acid Chemical group 0.000 description 18
- 125000006239 protecting group Chemical group 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 16
- 102000004877 Insulin Human genes 0.000 description 15
- 108090001061 Insulin Proteins 0.000 description 15
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 15
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 229940125396 insulin Drugs 0.000 description 15
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 14
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
- VTZDPQGGOUEESD-UHFFFAOYSA-N 4-hexynoic acid Chemical compound CC#CCCC(O)=O VTZDPQGGOUEESD-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- ZWRUINPWMLAQRD-UHFFFAOYSA-N nonan-1-ol Chemical compound CCCCCCCCCO ZWRUINPWMLAQRD-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 239000000284 extract Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 125000003003 spiro group Chemical group 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 230000004913 activation Effects 0.000 description 9
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 9
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 101150041968 CDC13 gene Proteins 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000009739 binding Methods 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 108010016731 PPAR gamma Proteins 0.000 description 6
- 102000000536 PPAR gamma Human genes 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 101150014691 PPARA gene Proteins 0.000 description 5
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 101100202237 Danio rerio rxrab gene Proteins 0.000 description 4
- 101100309320 Danio rerio rxrga gene Proteins 0.000 description 4
- 108010001515 Galectin 4 Proteins 0.000 description 4
- 102100039556 Galectin-4 Human genes 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 206010022489 Insulin Resistance Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 101150050070 RXRA gene Proteins 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
- 238000002825 functional assay Methods 0.000 description 4
- 230000003914 insulin secretion Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 3
- RBZMSGOBSOCYHR-UHFFFAOYSA-N 1,4-bis(bromomethyl)benzene Chemical compound BrCC1=CC=C(CBr)C=C1 RBZMSGOBSOCYHR-UHFFFAOYSA-N 0.000 description 3
- PLEHSLVXSJBCKV-UHFFFAOYSA-N 1-methylspiro[2h-indole-3,4'-piperidine] Chemical compound C12=CC=CC=C2N(C)CC21CCNCC2 PLEHSLVXSJBCKV-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101710142060 Free fatty acid receptor 1 Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 3
- 108091027981 Response element Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- IHSMNXDTRPKCCG-LBPRGKRZSA-N ethyl (3s)-3-(4-hydroxyphenyl)hex-4-ynoate Chemical compound CCOC(=O)C[C@H](C#CC)C1=CC=C(O)C=C1 IHSMNXDTRPKCCG-LBPRGKRZSA-N 0.000 description 3
- 238000007446 glucose tolerance test Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 206010022498 insulinoma Diseases 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 208000021255 pancreatic insulinoma Diseases 0.000 description 3
- HRVXPXCISZSDCC-UHFFFAOYSA-N piperidine-4-carbaldehyde Chemical compound O=CC1CCNCC1 HRVXPXCISZSDCC-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- JCMVPOVHKWWBAU-UHFFFAOYSA-N 1,2-dichlorohydrazine Chemical compound ClNNCl JCMVPOVHKWWBAU-UHFFFAOYSA-N 0.000 description 2
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- QFYGPUAIMQUIOO-UHFFFAOYSA-N 3-(4-hydroxyphenyl)hex-4-ynoic acid Chemical compound CC#CC(CC(O)=O)C1=CC=C(O)C=C1 QFYGPUAIMQUIOO-UHFFFAOYSA-N 0.000 description 2
- DGENZVKCTGIDRZ-UHFFFAOYSA-N 3-[4-[(3-phenoxyphenyl)methylamino]phenyl]propanoic acid Chemical compound C1=CC(CCC(=O)O)=CC=C1NCC1=CC=CC(OC=2C=CC=CC=2)=C1 DGENZVKCTGIDRZ-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 229940125827 GPR40 agonist Drugs 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 229940126033 PPAR agonist Drugs 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102000034527 Retinoid X Receptors Human genes 0.000 description 2
- 108010038912 Retinoid X Receptors Proteins 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 230000003178 anti-diabetic effect Effects 0.000 description 2
- 239000003855 balanced salt solution Substances 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 108700023159 delta Opioid Receptors Proteins 0.000 description 2
- 102000048124 delta Opioid Receptors Human genes 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940125542 dual agonist Drugs 0.000 description 2
- IHSMNXDTRPKCCG-UHFFFAOYSA-N ethyl 3-(4-hydroxyphenyl)hex-4-ynoate Chemical compound CCOC(=O)CC(C#CC)C1=CC=C(O)C=C1 IHSMNXDTRPKCCG-UHFFFAOYSA-N 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- QBNOPZJAURRQCE-UHFFFAOYSA-M magnesium;prop-1-yne;bromide Chemical compound [Mg+2].[Br-].CC#[C-] QBNOPZJAURRQCE-UHFFFAOYSA-M 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 150000004667 medium chain fatty acids Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 210000002824 peroxisome Anatomy 0.000 description 2
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000003151 propanoic acid esters Chemical class 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000003981 vehicle Substances 0.000 description 2
- QUIMJTKRVOBTQN-UHFFFAOYSA-N (2,4-dimethylphenyl)methanol Chemical compound CC1=CC=C(CO)C(C)=C1 QUIMJTKRVOBTQN-UHFFFAOYSA-N 0.000 description 1
- QFYGPUAIMQUIOO-JTQLQIEISA-N (3s)-3-(4-hydroxyphenyl)hex-4-ynoic acid Chemical compound CC#C[C@@H](CC(O)=O)C1=CC=C(O)C=C1 QFYGPUAIMQUIOO-JTQLQIEISA-N 0.000 description 1
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- KHYGCPCPXTZJBM-UHFFFAOYSA-N 2,2-dimethyl-4h-1,3-dioxine Chemical compound CC1(C)OCC=CO1 KHYGCPCPXTZJBM-UHFFFAOYSA-N 0.000 description 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- LQIIEHBULBHJKX-UHFFFAOYSA-N 2-methylpropylalumane Chemical compound CC(C)C[AlH2] LQIIEHBULBHJKX-UHFFFAOYSA-N 0.000 description 1
- XALDKHBGQCHBAF-UHFFFAOYSA-N 3-(2-fluoro-4-hydroxyphenyl)hex-4-ynoic acid Chemical compound CC#CC(CC(O)=O)C1=CC=C(O)C=C1F XALDKHBGQCHBAF-UHFFFAOYSA-N 0.000 description 1
- ZVONSEXCUCTSMF-UHFFFAOYSA-N 3-(2-fluoro-4-methoxyphenyl)hex-4-ynoic acid Chemical compound COC1=CC=C(C(CC(O)=O)C#CC)C(F)=C1 ZVONSEXCUCTSMF-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- ZZBUURIDLIQRJA-UHFFFAOYSA-N C(C)(=O)O.C(C)PCC Chemical compound C(C)(=O)O.C(C)PCC ZZBUURIDLIQRJA-UHFFFAOYSA-N 0.000 description 1
- CHLQKNSGNOIPMZ-UHFFFAOYSA-N C(C)(C)(C)C(C(CCCCCCCCCC)(CCCCCCCCCC)Cl)CCCCCCCC Chemical compound C(C)(C)(C)C(C(CCCCCCCCCC)(CCCCCCCCCC)Cl)CCCCCCCC CHLQKNSGNOIPMZ-UHFFFAOYSA-N 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 241000266847 Mephitidae Species 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 101150023417 PPARG gene Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- RDHSYXFAOVTAEH-UHFFFAOYSA-N [4-(bromomethyl)phenyl]methanol Chemical compound OCC1=CC=C(CBr)C=C1 RDHSYXFAOVTAEH-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical group CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PTLIZOFGXLGHSY-UHFFFAOYSA-N dibutylphosphane Chemical compound CCCCPCCCC PTLIZOFGXLGHSY-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- VXHUBGOVNPJIEI-UHFFFAOYSA-N ethyl acetate;propanoic acid Chemical compound CCC(O)=O.CCOC(C)=O VXHUBGOVNPJIEI-UHFFFAOYSA-N 0.000 description 1
- WZVBZDZPAHTRES-UHFFFAOYSA-N ethyl hex-4-ynoate Chemical compound CCOC(=O)CCC#CC WZVBZDZPAHTRES-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- AKYAUBWOTZJUBI-UHFFFAOYSA-N hex-2-ynoic acid Chemical compound CCCC#CC(O)=O AKYAUBWOTZJUBI-UHFFFAOYSA-N 0.000 description 1
- 102000052080 human FFAR1 Human genes 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical compound O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- OENLEHTYJXMVBG-UHFFFAOYSA-N pyridine;hydrate Chemical compound [OH-].C1=CC=[NH+]C=C1 OENLEHTYJXMVBG-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 229940074446 sodium potassium tartrate tetrahydrate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- JHMKGUPCKJSSEF-UHFFFAOYSA-N spiro[1,2-dihydroindole-3,4'-piperidine] Chemical class C1NC2=CC=CC=C2C11CCNCC1 JHMKGUPCKJSSEF-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 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 description 1
- UIEGYIFDVIDYHB-UHFFFAOYSA-N tert-butyl spiro[2h-indole-3,4'-piperidine]-1-carboxylate Chemical compound C12=CC=CC=C2N(C(=O)OC(C)(C)C)CC21CCNCC2 UIEGYIFDVIDYHB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25183909P | 2009-10-15 | 2009-10-15 | |
| US30333410P | 2010-02-11 | 2010-02-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201124415A true TW201124415A (en) | 2011-07-16 |
Family
ID=43719548
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW099134098A TW201124415A (en) | 2009-10-15 | 2010-10-06 | Novel spiropiperidine compunds |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US8383642B2 (enExample) |
| EP (1) | EP2488500A1 (enExample) |
| JP (1) | JP2013508279A (enExample) |
| KR (1) | KR20120051777A (enExample) |
| CN (1) | CN102574807A (enExample) |
| AR (1) | AR078522A1 (enExample) |
| AU (1) | AU2010307094A1 (enExample) |
| BR (1) | BR112012008889A2 (enExample) |
| CA (1) | CA2777775A1 (enExample) |
| CL (1) | CL2012000921A1 (enExample) |
| CO (1) | CO6531458A2 (enExample) |
| CR (1) | CR20120177A (enExample) |
| DO (1) | DOP2012000105A (enExample) |
| EA (1) | EA201270560A1 (enExample) |
| EC (1) | ECSP12011799A (enExample) |
| IL (1) | IL218344A0 (enExample) |
| MA (1) | MA33662B1 (enExample) |
| MX (1) | MX2012004420A (enExample) |
| NZ (1) | NZ598972A (enExample) |
| PE (1) | PE20121437A1 (enExample) |
| PH (1) | PH12012500705A1 (enExample) |
| TN (1) | TN2012000152A1 (enExample) |
| TW (1) | TW201124415A (enExample) |
| WO (1) | WO2011046851A1 (enExample) |
| ZA (1) | ZA201202560B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2411393B1 (en) | 2009-03-23 | 2014-01-22 | Glenmark Pharmaceuticals S.A. | Fused pyrimidine-dione derivatives as trpa1 modulators |
| PE20120834A1 (es) | 2009-03-23 | 2012-07-25 | Glenmark Pharmaceuticals Sa | Derivados de furopirimidindiona como moduladores de trpa1 |
| AR078948A1 (es) * | 2009-11-30 | 2011-12-14 | Lilly Co Eli | Compuestos de espiropiperidina, composicion farmaceutica que lo comprenden y su uso para preparar un medicamento util para tratar la diabetes |
| EA201290574A1 (ru) | 2009-12-25 | 2012-12-28 | Мотида Фармасьютикал Ко., Лтд. | Новое производное 3-гидрокси-5-арилизотиазола |
| US9040525B2 (en) | 2010-10-08 | 2015-05-26 | Mochida Pharmaceutical Co., Ltd. | Cyclic amide derivative |
| MX336898B (es) | 2011-03-11 | 2016-02-05 | Intercontinental Great Brands Llc | Sistema y metodo para conformar confiteria de capas multiples. |
| CN105153146A (zh) | 2011-04-27 | 2015-12-16 | 持田制药株式会社 | 新的3-羟基异噻唑1-氧化物衍生物 |
| EP2716636A4 (en) | 2011-04-28 | 2014-11-26 | Mochida Pharm Co Ltd | CYCLIC AMIDE DERIVATIVE |
| AR087451A1 (es) | 2011-08-17 | 2014-03-26 | Lilly Co Eli | Derivado de 1,2,3,4-tetrahidroquinolina util para tratamiento de diabetes |
| WO2013139341A1 (en) * | 2012-03-20 | 2013-09-26 | Syddansk Universitet | Gpr120 receptor modulators |
| WO2013185766A1 (en) * | 2012-06-15 | 2013-12-19 | Syddansk Universitet | Gpr120 receptor modulators |
| CN104812748B (zh) | 2012-11-16 | 2017-10-24 | 百时美施贵宝公司 | 二氢吡唑gpr40调节剂 |
| KR101569522B1 (ko) * | 2013-04-18 | 2015-11-17 | 현대약품 주식회사 | 신규한 3-(4-(벤질옥시)페닐)헥스-4-이노익 산 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 대사성 질환의 예방 또는 치료용 약학적 조성물 |
| KR20160077213A (ko) * | 2013-11-14 | 2016-07-01 | 카딜라 핼쓰캐어 리미티드 | 새로운 헤테로시클릭 화합물 |
| US20150351889A1 (en) | 2014-06-05 | 2015-12-10 | Vivex Biomedical Inc. | Dynamic Biometric Mesh |
| DK3207928T3 (da) * | 2014-10-17 | 2021-04-26 | Hyundai Pharm Co Ltd | Sammensat præparat, der indeholder hidtil ukendt 3-(4-(benzyloxy)phenyl)hex-4-inonsyrederivat og en anden aktiv bestanddel, til forebyggelse eller behandling af metaboliske sygdomme |
| CN109666027A (zh) * | 2017-10-17 | 2019-04-23 | 中国科学院上海药物研究所 | 一类酰胺结构的gpr40激动剂化合物及其用途 |
| DK3737470T5 (da) | 2018-01-08 | 2024-05-27 | Celon Pharma Sa | 3-phenyl-4-hexynsyrederivater som gpr40-agonister |
| MX2020008404A (es) | 2018-02-13 | 2020-09-25 | Gilead Sciences Inc | Inhibidores de molecula de muerte programada 1 (pd-1)/ligando de molecula de muerte programada 1 (pd-l1). |
| ES3035911T3 (en) | 2018-04-19 | 2025-09-11 | Gilead Sciences Inc | Pd-1/pd-l1 inhibitors |
| SI3820572T1 (sl) | 2018-07-13 | 2023-12-29 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ， インコーポレイテッド | Ｐｄ－１／ｐｄ－ｌ１阻害剤 |
| CA3156985A1 (en) | 2019-10-07 | 2021-04-15 | Kallyope, Inc. | Gpr119 agonists |
| CN115667277A (zh) | 2020-02-28 | 2023-01-31 | 卡尔优普公司 | Gpr40激动剂 |
| CA3178994A1 (en) | 2020-05-19 | 2021-11-25 | Iyassu Sebhat | Ampk activators |
| AU2021297323A1 (en) | 2020-06-26 | 2023-02-16 | Kallyope, Inc. | AMPK activators |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1385514T5 (da) | 2001-04-18 | 2009-03-09 | Euro Celtique Sa | Spiroinden- og spiroindanforbindelser |
| AU2004227835B2 (en) * | 2003-04-04 | 2007-06-14 | Merck & Co., Inc. | Acylated spiropiperidine derivatives as melanocortin-4 receptor agonists |
| CN1901908A (zh) * | 2003-11-04 | 2007-01-24 | 伊利舍医药品公司 | 治疗性化合物及其用途 |
| WO2005051890A1 (en) | 2003-11-19 | 2005-06-09 | Smithkline Beecham Corporation | Aminophenylcyclopropyl carboxylic acids and derivatives as agonists to gpr40 |
| BRPI0508098A (pt) | 2004-02-27 | 2007-07-17 | Amgen Inc | compostos, composições farmacêuticas e métodos para uso no tratamento de distúrbios metabólicos |
| EP2253315A1 (en) | 2004-03-30 | 2010-11-24 | Takeda Pharmaceutical Company Limited | Alkoxyphenylpropanoic acid derivatives |
| CA2621949A1 (en) | 2005-09-14 | 2007-03-22 | Amgen Inc. | Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders |
| WO2008030618A1 (en) | 2006-09-07 | 2008-03-13 | Amgen Inc. | Benzo-fused compounds for use in treating metabolic disorders |
| ME02338B (me) * | 2007-10-26 | 2013-02-28 | Japan Tobacco Inc | Spiro-ciklično jedinjenje i njegova upotreba u medicinske svrhe |
| WO2009067202A1 (en) | 2007-11-21 | 2009-05-28 | Janssen Pharmaceutica, N.V. | Spiropiperidines for use as tryptase inhibitors |
| AR078948A1 (es) | 2009-11-30 | 2011-12-14 | Lilly Co Eli | Compuestos de espiropiperidina, composicion farmaceutica que lo comprenden y su uso para preparar un medicamento util para tratar la diabetes |
-
2010
- 2010-10-04 AR ARP100103604A patent/AR078522A1/es not_active Application Discontinuation
- 2010-10-06 TW TW099134098A patent/TW201124415A/zh unknown
- 2010-10-11 BR BR112012008889A patent/BR112012008889A2/pt not_active IP Right Cessation
- 2010-10-11 EP EP10793349A patent/EP2488500A1/en not_active Withdrawn
- 2010-10-11 AU AU2010307094A patent/AU2010307094A1/en not_active Abandoned
- 2010-10-11 CA CA2777775A patent/CA2777775A1/en not_active Abandoned
- 2010-10-11 JP JP2012534259A patent/JP2013508279A/ja not_active Withdrawn
- 2010-10-11 NZ NZ598972A patent/NZ598972A/xx not_active IP Right Cessation
- 2010-10-11 PH PH1/2012/500705A patent/PH12012500705A1/en unknown
- 2010-10-11 PE PE2012000492A patent/PE20121437A1/es not_active Application Discontinuation
- 2010-10-11 MX MX2012004420A patent/MX2012004420A/es not_active Application Discontinuation
- 2010-10-11 EA EA201270560A patent/EA201270560A1/ru unknown
- 2010-10-11 CN CN2010800462763A patent/CN102574807A/zh active Pending
- 2010-10-11 WO PCT/US2010/052126 patent/WO2011046851A1/en not_active Ceased
- 2010-10-11 US US12/901,597 patent/US8383642B2/en not_active Expired - Fee Related
- 2010-10-11 KR KR1020127009501A patent/KR20120051777A/ko not_active Ceased
-
2012
- 2012-02-27 IL IL218344A patent/IL218344A0/en unknown
- 2012-04-02 TN TNP2012000152A patent/TN2012000152A1/en unknown
- 2012-04-09 MA MA34760A patent/MA33662B1/fr unknown
- 2012-04-10 ZA ZA2012/02560A patent/ZA201202560B/en unknown
- 2012-04-12 CR CR20120177A patent/CR20120177A/es not_active Application Discontinuation
- 2012-04-12 CL CL2012000921A patent/CL2012000921A1/es unknown
- 2012-04-13 DO DO2012000105A patent/DOP2012000105A/es unknown
- 2012-04-13 EC ECSP12011799 patent/ECSP12011799A/es unknown
- 2012-04-20 CO CO12065315A patent/CO6531458A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP2488500A1 (en) | 2012-08-22 |
| ZA201202560B (en) | 2013-09-25 |
| NZ598972A (en) | 2013-06-28 |
| EA201270560A1 (ru) | 2012-09-28 |
| DOP2012000105A (es) | 2013-01-31 |
| CO6531458A2 (es) | 2012-09-28 |
| JP2013508279A (ja) | 2013-03-07 |
| ECSP12011799A (es) | 2012-07-31 |
| IL218344A0 (en) | 2012-04-30 |
| PE20121437A1 (es) | 2012-10-26 |
| US20110092531A1 (en) | 2011-04-21 |
| KR20120051777A (ko) | 2012-05-22 |
| MX2012004420A (es) | 2012-05-08 |
| AR078522A1 (es) | 2011-11-16 |
| US8383642B2 (en) | 2013-02-26 |
| PH12012500705A1 (en) | 2012-10-29 |
| CN102574807A (zh) | 2012-07-11 |
| WO2011046851A1 (en) | 2011-04-21 |
| BR112012008889A2 (pt) | 2019-09-24 |
| CL2012000921A1 (es) | 2012-09-14 |
| AU2010307094A1 (en) | 2012-04-19 |
| MA33662B1 (fr) | 2012-10-01 |
| TN2012000152A1 (en) | 2013-12-12 |
| CA2777775A1 (en) | 2011-04-21 |
| CR20120177A (es) | 2012-06-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW201124415A (en) | Novel spiropiperidine compunds | |
| CA2781292C (en) | Novel spiropiperidine compounds | |
| JP6695457B2 (ja) | エストロゲン受容体調節剤としての６，７−ジヒドロ−５ｈ−ベンゾ［７］アヌレン誘導体 | |
| RU2650506C2 (ru) | Агонист рецептора gpr40, способы его получения и фармацевтические композиции, содержащие его в качестве активного ингредиента | |
| CN103687856B (zh) | 用于治疗糖尿病的新的1,2,3,4-四氢喹啉衍生物 | |
| JP5964756B2 (ja) | 選択的アンドロゲン受容体モジュレーター | |
| TWI426904B (zh) | １，１，１－三氟－２－羥基－３－苯丙烷衍生物 | |
| TW202532387A (zh) | 官能化的長鏈烴一元及二元羧酸及其用於預防或治療疾病的用途 | |
| JP2007530653A (ja) | ＯＲＬ１−受容体拮抗薬としてのαアリールまたはヘテロアリールメチルβピペリジノプロパン酸化合物 | |
| KR20140072090A (ko) | ＲＯＲγｔ 조정제로서의 아미도 화합물 및 이의 용도 | |
| CN101356178A (zh) | 作为ppar调节剂的化合物和组合物 | |
| JP2014141522A (ja) | エストロゲン関連受容体モジュレータ化合物及びその使用 | |
| WO2020210366A1 (en) | Condensed azines for ep300 or cbp modulation and indications therefor | |
| BRPI0609207A2 (pt) | derivados de Ácido pirimidincarboxÍlico e seu uso | |
| WO2005017185A2 (en) | HEPATOCYTE NUCLEAR FACTOR 4α MODULATOR COMPOUNDS | |
| NZ710293A (en) | Amides as modulators of sodium channels |