HRP20120368A2 - Postupci sinteze spiro-oksindolskih spojeva - Google Patents
Postupci sinteze spiro-oksindolskih spojeva Download PDFInfo
- Publication number
- HRP20120368A2 HRP20120368A2 HRP20120368AA HRP20120368A HRP20120368A2 HR P20120368 A2 HRP20120368 A2 HR P20120368A2 HR P20120368A A HRP20120368A A HR P20120368AA HR P20120368 A HRP20120368 A HR P20120368A HR P20120368 A2 HRP20120368 A2 HR P20120368A2
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- pharmaceutically acceptable
- obtaining
- image
- Prior art date
Links
- 238000010189 synthetic method Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 79
- 230000008569 process Effects 0.000 claims abstract description 46
- 150000001875 compounds Chemical class 0.000 claims description 212
- 150000003839 salts Chemical class 0.000 claims description 100
- 239000000203 mixture Substances 0.000 claims description 78
- 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 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 238000012545 processing Methods 0.000 claims description 12
- 238000000926 separation method Methods 0.000 claims description 10
- 239000007818 Grignard reagent Substances 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 150000004795 grignard reagents Chemical class 0.000 claims description 7
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 4
- 239000013067 intermediate product Substances 0.000 claims description 4
- 238000006751 Mitsunobu reaction Methods 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 15
- 208000002193 Pain Diseases 0.000 abstract description 8
- 102000018674 Sodium Channels Human genes 0.000 abstract description 8
- 108010052164 Sodium Channels Proteins 0.000 abstract description 8
- 230000036407 pain Effects 0.000 abstract description 8
- 238000002360 preparation method Methods 0.000 abstract description 3
- 230000006806 disease prevention Effects 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 27
- 238000003786 synthesis reaction Methods 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 22
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 239000012071 phase Substances 0.000 description 19
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 201000010099 disease Diseases 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- -1 but not limited to Chemical class 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 239000008367 deionised water Substances 0.000 description 14
- 229910021641 deionized water Inorganic materials 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 239000002585 base Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 239000012065 filter cake Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 238000004821 distillation Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000004296 chiral HPLC Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229960004198 guanidine Drugs 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 208000004296 neuralgia Diseases 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine group Chemical group N[C@H](CCCCN)C(=O)O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 4
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 4
- 230000004941 influx Effects 0.000 description 4
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 4
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 208000021722 neuropathic pain Diseases 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- 230000004224 protection Effects 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- DBPZCGJRCAALLW-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-ol Chemical compound O1CCOC2=CC(O)=CC=C21 DBPZCGJRCAALLW-UHFFFAOYSA-N 0.000 description 3
- CWKXDPPQCVWXAG-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound O1CCOC2=CC(C=O)=CC=C21 CWKXDPPQCVWXAG-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- BXXNTMHHZOCUDY-UHFFFAOYSA-N 3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-bis(hydroxymethyl)indol-2-one Chemical compound C12=CC=CC=C2N(CO)C(=O)C1(CO)C(C(=C1)O)=CC2=C1OCO2 BXXNTMHHZOCUDY-UHFFFAOYSA-N 0.000 description 3
- DYKNSPFBRMMODE-UHFFFAOYSA-N 3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydroindol-2-one Chemical compound O=C1NC2=CC=CC=C2C1C1=CC(OCO2)=C2C=C1O DYKNSPFBRMMODE-UHFFFAOYSA-N 0.000 description 3
- OYKAKASLTRZSEN-UHFFFAOYSA-N 3-(6-hydroxy-2,3-dihydro-1,4-benzodioxin-7-yl)-1,3-dihydroindol-2-one Chemical compound O=C1NC2=CC=CC=C2C1C1=CC(OCCO2)=C2C=C1O OYKAKASLTRZSEN-UHFFFAOYSA-N 0.000 description 3
- NMCJVNMFMUWXCH-UHFFFAOYSA-N 3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2C1(O)C1=CC(OCO2)=C2C=C1O NMCJVNMFMUWXCH-UHFFFAOYSA-N 0.000 description 3
- UKTIGKLYJILPIL-UHFFFAOYSA-N 3-hydroxy-3-(6-hydroxy-2,3-dihydro-1,4-benzodioxin-7-yl)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2C1(O)C1=CC(OCCO2)=C2C=C1O UKTIGKLYJILPIL-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000012039 electrophile Substances 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- KICNGTSGLUFGHH-UHFFFAOYSA-N spiro[1h-indole-3,7'-6h-furo[2,3-f][1,3]benzodioxole]-2-one Chemical compound C1OC2=CC=3OCOC=3C=C2C21C1=CC=CC=C1NC2=O KICNGTSGLUFGHH-UHFFFAOYSA-N 0.000 description 3
- IKLODGBPSWONQT-UHFFFAOYSA-N spiro[1h-indole-3,8'-3,7-dihydro-2h-furo[2,3-g][1,4]benzodioxine]-2-one Chemical compound O1CCOC(C=C23)=C1C=C3OCC12C2=CC=CC=C2NC1=O IKLODGBPSWONQT-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- XGYVWWLZOMQVRF-UHFFFAOYSA-N 1'-[[3-(trifluoromethyl)pyridin-2-yl]methyl]spiro[3,7-dihydro-2h-furo[2,3-g][1,4]benzodioxine-8,3'-indole]-2'-one Chemical compound FC(F)(F)C1=CC=CN=C1CN1C2=CC=CC=C2C2(C3=CC=4OCCOC=4C=C3OC2)C1=O XGYVWWLZOMQVRF-UHFFFAOYSA-N 0.000 description 2
- NEBUOXBYNAHKFV-UHFFFAOYSA-N 1'-[[5-(trifluoromethyl)furan-2-yl]methyl]spiro[6h-furo[2,3-f][1,3]benzodioxole-7,3'-indole]-2'-one Chemical compound O1C(C(F)(F)F)=CC=C1CN1C2=CC=CC=C2C2(C3=CC=4OCOC=4C=C3OC2)C1=O NEBUOXBYNAHKFV-UHFFFAOYSA-N 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 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 2
- IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical compound CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 208000004454 Hyperalgesia Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 229910006124 SOCl2 Inorganic materials 0.000 description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 206010053552 allodynia Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229960000789 guanidine hydrochloride Drugs 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 229940071870 hydroiodic acid Drugs 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- ULYZAYCEDJDHCC-UHFFFAOYSA-N isopropyl chloride Chemical compound CC(C)Cl ULYZAYCEDJDHCC-UHFFFAOYSA-N 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000163 radioactive labelling Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- 239000010802 sludge Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-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
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- NEBUOXBYNAHKFV-OAQYLSRUSA-N (7r)-1'-[[5-(trifluoromethyl)furan-2-yl]methyl]spiro[6h-furo[2,3-f][1,3]benzodioxole-7,3'-indole]-2'-one Chemical compound O1C(C(F)(F)F)=CC=C1CN1C2=CC=CC=C2[C@]2(C3=CC=4OCOC=4C=C3OC2)C1=O NEBUOXBYNAHKFV-OAQYLSRUSA-N 0.000 description 1
- NEBUOXBYNAHKFV-NRFANRHFSA-N (7s)-1'-[[5-(trifluoromethyl)furan-2-yl]methyl]spiro[6h-furo[2,3-f][1,3]benzodioxole-7,3'-indole]-2'-one Chemical compound O1C(C(F)(F)F)=CC=C1CN1C2=CC=CC=C2[C@@]2(C3=CC=4OCOC=4C=C3OC2)C1=O NEBUOXBYNAHKFV-NRFANRHFSA-N 0.000 description 1
- XGYVWWLZOMQVRF-HSZRJFAPSA-N (8r)-1'-[[3-(trifluoromethyl)pyridin-2-yl]methyl]spiro[3,7-dihydro-2h-furo[2,3-g][1,4]benzodioxine-8,3'-indole]-2'-one Chemical compound FC(F)(F)C1=CC=CN=C1CN1C2=CC=CC=C2[C@]2(C3=CC=4OCCOC=4C=C3OC2)C1=O XGYVWWLZOMQVRF-HSZRJFAPSA-N 0.000 description 1
- XGYVWWLZOMQVRF-QHCPKHFHSA-N (8s)-1'-[[3-(trifluoromethyl)pyridin-2-yl]methyl]spiro[3,7-dihydro-2h-furo[2,3-g][1,4]benzodioxine-8,3'-indole]-2'-one Chemical compound FC(F)(F)C1=CC=CN=C1CN1C2=CC=CC=C2[C@@]2(C3=CC=4OCCOC=4C=C3OC2)C1=O XGYVWWLZOMQVRF-QHCPKHFHSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- VLSDXINSOMDCBK-UHFFFAOYSA-N 1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)N=NC(=O)N(C)C VLSDXINSOMDCBK-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- XFSBVAOIAHNAPC-XTHSEXKGSA-N 16-Ethyl-1alpha,6alpha,19beta-trimethoxy-4-(methoxymethyl)-aconitane-3alpha,8,10alpha,11,18alpha-pentol, 8-acetate 10-benzoate Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45C6[C@@H]([C@@]([C@H]31)(OC(C)=O)[C@@H](O)[C@@H]2OC)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-XTHSEXKGSA-N 0.000 description 1
- YNHVBNGRNNVEMD-UHFFFAOYSA-N 2-(bromomethyl)-5-(trifluoromethyl)furan Chemical compound FC(F)(F)C1=CC=C(CBr)O1 YNHVBNGRNNVEMD-UHFFFAOYSA-N 0.000 description 1
- LSTLOPHZEUSOQI-UHFFFAOYSA-N 2-(chloromethyl)-3-(trifluoromethyl)pyridine;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CN=C1CCl LSTLOPHZEUSOQI-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- PCYGLFXKCBFGPC-UHFFFAOYSA-N 3,4-Dihydroxy hydroxymethyl benzene Natural products OCC1=CC=C(O)C(O)=C1 PCYGLFXKCBFGPC-UHFFFAOYSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 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
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- XFSBVAOIAHNAPC-UHFFFAOYSA-N Aconitin Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(OC(C)=O)C(O)C6OC)C1C32C4CC6(O)C5OC(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000031976 Channelopathies Diseases 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 239000005892 Deltamethrin Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 241000239271 Leiurus quinquestriatus hebraeus Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000000450 Pelvic Pain Diseases 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 206010036772 Proctalgia Diseases 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Natural products OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- FVECELJHCSPHKY-UHFFFAOYSA-N Veratridine Natural products C1=C(OC)C(OC)=CC=C1C(=O)OC1C2(O)OC34CC5(O)C(CN6C(CCC(C)C6)C6(C)O)C6(O)C(O)CC5(O)C4CCC2C3(C)CC1 FVECELJHCSPHKY-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 229940039750 aconitine Drugs 0.000 description 1
- STDXGNLCJACLFY-UHFFFAOYSA-N aconitine Natural products CCN1CC2(COC)C(O)CC(O)C34C5CC6(O)C(OC)C(O)C(OC(=O)C)(C5C6OC(=O)c7ccccc7)C(C(OC)C23)C14 STDXGNLCJACLFY-UHFFFAOYSA-N 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 229960000250 adipic acid Drugs 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000010936 aqueous wash Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960002887 deanol Drugs 0.000 description 1
- 229960002483 decamethrin Drugs 0.000 description 1
- OWZREIFADZCYQD-NSHGMRRFSA-N deltamethrin Chemical compound CC1(C)[C@@H](C=C(Br)Br)[C@H]1C(=O)O[C@H](C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 OWZREIFADZCYQD-NSHGMRRFSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 201000011384 erythromelalgia Diseases 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical group C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 210000000929 nociceptor Anatomy 0.000 description 1
- 108091008700 nociceptors Proteins 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960005010 orotic acid Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 229940098695 palmitic acid Drugs 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
- 229960001233 pregabalin Drugs 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 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 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229940116353 sebacic acid Drugs 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/20—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25133509P | 2009-10-14 | 2009-10-14 | |
| PCT/US2010/052704 WO2011047174A1 (en) | 2009-10-14 | 2010-10-14 | Synthetic methods for spiro-oxindole compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20120368A2 true HRP20120368A2 (hr) | 2012-06-30 |
Family
ID=43733239
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20120368AA HRP20120368A2 (hr) | 2009-10-14 | 2012-04-27 | Postupci sinteze spiro-oksindolskih spojeva |
| HRP20140486AT HRP20140486T1 (hr) | 2009-10-14 | 2014-05-29 | Postupci sinteze spojeva spirooksindola |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20140486AT HRP20140486T1 (hr) | 2009-10-14 | 2014-05-29 | Postupci sinteze spojeva spirooksindola |
Country Status (23)
| Country | Link |
|---|---|
| US (4) | US8445696B2 (ar) |
| EP (2) | EP2488531B1 (ar) |
| JP (3) | JP5752136B2 (ar) |
| KR (1) | KR20120099429A (ar) |
| CN (1) | CN102753556B (ar) |
| AU (2) | AU2010306768B2 (ar) |
| BR (1) | BR112012008993A2 (ar) |
| CA (1) | CA2777543A1 (ar) |
| CL (3) | CL2012000953A1 (ar) |
| CO (1) | CO6531444A2 (ar) |
| EC (1) | ECSP12011815A (ar) |
| ES (1) | ES2467166T3 (ar) |
| HK (2) | HK1174908A1 (ar) |
| HR (2) | HRP20120368A2 (ar) |
| MA (1) | MA33730B1 (ar) |
| MX (1) | MX2012004373A (ar) |
| MY (2) | MY165579A (ar) |
| NZ (3) | NZ622072A (ar) |
| PE (2) | PE20170202A1 (ar) |
| RU (2) | RU2015103694A (ar) |
| TN (1) | TN2012000171A1 (ar) |
| WO (1) | WO2011047174A1 (ar) |
| ZA (1) | ZA201202703B (ar) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY145694A (en) * | 2005-04-11 | 2012-03-30 | Xenon Pharmaceuticals Inc | Spiroheterocyclic compounds and their uses as therapeutic agents |
| MY158766A (en) * | 2005-04-11 | 2016-11-15 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their uses as therapeutic agents |
| US20110294842A9 (en) * | 2006-10-12 | 2011-12-01 | Xenon Pharmaceuticals Inc. | Spiro (furo [3, 2-c] pyridine-3-3' -indol) -2' (1'h)-one derivatives and related compounds for the treatment of sodium-channel mediated diseases, such as pain |
| CN103271906A (zh) | 2006-10-12 | 2013-09-04 | 泽农医药公司 | 螺-吲哚酮化合物作为治疗剂的用途 |
| WO2010045197A1 (en) * | 2008-10-17 | 2010-04-22 | Xenon Pharmaceuticals, Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
| NZ592275A (en) | 2008-10-17 | 2013-04-26 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their use as therapeutic agents |
| AR077252A1 (es) * | 2009-06-29 | 2011-08-10 | Xenon Pharmaceuticals Inc | Enantiomeros de compuestos de espirooxindol y sus usos como agentes terapeuticos |
| MY165579A (en) | 2009-10-14 | 2018-04-05 | Xenon Pharmaceuticals Inc | Synthetic methods for spiro-oxindole compounds |
| WO2011047173A2 (en) * | 2009-10-14 | 2011-04-21 | Xenon Pharmaceuticals Inc. | Pharmaceutical compositions for oral administration |
| CN105726531A (zh) | 2010-02-26 | 2016-07-06 | 泽农医药公司 | 用于局部给药的螺-羟吲哚化合物的药物组合物及其作为治疗剂的用途 |
| GB201122113D0 (en) * | 2011-12-22 | 2012-02-01 | Convergence Pharmaceuticals | Novel compounds |
| CA2869547A1 (en) | 2012-04-12 | 2013-10-17 | Xenon Pharmaceuticals Inc. | Asymmetric syntheses for spiro-oxindole compounds useful as therapeutic agents |
| CN103724340A (zh) * | 2012-10-15 | 2014-04-16 | 南京大学 | 一类具有苯并含氧杂环结构的噻唑类衍生物及其制法 |
| CN104326922B (zh) * | 2014-11-03 | 2016-08-17 | 成都百裕制药股份有限公司 | 替格瑞洛中间体(1r,2s)-2-(2,3-二氟苯基)环丙胺的制备方法 |
| WO2016109795A1 (en) | 2014-12-31 | 2016-07-07 | Concert Pharmaceuticals, Inc. | Deuterated funapide and difluorofunapide |
| CN105801556A (zh) * | 2014-12-31 | 2016-07-27 | 上海药谷药业有限公司 | 一种2,3-二氢-1,4-苯并二烷-6-羧酸化合物的制备方法 |
| TW201636017A (zh) | 2015-02-05 | 2016-10-16 | 梯瓦製藥國際有限責任公司 | 以螺吲哚酮化合物之局部調配物治療帶狀疱疹後遺神經痛之方法 |
| JP6572392B2 (ja) | 2015-12-18 | 2019-09-11 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | 電位作動型ナトリウムチャネルにおいて選択的活性を有する、ヒドロキシアルキルアミンおよびヒドロキシシクロアルキルアミンで置換されたジアミン−アリールスルホンアミド化合物 |
| CA3026885A1 (en) * | 2016-06-16 | 2017-12-21 | Xenon Pharmaceuticals Inc. | Solid state forms of spiro-oxindole compounds |
| WO2017218920A1 (en) | 2016-06-16 | 2017-12-21 | Teva Pharmaceuticals International Gmbh | Asymmetric synthesis of funapide |
| WO2018163216A1 (en) | 2017-03-10 | 2018-09-13 | Council Of Scientific & Industrial Research | Spirooxindole compounds as gsk3β inhibitors and process for preparation thereof |
| MX2023005983A (es) | 2020-11-23 | 2023-08-15 | Enanta Pharm Inc | Nuevos agentes antivirales derivados de la espiropirrolidina. |
| US11970502B2 (en) | 2021-05-04 | 2024-04-30 | Enanta Pharmaceuticals, Inc. | Macrocyclic antiviral agents |
| WO2023086352A1 (en) | 2021-11-12 | 2023-05-19 | Enanta Pharmaceuticals, Inc. | Novel spiropyrrolidine derived antiviral agents |
| WO2023086350A1 (en) | 2021-11-12 | 2023-05-19 | Enanta Pharmaceuticals, Inc. | Alkyne-containing antiviral agents |
| US11919910B2 (en) | 2021-11-12 | 2024-03-05 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| US11993600B2 (en) | 2021-12-08 | 2024-05-28 | Enanta Pharmaceuticals, Inc. | Saturated spirocyclics as antiviral agents |
| US20230295175A1 (en) * | 2022-03-18 | 2023-09-21 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of substituted spirooxindole derivatives |
| CN115353499B (zh) * | 2022-10-21 | 2023-02-28 | 南京远淑医药科技有限公司 | 一种2-卤甲基-5-三氟甲基呋喃的合成方法 |
| US11840545B1 (en) | 2023-07-14 | 2023-12-12 | King Faisal University | Spirooxindole-copper complex as novel efficient anticorrosion agent for C-steel |
Family Cites Families (151)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3189617A (en) * | 1961-02-03 | 1965-06-15 | Sterling Drug Inc | 1-aryloxindoles and their preparation |
| DE1956237A1 (de) | 1969-11-08 | 1971-05-13 | Basf Ag | Spiro-pyrrolizidon-oxindole |
| DE2113343A1 (de) | 1971-03-19 | 1972-09-21 | Thiemann Chem Pharm Fab | Indolo[2,3-b] chinolone und Verfahren zu ihrer Herstellung |
| US3723459A (en) * | 1971-04-23 | 1973-03-27 | Mc Neil Labor Inc | 2-oxospiro (indoline -3,4{40 -thiochroman) derivatives |
| US3845770A (en) * | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| SE400966B (sv) * | 1975-08-13 | 1978-04-17 | Robins Co Inc A H | Forfarande for framstellning av 2-amino-3-(eller 5-)bensoyl-fenylettiksyror |
| US4670566A (en) * | 1979-07-12 | 1987-06-02 | A. H. Robins Company, Incorporated | 3-methyl-hio-4-(5-, 6-, or 7-)phenylindolindolin-2-ones |
| US4326525A (en) * | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
| US4440785A (en) * | 1980-10-30 | 1984-04-03 | A. H. Robins Company, Inc. | Methods of using 2-aminobiphenylacetic acids, esters, and metal salts thereof to treat inflammation |
| US4438130A (en) * | 1981-11-12 | 1984-03-20 | The Upjohn Company | Analgesic 1-oxa-, aza- and thia-spirocyclic compounds |
| JPS60142984A (ja) | 1983-12-28 | 1985-07-29 | Kyorin Pharmaceut Co Ltd | 新規なスピロピロリジン−２，５−ジオン誘導体およびその製造法 |
| US4569942A (en) | 1984-05-04 | 1986-02-11 | Pfizer Inc. | N,3-Disubstituted 2-oxindole-1-carboxamides as analgesic and antiinflammatory agents |
| JPS6130554A (ja) * | 1984-07-23 | 1986-02-12 | Ono Pharmaceut Co Ltd | プロスタグランジン類似化合物のある特定の立体配置を有する異性体及びそれらを有効成分として含有する治療剤 |
| US4690943A (en) | 1984-09-19 | 1987-09-01 | Pfizer Inc. | Analgesic and antiinflammatory 1,3-diacyl-2-oxindole compounds |
| US4721721A (en) | 1984-12-18 | 1988-01-26 | Rorer Pharmaceutical Corporation | 6-(4-thiazole) compounds, cardiotonic compositions including the same, and their uses |
| DE3608088C2 (de) * | 1986-03-07 | 1995-11-16 | Schering Ag | Pharmazeutische Präparate, enthaltend Cyclodextrinclathrate von Carbacyclinderivaten |
| WO1993012786A1 (en) | 1986-07-10 | 1993-07-08 | Howard Harry R Jr | Indolinone derivatives |
| ES2054860T5 (es) * | 1987-07-17 | 2003-11-01 | Schering Ag | Derivados de 9-halogeno-(z)-prostaglandinas, procedimiento para su preparacion y su utilizacion como medicamentos. |
| US5182289A (en) * | 1988-06-14 | 1993-01-26 | Schering Corporation | Heterobicyclic compounds having antiinflammatory activity |
| US5206261A (en) | 1989-07-25 | 1993-04-27 | Taiho Pharmaceutical Company, Limited | Oxindole derivative |
| DE3932953A1 (de) | 1989-10-03 | 1991-04-11 | Boehringer Mannheim Gmbh | Neue 2-bicyclo-benzimidazole, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3935514A1 (de) | 1989-10-25 | 1991-05-02 | Boehringer Mannheim Gmbh | Neue bicyclo-imidazole, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US5304121A (en) * | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| US5023265A (en) * | 1990-06-01 | 1991-06-11 | Schering Corporation | Substituted 1-H-pyrrolopyridine-3-carboxamides |
| US5484778C1 (en) | 1990-07-17 | 2001-05-08 | Univ Cleveland Hospitals | Phthalocynine photosensitizers for photodynamic therapy and methods for their use |
| CA2095718A1 (en) | 1990-11-22 | 1992-05-23 | Hans-Rudolf Waespe | Isonicotinic acid derivatives and related spiro compounds with herbicidal action |
| US5116854A (en) * | 1991-06-28 | 1992-05-26 | Pfizer Inc. | Anti-inflammatory 1-heteroaryl-3-acyl-2-oxindoles |
| US5663431A (en) * | 1992-01-30 | 1997-09-02 | Sanofi | 1-benzenesulfonyl-1,3-dihydro-indol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present |
| US5686624A (en) * | 1992-01-30 | 1997-11-11 | Sanofi | 1-benzenesulfonyl-1,3-dihydro-indol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present |
| FR2686878B1 (fr) | 1992-01-30 | 1995-06-30 | Sanofi Elf | Derives du n-sulfonyl oxo-2 indole, leur preparation, les compositions pharmaceutiques en contenant. |
| FR2708605A1 (fr) | 1993-07-30 | 1995-02-10 | Sanofi Sa | Dérivés du N-sulfonylindol-2-one, leur préparation, les compositions pharmaceutiques en contenant. |
| US5849780A (en) * | 1992-01-30 | 1998-12-15 | Sanofi | 1-benzenesulfonyl-1-1,3-dihydroindol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present |
| US5314685A (en) | 1992-05-11 | 1994-05-24 | Agouron Pharmaceuticals, Inc. | Anhydrous formulations for administering lipophilic agents |
| CZ283965B6 (cs) | 1992-08-06 | 1998-07-15 | Warner-Lambert Company | 2-thioindolové, 2-indolinthionové a polysulfidové sloučeniny, 2-selenoindolové, 2-indolinselenonové a selenidové sloučeniny a farmaceutické prostředky na jejich bázi |
| US5278162A (en) * | 1992-09-18 | 1994-01-11 | The Du Pont Merck Pharmaceutical Company | 3,3'-disubstituted-1,3-dihydro-2H-pyrrolo[2,3-b]heterocyclic-2-one useful in the treatment of cognitive disorders of man |
| US5296478A (en) * | 1992-10-07 | 1994-03-22 | The Dupont Merck Pharmaceutical Co. | 1-substituted oxindoles as cognition enhancers |
| US5776936A (en) * | 1992-11-13 | 1998-07-07 | Pharmacia & Upjohn Company | Marcfortine/paraherquamide derivatives useful as antiparasitic agents |
| DE4242451A1 (de) * | 1992-12-16 | 1994-06-23 | Basf Ag | Verfahren zur Herstellung von 5-Ringheterocyclen |
| US5298522A (en) | 1993-01-22 | 1994-03-29 | Pfizer Inc. | 6-chloro-5-fluoro-3-(2-thenoyl)-2-oxindole-1-carboxamide as an analgesic and anti-inflammatory agent while maintaining a normal urine protein/creatinine ratio |
| US5994341A (en) * | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
| FR2708606B1 (fr) * | 1993-07-30 | 1995-10-27 | Sanofi Sa | Dérivés du N-phénylalkylindol-2-one, leur préparation, les compositions pharmaceutiques en contenant. |
| US5502072A (en) | 1993-11-26 | 1996-03-26 | Pfizer Inc. | Substituted oxindoles |
| AT400950B (de) * | 1994-02-04 | 1996-04-25 | Immodal Pharmaka Gmbh | Verfahren zur technischen herstellung definierter isomerengemische aus verbindungen mit spirozyklischen - aminocarboxyl- und/oder spirozyklischen - aminocarbonyl-systemen |
| US5763471A (en) * | 1994-04-07 | 1998-06-09 | Cemaf | Melatoninergic agonist spiro indolepyrrolidine! derivatives, process for their preparation and their use as medicinal products |
| US5618819A (en) | 1994-07-07 | 1997-04-08 | Adir Et Compagnie | 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-(3H)-one compounds |
| FR2722195B1 (fr) | 1994-07-07 | 1996-08-23 | Adir | Nouveaux derives de 1,3-dihydro-2h-pyrrolo(2,3-b) pyridin-2-ones et oxazolo(4,5-b) pyridin-2(3h)-ones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CA2208244A1 (en) | 1994-12-22 | 1996-06-27 | Laramie Mary Gaster | Tetracyclic spiro compounds, process for their preparation and their use as 5ht1d receptor antagonists |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| FR2740136B1 (fr) * | 1995-10-24 | 1998-01-09 | Sanofi Sa | Derives d'indolin-2-one, procede pour leur preparation et les compositions pharmaceutiques les contenant |
| CA2235686C (en) | 1995-10-24 | 2007-06-26 | Sanofi | Indolin-2-one derivatives, process for their production and the pharmaceutical compositions containing them |
| HUP9600855A3 (en) | 1996-04-03 | 1998-04-28 | Egyt Gyogyszervegyeszeti Gyar | Process for producing tenidap |
| JPH1095766A (ja) | 1996-09-19 | 1998-04-14 | Sanwa Kagaku Kenkyusho Co Ltd | アセトアミド誘導体、及びその用途 |
| FR2757157B1 (fr) | 1996-12-13 | 1999-12-31 | Sanofi Sa | Derives d'indolin-2-one, procede pour leur preparation et compositions pharmaceutiques les contenant |
| WO1998031378A1 (de) * | 1997-01-20 | 1998-07-23 | Immodal Pharmaka Gesellschaft Mbh | Verfahren und stoffe zur freisetzung eines wachstumsfaktors aus endothelzellen, und nach dem verfahren freigesetzter wachstumsfaktor sowie seine verwendung |
| NO317155B1 (no) * | 1997-02-04 | 2004-08-30 | Ono Pharmaceutical Co | <omega>-cykloalkyl-prostagladin-E<N>2</N>-derivater |
| ATE237587T1 (de) * | 1997-02-10 | 2003-05-15 | Ono Pharmaceutical Co | 11,15-o-dialkylprostaglandin-e-derivate, verfahren zu ihrer herstellung und arzneimittel, die diese als aktiven inhaltsstoff enthalten |
| CN1184957C (zh) | 1997-05-07 | 2005-01-19 | 盖伦(化学制品)有限公司 | 用于给药睾酮和睾酮前体的阴道内给药装置 |
| ATE260254T1 (de) * | 1997-12-25 | 2004-03-15 | Ono Pharmaceutical Co | Omega-cycloalkyl-prostaglandin e2 derivate |
| JP4087938B2 (ja) * | 1998-02-04 | 2008-05-21 | 高砂香料工業株式会社 | ヒノキチオ−ル類の分岐サイクロデキストリン包接化合物からなる抗菌剤およびそれを含有する組成物 |
| CA2326777C (en) | 1998-04-01 | 2011-12-20 | Nortran Pharmaceuticals Inc. | Aminocyclohexyl ether compounds and uses thereof |
| US20040038970A1 (en) * | 1998-06-12 | 2004-02-26 | Societe De Conseils De Recherches Etd' Application Scientifiques, S.A.S. A Paris, France Corp. | Beta-carboline compounds |
| US6235780B1 (en) * | 1998-07-21 | 2001-05-22 | Ono Pharmaceutical Co., Ltd. | ω-cycloalkyl-prostaglandin E1 derivatives |
| WO2000006556A1 (en) | 1998-07-27 | 2000-02-10 | Abbott Laboratories | Substituted oxazolines as antiproliferative agents |
| SE9900100D0 (sv) | 1999-01-15 | 1999-01-15 | Astra Ab | New compounds |
| US6407101B1 (en) * | 1999-05-04 | 2002-06-18 | American Home Products Corporation | Cyanopyrroles |
| US6355648B1 (en) * | 1999-05-04 | 2002-03-12 | American Home Products Corporation | Thio-oxindole derivatives |
| RU2331640C2 (ru) | 1999-05-21 | 2008-08-20 | Бристол-Маерс Сквибб Ко. | Пирролтриазиновые ингибиторы киназ |
| ATE396722T1 (de) * | 1999-07-21 | 2008-06-15 | Boehringer Ingelheim Pharma | Kleine moleküle zur behandlung von endzündlichen erkrankungen |
| BR0012590A (pt) | 1999-07-21 | 2002-04-09 | Astrazeneca Ab | Composto, processo para a preparação do mesmo, formulação farmacêutica, uso de um composto, e, métodos para tratamento ou profilaxia de dor ou desconforto, e para tratamento ou profilaxia de dor neuropática ou central |
| US6566372B1 (en) * | 1999-08-27 | 2003-05-20 | Ligand Pharmaceuticals Incorporated | Bicyclic androgen and progesterone receptor modulator compounds and methods |
| WO2001038564A2 (en) | 1999-11-26 | 2001-05-31 | Mcgill University | Loci for idiopathic generalized epilepsy, mutations thereof and method using same to assess, diagnose, prognose or treat epilepsy |
| FR2807038B1 (fr) | 2000-04-03 | 2002-08-16 | Sanofi Synthelabo | Nouveaux derives d'indolin-2-one, leur preparation et les compositions pharmaceutiques les contenant |
| US20020045566A1 (en) | 2000-10-13 | 2002-04-18 | Gribkoff Valentin K. | Selective maxi-K potassium channel openers functional under conditions of high intracellular calcium concentration, methods and uses thereof |
| JP2004513164A (ja) | 2000-11-10 | 2004-04-30 | イーライ・リリー・アンド・カンパニー | ３−置換オキシインドールβ３アゴニスト |
| US6670357B2 (en) * | 2000-11-17 | 2003-12-30 | Bristol-Myers Squibb Company | Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors |
| US20030078278A1 (en) | 2001-06-26 | 2003-04-24 | Pfizer Inc. | Spiropiperidine compounds as ligands for ORL-1 receptor |
| EP1444224B1 (en) * | 2001-08-14 | 2006-05-03 | Eli Lilly And Company | 3-substituted oxindole beta-3 agonists |
| EP1451173A4 (en) | 2001-11-01 | 2005-10-26 | Icagen Inc | PIPERIDINE |
| DE60235114D1 (de) | 2001-11-01 | 2010-03-04 | Icagen Inc | Pyrazolamide zur anwendung in der behandlung von schmerz |
| US7205407B2 (en) * | 2001-11-20 | 2007-04-17 | Eli Lilly And Company | 3-Substituted oxindole β3 agonists |
| SE0104341D0 (sv) * | 2001-12-20 | 2001-12-20 | Astrazeneca Ab | New use |
| CA2466915A1 (en) | 2002-01-28 | 2003-08-07 | Pfizer Inc. | N-substituted spiropiperidine compounds as ligands for orl-1 receptor |
| US6995144B2 (en) * | 2002-03-14 | 2006-02-07 | Eisai Co., Ltd. | Nitrogen containing heterocyclic compounds and medicines containing the same |
| CA2478172A1 (en) | 2002-03-15 | 2003-09-25 | Eli Lilly And Company | Dihydroindol-2-one derivatives as steroid hormone nuclear receptor modulators |
| US7595311B2 (en) | 2002-05-24 | 2009-09-29 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
| GB0213715D0 (en) | 2002-06-14 | 2002-07-24 | Syngenta Ltd | Chemical compounds |
| WO2004000227A2 (en) | 2002-06-25 | 2003-12-31 | Wyeth | Use of thio-oxindole derivatives in treatment of skin disorders |
| AU2003245637A1 (en) | 2002-06-25 | 2004-01-06 | Wyeth | Use of thio-oxindole derivatives in treatment of hormone-related conditions |
| US7256218B2 (en) | 2002-11-22 | 2007-08-14 | Jacobus Pharmaceutical Company, Inc. | Biguanide and dihydrotriazine derivatives |
| WO2004074285A1 (en) | 2003-02-24 | 2004-09-02 | Mitsubishi Pharma Corporation | The enantiomer of tenatoprazole and the use thereof in therapy |
| CA2525868A1 (en) * | 2003-05-16 | 2004-11-25 | Pfizer Products Inc. | Anxiety treatments with ziprasidone |
| CA2525323A1 (en) * | 2003-05-16 | 2004-11-25 | Pfizer Products Inc. | Method for enhancing cognition using ziprasidone |
| EP1633360A1 (en) * | 2003-05-16 | 2006-03-15 | Pfizer Products Incorporated | Treatment of psychotic and depressive disorders |
| CN1780626A (zh) * | 2003-05-16 | 2006-05-31 | 辉瑞产品公司 | 双相性精神障碍和相关症状的治疗 |
| RU2006105717A (ru) | 2003-07-30 | 2007-09-20 | Зинон Фармасьютиклз Инк. (Ca) | Производные пиперазина и их применение в качестве терапевтических агентов |
| DE10337184A1 (de) | 2003-08-13 | 2005-03-10 | Gruenenthal Gmbh | Substituierte 3-Pyrrolidin-Indol-Derivate |
| WO2005016913A1 (en) * | 2003-08-19 | 2005-02-24 | Pfizer Japan, Inc. | Tetrahydroisoquinoline or isochroman compounds as orl-1 receptor ligands for the treatment of pain and cns disorders |
| JPWO2005035498A1 (ja) | 2003-10-08 | 2006-12-21 | 住友製薬株式会社 | 含窒素二環性化合物の摂食調節剤としての用途 |
| EP1557166A1 (en) | 2004-01-21 | 2005-07-27 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful in the treatment of lower urinary tract disorders |
| US7507760B2 (en) | 2004-01-22 | 2009-03-24 | Neuromed Pharmaceuticals Ltd. | N-type calcium channel blockers |
| GB0406867D0 (en) | 2004-03-26 | 2004-04-28 | F2G Ltd | Antifungal agents |
| CA2563164A1 (en) | 2004-03-29 | 2005-10-06 | Pfizer Inc. | Alpha aryl or heteroaryl methyl beta piperidino propanoic acid compounds as orl1-receptor antagonists |
| WO2005097136A1 (en) | 2004-03-29 | 2005-10-20 | Merck & Co., Inc. | Biaryl substituted pyrazinones as sodium channel blockers |
| WO2005099689A1 (en) | 2004-04-01 | 2005-10-27 | Case Western Reserve University | Topical delivery of phthalocyanines |
| GT200500063A (es) | 2004-04-01 | 2005-10-14 | Metodo para tratar la esquizofrenia y/o anormalidades glucoregulatorias | |
| WO2005097107A2 (en) | 2004-04-08 | 2005-10-20 | Topotarget A/S | Diphenyl - indol-2-on compounds and their use in the treatment of cancer |
| AU2005237520B2 (en) | 2004-04-27 | 2012-01-19 | Wyeth | Purification of progesterone receptor modulators |
| ZA200607620B (en) * | 2004-05-05 | 2008-05-28 | Unibioscreen Sa | Naphthalimide derivatives, methods for their production and pharmaceutical composition therefrom |
| AU2005238096A1 (en) * | 2004-05-05 | 2005-11-10 | Unibioscreen S.A. | Naphthalimide derivatives, methods for their production and pharmaceutical compositions therefrom |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| BRPI0511132A (pt) * | 2004-05-14 | 2007-11-27 | Pfizer Prod Inc | derivados de pirimidina e composição farmacêutica compreendendo os mesmos |
| WO2006012173A1 (en) | 2004-06-24 | 2006-02-02 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| GT200500186A (es) | 2004-07-07 | 2006-03-02 | Regimenes anticonceptivos con antagonistas del receptor de progesterona y kits | |
| GT200500185A (es) | 2004-08-09 | 2006-04-10 | Moduladores del receptor de progesterona que comprenden derivados de pirrol-oxindol y sus usos | |
| GT200500183A (es) | 2004-08-09 | 2006-04-10 | Moduladores del receptor de progesterona que comprenden derivados de pirrol-oxindol y sus usos | |
| JP4677323B2 (ja) | 2004-11-01 | 2011-04-27 | キヤノン株式会社 | 画像処理装置及び画像処理方法 |
| US20060122210A1 (en) | 2004-11-18 | 2006-06-08 | Wenqing Yao | Inhibitors of 11-beta hydroxyl steroid dehydrogenase type I and methods of using the same |
| DE102005007694A1 (de) | 2005-02-18 | 2006-09-21 | Henkel Kgaa | Mittel zum Färben von keratinhaltigen Fasern |
| CA2752738C (en) | 2005-02-22 | 2014-05-27 | The Regents Of The University Of Michigan | Small molecule inhibitors of mdm2 and uses thereof |
| MY158766A (en) * | 2005-04-11 | 2016-11-15 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their uses as therapeutic agents |
| MY145694A (en) * | 2005-04-11 | 2012-03-30 | Xenon Pharmaceuticals Inc | Spiroheterocyclic compounds and their uses as therapeutic agents |
| AR053713A1 (es) | 2005-04-20 | 2007-05-16 | Xenon Pharmaceuticals Inc | Compuestos heterociclicos y sus usos como agentes terapeuticos |
| AR056317A1 (es) * | 2005-04-20 | 2007-10-03 | Xenon Pharmaceuticals Inc | Compuestos de oxindol y composicion farmaceutica |
| CN101166722A (zh) * | 2005-04-29 | 2008-04-23 | 惠氏公司 | 制备3,3-二取代的羟吲哚和硫代羟吲哚的方法 |
| WO2006125048A2 (en) * | 2005-05-16 | 2006-11-23 | Gilead Sciences, Inc. | Hiv-integrase inhibitor compounds |
| CN101300012B (zh) | 2005-09-01 | 2011-09-14 | 弗·哈夫曼-拉罗切有限公司 | 作为p2x3和p2x2/3调节剂的二氨基嘧啶类化合物在制备治疗呼吸系统疾病的药物中的应用 |
| US7888345B2 (en) | 2006-06-09 | 2011-02-15 | Merck Sharp & Dohme Corp. | Benzaepinones as sodium channel blockers |
| MX2009003874A (es) * | 2006-10-12 | 2009-04-22 | Xenon Pharmaceuticals Inc | Derivados de espiro-oxindol triciclicos y sus usos como agentes terapeuticos. |
| CN103271906A (zh) * | 2006-10-12 | 2013-09-04 | 泽农医药公司 | 螺-吲哚酮化合物作为治疗剂的用途 |
| WO2008046082A2 (en) | 2006-10-12 | 2008-04-17 | Xenon Pharmaceuticals Inc. | Use of heterocyclic compounds as therapeutic agents |
| WO2008046083A2 (en) | 2006-10-12 | 2008-04-17 | Xenon Pharmaceuticals Inc. | Use of oxindole compounds as therapeutic agents |
| WO2008046087A2 (en) * | 2006-10-12 | 2008-04-17 | Xenon Pharmaceuticals Inc. | Spiro compounds and their uses as therapeutic agents |
| WO2008046084A2 (en) | 2006-10-12 | 2008-04-17 | Xenon Pharmaceuticals Inc. | Spiroheterocyclic compounds and their uses as therapeutic agents |
| AR063277A1 (es) | 2006-10-12 | 2009-01-14 | Xenon Pharmaceuticals Inc | Compuestos espiroheterociclicos y usos como agentes terapeuticos |
| US20110294842A9 (en) * | 2006-10-12 | 2011-12-01 | Xenon Pharmaceuticals Inc. | Spiro (furo [3, 2-c] pyridine-3-3' -indol) -2' (1'h)-one derivatives and related compounds for the treatment of sodium-channel mediated diseases, such as pain |
| GB0704846D0 (en) | 2007-03-13 | 2007-04-18 | Futura Medical Dev Ltd | Topical pharmaceutical formulation |
| WO2008117050A1 (en) | 2007-03-27 | 2008-10-02 | Astrazeneca Ab | Pyrazolyl-amino-substituted pyrazines and their use for the treatment of cancer |
| CA2689137C (en) | 2007-05-29 | 2017-05-02 | Intrexon Corporation | Chiral diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex |
| US7982036B2 (en) * | 2007-10-19 | 2011-07-19 | Avila Therapeutics, Inc. | 4,6-disubstitued pyrimidines useful as kinase inhibitors |
| US20110086889A1 (en) * | 2008-06-11 | 2011-04-14 | Hamed Aissaoui | Tetrazole compounds as orexin receptor antagonists |
| US20100040187A1 (en) | 2008-08-12 | 2010-02-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Heat pipe nuclear fission deflagration wave reactor cooling |
| WO2010045197A1 (en) | 2008-10-17 | 2010-04-22 | Xenon Pharmaceuticals, Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
| NZ592275A (en) | 2008-10-17 | 2013-04-26 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their use as therapeutic agents |
| WO2010053998A1 (en) | 2008-11-05 | 2010-05-14 | Xenon Pharmaceuticals, Inc. | Spiro-condensed indole derivatives as sodium channel inhibitors |
| US20110269788A1 (en) * | 2008-12-29 | 2011-11-03 | Xenon Pharmaceuticals Inc. | Spiro-oxindole-derivatives as sodium channel blockers |
| WO2010132352A2 (en) | 2009-05-11 | 2010-11-18 | Xenon Pharmaceuticals Inc. | Spiro compounds and their use as therapeutic agents |
| AR077252A1 (es) * | 2009-06-29 | 2011-08-10 | Xenon Pharmaceuticals Inc | Enantiomeros de compuestos de espirooxindol y sus usos como agentes terapeuticos |
| WO2011047173A2 (en) | 2009-10-14 | 2011-04-21 | Xenon Pharmaceuticals Inc. | Pharmaceutical compositions for oral administration |
| MY165579A (en) | 2009-10-14 | 2018-04-05 | Xenon Pharmaceuticals Inc | Synthetic methods for spiro-oxindole compounds |
| CN105726531A (zh) | 2010-02-26 | 2016-07-06 | 泽农医药公司 | 用于局部给药的螺-羟吲哚化合物的药物组合物及其作为治疗剂的用途 |
| CA2869547A1 (en) | 2012-04-12 | 2013-10-17 | Xenon Pharmaceuticals Inc. | Asymmetric syntheses for spiro-oxindole compounds useful as therapeutic agents |
-
2010
- 2010-10-14 MY MYPI2012001670A patent/MY165579A/en unknown
- 2010-10-14 NZ NZ622072A patent/NZ622072A/en not_active IP Right Cessation
- 2010-10-14 NZ NZ712378A patent/NZ712378A/en not_active IP Right Cessation
- 2010-10-14 MY MYPI2016001835A patent/MY179342A/en unknown
- 2010-10-14 JP JP2012534362A patent/JP5752136B2/ja not_active Expired - Fee Related
- 2010-10-14 RU RU2015103694/04A patent/RU2015103694A/ru not_active Application Discontinuation
- 2010-10-14 KR KR1020127012050A patent/KR20120099429A/ko not_active Application Discontinuation
- 2010-10-14 US US12/904,880 patent/US8445696B2/en active Active
- 2010-10-14 EP EP10771606.0A patent/EP2488531B1/en active Active
- 2010-10-14 EP EP14000519.0A patent/EP2733145A1/en not_active Withdrawn
- 2010-10-14 AU AU2010306768A patent/AU2010306768B2/en not_active Ceased
- 2010-10-14 CA CA2777543A patent/CA2777543A1/en not_active Abandoned
- 2010-10-14 ES ES10771606.0T patent/ES2467166T3/es active Active
- 2010-10-14 RU RU2012119550/04A patent/RU2544852C2/ru not_active IP Right Cessation
- 2010-10-14 PE PE2016001459A patent/PE20170202A1/es not_active Application Discontinuation
- 2010-10-14 PE PE2012000480A patent/PE20121350A1/es not_active Application Discontinuation
- 2010-10-14 NZ NZ599334A patent/NZ599334A/en not_active IP Right Cessation
- 2010-10-14 MX MX2012004373A patent/MX2012004373A/es active IP Right Grant
- 2010-10-14 CN CN201080056856.0A patent/CN102753556B/zh not_active Expired - Fee Related
- 2010-10-14 BR BR112012008993A patent/BR112012008993A2/pt not_active Application Discontinuation
- 2010-10-14 WO PCT/US2010/052704 patent/WO2011047174A1/en active Application Filing
-
2012
- 2012-04-13 CL CL2012000953A patent/CL2012000953A1/es unknown
- 2012-04-13 TN TNP2012000171A patent/TN2012000171A1/en unknown
- 2012-04-13 CO CO12061009A patent/CO6531444A2/es unknown
- 2012-04-13 ZA ZA2012/02703A patent/ZA201202703B/en unknown
- 2012-04-18 EC ECSP12011815 patent/ECSP12011815A/es unknown
- 2012-04-27 HR HRP20120368AA patent/HRP20120368A2/hr not_active Application Discontinuation
- 2012-05-07 MA MA34841A patent/MA33730B1/ar unknown
- 2012-09-14 US US13/620,391 patent/US8742109B2/en not_active Expired - Fee Related
-
2013
- 2013-02-15 HK HK13101970.7A patent/HK1174908A1/xx not_active IP Right Cessation
- 2013-12-18 CL CL2013003633A patent/CL2013003633A1/es unknown
-
2014
- 2014-05-07 US US14/272,297 patent/US9260446B2/en not_active Expired - Fee Related
- 2014-05-29 HR HRP20140486AT patent/HRP20140486T1/hr unknown
- 2014-10-22 HK HK14110536A patent/HK1197233A1/xx unknown
-
2015
- 2015-03-02 JP JP2015039888A patent/JP5951825B2/ja not_active Expired - Fee Related
-
2016
- 2016-01-06 US US14/989,600 patent/US9695185B2/en not_active Expired - Fee Related
- 2016-04-15 JP JP2016081755A patent/JP2016130260A/ja active Pending
- 2016-07-06 CL CL2016001732A patent/CL2016001732A1/es unknown
- 2016-07-27 AU AU2016208347A patent/AU2016208347A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20120368A2 (hr) | Postupci sinteze spiro-oksindolskih spojeva | |
| JP6290217B2 (ja) | 三環式キノリンおよびキノキサリン誘導体 | |
| JP2009541392A (ja) | アルファ７受容体サブタイプ選択的なニコチン性アゴニスト、その製造方法およびそれの医薬組成物 | |
| EP3044226A1 (en) | Aryl ether-base kinase inhibitors | |
| ES2230490T3 (es) | Derivados antidepresivos indoltetrahidropiridinicos de 2,3-dihidro-7h-(1,4)dioxino(2,3-e)indol. | |
| ES2269678T3 (es) | Derivados azaheterociclilmetilicos antidepresivos de 2,3-dihidro-1,4-dioxino (2,3f) quinolaxina. | |
| ES2247327T3 (es) | Derivados azaheterociclimetilicos antidepresivos (isrs) de 7,8-dihidro-3h-6,9-dioxa-1,3-diazaciclopenta(a) naftaleno. | |
| WO2024088109A1 (zh) | 一种芳基并杂环化合物及其制备方法和用途 | |
| WO2018083171A1 (en) | Spiro-compounds as s1p modulators | |
| MXPA03009829A (es) | Azaheterociclilmetil derivados de 7,8-dihidro-1,6,9-trioxa-3-azaciclopenta[a]naftaleno como agentes antidepresivos. | |
| US20170158693A1 (en) | Hexahydrodiazepinoquinolines carrying a cyclic radical | |
| AU2015255181A1 (en) | Spiro-cyclic amine derivatives as s1p modulators | |
| JP2018095656A (ja) | 三環式キノリンおよびキノキサリン誘導体 | |
| EP2516446B1 (en) | Substituted hexahydrochromeno[3,4-b]pyrroles with affinity for the serotonin receptor (5-ht) family |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
| ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20130927 Year of fee payment: 4 |
|
| OBST | Application withdrawn |