CN110229093B - 用于体内成像的咔唑化合物 - Google Patents
用于体内成像的咔唑化合物 Download PDFInfo
- Publication number
- CN110229093B CN110229093B CN201910451008.2A CN201910451008A CN110229093B CN 110229093 B CN110229093 B CN 110229093B CN 201910451008 A CN201910451008 A CN 201910451008A CN 110229093 B CN110229093 B CN 110229093B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- tspo
- vivo imaging
- ppm
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000011503 in vivo imaging Methods 0.000 title claims abstract description 33
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- 238000000034 method Methods 0.000 claims abstract description 45
- 239000000203 mixture Substances 0.000 claims abstract description 22
- 239000002243 precursor Substances 0.000 claims abstract description 21
- 239000012217 radiopharmaceutical Substances 0.000 claims abstract description 10
- 229940121896 radiopharmaceutical Drugs 0.000 claims abstract description 10
- 230000002799 radiopharmaceutical effect Effects 0.000 claims abstract description 10
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 9
- 238000009826 distribution Methods 0.000 claims description 7
- 238000002600 positron emission tomography Methods 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 238000002405 diagnostic procedure Methods 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 230000002596 correlated effect Effects 0.000 claims description 2
- UJJUJHTVDYXQON-UHFFFAOYSA-N nitro benzenesulfonate Chemical compound [O-][N+](=O)OS(=O)(=O)C1=CC=CC=C1 UJJUJHTVDYXQON-UHFFFAOYSA-N 0.000 claims description 2
- 238000011269 treatment regimen Methods 0.000 claims description 2
- MEZFQICOVFZJQN-UHFFFAOYSA-N 2-bromo-3-chloro-4-methylbenzenesulfonyl iodide Chemical compound ClC=1C(=C(S(=O)(=O)I)C=CC1C)Br MEZFQICOVFZJQN-UHFFFAOYSA-N 0.000 claims 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims 1
- 230000007170 pathology Effects 0.000 claims 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims 1
- 101000845233 Homo sapiens Translocator protein Proteins 0.000 abstract description 48
- 101000845237 Cereibacter sphaeroides Tryptophan-rich sensory protein Proteins 0.000 abstract description 47
- 101000845206 Homo sapiens Putative peripheral benzodiazepine receptor-related protein Proteins 0.000 abstract description 47
- 230000027455 binding Effects 0.000 abstract description 19
- 239000012216 imaging agent Substances 0.000 abstract description 13
- 230000015572 biosynthetic process Effects 0.000 abstract description 11
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 238000001727 in vivo Methods 0.000 abstract description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 4
- 230000002093 peripheral effect Effects 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 229940049706 benzodiazepine Drugs 0.000 abstract description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 2
- 108020003175 receptors Proteins 0.000 abstract description 2
- 102100031269 Putative peripheral benzodiazepine receptor-related protein Human genes 0.000 abstract 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 abstract 1
- 102100031274 Translocator protein Human genes 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- SLJDUPUOYWPBAB-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-n-(6-phenoxypyridin-3-yl)acetamide Chemical compound COC1=CC=CC=C1CN(C(C)=O)C(C=N1)=CC=C1OC1=CC=CC=C1 SLJDUPUOYWPBAB-UHFFFAOYSA-N 0.000 description 11
- 230000002285 radioactive effect Effects 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 229960004756 ethanol Drugs 0.000 description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000004808 supercritical fluid chromatography Methods 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 238000012875 competitive assay Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000013207 serial dilution Methods 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 3
- AEWAUHRPGXMXRE-UHFFFAOYSA-N 9-(2-fluoroethyl)-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carbonyl chloride Chemical compound C1CCC(C(Cl)=O)C2=C1N(CCF)C1=C2C(OC)=CC=C1 AEWAUHRPGXMXRE-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- -1 fluoride compound Chemical class 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- RRDYBCJITNUVNY-FQEVSTJZSA-N (4S)-N-benzyl-N-ethyl-9-(2-fluoroethyl)-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C(C1=CC=CC=C1)N(C(=O)[C@H]1CCCC=2N(C3=CC=CC=C3C1=2)CCF)CC RRDYBCJITNUVNY-FQEVSTJZSA-N 0.000 description 2
- AKWIAIDKXNKXDI-UHFFFAOYSA-N 1h-pyrrole-3-carboxamide Chemical class NC(=O)C=1C=CNC=1 AKWIAIDKXNKXDI-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- XQSORCOJGRXWFT-UHFFFAOYSA-N 2-chloro-n-(2-fluoroethyl)-5-methoxyaniline Chemical compound COC1=CC=C(Cl)C(NCCF)=C1 XQSORCOJGRXWFT-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- PLQUQJCJQMMJLR-UHFFFAOYSA-N 9-(2-fluoroethyl)-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxylic acid Chemical compound C1CCC(C(O)=O)C2=C1N(CCF)C1=C2C(OC)=CC=C1 PLQUQJCJQMMJLR-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
- ZNELSKDWMSBMCL-UHFFFAOYSA-N COc1ccc(Cl)c(NC(=O)CF)c1 Chemical compound COc1ccc(Cl)c(NC(=O)CF)c1 ZNELSKDWMSBMCL-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- FSBNGVSRDFQVMC-UHFFFAOYSA-N ethyl 8-chloro-9-(2-fluoroethyl)-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxylate Chemical class C12=C(OC)C=CC(Cl)=C2N(CCF)C2=C1C(C(=O)OCC)CCC2 FSBNGVSRDFQVMC-UHFFFAOYSA-N 0.000 description 2
- YFJLJIDDXBFGPR-UHFFFAOYSA-N ethyl 9-(2-fluoroethyl)-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxylate Chemical compound C12=C(OC)C=CC=C2N(CCF)C2=C1C(C(=O)OCC)CCC2 YFJLJIDDXBFGPR-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- ZVDVQPLDTTXLKI-UHFFFAOYSA-N n,n-diethyl-9-(2-fluoroethyl)-5-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C12=C(OC)C=CC=C2N(CCF)C2=C1C(C(=O)N(CC)CC)CCC2 ZVDVQPLDTTXLKI-UHFFFAOYSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920001601 polyetherimide Polymers 0.000 description 2
- 229920000136 polysorbate 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
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000012360 testing method Methods 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
- 238000011282 treatment Methods 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 1
- BPGOUCVJJZHKQE-HNNXBMFYSA-N (4s)-9-(2-fluoroethyl)-n-methyl-n-propan-2-yl-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C12=CC=CC=C2N(CCF)C2=C1[C@@H](C(=O)N(C)C(C)C)CCC2 BPGOUCVJJZHKQE-HNNXBMFYSA-N 0.000 description 1
- NLMDJJTUQPXZFG-UHFFFAOYSA-N 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane Chemical compound C1COCCOCCNCCOCCOCCN1 NLMDJJTUQPXZFG-UHFFFAOYSA-N 0.000 description 1
- YFXIZOLPHFYYMF-UHFFFAOYSA-N 2-[6-chloro-2-[4-(3-fluoropropoxy)phenyl]imidazo[1,2-a]pyridin-3-yl]-n,n-diethylacetamide Chemical compound N1=C2C=CC(Cl)=CN2C(CC(=O)N(CC)CC)=C1C1=CC=C(OCCCF)C=C1 YFXIZOLPHFYYMF-UHFFFAOYSA-N 0.000 description 1
- GBOUQGUQUUPGLO-UHFFFAOYSA-N 2-chloro-5-methoxyaniline Chemical compound COC1=CC=C(Cl)C(N)=C1 GBOUQGUQUUPGLO-UHFFFAOYSA-N 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UFAXLWZYMXDRMA-IBGZPJMESA-N C(C1=CC=CC=C1)N(C(=O)[C@H]1CCCC=2N(C3=CC=CC(=C3C12)OC)CCF)CC Chemical compound C(C1=CC=CC=C1)N(C(=O)[C@H]1CCCC=2N(C3=CC=CC(=C3C12)OC)CCF)CC UFAXLWZYMXDRMA-IBGZPJMESA-N 0.000 description 1
- ROMBKODHKIYGDN-AWEZNQCLSA-N COc1cccc2n(CCF)c3CCC[C@H](C(=O)N(C)C(C)C)c3c12 Chemical compound COc1cccc2n(CCF)c3CCC[C@H](C(=O)N(C)C(C)C)c3c12 ROMBKODHKIYGDN-AWEZNQCLSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000001640 Fibromyalgia Diseases 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
- 208000000903 Herpes simplex encephalitis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000010886 Peripheral nerve injury Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 238000009009 Protein Assay Kit II Methods 0.000 description 1
- 206010071141 Rasmussen encephalitis Diseases 0.000 description 1
- 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 102000009206 Translocator proteins Human genes 0.000 description 1
- 108050000091 Translocator proteins Proteins 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000037328 acute stress Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 230000007177 brain activity Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000004098 cellular respiration Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000002739 cryptand Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- GCNJPHUARCLNHO-UHFFFAOYSA-N ethyl 3-[2-chloro-n-(2-fluoroethyl)-5-methoxyanilino]-2-oxocyclohexane-1-carboxylate Chemical class O=C1C(C(=O)OCC)CCCC1N(CCF)C1=CC(OC)=CC=C1Cl GCNJPHUARCLNHO-UHFFFAOYSA-N 0.000 description 1
- VKCMWLOBUILIOQ-UHFFFAOYSA-N ethyl 3-bromo-2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCC(Br)C1=O VKCMWLOBUILIOQ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- KRHYYFGTRYWZRS-BJUDXGSMSA-M fluorine-18(1-) Chemical compound [18F-] KRHYYFGTRYWZRS-BJUDXGSMSA-M 0.000 description 1
- ZBHDTYQJAQDBIH-UHFFFAOYSA-N fluoroacetyl chloride Chemical compound FCC(Cl)=O ZBHDTYQJAQDBIH-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- DHZBNHMEIOBPAE-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-n-(4-phenoxypyridin-3-yl)acetamide Chemical compound COC1=CC=CC=C1CN(C(C)=O)C1=CN=CC=C1OC1=CC=CC=C1 DHZBNHMEIOBPAE-UHFFFAOYSA-N 0.000 description 1
- HCUHRHHLUUZJEQ-UHFFFAOYSA-N n-[[2-(2-fluoroethoxy)phenyl]methyl]-n-(4-phenoxypyridin-3-yl)acetamide Chemical compound C=1N=CC=C(OC=2C=CC=CC=2)C=1N(C(=O)C)CC1=CC=CC=C1OCCF HCUHRHHLUUZJEQ-UHFFFAOYSA-N 0.000 description 1
- HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000007141 radiochemical reaction Methods 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000010009 steroidogenesis Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0446—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1316762.2A GB201316762D0 (en) | 2013-09-20 | 2013-09-20 | Novel compounds |
| GB1316762.2 | 2013-09-20 | ||
| PCT/EP2014/069969 WO2015040148A1 (en) | 2013-09-20 | 2014-09-19 | Carbazole compounds for in vivo imaging |
| CN201480051648.XA CN105593210B (zh) | 2013-09-20 | 2014-09-19 | 用于体内成像的咔唑化合物 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480051648.XA Division CN105593210B (zh) | 2013-09-20 | 2014-09-19 | 用于体内成像的咔唑化合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110229093A CN110229093A (zh) | 2019-09-13 |
| CN110229093B true CN110229093B (zh) | 2022-12-13 |
Family
ID=49553181
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480051648.XA Active CN105593210B (zh) | 2013-09-20 | 2014-09-19 | 用于体内成像的咔唑化合物 |
| CN201910451008.2A Active CN110229093B (zh) | 2013-09-20 | 2014-09-19 | 用于体内成像的咔唑化合物 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480051648.XA Active CN105593210B (zh) | 2013-09-20 | 2014-09-19 | 用于体内成像的咔唑化合物 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9951011B2 (enExample) |
| EP (1) | EP3046904B1 (enExample) |
| JP (1) | JP6401791B2 (enExample) |
| CN (2) | CN105593210B (enExample) |
| GB (1) | GB201316762D0 (enExample) |
| WO (1) | WO2015040148A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201316762D0 (en) * | 2013-09-20 | 2013-11-06 | Ge Healthcare Ltd | Novel compounds |
| CN109776394B (zh) * | 2019-03-05 | 2020-10-27 | 朱晓琴 | 一种咔唑衍生物及其制备方法与制备h2s供体的应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102448933A (zh) * | 2009-03-27 | 2012-05-09 | 通用电气健康护理有限公司 | 作为pbr配体的吲哚衍生物 |
| CN103179991A (zh) * | 2010-09-30 | 2013-06-26 | 通用电气健康护理有限公司 | 癌症的体内成像方法 |
| CN103209713A (zh) * | 2010-09-24 | 2013-07-17 | 通用电气健康护理有限公司 | 心境障碍的体内成像方法 |
| CN105593210B (zh) * | 2013-09-20 | 2020-06-05 | 通用电气健康护理有限公司 | 用于体内成像的咔唑化合物 |
-
2013
- 2013-09-20 GB GBGB1316762.2A patent/GB201316762D0/en not_active Ceased
-
2014
- 2014-09-19 CN CN201480051648.XA patent/CN105593210B/zh active Active
- 2014-09-19 EP EP14767023.6A patent/EP3046904B1/en active Active
- 2014-09-19 JP JP2016543407A patent/JP6401791B2/ja active Active
- 2014-09-19 US US14/917,707 patent/US9951011B2/en active Active
- 2014-09-19 WO PCT/EP2014/069969 patent/WO2015040148A1/en not_active Ceased
- 2014-09-19 CN CN201910451008.2A patent/CN110229093B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102448933A (zh) * | 2009-03-27 | 2012-05-09 | 通用电气健康护理有限公司 | 作为pbr配体的吲哚衍生物 |
| CN103209713A (zh) * | 2010-09-24 | 2013-07-17 | 通用电气健康护理有限公司 | 心境障碍的体内成像方法 |
| CN103179991A (zh) * | 2010-09-30 | 2013-06-26 | 通用电气健康护理有限公司 | 癌症的体内成像方法 |
| CN105593210B (zh) * | 2013-09-20 | 2020-06-05 | 通用电气健康护理有限公司 | 用于体内成像的咔唑化合物 |
Non-Patent Citations (1)
| Title |
|---|
| [18F]GE-180: A novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO).;HarryWadsworth 等;《Bioorganic & Medicinal Chemistry Letters》;20111227;第22卷(第3期);1308-1313 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3046904A1 (en) | 2016-07-27 |
| JP6401791B2 (ja) | 2018-10-10 |
| CN105593210A (zh) | 2016-05-18 |
| US20160214936A1 (en) | 2016-07-28 |
| CN105593210B (zh) | 2020-06-05 |
| US9951011B2 (en) | 2018-04-24 |
| GB201316762D0 (en) | 2013-11-06 |
| CN110229093A (zh) | 2019-09-13 |
| EP3046904B1 (en) | 2020-02-12 |
| JP2016530337A (ja) | 2016-09-29 |
| WO2015040148A1 (en) | 2015-03-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2525196C2 (ru) | Трициклические индольные производные в качестве лигандов pbr | |
| JP5830519B2 (ja) | Ｐｂｒリガンドとしての三環式インドール誘導体 | |
| KR20130136457A (ko) | 암의 생체내 영상화 방법 | |
| Fujinaga et al. | Development of N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1, 3-thiazol-2-yl]-N-methyl-4-[11C] methylbenzamide for positron emission tomography imaging of metabotropic glutamate 1 receptor in monkey brain | |
| US9168317B2 (en) | In vivo imaging method of mood disorders | |
| RU2756604C2 (ru) | ЛИГАНДНОЕ СОЕДИНЕНИЕ α7-НИКОТИНОВОГО АЦЕТИЛХОЛИНОВОГО РЕЦЕПТОРА И ЕГО ПРИМЕНЕНИЕ | |
| CN110229093B (zh) | 用于体内成像的咔唑化合物 | |
| JP2016534145A (ja) | Ｐｂｒリガンドとしての四環式インドール誘導体のｓ−エナンチオマー | |
| US9186424B2 (en) | Aryloxyanilide imaging agents | |
| US9220795B2 (en) | Indole derivatives | |
| JP2021102593A (ja) | タウを画像化する新規化合物 | |
| HK1167393B (en) | Tricyclic indole derivates as pbr ligands | |
| HK1179946B (en) | Tricyclic indole derivatives as pbr ligands |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |