KR102718221B1 - 양전자 방출 핵종으로 표지된 지방산 유도체 - Google Patents
양전자 방출 핵종으로 표지된 지방산 유도체 Download PDFInfo
- Publication number
- KR102718221B1 KR102718221B1 KR1020217001389A KR20217001389A KR102718221B1 KR 102718221 B1 KR102718221 B1 KR 102718221B1 KR 1020217001389 A KR1020217001389 A KR 1020217001389A KR 20217001389 A KR20217001389 A KR 20217001389A KR 102718221 B1 KR102718221 B1 KR 102718221B1
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- KR
- South Korea
- Prior art keywords
- fatty acid
- salt
- acid derivative
- compound
- labeled fatty
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 81
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 75
- 239000000194 fatty acid Substances 0.000 claims abstract description 75
- 229930195729 fatty acid Natural products 0.000 claims abstract description 75
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 75
- 238000003384 imaging method Methods 0.000 claims abstract description 43
- 208000019622 heart disease Diseases 0.000 claims abstract description 28
- 238000003745 diagnosis Methods 0.000 claims abstract description 27
- 208000031225 myocardial ischemia Diseases 0.000 claims abstract description 9
- XLHOLOJPVDSSDQ-AVGIDEFSSA-N 3-[(Z)-3-(18F)fluoranyltetradec-5-enyl]sulfanylpropanoic acid Chemical compound [18F]C(CCSCCC(=O)O)C\C=C/CCCCCCCC XLHOLOJPVDSSDQ-AVGIDEFSSA-N 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 89
- 239000000203 mixture Substances 0.000 claims description 55
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- KRHYYFGTRYWZRS-BJUDXGSMSA-M fluorine-18(1-) Chemical compound [18F-] KRHYYFGTRYWZRS-BJUDXGSMSA-M 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- KZLMDUNDGBJYQB-AVGIDEFSSA-N 3-[(Z)-2-(18F)fluoranyltetradec-5-enyl]sulfanylpropanoic acid Chemical group [18F]C(CSCCC(=O)O)CC\C=C/CCCCCCCC KZLMDUNDGBJYQB-AVGIDEFSSA-N 0.000 claims description 3
- 238000002600 positron emission tomography Methods 0.000 abstract description 35
- 238000000034 method Methods 0.000 abstract description 33
- 208000020446 Cardiac disease Diseases 0.000 abstract description 11
- 210000004165 myocardium Anatomy 0.000 abstract description 11
- 239000000700 radioactive tracer Substances 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 9
- 230000002503 metabolic effect Effects 0.000 abstract description 9
- 230000010354 integration Effects 0.000 abstract description 8
- 238000011002 quantification Methods 0.000 abstract description 5
- 229940124597 therapeutic agent Drugs 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 35
- 239000000126 substance Substances 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- -1 and in ω-oxidation Chemical class 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000008569 process Effects 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 210000000988 bone and bone Anatomy 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000002994 raw material Substances 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- 238000010898 silica gel chromatography Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000009825 accumulation Methods 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 11
- 210000002216 heart Anatomy 0.000 description 11
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 208000010125 myocardial infarction Diseases 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000012879 PET imaging Methods 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- YCKRFDGAMUMZLT-BJUDXGSMSA-N fluorine-18 atom Chemical compound [18F] YCKRFDGAMUMZLT-BJUDXGSMSA-N 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- QNWRQQSASSIICT-UHFFFAOYSA-N 5-[tert-butyl(dimethyl)silyl]oxy-4-[tert-butyl(diphenyl)silyl]oxypentanal Chemical compound C(C)(C)(C)[Si](OCC(CCC=O)O[Si](C1=CC=CC=C1)(C1=CC=CC=C1)C(C)(C)C)(C)C QNWRQQSASSIICT-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- NPCIWINHUDIWAV-NSYCNWAXSA-N I-123 BMIPP Chemical compound OC(=O)CC(C)CCCCCCCCCCCCC1=CC=C([123I])C=C1 NPCIWINHUDIWAV-NSYCNWAXSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 238000000752 ionisation method Methods 0.000 description 4
- NKGNJIDNCZMBNC-KHPPLWFESA-N methyl 3-[(Z)-3-hydroxytetradec-5-enyl]sulfanylpropanoate Chemical compound OC(CCSCCC(=O)OC)C\C=C/CCCCCCCC NKGNJIDNCZMBNC-KHPPLWFESA-N 0.000 description 4
- 230000002107 myocardial effect Effects 0.000 description 4
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000002603 single-photon emission computed tomography Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 3
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000005703 Trimethylamine hydrochloride Substances 0.000 description 3
- 230000003444 anaesthetic effect Effects 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229960002725 isoflurane Drugs 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- MBHDJQUJQGWXQD-KHPPLWFESA-N methyl 3-[(Z)-2-hydroxytetradec-5-enyl]sulfanylpropanoate Chemical compound OC(CSCCC(=O)OC)CC\C=C/CCCCCCCC MBHDJQUJQGWXQD-KHPPLWFESA-N 0.000 description 3
- MJGMJBFYWONSDG-KHPPLWFESA-N methyl 3-[(Z)-3-(4-nitrophenyl)sulfonyloxytetradec-5-enyl]sulfanylpropanoate Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)S(=O)(=O)OC(CCSCCC(=O)OC)C\C=C/CCCCCCCC MJGMJBFYWONSDG-KHPPLWFESA-N 0.000 description 3
- NVPCJCNEURVLGA-KHPPLWFESA-N methyl 3-[(Z)-3-bromotetradec-5-enyl]sulfanylpropanoate Chemical compound BrC(CCSCCC(=O)OC)C\C=C/CCCCCCCC NVPCJCNEURVLGA-KHPPLWFESA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- SZYJELPVAFJOGJ-UHFFFAOYSA-N trimethylamine hydrochloride Chemical compound Cl.CN(C)C SZYJELPVAFJOGJ-UHFFFAOYSA-N 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- RDHAZEMTRHXKGT-SEYXRHQNSA-N (Z)-2-[tert-butyl(diphenyl)silyl]oxytetradec-5-en-1-ol Chemical compound [Si](C1=CC=CC=C1)(C1=CC=CC=C1)(C(C)(C)C)OC(CO)CC\C=C/CCCCCCCC RDHAZEMTRHXKGT-SEYXRHQNSA-N 0.000 description 2
- CVVMLSUXFCXKEG-QINSGFPZSA-N (Z)-3-[tert-butyl(diphenyl)silyl]oxytetradec-5-en-1-ol Chemical compound [Si](C1=CC=CC=C1)(C1=CC=CC=C1)(C(C)(C)C)OC(CCO)C\C=C/CCCCCCCC CVVMLSUXFCXKEG-QINSGFPZSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- BHAVPOGLYRBECO-UHFFFAOYSA-N 2-(9-bromononan-4-yloxy)oxane Chemical compound BrCCCCCC(CCC)OC1OCCCC1 BHAVPOGLYRBECO-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- UIDYEXGBCAVMAM-GKTGUEEDSA-N 3-(12-fluoranyldodecylsulfanyl)propanoic acid Chemical compound OC(=O)CCSCCCCCCCCCCCC[18F] UIDYEXGBCAVMAM-GKTGUEEDSA-N 0.000 description 2
- KXUIWEKGABOUNX-HFOCOGKHSA-N 3-[(Z)-11-(18F)fluoranyltetradec-5-enyl]sulfanylpropanoic acid Chemical compound [18F]C(CCCC\C=C/CCCCSCCC(=O)O)CCC KXUIWEKGABOUNX-HFOCOGKHSA-N 0.000 description 2
- ONEIYNABWFFWSI-CLSPLTCCSA-N 3-[(Z)-13-(18F)fluoranyltetradec-5-enyl]sulfanylpropanoic acid Chemical compound [18F]C(CCCCCC\C=C/CCCCSCCC(=O)O)C ONEIYNABWFFWSI-CLSPLTCCSA-N 0.000 description 2
- KZLMDUNDGBJYQB-KTKRTIGZSA-N 3-[(Z)-2-fluorotetradec-5-enyl]sulfanylpropanoic acid Chemical compound FC(CSCCC(=O)O)CC\C=C/CCCCCCCC KZLMDUNDGBJYQB-KTKRTIGZSA-N 0.000 description 2
- XLHOLOJPVDSSDQ-KTKRTIGZSA-N 3-[(Z)-3-fluorotetradec-5-enyl]sulfanylpropanoic acid Chemical compound FC(CCSCCC(=O)O)C\C=C/CCCCCCCC XLHOLOJPVDSSDQ-KTKRTIGZSA-N 0.000 description 2
- YFSQQMGSLWYHBL-XRQCYVQQSA-N 3-[(z)-14-fluoranyltetradec-5-enyl]sulfanylpropanoic acid Chemical compound OC(=O)CCSCCCC\C=C/CCCCCCCC[18F] YFSQQMGSLWYHBL-XRQCYVQQSA-N 0.000 description 2
- QKUXQKVABHFQKT-UHFFFAOYSA-N 5-[tert-butyl(dimethyl)silyl]oxy-4-[tert-butyl(diphenyl)silyl]oxypentan-1-ol Chemical compound [Si](C)(C)(C(C)(C)C)OCC(CCCO)O[Si](C1=CC=CC=C1)(C1=CC=CC=C1)C(C)(C)C QKUXQKVABHFQKT-UHFFFAOYSA-N 0.000 description 2
- KPLOBHKFLFONAI-UHFFFAOYSA-N 9-bromononan-4-ol Chemical compound CCCC(O)CCCCCBr KPLOBHKFLFONAI-UHFFFAOYSA-N 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000006192 iodination reaction Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- XYRXHQGCOPBNEL-SSZFMOIBSA-N methyl 3-[(Z)-3-[tert-butyl(diphenyl)silyl]oxytetradec-5-enyl]sulfanylpropanoate Chemical compound [Si](C1=CC=CC=C1)(C1=CC=CC=C1)(C(C)(C)C)OC(CCSCCC(=O)OC)C\C=C/CCCCCCCC XYRXHQGCOPBNEL-SSZFMOIBSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 230000004783 oxidative metabolism Effects 0.000 description 2
- 239000003186 pharmaceutical solution Substances 0.000 description 2
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- OQGNEJPJKNWOCC-ZCXUNETKSA-N tert-butyl-[(Z)-1-[tert-butyl(dimethyl)silyl]oxytetradec-5-en-2-yl]oxy-diphenylsilane Chemical compound C(C\C=C/CCCCCCCC)C(O[Si](C(C)(C)C)(C1=CC=CC=C1)C1=CC=CC=C1)CO[Si](C(C)(C)C)(C)C OQGNEJPJKNWOCC-ZCXUNETKSA-N 0.000 description 2
- XYJFMCYKHHIQBZ-SEYXRHQNSA-N tert-butyl-[(Z)-1-iodotetradec-5-en-2-yl]oxy-diphenylsilane Chemical compound C(C)(C)(C)[Si](C1=CC=CC=C1)(C1=CC=CC=C1)OC(CI)CC\C=C/CCCCCCCC XYJFMCYKHHIQBZ-SEYXRHQNSA-N 0.000 description 2
- JUAOFZXSAYSTLV-QINSGFPZSA-N tert-butyl-[(Z)-1-iodotetradec-5-en-3-yl]oxy-diphenylsilane Chemical compound C(C)(C)(C)[Si](C1=CC=CC=C1)(C1=CC=CC=C1)OC(CCI)C\C=C/CCCCCCCC JUAOFZXSAYSTLV-QINSGFPZSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
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- G01T1/16—Measuring radiation intensity
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| PCT/JP2019/028380 WO2020017620A1 (ja) | 2018-07-20 | 2019-07-19 | 陽電子放出核種で標識された脂肪酸誘導体 |
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| DE2828623C2 (de) * | 1978-06-29 | 1983-11-17 | Kernforschungsanlage Jülich GmbH, 5170 Jülich | Mit radioaktivem Flour markierte C↓1↓↓6↓-bis C↓1↓↓8↓- Fettsäuren, ein Verfahren zu ihrer Herstellung sowie deren Verwendung |
| WO2000063216A1 (en) | 1999-04-19 | 2000-10-26 | Duke University | F-18-labeled thia fatty acids and methods of making and using the same |
| WO2004093650A2 (en) | 2003-04-17 | 2004-11-04 | The General Hospital Corporation | Method for monitoring blood flow and metabolic uptake in tissue with radiolabeled alkanoic acid |
| CN1217924C (zh) | 2003-10-17 | 2005-09-07 | 江苏省原子医学研究所 | 一种氟标记脂肪酸心肌代谢显像剂14(r,s)－氟[18f]－6－硫十七烷酸的纯化方法 |
| AU2010246010A1 (en) | 2009-05-04 | 2011-11-17 | Washington University | PET radiotracers for imaging fatty acid metablolism and storage |
| WO2014179341A1 (en) * | 2013-04-29 | 2014-11-06 | Matinas Biopharma, Inc. | Treatment with omega-3 fatty acid compositions |
| WO2015023631A2 (en) | 2013-08-12 | 2015-02-19 | Carolyn Anderson | Fatty acid analogs and their use |
| CN105523977B (zh) | 2016-02-04 | 2017-05-24 | 河南中医学院 | [11c]‑巯甲基脂肪酸的制备方法与应用 |
| KR102718221B1 (ko) | 2018-07-20 | 2024-10-15 | 아스텔라스세이야쿠 가부시키가이샤 | 양전자 방출 핵종으로 표지된 지방산 유도체 |
| JP7652084B2 (ja) | 2020-01-17 | 2025-03-27 | アステラス製薬株式会社 | 陽電子放出核種で標識された脂肪酸誘導体 |
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Non-Patent Citations (2)
| Title |
|---|
| Journal of Nuclear Medicine, 2010, vol. 51, no. 8, pp. 1310-1317 |
| Nuclear Medicine and Biology, 2016, vol. 43, no. 1, pp. 108-115 |
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| CN112638868A (zh) | 2021-04-09 |
| WO2020017620A1 (ja) | 2020-01-23 |
| CN112638868B (zh) | 2023-06-20 |
| KR20210032392A (ko) | 2021-03-24 |
| US12029797B2 (en) | 2024-07-09 |
| EP3825302A4 (en) | 2022-05-04 |
| CA3106903A1 (en) | 2020-01-23 |
| JP7375755B2 (ja) | 2023-11-08 |
| US20210338845A1 (en) | 2021-11-04 |
| EP3825302A1 (en) | 2021-05-26 |
| EP3825302B1 (en) | 2025-01-08 |
| ES3009015T3 (en) | 2025-03-25 |
| AU2019304781A1 (en) | 2021-02-11 |
| JPWO2020017620A1 (ja) | 2021-08-02 |
| AU2019304781B2 (en) | 2023-12-21 |
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