KR101920902B1 - A PET contrast compound for early diagnosis of cardiovascular diseases and use thereof - Google Patents
A PET contrast compound for early diagnosis of cardiovascular diseases and use thereof Download PDFInfo
- Publication number
- KR101920902B1 KR101920902B1 KR1020170181493A KR20170181493A KR101920902B1 KR 101920902 B1 KR101920902 B1 KR 101920902B1 KR 1020170181493 A KR1020170181493 A KR 1020170181493A KR 20170181493 A KR20170181493 A KR 20170181493A KR 101920902 B1 KR101920902 B1 KR 101920902B1
- Authority
- KR
- South Korea
- Prior art keywords
- phosphonium
- ethyl
- pyrimidin
- pyridin
- butyl
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 57
- 238000013399 early diagnosis Methods 0.000 title description 2
- 208000024172 Cardiovascular disease Diseases 0.000 title 1
- 230000002285 radioactive effect Effects 0.000 claims abstract description 32
- 239000002872 contrast media Substances 0.000 claims abstract description 11
- -1 succinimidyl group Chemical group 0.000 claims description 85
- 125000004432 carbon atom Chemical group C* 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000002947 alkylene group Chemical group 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000004419 alkynylene group Chemical group 0.000 claims description 14
- 125000000732 arylene group Chemical group 0.000 claims description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000004450 alkenylene group Chemical group 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 238000002600 positron emission tomography Methods 0.000 claims description 10
- HAEUOUZZVSHGKX-UHFFFAOYSA-N tripyridin-3-ylphosphane Chemical compound C1=CN=CC(P(C=2C=NC=CC=2)C=2C=NC=CC=2)=C1 HAEUOUZZVSHGKX-UHFFFAOYSA-N 0.000 claims description 9
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 8
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 claims description 8
- QCZDIMNUBWUWQI-UHFFFAOYSA-N N1=NN=C(C=C1)P(C1=NN=NC=C1)C1=NN=NC=C1 Chemical compound N1=NN=C(C=C1)P(C1=NN=NC=C1)C1=NN=NC=C1 QCZDIMNUBWUWQI-UHFFFAOYSA-N 0.000 claims description 8
- 150000004696 coordination complex Chemical class 0.000 claims description 8
- 125000004185 ester group Chemical group 0.000 claims description 8
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 8
- RBNQMJPEQMHIJZ-LRFGSCOBSA-N 2-(2-(18F)fluoranylethoxy)ethyl-tripyridin-3-ylphosphanium Chemical compound [18F]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 RBNQMJPEQMHIJZ-LRFGSCOBSA-N 0.000 claims description 7
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 claims description 7
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 claims description 7
- XUKFHRNWSCWRFI-LRFGSCOBSA-N 2-(2-(18F)fluoranylethoxy)ethyl-tripyridin-4-ylphosphanium Chemical compound [18F]CCOCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 XUKFHRNWSCWRFI-LRFGSCOBSA-N 0.000 claims description 6
- JHALWMSZGCVVEM-UHFFFAOYSA-N 2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]acetic acid Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CC1 JHALWMSZGCVVEM-UHFFFAOYSA-N 0.000 claims description 6
- PRTGATZAXAWVCH-GJQNQZCXSA-N 5-(18F)fluoranylpentyl(tripyridin-3-yl)phosphanium Chemical compound [18F]CCCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 PRTGATZAXAWVCH-GJQNQZCXSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- PRFKKRCXABARPL-LRFGSCOBSA-N 2-(2-(18F)fluoranylethoxy)ethyl-tripyridin-2-ylphosphanium Chemical compound [18F]CCOCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 PRFKKRCXABARPL-LRFGSCOBSA-N 0.000 claims description 5
- 235000010290 biphenyl Nutrition 0.000 claims description 5
- 239000004305 biphenyl Substances 0.000 claims description 5
- ZRLYFRSIROIBSJ-UHFFFAOYSA-N diphenyl(pyrimidin-4-yl)phosphane Chemical compound C1=CC=CC=C1P(C=1N=CN=CC=1)C1=CC=CC=C1 ZRLYFRSIROIBSJ-UHFFFAOYSA-N 0.000 claims description 5
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 5
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 5
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 5
- MRLKMCJVGAIGGE-UHFFFAOYSA-N 1,4,8,11-tetrazacyclotetradec-10-ene Chemical compound C1CNCCNCCCN=CCNC1 MRLKMCJVGAIGGE-UHFFFAOYSA-N 0.000 claims description 4
- LKAPVCUYLHQQNU-UTFYOAIGSA-N 2-(2-(123I)iodanylethoxy)ethyl-phenyl-di(pyrimidin-4-yl)phosphanium Chemical compound [123I]CCOCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 LKAPVCUYLHQQNU-UTFYOAIGSA-N 0.000 claims description 4
- LKAPVCUYLHQQNU-OWFUXLEOSA-N 2-(2-(131I)iodanylethoxy)ethyl-phenyl-di(pyrimidin-4-yl)phosphanium Chemical compound [131I]CCOCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 LKAPVCUYLHQQNU-OWFUXLEOSA-N 0.000 claims description 4
- BABTVSHYUOXACT-GLOFJIOZSA-O 4-[(6-(18F)fluoranylpyridine-3-carbonyl)amino]butyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [18F]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 BABTVSHYUOXACT-GLOFJIOZSA-O 0.000 claims description 4
- JOJSKEBNODOLOE-VEFBWTBNSA-O [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=CC=CC=C2)C=C1 Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=CC=CC=C2)C=C1 JOJSKEBNODOLOE-VEFBWTBNSA-O 0.000 claims description 4
- BITQWUJJUPWBKP-AWDFDDCISA-N [18F]CCOCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 Chemical compound [18F]CCOCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 BITQWUJJUPWBKP-AWDFDDCISA-N 0.000 claims description 4
- SYOQTXKDDDERIP-SJPDSGJFSA-N [18F]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 Chemical compound [18F]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 SYOQTXKDDDERIP-SJPDSGJFSA-N 0.000 claims description 4
- YCBXRTLTNRXHOO-UTFYOAIGSA-N [76Br]CCOCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 Chemical compound [76Br]CCOCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 YCBXRTLTNRXHOO-UTFYOAIGSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000005647 linker group Chemical group 0.000 claims description 4
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 4
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 claims description 4
- 229960003330 pentetic acid Drugs 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229960002317 succinimide Drugs 0.000 claims description 4
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 4
- ZVUHJAOPEJANFB-UHFFFAOYSA-N tri(pyrimidin-4-yl)phosphane Chemical compound N1=CN=C(C=C1)P(C1=NC=NC=C1)C1=NC=NC=C1 ZVUHJAOPEJANFB-UHFFFAOYSA-N 0.000 claims description 4
- LKAPVCUYLHQQNU-JVYRTNJDSA-N 2-(2-(124I)iodanylethoxy)ethyl-phenyl-di(pyrimidin-4-yl)phosphanium Chemical compound [124I]CCOCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 LKAPVCUYLHQQNU-JVYRTNJDSA-N 0.000 claims description 3
- OVZWAQKIZALUFC-PZAKOYRYSA-N 2-(2-(131I)iodanylethoxy)ethyl-tris(triazin-4-yl)phosphanium Chemical compound [131I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 OVZWAQKIZALUFC-PZAKOYRYSA-N 0.000 claims description 3
- YTGXCRUHGAEKDO-UMSOTBISSA-N 2-(2-(18F)fluoranylethoxy)ethyl-tris(triazin-4-yl)phosphanium Chemical compound [18F]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 YTGXCRUHGAEKDO-UMSOTBISSA-N 0.000 claims description 3
- PWXFCYXXNMIXRF-GJQNQZCXSA-N 5-(18F)fluoranylpentyl(tripyridin-2-yl)phosphanium Chemical compound [18F]CCCCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 PWXFCYXXNMIXRF-GJQNQZCXSA-N 0.000 claims description 3
- RZEHQSVXMPJDFT-UHFFFAOYSA-N NCCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 Chemical compound NCCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 RZEHQSVXMPJDFT-UHFFFAOYSA-N 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- AFQDTOJPMUTYFK-PIRNEEEYSA-N 2-(2-(123I)iodanylethoxy)ethyl-phenyl-dipyridin-3-ylphosphanium Chemical compound [123I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 AFQDTOJPMUTYFK-PIRNEEEYSA-N 0.000 claims description 2
- AFQDTOJPMUTYFK-XNXCDXPKSA-N 2-(2-(124I)iodanylethoxy)ethyl-phenyl-dipyridin-3-ylphosphanium Chemical compound [124I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 AFQDTOJPMUTYFK-XNXCDXPKSA-N 0.000 claims description 2
- KFQNYOBJRDENET-URWOLLDTSA-N 2-(2-(131I)iodanylethoxy)ethyl-diphenyl-(triazin-4-yl)phosphanium Chemical compound [131I]CCOCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 KFQNYOBJRDENET-URWOLLDTSA-N 0.000 claims description 2
- SOCOYPSOFWZJSX-ITIOBDTJSA-N 2-(2-(131I)iodanylethoxy)ethyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [131I]CCOCC[P+](C=1C=NC=CC=1)(C1=CC=CC=C1)C1=CC=CC=C1 SOCOYPSOFWZJSX-ITIOBDTJSA-N 0.000 claims description 2
- LYJSQWJEEUQPHJ-TWYGLIRSSA-N 2-(2-(131I)iodanylethoxy)ethyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [131I]CCOCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 LYJSQWJEEUQPHJ-TWYGLIRSSA-N 0.000 claims description 2
- AFQDTOJPMUTYFK-TWYGLIRSSA-N 2-(2-(131I)iodanylethoxy)ethyl-phenyl-dipyridin-3-ylphosphanium Chemical compound [131I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 AFQDTOJPMUTYFK-TWYGLIRSSA-N 0.000 claims description 2
- CNOZQERLCQTGRW-KVTPGWOSSA-N 2-(2-(18F)fluoranylethoxy)ethyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [18F]CCOCC[P+](C=1C=NC=CC=1)(C1=CC=CC=C1)C1=CC=CC=C1 CNOZQERLCQTGRW-KVTPGWOSSA-N 0.000 claims description 2
- YKTRCBWTRSPLBW-GJQNQZCXSA-N 2-(2-(18F)fluoranylethoxy)ethyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [18F]CCOCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 YKTRCBWTRSPLBW-GJQNQZCXSA-N 0.000 claims description 2
- AXSPSUMLLUSFQM-GLOFJIOZSA-O 2-[2-[(6-(18F)fluoranylpyridine-3-carbonyl)amino]ethoxy]ethyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [18F]C1=NC=C(C(=O)NCCOCC[P+](C=2C=NC=CC=2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 AXSPSUMLLUSFQM-GLOFJIOZSA-O 0.000 claims description 2
- ZKZKUVRRZCZEIP-BMILMZPDSA-N 4-(123I)iodanylbutyl(tripyridin-3-yl)phosphanium Chemical compound [123I]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 ZKZKUVRRZCZEIP-BMILMZPDSA-N 0.000 claims description 2
- DCXCKBICDUNYFR-BMILMZPDSA-N 4-(123I)iodanylbutyl-diphenyl-(triazin-4-yl)phosphanium Chemical compound [123I]CCCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 DCXCKBICDUNYFR-BMILMZPDSA-N 0.000 claims description 2
- MCAIIAUKFSFQMW-PIRNEEEYSA-N 4-(123I)iodanylbutyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [123I]CCCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 MCAIIAUKFSFQMW-PIRNEEEYSA-N 0.000 claims description 2
- LWBITOFXZWNGTR-HHRLKWFBSA-N 4-(123I)iodanylbutyl-phenyl-bis(triazin-4-yl)phosphanium Chemical compound [123I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 LWBITOFXZWNGTR-HHRLKWFBSA-N 0.000 claims description 2
- MCAIIAUKFSFQMW-XNXCDXPKSA-N 4-(124I)iodanylbutyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [124I]CCCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 MCAIIAUKFSFQMW-XNXCDXPKSA-N 0.000 claims description 2
- ZKZKUVRRZCZEIP-URWOLLDTSA-N 4-(131I)iodanylbutyl(tripyridin-3-yl)phosphanium Chemical compound [131I]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 ZKZKUVRRZCZEIP-URWOLLDTSA-N 0.000 claims description 2
- DCXCKBICDUNYFR-URWOLLDTSA-N 4-(131I)iodanylbutyl-diphenyl-(triazin-4-yl)phosphanium Chemical compound [131I]CCCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 DCXCKBICDUNYFR-URWOLLDTSA-N 0.000 claims description 2
- MCAIIAUKFSFQMW-TWYGLIRSSA-N 4-(131I)iodanylbutyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [131I]CCCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 MCAIIAUKFSFQMW-TWYGLIRSSA-N 0.000 claims description 2
- LWBITOFXZWNGTR-UOJYAKQPSA-N 4-(131I)iodanylbutyl-phenyl-bis(triazin-4-yl)phosphanium Chemical compound [131I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 LWBITOFXZWNGTR-UOJYAKQPSA-N 0.000 claims description 2
- FKARTOJDVFLQLG-UOJYAKQPSA-N 4-(131I)iodanylbutyl-tri(pyrimidin-4-yl)phosphanium Chemical compound [131I]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=NC=NC=C1 FKARTOJDVFLQLG-UOJYAKQPSA-N 0.000 claims description 2
- MJFCVZGHSCSEHJ-LRFGSCOBSA-N 4-(18F)fluoranylbutyl-diphenyl-(triazin-4-yl)phosphanium Chemical compound [18F]CCCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 MJFCVZGHSCSEHJ-LRFGSCOBSA-N 0.000 claims description 2
- ILJKEDMEELTXLX-KVTPGWOSSA-N 4-(18F)fluoranylbutyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [18F]CCCC[P+](C=1C=NC=CC=1)(C1=CC=CC=C1)C1=CC=CC=C1 ILJKEDMEELTXLX-KVTPGWOSSA-N 0.000 claims description 2
- MWYYQQACUDGCNZ-GJQNQZCXSA-N 4-(18F)fluoranylbutyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [18F]CCCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 MWYYQQACUDGCNZ-GJQNQZCXSA-N 0.000 claims description 2
- MBQYBSBBMSOLFT-AWDFDDCISA-N 4-(18F)fluoranylbutyl-phenyl-di(pyrimidin-4-yl)phosphanium Chemical compound [18F]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 MBQYBSBBMSOLFT-AWDFDDCISA-N 0.000 claims description 2
- ISWYMNGAXURZDM-SJPDSGJFSA-N 4-(18F)fluoranylbutyl-tri(pyrimidin-4-yl)phosphanium Chemical compound [18F]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=NC=NC=C1 ISWYMNGAXURZDM-SJPDSGJFSA-N 0.000 claims description 2
- MCBCTQZLVVYANN-UMSOTBISSA-N 4-(18F)fluoranylbutyl-tris(triazin-4-yl)phosphanium Chemical compound [18F]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 MCBCTQZLVVYANN-UMSOTBISSA-N 0.000 claims description 2
- MKXHYEALNTVBKI-VNRZBHCFSA-N 4-(18F)fluoranylpentyl-diphenyl-pyridin-2-ylphosphanium Chemical compound [18F]C(CCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)C MKXHYEALNTVBKI-VNRZBHCFSA-N 0.000 claims description 2
- FEIIDDGYQZRENA-CKVWVWRJSA-N 4-(76Br)bromanylbutyl-tris(triazin-4-yl)phosphanium Chemical compound [76Br]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 FEIIDDGYQZRENA-CKVWVWRJSA-N 0.000 claims description 2
- WAOFOYGNTKKNIT-NSYCNWAXSA-O 4-[(6-(123I)iodanylpyridine-3-carbonyl)amino]butyl-tri(pyrimidin-4-yl)phosphanium Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 WAOFOYGNTKKNIT-NSYCNWAXSA-O 0.000 claims description 2
- KMBYXRNPSMFKPE-PMKPTOLGSA-O 4-[(6-(131I)iodanylpyridine-3-carbonyl)amino]butyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 KMBYXRNPSMFKPE-PMKPTOLGSA-O 0.000 claims description 2
- JBOMJOMACSOGBJ-BLVGABTOSA-O 4-[(6-(131I)iodanylpyridine-3-carbonyl)amino]butyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 JBOMJOMACSOGBJ-BLVGABTOSA-O 0.000 claims description 2
- WAOFOYGNTKKNIT-AWUWEVMDSA-O 4-[(6-(131I)iodanylpyridine-3-carbonyl)amino]butyl-tri(pyrimidin-4-yl)phosphanium Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 WAOFOYGNTKKNIT-AWUWEVMDSA-O 0.000 claims description 2
- TWAJWGVBWQTHMY-WGQBEPEPSA-O 4-[(6-(131I)iodanylpyridine-3-carbonyl)amino]butyl-tripyridin-3-ylphosphanium Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C=2C=NC=CC=2)C=C1 TWAJWGVBWQTHMY-WGQBEPEPSA-O 0.000 claims description 2
- FLQVSWJRDKVSQF-FMLNDMEQSA-O 4-[(6-(18F)fluoranylpyridine-3-carbonyl)amino]butyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [18F]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 FLQVSWJRDKVSQF-FMLNDMEQSA-O 0.000 claims description 2
- UUOLYGMEXXGBQI-FMLNDMEQSA-O 4-[(6-(18F)fluoranylpyridine-3-carbonyl)amino]butyl-phenyl-dipyridin-3-ylphosphanium Chemical compound [18F]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 UUOLYGMEXXGBQI-FMLNDMEQSA-O 0.000 claims description 2
- ZYHMIVZACCTHFJ-KPVNRNJOSA-O 4-[(6-(18F)fluoranylpyridine-3-carbonyl)amino]butyl-tripyridin-3-ylphosphanium Chemical compound [18F]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C=2C=NC=CC=2)C=C1 ZYHMIVZACCTHFJ-KPVNRNJOSA-O 0.000 claims description 2
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- XKAAOZZHCWLVIU-UHFFFAOYSA-N 4-aminobutyl-diphenyl-pyrimidin-5-ylphosphanium Chemical compound NCCCC[P+](C=1C=NC=NC=1)(C1=CC=CC=C1)C1=CC=CC=C1 XKAAOZZHCWLVIU-UHFFFAOYSA-N 0.000 claims description 2
- ISENJYOZGPJSFA-HLVDMQJYSA-N 5-(124I)iodanylpentyl-phenyl-dipyridin-3-ylphosphanium Chemical compound [124I]CCCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 ISENJYOZGPJSFA-HLVDMQJYSA-N 0.000 claims description 2
- ZHFPIUFQZIFMAH-LYUARWLDSA-N 5-(124I)iodanylpentyl-tri(pyrimidin-4-yl)phosphanium Chemical compound [124I]CCCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=NC=NC=C1 ZHFPIUFQZIFMAH-LYUARWLDSA-N 0.000 claims description 2
- SNODKASGWOBFFQ-NHTLRXQVSA-O [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 SNODKASGWOBFFQ-NHTLRXQVSA-O 0.000 claims description 2
- XPCUTKYTBPQZCX-BMILMZPDSA-O [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NN=NC=C2)C2=NN=NC=C2)C=C1 Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NN=NC=C2)C2=NN=NC=C2)C=C1 XPCUTKYTBPQZCX-BMILMZPDSA-O 0.000 claims description 2
- PMPKNDSNNQTQLY-AHGYSWSPSA-O [123I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 PMPKNDSNNQTQLY-AHGYSWSPSA-O 0.000 claims description 2
- NAIOZSUHDYITMZ-CKVWVWRJSA-N [123I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 Chemical compound [123I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 NAIOZSUHDYITMZ-CKVWVWRJSA-N 0.000 claims description 2
- RBXPCMUZVPPVAA-PIRNEEEYSA-N [123I]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 Chemical compound [123I]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 RBXPCMUZVPPVAA-PIRNEEEYSA-N 0.000 claims description 2
- GEHDMRPZUMUXES-HHRLKWFBSA-N [123I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 Chemical compound [123I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 GEHDMRPZUMUXES-HHRLKWFBSA-N 0.000 claims description 2
- GUEIFPFYBQUNAQ-BMILMZPDSA-N [123I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 Chemical compound [123I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 GUEIFPFYBQUNAQ-BMILMZPDSA-N 0.000 claims description 2
- PMPKNDSNNQTQLY-JJCFWKRZSA-O [124I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 Chemical compound [124I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 PMPKNDSNNQTQLY-JJCFWKRZSA-O 0.000 claims description 2
- XMBAVWKVQXDLOV-JVYRTNJDSA-N [124I]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 Chemical compound [124I]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 XMBAVWKVQXDLOV-JVYRTNJDSA-N 0.000 claims description 2
- NAIOZSUHDYITMZ-PSMZMCHFSA-N [124I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 Chemical compound [124I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 NAIOZSUHDYITMZ-PSMZMCHFSA-N 0.000 claims description 2
- GEHDMRPZUMUXES-QFAUIMOFSA-N [124I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 Chemical compound [124I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 GEHDMRPZUMUXES-QFAUIMOFSA-N 0.000 claims description 2
- JOJSKEBNODOLOE-XADVXNQXSA-O [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=CC=CC=C2)C=C1 Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=CC=CC=C2)C=C1 JOJSKEBNODOLOE-XADVXNQXSA-O 0.000 claims description 2
- SNODKASGWOBFFQ-ITIOBDTJSA-O [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 SNODKASGWOBFFQ-ITIOBDTJSA-O 0.000 claims description 2
- PMPKNDSNNQTQLY-BLVGABTOSA-O [131I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 PMPKNDSNNQTQLY-BLVGABTOSA-O 0.000 claims description 2
- XMBAVWKVQXDLOV-OWFUXLEOSA-N [131I]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 Chemical compound [131I]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 XMBAVWKVQXDLOV-OWFUXLEOSA-N 0.000 claims description 2
- NAIOZSUHDYITMZ-PZAKOYRYSA-N [131I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 Chemical compound [131I]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 NAIOZSUHDYITMZ-PZAKOYRYSA-N 0.000 claims description 2
- RBXPCMUZVPPVAA-TWYGLIRSSA-N [131I]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 Chemical compound [131I]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 RBXPCMUZVPPVAA-TWYGLIRSSA-N 0.000 claims description 2
- GEHDMRPZUMUXES-UOJYAKQPSA-N [131I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 Chemical compound [131I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 GEHDMRPZUMUXES-UOJYAKQPSA-N 0.000 claims description 2
- GUEIFPFYBQUNAQ-URWOLLDTSA-N [131I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 Chemical compound [131I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 GUEIFPFYBQUNAQ-URWOLLDTSA-N 0.000 claims description 2
- XXHQLTBGKINOJK-VNRZBHCFSA-O [18F]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 Chemical compound [18F]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 XXHQLTBGKINOJK-VNRZBHCFSA-O 0.000 claims description 2
- NXGXZMZYGMPEMB-SJPDSGJFSA-N [18F]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 Chemical compound [18F]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 NXGXZMZYGMPEMB-SJPDSGJFSA-N 0.000 claims description 2
- FYJOUKLFODUCNL-VEFBWTBNSA-O [76Br]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=CC=CC=C2)C=C1 Chemical compound [76Br]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=CC=CC=C2)C=C1 FYJOUKLFODUCNL-VEFBWTBNSA-O 0.000 claims description 2
- XTMQFWQKOSUDLO-QCAIBXFOSA-O [76Br]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C=2C=NC=CC=2)C=C1 Chemical compound [76Br]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C=2C=NC=CC=2)C=C1 XTMQFWQKOSUDLO-QCAIBXFOSA-O 0.000 claims description 2
- XPXONMAIRYGSIQ-PIRNEEEYSA-N [76Br]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 Chemical compound [76Br]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 XPXONMAIRYGSIQ-PIRNEEEYSA-N 0.000 claims description 2
- SNJOBNJHAWFTMP-BMILMZPDSA-N [76Br]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 Chemical compound [76Br]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 SNJOBNJHAWFTMP-BMILMZPDSA-N 0.000 claims description 2
- HELVSMXTZMSMPD-BMILMZPDSA-N diphenyl-(4-(76Br)bromanylbutyl)-(triazin-4-yl)phosphanium Chemical compound [76Br]CCCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 HELVSMXTZMSMPD-BMILMZPDSA-N 0.000 claims description 2
- CNJQCEAUHWLUOJ-BMILMZPDSA-N diphenyl-[2-(2-(76Br)bromanylethoxy)ethyl]-(triazin-4-yl)phosphanium Chemical compound [76Br]CCOCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 CNJQCEAUHWLUOJ-BMILMZPDSA-N 0.000 claims description 2
- TXBYHKNZRNQOTC-NHTLRXQVSA-N diphenyl-pyridin-3-yl-[2-(2-(76Br)bromanylethoxy)ethyl]phosphanium Chemical compound [76Br]CCOCC[P+](C=1C=NC=CC=1)(C1=CC=CC=C1)C1=CC=CC=C1 TXBYHKNZRNQOTC-NHTLRXQVSA-N 0.000 claims description 2
- FUZYZXHRSKNPEB-XNHRRBRJSA-O diphenyl-pyridin-3-yl-[4-[(6-(76Br)bromanylpyridine-3-carbonyl)amino]butyl]phosphanium Chemical compound [76Br]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 FUZYZXHRSKNPEB-XNHRRBRJSA-O 0.000 claims description 2
- SJTDHTQMURDXNA-PIRNEEEYSA-N diphenyl-pyrimidin-4-yl-(4-(76Br)bromanylbutyl)phosphanium Chemical compound [76Br]CCCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 SJTDHTQMURDXNA-PIRNEEEYSA-N 0.000 claims description 2
- LIDMQJQNXGBODE-PIRNEEEYSA-N diphenyl-pyrimidin-4-yl-[2-(2-(76Br)bromanylethoxy)ethyl]phosphanium Chemical compound [76Br]CCOCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 LIDMQJQNXGBODE-PIRNEEEYSA-N 0.000 claims description 2
- ADFUQTBPKJHQCX-HHRLKWFBSA-N phenyl-(4-(76Br)bromanylbutyl)-bis(triazin-4-yl)phosphanium Chemical compound [76Br]CCCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=CC=CC=C1 ADFUQTBPKJHQCX-HHRLKWFBSA-N 0.000 claims description 2
- QZRFFGKGWLSETO-UTFYOAIGSA-N phenyl-di(pyrimidin-4-yl)-(4-(76Br)bromanylbutyl)phosphanium Chemical compound [76Br]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=CC=CC=C1 QZRFFGKGWLSETO-UTFYOAIGSA-N 0.000 claims description 2
- ZONFUJZVITWDBN-PIRNEEEYSA-N phenyl-dipyridin-3-yl-(4-(76Br)bromanylbutyl)phosphanium Chemical compound [76Br]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C1=CC=CC=C1 ZONFUJZVITWDBN-PIRNEEEYSA-N 0.000 claims description 2
- HLTQDBUZWVULJH-AHGYSWSPSA-O phenyl-dipyridin-3-yl-[4-[(6-(76Br)bromanylpyridine-3-carbonyl)amino]butyl]phosphanium Chemical compound [76Br]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C2=CC=CC=C2)C=C1 HLTQDBUZWVULJH-AHGYSWSPSA-O 0.000 claims description 2
- SNPDINAGDBABHB-UHFFFAOYSA-N pyridin-3-ylphosphane Chemical compound PC1=CC=CN=C1 SNPDINAGDBABHB-UHFFFAOYSA-N 0.000 claims description 2
- HNQZOVLXJAOKSW-HHRLKWFBSA-N tri(pyrimidin-4-yl)-(4-(76Br)bromanylbutyl)phosphanium Chemical compound [76Br]CCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=NC=NC=C1 HNQZOVLXJAOKSW-HHRLKWFBSA-N 0.000 claims description 2
- KHQQVFLRYWUQNR-NSYCNWAXSA-O tri(pyrimidin-4-yl)-[4-[(6-(76Br)bromanylpyridine-3-carbonyl)amino]butyl]phosphanium Chemical compound [76Br]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 KHQQVFLRYWUQNR-NSYCNWAXSA-O 0.000 claims description 2
- QWRBGNHWBOHJPQ-BMILMZPDSA-N tripyridin-3-yl(4-(76Br)bromanylbutyl)phosphanium Chemical compound [76Br]CCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 QWRBGNHWBOHJPQ-BMILMZPDSA-N 0.000 claims description 2
- HXRGCRJVGWWNCU-UHFFFAOYSA-N diphenyl(pyridin-3-yl)phosphane Chemical compound C1=CC=CC=C1P(C=1C=NC=CC=1)C1=CC=CC=C1 HXRGCRJVGWWNCU-UHFFFAOYSA-N 0.000 claims 4
- GSURATNYYWBGPT-UHFFFAOYSA-N C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=NN=NC=C1 Chemical compound C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=NN=NC=C1 GSURATNYYWBGPT-UHFFFAOYSA-N 0.000 claims 3
- XMUIKZODBRYDCK-UHFFFAOYSA-N 2,3,4,5,6,9-hexahydro-1h-1,4,7-triazonine Chemical compound C1CNCC=NCCN1 XMUIKZODBRYDCK-UHFFFAOYSA-N 0.000 claims 2
- PCRQDJYCQCZYOI-CKVWVWRJSA-N 2-(2-(76Br)bromanylethoxy)ethyl-tris(triazin-4-yl)phosphanium Chemical compound [76Br]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 PCRQDJYCQCZYOI-CKVWVWRJSA-N 0.000 claims 2
- FCUAIWQYPCMHAI-UHFFFAOYSA-O 4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound C(C)(C)(C)OC(=O)NCCCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 FCUAIWQYPCMHAI-UHFFFAOYSA-O 0.000 claims 1
- DWWOWTKXFAGARM-UHFFFAOYSA-N 4-aminobutyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound NCCCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 DWWOWTKXFAGARM-UHFFFAOYSA-N 0.000 claims 1
- PQEOCMDBQKNIRF-UHFFFAOYSA-N C(C=C1)=CC=C1P(C1=NC=NC=C1)C1=NC=NC=C1 Chemical compound C(C=C1)=CC=C1P(C1=NC=NC=C1)C1=NC=NC=C1 PQEOCMDBQKNIRF-UHFFFAOYSA-N 0.000 claims 1
- WKQXEWRZPYAVMU-UHFFFAOYSA-N C1=CC(P(C2=NC=CC=N2)C2=NC=CC=N2)=NC=C1 Chemical compound C1=CC(P(C2=NC=CC=N2)C2=NC=CC=N2)=NC=C1 WKQXEWRZPYAVMU-UHFFFAOYSA-N 0.000 claims 1
- ZEOKRWJKJBUXHU-UHFFFAOYSA-O CC(C)(C)OC(NCCCCC1=C(CCCCNC(OC(C)(C)C)=O)N=NN=C1[P+](C1=NC=CC=C1)(C1=NN=NC=C1)C1=NN=NC=C1)=O Chemical compound CC(C)(C)OC(NCCCCC1=C(CCCCNC(OC(C)(C)C)=O)N=NN=C1[P+](C1=NC=CC=C1)(C1=NN=NC=C1)C1=NN=NC=C1)=O ZEOKRWJKJBUXHU-UHFFFAOYSA-O 0.000 claims 1
- DMXWIAGXDIIIMV-UHFFFAOYSA-O CC(C)(C)OC(NCCCC[P+](C1=CC=CC=C1)(C1=CC=CN=C1)C1=CC=CN=C1)=O Chemical compound CC(C)(C)OC(NCCCC[P+](C1=CC=CC=C1)(C1=CC=CN=C1)C1=CC=CN=C1)=O DMXWIAGXDIIIMV-UHFFFAOYSA-O 0.000 claims 1
- YXBMYYLONRIXND-UHFFFAOYSA-N N1=NN=C(C=C1)PC1=NN=NC=C1 Chemical compound N1=NN=C(C=C1)PC1=NN=NC=C1 YXBMYYLONRIXND-UHFFFAOYSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 238000012879 PET imaging Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000002243 precursor Substances 0.000 abstract description 4
- 238000003384 imaging method Methods 0.000 abstract description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 61
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 28
- 238000004440 column chromatography Methods 0.000 description 25
- 238000000746 purification Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- VYVPNTJBGPQTFA-UHFFFAOYSA-N 2-[2-(4-methylphenyl)sulfonyloxyethoxy]ethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCOCCOS(=O)(=O)C1=CC=C(C)C=C1 VYVPNTJBGPQTFA-UHFFFAOYSA-N 0.000 description 15
- GMMNFKKJUMYAPM-UHFFFAOYSA-N 5-(4-methylphenyl)sulfonyloxypentyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCCCCOS(=O)(=O)C1=CC=C(C)C=C1 GMMNFKKJUMYAPM-UHFFFAOYSA-N 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 13
- WBSGGWFVABZVGV-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCCNC(=O)OC(C)(C)C)C=C1 WBSGGWFVABZVGV-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- VQTKDNCYXCDOSB-UHFFFAOYSA-N 2-(2-fluoroethoxy)ethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCOCCF)C=C1 VQTKDNCYXCDOSB-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 7
- OOWSDKUFKGVADH-UHFFFAOYSA-N 1-diphenylphosphoryloxy-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1OP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 OOWSDKUFKGVADH-UHFFFAOYSA-N 0.000 description 6
- 239000002738 chelating agent Substances 0.000 description 6
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 5
- RGFVAYFLDXQERH-UHFFFAOYSA-N 5-fluoropentyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCCCF)C=C1 RGFVAYFLDXQERH-UHFFFAOYSA-N 0.000 description 5
- SHZABHICTIBVMC-UHFFFAOYSA-N CC1=CC=C(CCCCCF)C=C1 Chemical compound CC1=CC=C(CCCCCF)C=C1 SHZABHICTIBVMC-UHFFFAOYSA-N 0.000 description 5
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 5
- ALQSHHUCVQOPAS-UHFFFAOYSA-N Pentane-1,5-diol Chemical compound OCCCCCO ALQSHHUCVQOPAS-UHFFFAOYSA-N 0.000 description 5
- 239000006087 Silane Coupling Agent Substances 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- SVABQOITNJTVNJ-UHFFFAOYSA-N diphenyl-2-pyridylphosphine Chemical compound C1=CC=CC=C1P(C=1N=CC=CC=1)C1=CC=CC=C1 SVABQOITNJTVNJ-UHFFFAOYSA-N 0.000 description 5
- 150000004714 phosphonium salts Chemical class 0.000 description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
- LIYMTLVBAVHPBU-UHFFFAOYSA-N tert-butyl n-(4-hydroxybutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCO LIYMTLVBAVHPBU-UHFFFAOYSA-N 0.000 description 5
- LDSMXGPRCFQXSK-UHFFFAOYSA-N tripyridin-2-ylphosphane Chemical compound N1=CC=CC=C1P(C=1N=CC=CC=1)C1=CC=CC=N1 LDSMXGPRCFQXSK-UHFFFAOYSA-N 0.000 description 5
- RIBNXKYQMSBWFD-UHFFFAOYSA-N tripyridin-4-ylphosphane Chemical compound C1=NC=CC(P(C=2C=CN=CC=2)C=2C=CN=CC=2)=C1 RIBNXKYQMSBWFD-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000009206 nuclear medicine Methods 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 4
- 239000012217 radiopharmaceutical Substances 0.000 description 4
- 229940121896 radiopharmaceutical Drugs 0.000 description 4
- 230000002799 radiopharmaceutical effect Effects 0.000 description 4
- PXYCJKZSCDFXLR-UHFFFAOYSA-N tris[4-(trifluoromethyl)phenyl]phosphane Chemical compound C1=CC(C(F)(F)F)=CC=C1P(C=1C=CC(=CC=1)C(F)(F)F)C1=CC=C(C(F)(F)F)C=C1 PXYCJKZSCDFXLR-UHFFFAOYSA-N 0.000 description 4
- WBOMQKKMPFCWEO-GJQNQZCXSA-N 5-(18F)fluoranylpentyl(tripyridin-4-yl)phosphanium Chemical compound [18F]CCCCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 WBOMQKKMPFCWEO-GJQNQZCXSA-N 0.000 description 3
- YWNKNMSPWJKZQO-VNRZBHCFSA-N 5-(18F)fluoranylpentyl-diphenyl-pyridin-2-ylphosphanium Chemical class [18F]CCCCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 YWNKNMSPWJKZQO-VNRZBHCFSA-N 0.000 description 3
- XUKFHRNWSCWRFI-UHFFFAOYSA-N FCCOCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 Chemical class FCCOCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 XUKFHRNWSCWRFI-UHFFFAOYSA-N 0.000 description 3
- BEFUMQHJQKBTRH-FMLNDMEQSA-N [18F]CCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F Chemical compound [18F]CCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F BEFUMQHJQKBTRH-FMLNDMEQSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 3
- CASAVLAOVCOUSA-KPVNRNJOSA-N 2-(2-(18F)fluoranylethoxy)ethyl-tris[4-(trifluoromethyl)phenyl]phosphanium Chemical compound [18F]CCOCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F CASAVLAOVCOUSA-KPVNRNJOSA-N 0.000 description 2
- KHFNYCGALGTCDH-UHFFFAOYSA-O 4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl-tripyridin-2-ylphosphanium Chemical class C(C)(C)(C)OC(=O)NCCCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 KHFNYCGALGTCDH-UHFFFAOYSA-O 0.000 description 2
- ALDJIBCTKNOEQU-UHFFFAOYSA-O 4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl-tripyridin-3-ylphosphanium Chemical class C(C)(C)(C)OC(=O)NCCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 ALDJIBCTKNOEQU-UHFFFAOYSA-O 0.000 description 2
- PALUUNDIYKTGQP-UHFFFAOYSA-N 4-aminobutyl-diphenyl-pyridin-2-ylphosphanium Chemical class NCCCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 PALUUNDIYKTGQP-UHFFFAOYSA-N 0.000 description 2
- WBOMQKKMPFCWEO-UHFFFAOYSA-N 5-fluoropentyl(tripyridin-4-yl)phosphanium Chemical class FCCCCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 WBOMQKKMPFCWEO-UHFFFAOYSA-N 0.000 description 2
- YWNKNMSPWJKZQO-UHFFFAOYSA-N 5-fluoropentyl-diphenyl-pyridin-2-ylphosphanium Chemical class FCCCCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 YWNKNMSPWJKZQO-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- JQADANBUVXYZFR-UHFFFAOYSA-O C(C)(C)(C)OC(=O)NCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F Chemical class C(C)(C)(C)OC(=O)NCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F JQADANBUVXYZFR-UHFFFAOYSA-O 0.000 description 2
- GSBRQAMZFKQYJG-UHFFFAOYSA-O C(C)(C)(C)OC(=O)NCCCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 Chemical class C(C)(C)(C)OC(=O)NCCCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 GSBRQAMZFKQYJG-UHFFFAOYSA-O 0.000 description 2
- BEFUMQHJQKBTRH-UHFFFAOYSA-N FCCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F Chemical class FCCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F BEFUMQHJQKBTRH-UHFFFAOYSA-N 0.000 description 2
- PWXFCYXXNMIXRF-UHFFFAOYSA-N FCCCCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 Chemical class FCCCCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 PWXFCYXXNMIXRF-UHFFFAOYSA-N 0.000 description 2
- PRTGATZAXAWVCH-UHFFFAOYSA-N FCCCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 Chemical class FCCCCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 PRTGATZAXAWVCH-UHFFFAOYSA-N 0.000 description 2
- CZGXBFSCHRLIEJ-UHFFFAOYSA-N FCCOCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical class FCCOCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 CZGXBFSCHRLIEJ-UHFFFAOYSA-N 0.000 description 2
- PRFKKRCXABARPL-UHFFFAOYSA-N FCCOCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 Chemical class FCCOCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 PRFKKRCXABARPL-UHFFFAOYSA-N 0.000 description 2
- RBNQMJPEQMHIJZ-UHFFFAOYSA-N FCCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 Chemical class FCCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 RBNQMJPEQMHIJZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- NTKNREVRFPRNMN-UHFFFAOYSA-N NCCCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 Chemical class NCCCC[P+](C1=CC=NC=C1)(C1=CC=NC=C1)C1=CC=NC=C1 NTKNREVRFPRNMN-UHFFFAOYSA-N 0.000 description 2
- JBOMJOMACSOGBJ-AHGYSWSPSA-O [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 JBOMJOMACSOGBJ-AHGYSWSPSA-O 0.000 description 2
- CZGXBFSCHRLIEJ-KVTPGWOSSA-N [18F]CCOCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical class [18F]CCOCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 CZGXBFSCHRLIEJ-KVTPGWOSSA-N 0.000 description 2
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 2
- 125000006267 biphenyl group Chemical group 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002586 coronary angiography Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000002592 echocardiography Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- KFQNYOBJRDENET-BMILMZPDSA-N 2-(2-(123I)iodanylethoxy)ethyl-diphenyl-(triazin-4-yl)phosphanium Chemical compound [123I]CCOCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 KFQNYOBJRDENET-BMILMZPDSA-N 0.000 description 1
- SOCOYPSOFWZJSX-NHTLRXQVSA-N 2-(2-(123I)iodanylethoxy)ethyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [123I]CCOCC[P+](C=1C=NC=CC=1)(C1=CC=CC=C1)C1=CC=CC=C1 SOCOYPSOFWZJSX-NHTLRXQVSA-N 0.000 description 1
- LYJSQWJEEUQPHJ-PIRNEEEYSA-N 2-(2-(123I)iodanylethoxy)ethyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [123I]CCOCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 LYJSQWJEEUQPHJ-PIRNEEEYSA-N 0.000 description 1
- OVZWAQKIZALUFC-CKVWVWRJSA-N 2-(2-(123I)iodanylethoxy)ethyl-tris(triazin-4-yl)phosphanium Chemical compound [123I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 OVZWAQKIZALUFC-CKVWVWRJSA-N 0.000 description 1
- KFQNYOBJRDENET-ZEMUAQPOSA-N 2-(2-(124I)iodanylethoxy)ethyl-diphenyl-(triazin-4-yl)phosphanium Chemical compound [124I]CCOCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 KFQNYOBJRDENET-ZEMUAQPOSA-N 0.000 description 1
- SOCOYPSOFWZJSX-HLVDMQJYSA-N 2-(2-(124I)iodanylethoxy)ethyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [124I]CCOCC[P+](C=1C=NC=CC=1)(C1=CC=CC=C1)C1=CC=CC=C1 SOCOYPSOFWZJSX-HLVDMQJYSA-N 0.000 description 1
- LYJSQWJEEUQPHJ-XNXCDXPKSA-N 2-(2-(124I)iodanylethoxy)ethyl-diphenyl-pyrimidin-4-ylphosphanium Chemical compound [124I]CCOCC[P+](C1=NC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 LYJSQWJEEUQPHJ-XNXCDXPKSA-N 0.000 description 1
- OVZWAQKIZALUFC-PSMZMCHFSA-N 2-(2-(124I)iodanylethoxy)ethyl-tris(triazin-4-yl)phosphanium Chemical compound [124I]CCOCC[P+](C1=NN=NC=C1)(C1=NN=NC=C1)C1=NN=NC=C1 OVZWAQKIZALUFC-PSMZMCHFSA-N 0.000 description 1
- ATUYORXNFCGADC-LRFGSCOBSA-N 2-(2-(18F)fluoranylethoxy)ethyl-diphenyl-(triazin-4-yl)phosphanium Chemical compound [18F]CCOCC[P+](C1=NN=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 ATUYORXNFCGADC-LRFGSCOBSA-N 0.000 description 1
- CASAVLAOVCOUSA-UHFFFAOYSA-N 2-(2-fluoroethoxy)ethyl-tris[4-(trifluoromethyl)phenyl]phosphanium Chemical class FCCOCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F CASAVLAOVCOUSA-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- YBNRDAJJMFTAHA-VNRZBHCFSA-N 4-(18F)fluoranylpentyl-diphenyl-pyridin-4-ylphosphanium Chemical compound [18F]C(CCC[P+](C1=CC=NC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)C YBNRDAJJMFTAHA-VNRZBHCFSA-N 0.000 description 1
- CJKVPTBYBAYEMU-UHFFFAOYSA-O 4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl-diphenyl-pyridin-3-ylphosphanium Chemical compound C(C)(C)(C)OC(=O)NCCCC[P+](C=1C=NC=CC=1)(C1=CC=CC=C1)C1=CC=CC=C1 CJKVPTBYBAYEMU-UHFFFAOYSA-O 0.000 description 1
- KMBYXRNPSMFKPE-XNHRRBRJSA-O 4-[(6-(123I)iodanylpyridine-3-carbonyl)amino]butyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 KMBYXRNPSMFKPE-XNHRRBRJSA-O 0.000 description 1
- TWAJWGVBWQTHMY-QCAIBXFOSA-O 4-[(6-(123I)iodanylpyridine-3-carbonyl)amino]butyl-tripyridin-3-ylphosphanium Chemical compound [123I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C=2C=NC=CC=2)C=C1 TWAJWGVBWQTHMY-QCAIBXFOSA-O 0.000 description 1
- KMBYXRNPSMFKPE-LUICUPIMSA-O 4-[(6-(124I)iodanylpyridine-3-carbonyl)amino]butyl-diphenyl-pyridin-3-ylphosphanium Chemical compound [124I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1 KMBYXRNPSMFKPE-LUICUPIMSA-O 0.000 description 1
- WAOFOYGNTKKNIT-RQUWHVIDSA-O 4-[(6-(124I)iodanylpyridine-3-carbonyl)amino]butyl-tri(pyrimidin-4-yl)phosphanium Chemical compound [124I]C1=NC=C(C(=O)NCCCC[P+](C2=NC=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 WAOFOYGNTKKNIT-RQUWHVIDSA-O 0.000 description 1
- TWAJWGVBWQTHMY-CBAPBOBXSA-O 4-[(6-(124I)iodanylpyridine-3-carbonyl)amino]butyl-tripyridin-3-ylphosphanium Chemical compound [124I]C1=NC=C(C(=O)NCCCC[P+](C=2C=NC=CC=2)(C=2C=NC=CC=2)C=2C=NC=CC=2)C=C1 TWAJWGVBWQTHMY-CBAPBOBXSA-O 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- BPPBTNIWHATOKD-UHFFFAOYSA-O C(C)(C)(C)OC(=O)NCCCCC=1C(=C(C=CC=1)[P+](C1=NN=NC=C1)(C1=CC=CC=C1)CCCCNC(=O)OC(C)(C)C)C1=NC=CC=C1 Chemical compound C(C)(C)(C)OC(=O)NCCCCC=1C(=C(C=CC=1)[P+](C1=NN=NC=C1)(C1=CC=CC=C1)CCCCNC(=O)OC(C)(C)C)C1=NC=CC=C1 BPPBTNIWHATOKD-UHFFFAOYSA-O 0.000 description 1
- YKICKAPWYHTFKW-UHFFFAOYSA-O C(C)(C)(C)OC(=O)NCCCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical class C(C)(C)(C)OC(=O)NCCCC[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 YKICKAPWYHTFKW-UHFFFAOYSA-O 0.000 description 1
- PJCUTFSEMYRGCA-UHFFFAOYSA-O C(C)(C)(C)OC(=O)NCCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=NC=NC=C1 Chemical compound C(C)(C)(C)OC(=O)NCCCC[P+](C1=NC=NC=C1)(C1=NC=NC=C1)C1=NC=NC=C1 PJCUTFSEMYRGCA-UHFFFAOYSA-O 0.000 description 1
- VURZPKMQGDUNGH-UHFFFAOYSA-N C(C=C1)=CC=C1P(C1=NN=NC=C1)C1=NN=NC=C1 Chemical compound C(C=C1)=CC=C1P(C1=NN=NC=C1)C1=NN=NC=C1 VURZPKMQGDUNGH-UHFFFAOYSA-N 0.000 description 1
- IXOBTZYKUPRDBA-LMANFOLPSA-N C1=CC(=CN=C1)PCCCC[18F] Chemical compound C1=CC(=CN=C1)PCCCC[18F] IXOBTZYKUPRDBA-LMANFOLPSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- YHLIIHKXAANGEH-UHFFFAOYSA-N NCCCCC1=C(C(=C(C=C1)[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=NC=CC=C1)C1=CC=CC=C1)C1=CC=CC=C1 Chemical class NCCCCC1=C(C(=C(C=C1)[P+](C1=NC=CC=C1)(C1=CC=CC=C1)C1=NC=CC=C1)C1=CC=CC=C1)C1=CC=CC=C1 YHLIIHKXAANGEH-UHFFFAOYSA-N 0.000 description 1
- NQGQADFGHRYROR-UHFFFAOYSA-N NCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F Chemical class NCCCC[P+](C1=CC=C(C=C1)C(F)(F)F)(C1=CC=C(C=C1)C(F)(F)F)C1=CC=C(C=C1)C(F)(F)F NQGQADFGHRYROR-UHFFFAOYSA-N 0.000 description 1
- PPXWEPWPQDWONU-UHFFFAOYSA-N NCCCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 Chemical class NCCCC[P+](C1=NC=CC=C1)(C1=NC=CC=C1)C1=NC=CC=C1 PPXWEPWPQDWONU-UHFFFAOYSA-N 0.000 description 1
- GUEIFPFYBQUNAQ-ZEMUAQPOSA-N [124I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 Chemical compound [124I]CCOCC[P+](C=1C=NC=CC=1)(C=1C=NC=CC=1)C=1C=NC=CC=1 GUEIFPFYBQUNAQ-ZEMUAQPOSA-N 0.000 description 1
- XPCUTKYTBPQZCX-URWOLLDTSA-O [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NN=NC=C2)C2=NN=NC=C2)C=C1 Chemical compound [131I]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NN=NC=C2)C2=NN=NC=C2)C=C1 XPCUTKYTBPQZCX-URWOLLDTSA-O 0.000 description 1
- DLAKYBWPASHDST-KVTPGWOSSA-O [18F]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 Chemical compound [18F]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 DLAKYBWPASHDST-KVTPGWOSSA-O 0.000 description 1
- GCILJGLBCJTURM-BMILMZPDSA-O [76Br]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NN=NC=C2)C2=NN=NC=C2)C=C1 Chemical compound [76Br]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NN=NC=C2)C2=NN=NC=C2)C=C1 GCILJGLBCJTURM-BMILMZPDSA-O 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- HSANJBZMPJBTRT-UHFFFAOYSA-N acetic acid;1,4,7,10-tetrazacyclododecane Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.C1CNCCNCCNCCN1 HSANJBZMPJBTRT-UHFFFAOYSA-N 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical class [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- JTOWPJUDLJVBHV-NHTLRXQVSA-O di(pyrimidin-4-yl)-[4-[(6-(76Br)bromanylpyridine-3-carbonyl)amino]butyl]-(triazin-4-yl)phosphanium Chemical compound [76Br]C1=NC=C(C(=O)NCCCC[P+](C2=NN=NC=C2)(C2=NC=NC=C2)C2=NC=NC=C2)C=C1 JTOWPJUDLJVBHV-NHTLRXQVSA-O 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 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
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- ANIDRZQDJXBHHM-UHFFFAOYSA-N pyridin-2-ylphosphane Chemical compound PC1=CC=CC=N1 ANIDRZQDJXBHHM-UHFFFAOYSA-N 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000008054 sulfonate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- FIBZWZNESGFSRR-UHFFFAOYSA-N tert-butyl N-(4-phosphanylbutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCP FIBZWZNESGFSRR-UHFFFAOYSA-N 0.000 description 1
- 229960004113 tetrofosmin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005490 tosylate group Chemical class 0.000 description 1
- HXVCCJDKPYRLJG-UHFFFAOYSA-N triazin-4-ylphosphane Chemical compound PC1=NN=NC=C1 HXVCCJDKPYRLJG-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical class C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- 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
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/004—Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pyridine Compounds (AREA)
Abstract
본 발명은 심장의 효율적인 조영을 위한 방사성 화합물의 제조를 위한 전구체 화합물 및 상기 전구체 화합물을 이용하여 제조된 방사성 화합물 및 그의 PET 조영용 조영제로서의 용도를 제공한다. The present invention provides a precursor compound for the production of a radioactive compound for efficient imaging of the heart, a radioactive compound prepared using the precursor compound, and its use as contrast medium for PET imaging.
Description
본 발명은 신규 화합물 및 그의 용도에 관한 것으로서, 보다 구체적으로는 PET 조영용 신규 화합물 및 그의 용도에 관한 것이다. The present invention relates to novel compounds and uses thereof, and more particularly to novel compounds for PET imaging and uses thereof.
관상동맥질환은 현재 우리나라 사망 원인 중 3-4위를 차지할 정도로 중요한 위치를 차지하고 있다. 특히 지난 20여년간 그 유병률이 5배 가까이 빠르게 증가하고 있으며 이는 세계적인 추세에 미루어 볼 때 더욱더 가속화가 될 것이다. 관상동맥질환의 증상은 45-50세 이후에 주로 나타나지만, 최근 들어 관상동맥질환의 유병률이 증가하고, 젊은 환자에서 증상이 발생하는 경우도 늘어나고 있어 점차 조기 진단 및 예방의 중요성이 커지고 있다.Coronary artery disease accounts for 3-4 of the causes of death in Korea. In particular, the prevalence has increased nearly five times over the past two decades, and this will accelerate further in the global trend. Symptoms of coronary artery disease appear mainly after 45-50 years of age, but the prevalence of coronary artery disease has increased in recent years, and the number of cases with symptoms in younger patients has been increasing, and the importance of early diagnosis and prevention is gradually increasing.
관상동맥질환은 운동부하 검사, 심장 초음파 검사, 관상동맥 조영술, 핵의학 검사의 방법들을 통해서 조기진단을 시행한다. 하지만 운동부하 검사는 협심증의 경우 증상이 없는 안정 상태에서 검사할 경우 이상 소견이 나타나지 않을 수 있으며 심장 초음파 검사는 심장을 완전히 포함하지 못하는 경우 그 크기나 기능을 확실히 계산하지 못하며 화상의 입수에서부터 결과를 보는데 까지 시간이 많이 걸리는 단점이 있다. 또한 관상동맥 조영술은 0.1% 미만에서 사망이나 급성심근경색증 등의 합병증을 일으킬 수 있어 협심증을 의심하는 모든 환자에게 시행할 수는 없다. 그에 비해 극소량의 방사성 의약품을 팔의 정맥에 주입하고 이것이 심장 근육에 흡수되는 양상을 촬영해 확인하는 핵의학적 방법은 심장에서 방사성물질의 흡수가 적은 부위가 혈류가 부족한 부분을 의미하므로 운동부하 검사에 비해 이상 부위를 빠르게 구분할 수 있으며 극소량의 방사성의약품을 사용하기 때문에 안전성 역시 높다고 할 수 있다.Coronary artery disease is diagnosed early by methods of exercise testing, echocardiography, coronary angiography, and nuclear medicine. However, exercise testing may not reveal any abnormality when examined in a stable state with no symptoms in angina pectoris. Echocardiography can not reliably calculate the size or function of heart if it does not completely contain the heart. There is a drawback that it takes much time to see. In addition, coronary angiography can cause complications such as death or acute myocardial infarction at less than 0.1%, so it can not be applied to all patients suspected of angina. In contrast, a nuclear medicine method that injects a very small amount of radiopharmaceuticals into the veins of the arm and captures the patterns of absorption into the heart muscle is a part of the heart where there is less absorption of radioactive material, And the use of a very small amount of radiopharmaceuticals makes it safer.
현재 사용되는 핵의학적 방법은 단일광자방출 전산화 단층촬영(Single photon emission computed tomography, SPECT)를 이용하는 것이며, 대표적으로 심장 영상을 확인하기 위해 사용되는 방사성 의약품은 201Tl 착화합물이나 99mTc-sestamibi, 99mTc-tetrofosmin이 사용된다. 하지만 조직의 감쇄현상을 보정할 수 있는 정형화된 방법이 없으며, 특히 심장 밑에 바로 위치한 간에 의한 광자의 산란 현상 때문에 정확한 진단의 어려움이 있다. 따라서 이러한 단점을 극복하여 핵의학적 진단 방법의 효과를 극대화하기 위해서는 SPECT가 아닌 양전자 방출 단층촬영(Positron Emission Tomography, PET)을 이용할 수 있어야 하며 이를 위해서는 양전자 방출 핵종이 표지된 방사성의약품이 필요하다.Currently, the nuclear medicine method used is single photon emission computed tomography (SPECT). Typically, the radiopharmaceutical used to identify the heart image is 201 Tl complex, 99m Tc-sestamibi, 99m Tc -tetrofosmin is used. However, there is no formalized method for correcting the attenuation of tissues, and there is a difficulty in accurate diagnosis due to the photon scattering phenomenon, especially located directly under the heart. Therefore, in order to overcome these shortcomings and maximize the effect of nuclear medicine diagnosis, Positron Emission Tomography (PET), not SPECT, should be used. For this, radiopharmaceuticals labeled with positron emission nuclei are needed.
이와 관련하여, 다른 심장 영상 확인을 위해 양전자 방출 핵종인 11C을 표지한 구조가 다른 지방 친화성 양이온 물질을 합성하여, 이 화합물로 개의 dynamic PET 연구를 시행하여 심근에서의 오랜 머무름 시간을 보이는 것과 혈액과 폐에서 소량의 방사성 물질을 확인할 수 있었음이 보고된 바 있다(Rimoldi et al., Eur. J. Nucl. Med. Mol. Imaging 34(2): 197-205, 2007. 그러나 11C의 반감기가 20분이기 때문에 임상에서의 응용을 하기 위해서는 많은 제약이 있다.In this regard, for the purpose of identifying other cardiac images, we have synthesized a lipophilic cationic material with a structure that has a positron emission nucleus, 11 C, which has a structure that shows long retention time in the myocardium (Rimoldi et al ., Eur., J. Nucl. Med., Imaging 34 (2): 197-205, 2007) . However, the half-life of 11 C Is 20 minutes, there are many limitations to apply in clinical applications.
이에 본 발명자들은 Tetraphenylphosphonium(TPP) 염 기반의 18F를 포함하는 PET용 조영제를 개발한 바 있다(특허 제1172157호). Accordingly, the present inventors have developed a contrast agent for PET containing 18 F based on tetraphenylphosphonium (TPP) salt (Patent No. 1172157).
그러나 상기 TPP 염 기반의 PET용 조영제의 경우, 심장선택성이 다소 떨어지고 뼈에서의 섭취율이 높은 편일 뿐만 아니라, 심장에 인접한 간에서의 높은 섭취율로 인해서 심장 영상 분석 시 문제를 일으킬 가능성이 존재한다. However, the TPP salt-based contrast agent for PET has a problem in that it has a low cardiac selectivity and a high uptake rate in bones, as well as a problem in heart image analysis due to a high uptake rate in the liver adjacent to the heart.
본 발명은 상기와 같은 문제점을 포함하여 여러 문제점들을 해결하기 위한 것으로서, 심장섭취도가 향상되고 뼈흡수율이 낮으며, 간에서의 제거율이 향상된 개선된 신규 PET 조영용 화합물을 제공하는 것을 목적으로 한다. It is an object of the present invention to provide an improved novel PET imaging compound having improved cardiac uptake, lowered bone uptake rate, and improved liver removal rate.
또한 본 발명은 상기 화합물를 포함하는 PET 조영제 등 상기 화합물의 다양한 용도를 제공하는 것을 제공하는 것을 목적으로 한다.It is another object of the present invention to provide various uses of the above-mentioned compounds such as a PET contrast agent containing the compound.
그러나 이러한 과제는 예시적인 것으로, 이에 의해 본 발명의 범위가 한정되는 것은 아니다. However, these problems are exemplary and do not limit the scope of the present invention.
본 발명의 다른 일 관점에 따르면, 하기 화학식 I을 갖는 신규 화합물 또는 그의 허용가능한 염이 제공된다:According to another aspect of the present invention there is provided a novel compound having the formula (I): < EMI ID =
(상기 식에서 X1은 O, S, N, 또는 C이고, X2 내지 X10은 각각 독립적으로 C 또는 N으로, 상기 X2 내지 X10는 독립적으로 C 또는 N이고, 상기 L1 및 L2는 각각 독립적으로 없거나 탄소수 1 내지 6인 알킬렌기, 알케닐렌기, 알키닐렌기, 탄소수 6 또는 10의 아릴렌기, 탄소수 2 내지 6의 알킬렌 옥사이드기 또는 그의 반복단위 2 내지 4의 중합체, 카르복실 에스테르기, 숙시니미딜기, 카르보닐기 및 
본 발명의 다른 일 관점에 따르면, 상기 화합물 또는 그의 허용가능한 염의 R1 또는 상기 R1 내의 적어도 하나 이상의 수소가 118F, 76Br, 123I, 124I, 및 131I로 구성되는 군으로부터 선택되는 하나 이상의 방사성 동위원소로 치환되거나, 상기 방사성 동위원소를 포함하는 탄소수 2 내지 6의 할로알킬, 할로폴리에틸렌 옥사이드, 할로알킬 티올, 할로폴리에틸렌옥사이드 티올과 공유결합에 의해 연결된, 방사성 화합물 또는 그의 허용가능한 염이 제공된다.According to another aspect of the present invention there is provided a compound of formula I wherein R 1 of said compound or an acceptable salt thereof or at least one hydrogen in said R 1 is selected from the group consisting of 118 F, 76 Br, 123 I, 124 I, and 131 I A radioactive compound or an acceptable salt thereof, which is substituted with at least one radioisotope, or is linked by a covalent bond with a haloalkyl, halopolyethylene oxide, haloalkylthiol or halopolyethylene oxide thiol having 2 to 6 carbon atoms containing the radioactive isotope / RTI >
본 발명의 다른 일 관점에 따르면, 하기 화학식 II의 구조를 갖는 화합물 및 방사성 동위 금속원소를 포함하는 방사성 금속 착물이 제공된다:According to another aspect of the present invention there is provided a radial metal complex comprising a compound having a structure of formula II and a radioisotope element:
(상기 식에서 X1은 O, S, N, 또는 C이고, X2 내지 X10은 각각 독립적으로 C 또는 N으로, 상기 X2 내지 X10는 독립적으로 C 또는 N이며, 상기 L1 및 L2는 각각 독립적으로 없거나 탄소수 1 내지 6인 알킬렌기, 알케닐렌기, 알키닐렌기, 탄소수 6 또는 10의 아릴렌기, 탄소수 2 내지 6의 알킬렌 옥사이드기 또는 그의 반복단위 2 내지 4의 중합체, 카르복실 에스테르기, 숙시니미딜기, 카르보닐기 및 
본 발명의 다른 일 관점에 따르면, 상기 화학식 1의 화합물 또는 그의 허용가능한 염의 R1 또는 상기 R1 내의 적어도 하나 이상의 수소원자를 118F, 76Br, 123I, 124I 및 131I로 구성되는 군으로부터 선택되는 하나 이상의 방사성 동위원소로 치환하는 단계를 포함하는 방사성 화합물 또는 그의 허용가능한 염의 제조방법이 제공된다.According to another aspect of the invention, the group consisting of at least one hydrogen atom in the formula (I) compound or a acceptable salt thereof R 1 or the R 1 to 118 F, 76 Br, 123 I , 124 I and 131 I With one or more radioactive isotopes selected from the group consisting of: < RTI ID = 0.0 > (I) < / RTI >
본 발명의 다른 일 관점에 따르면, 상기 방사성 화합물 또는 그의 허용가능한 염 또는 상기 방사성 금속 착물을 유효성분으로 포함하는 양전자 방출 단층촬영(PET)용 조영제가 제공된다.According to another aspect of the present invention, there is provided a contrast agent for positron emission tomography (PET) comprising the radioactive compound or an acceptable salt thereof or the radioactive metal complex as an active ingredient.
본 발명의 일 실시예에 따른 신규 화합물 및 그의 허용가능한 염은 PET 조영용 방사성 화합물의 제조를 위한 전구체로 사용가능하며, 상기 전구체를 이용하여 제조된 방사성 화합물은 심장 표적능이 향상되고, 뼈 흡수능이 약화되어 보다 양전자 단층 촬영시 선명한 심장영상을 얻을 수 있게 해준다. 그러나, 본 발명의 범위는 상기 효과에 의해 제한되는 것은 아니다.The novel compounds and their acceptable salts according to one embodiment of the present invention can be used as precursors for the production of radiological compounds for PET imaging and the radioactive compounds prepared using the precursors have improved cardiac targeting capacity and reduced bone resorption capacity This allows us to obtain clear cardiac images during positron tomography. However, the scope of the present invention is not limited by the above effects.
도 1은 종래 특허 제1172157호에 기재된 트리포스포니움염([18F]FPTP)을 이용하여 수득한 실험동물의 양전자 단층 촬영 영상이다.
도 2는 본 발명의 일 실시예에 따른 [18F]FEPP를 이용하여 수득한 실험동물의 양전자 단층 촬영 영상이다.
도 3은 본 발명의 일 실시예에 따른 [18F]FDPP를 이용하여 수득한 실험동물의 양전자 단층 촬영 영상이다.FIG. 1 is a positron emission tomographic image of an experimental animal obtained using the triphosphonium salt ([ 18 F] FPTP) described in the conventional patent No. 1172157.
2 is a positron emission tomographic image of an experimental animal obtained using [ 18 F] FEPP according to an embodiment of the present invention.
3 is a positron emission tomographic image of an experimental animal obtained using [ 18 F] FDPP according to an embodiment of the present invention.
본 발명의 다른 일 관점에 따르면, 하기 화학식 I을 갖는 신규 화합물 또는 그의 허용가능한 염이 제공된다:According to another aspect of the present invention there is provided a novel compound having the formula (I): < EMI ID =
(상기 식에서 X1은 O, S, N, 또는 C이고, X2 내지 X10은 각각 독립적으로 C 또는 N으로, 상기 X2 내지 X10는 독립적으로 C 또는 N이고, 상기 L1 및 L2는 각각 독립적으로 없거나 탄소수 1 내지 6인 알킬렌기, 알케닐렌기, 알키닐렌기, 탄소수 6 또는 10의 아릴렌기, 탄소수 2 내지 6의 알킬렌 옥사이드기 또는 그의 반복단위 2 내지 4의 중합체, 카르복실 에스테르기, 숙시니미딜기, 카르보닐기 및 
단, 상기 화합물에서, R2 내지 R4가 모두 수소일 경우에는 상기 X2 내지 X10 중 적어도 하나 이상은 N이다.With the proviso that when all of R 2 to R 4 are hydrogen, at least one of X 2 to X 10 is N.
상기 화합물은 하기와 같은 반응식에 의해 제조가 될 수 있다:The compound can be prepared by the following reaction scheme:
상기 화합물 또는 그의 허용가능한 염은 (4-((tert-butoxycarbonyl)amino)butyl)diphenyl(pyridin-3-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)tri(pyridin-3-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)tri(pyrimidin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)di(pyridin-2-yl)(pyrimidin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)(pyridin-2-yl)di(pyrimidin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,(4-((tert-butoxycarbonyl)amino)butyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)(phenyl)(pyridin-2-yl)(1,2,3-triazin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)(pyridin-2-yl)di(1,2,3-triazin-4-yl)phosphonium, (4-((tert-butoxycarbonyl)amino)butyl)(pyrimidin-4-yl)di(1,2,3-triazin-4-yl)phosphonium, (4-aminobutyl)diphenyl(pyrimidin-5-yl)phosphonium, (5-aminopropyl)diphenyl(pyridin-3-yl)phosphonium, (5-aminopropyl)(phenyl)di(pyridin-3-yl)phosphonium, (5-aminopropyl)tri(pyridin-3-yl)phosphonium, (5-aminopropyl)diphenyl(pyrimidin-4-yl)phosphonium, (5-aminopropyl)(phenyl)di(pyrimidin-4-yl)phosphonium 또는 (5-aminopropyl)tri(pyrimidin-4-yl)phosphonium일 수 있다.The compound or an acceptable salt thereof may be prepared by reacting (4 - ((tert-butoxycarbonyl) amino) butyl) diphenyl (pyridin-3-yl) phosphonium, (4- (tert-butoxycarbonyl) amino) -3-yl) phosphonium, (4 - ((tert-butoxycarbonyl) amino) butyl) tri (pyridin-3- ) phosphonium, (4 - ((tert-butoxycarbonyl) amino) butyl) tri (pyrimidin-4-yl) phosphonium, (4 - ((tert-butoxycarbonyl) amino) butyl) (pyridin-2-yl) (4 - ((tert-butoxycarbonyl) amino) butyl) diphenyl (1,2,3-triazin-4-yl) phosphonium, (1,2,3-triazin-4-yl) phosphonium, (4 - ((tert-butoxycarbonyl) amino) butyl) phosphonium, (4 - ((tert-butoxycarbonyl) amino) butyl (phenyl) (pyridin-2-yl) (1,2,3-triazin- (pyridin-2-yl) di (1,2,3-triazin-4-yl) phosphonium, (4 - ((tert-butoxycarbonyl) amino) butyl) , 2,3-triazin-4-yl) phosphonium, (4-aminobutyl) diphenyl (pyrimidin-5-yl) phosphonium, (5-aminopropyl) diphenyl (5-aminopropyl) phenyl di (pyridin-3-yl) phosphonium, (5-aminopropyl) tri (pyrimidin-4-yl) phosphonium or (5-aminopropyl) tri (pyrimidin-4-yl) phosphonium.
상기 "허용가능한 염"은 무기산 또는 유기산을 이용한 염이 바람직하며, 더욱 바람직하게는 메톡시, 아세톡시, 트리플루오로아세톡시 음이온 등과 같은 지방족을 이용한 염, 염화물, 브롬화물, 요오드화물, 방향족 또는 아릴지방족 카르복실산염, 질산염, 황산염, 인산염, 설폰산염, 메실산염, 베실산염, 토실산염 등의 염일 수 있으나 이에 한정되는 것은 아니다. 또한 본 발명의 허용 가능한 염은 -OTos, F-, Cl-, Br-, 또는 I-를 이용한 염들도 포함된다. 그러나 이들로 본 발명의 허용 가능한 염이 한정되는 것은 아니다The "acceptable salt" is preferably a salt with an inorganic or organic acid, more preferably a salt with an aliphatic such as methoxy, acetoxy, trifluoroacetoxy anion, etc., a chloride, a bromide, an iodide, Aliphatic carboxylic acid salts, aliphatic carboxylic acid salts, nitrate salts, sulfate salts, phosphate salts, sulfonate salts, mesylate salts, besylate salts and tosylate salts. In addition, acceptable salts of the present invention, -OTos, F - also includes salts with -, Cl -, Br -, or I. However, these do not limit the acceptable salts of the present invention
본 발명의 다른 일 관점에 따르면, 상기 화합물 또는 그의 허용가능한 염의 R1 또는 상기 R1 내의 적어도 하나 이상의 수소가 118F, 76Br, 123I, 124I, 및 131I로 구성되는 군으로부터 선택되는 하나 이상의 방사성 동위원소로 치환되거나, 상기 방사성 동위원소를 포함하는 탄소수 2 내지 6의 할로알킬, 할로폴리에틸렌 옥사이드, 할로알킬 티올, 할로폴리에틸렌옥사이드 티올과 공유결합에 의해 연결된, 방사성 화합물 또는 그의 허용가능한 염이 제공된다.According to another aspect of the present invention there is provided a compound of formula I wherein R 1 of said compound or an acceptable salt thereof or at least one hydrogen in said R 1 is selected from the group consisting of 118 F, 76 Br, 123 I, 124 I, and 131 I A radioactive compound or an acceptable salt thereof, which is substituted with at least one radioisotope, or is linked by a covalent bond with a haloalkyl, halopolyethylene oxide, haloalkylthiol or halopolyethylene oxide thiol having 2 to 6 carbon atoms containing the radioactive isotope / RTI >
상기 방사성 화합물 또는 그의 허용가능한 염은 (2-(2-[18F]fluoroethoxy)ethyl)tris(4-(trifluoromethyl)phenyl)phosphonium,The radioactive compound or an acceptable salt thereof is (2- (2- [ 18 F] fluoroethoxy) ethyl) tris (4- (trifluoromethyl) phenyl) phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-2-ylphosphonium,(2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-2-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-3-ylphosphonium,(2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-3-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-4-ylphosphonium,(2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-4-ylphosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium, (4-(6-[18F]fluoronicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-(6-[18F]fluoronicotinamido)butyl)tripyridin-3-ylphosphonium, (4- (6- [18 F] fluoronicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium, (4- (6- [18 F] fluoronicotinamido) butyl) (phenyl) di (pyridin-3-yl) phosphonium , (4- (6- [ 18 F] fluoronicotinamido) butyl) tripyridin-3-ylphosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium,(4- (6- [ 18 F] fluoronicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium, (4-(6-[76Br]bromonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-(6-[76Br]bromonicotinamido)butyl)tri(pyridin-3-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)tri(pyridin-3-yl)phosphonium, (4-(6-[124I]iodonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium, (4-(6-[124I]iodonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-(6-[124I]iodonicotinamido)butyl)tri(pyridin-3-yl)phosphonium, (4-(6-[131I]iodonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium, (4-(6-[131I]iodonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-(6-[131I]iodonicotinamido)butyl)tri(pyridin-3-yl)phosphonium, (4-(6-[18F]fluoronicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-(6-[18F]fluoronicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-(6-[18F]fluoronicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium, (4-(6-[18F]fluoronicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium, (4-(6-[18F]fluoronicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-(6-[76Br]bromonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-(6-[76Br]bromonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-(6-[76Br]bromonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium, (4-(6-[76Br]bromonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium, (4-(6-[76Br]bromonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium, (4- (6- [76 Br] bromonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium, (4- (6- [76 Br] bromonicotinamido) butyl) (phenyl) di (pyridin-3-yl) phosphonium , (4- (6- [76 Br ] bromonicotinamido) butyl) tri (pyridin-3-yl) phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium, ( 4- (6- [123 I] iodonicotinamido ) butyl) (phenyl) di (pyridin-3-yl) phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) tri (pyridin-3-yl) phosphonium, (4- (6- [124 I] iodonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium, (4- (6- [124 I] iodonicotinamido) butyl) (phenyl) di (pyridin-3-yl) phosphonium , (4- (6- [124 I ] iodonicotinamido) butyl) tri (pyridin-3-yl) phosphonium, (4- (6- [131 I] iodonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium, ( 4- (6- [131 I] iodonicotinamido ) butyl) (phenyl) di (pyridin-3-yl) phosphonium, (4- (6- [131 I] iodonicotinamido) butyl) tri (pyridin-3-yl) phosphonium, (4- (6- [18 F] fluoronicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium, (4- (6- [18 F] fluoronicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosph onium, (4- (6- [18 F] fluoronicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium, (4- (6- [18 F] fluoronicotinamido) butyl) di (pyrimidin-4-yl) (1 , 2,3- triazin-4-yl) phosphonium, (4- (6- [ 18 F] fluoronicotinamido) butyl) 76 Br] bromonicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium, (4- (6- [76 Br] bromonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (4- (6- [76 Br] bromonicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium, (4- (6- [76 Br] bromonicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3-triazin-4 -yl) phosphonium, (4- (6- [76 Br] bromonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium , (4- (6- [123 I] iodonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3-triazin-4-yl) phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-(6-[123I]iodonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-(6-[124I]iodonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium, (4-(6-[124I]iodonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) diphenyl (pyrimidin-4- yl) phosphonium, (4- (6- [123 I] iodonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (4- (6- [124 I] iodonicotinamido) butyl) tri (pyrimidin-4 -yl) phosphonium, (4- (6- [ 124 I] iodonicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3- triazin-
(4-(6-[124I]iodonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium, (4- (6- [ 124 ] iodonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-(6-[131I]iodonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-(6-[131I]iodonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium, (4-(6-[131I]iodonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium, (4- (6- [131 I] iodonicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium, (4- (6- [131 I] iodonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium , (4- (6- [131 I ] iodonicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium, (4- (6- [131 I] iodonicotinamido) butyl) di (pyrimidin-4-yl) (1, 2,3-triazin-4-yl) phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-[18F]fluorobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (4-[18F]fluorobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (4-[18F]fluorobutyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-[18F]fluorobutyl)diphenyl(pyrimidin-4-yl)phosphonium, (4- (6- [131 I] iodonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium, (4- [18 F] fluorobutyl) diphenyl (1,2,3-triazin-4 -yl) phosphonium, (4- [18 F] fluorobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (4- [18 F] fluorobutyl) tri (1,2,3- triazin-4-yl) phosphonium, (4- [ 18 F] fluorobutyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4-[18F]fluorobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-[18F]fluorobutyl)tri(pyrimidin-4-yl)phosphonium, (4-[18F]fluorobutyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-[18F]fluorobutyl)tri(pyridin-3-yl)phosphonium, (4- [18 F] fluorobutyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (4- [18 F] fluorobutyl) tri (pyrimidin-4-yl) phosphonium, (4- [18 F] fluorobutyl) (pyridin-3-yl) phosphonium, (4- [ 18 F] fluorobutyl) tri (pyridin-
(4-[18F]fluoropentyl)diphenyl(pyridin-2-yl)phosphonium,(4- [ 18 F] fluoropentyl) diphenyl (pyridin-2-yl) phosphonium,
(4-[18F]fluorobutyl)diphenyl(pyridin-3-yl)phosphonium,(4- [ 18 F] fluorobutyl) diphenyl (pyridin-3-yl) phosphonium,
(4-[18F]fluoropentyl)diphenyl(pyridin-4-yl)phosphonium,(4- [ 18 F] fluoropentyl) diphenyl (pyridin-4-yl) phosphonium,
(4-[76Br]bromobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (4-[76Br]bromobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (4-[76Br]bromobutyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-[76Br]bromobutyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-[76Br]bromobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-[76Br]bromobutyl)tri(pyrimidin-4-yl)phosphonium, (4-[76Br]bromobutyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-[76Br]bromobutyl)tri(pyridin-3-yl)phosphonium, (4-[123I]iodobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (4-[123I]iodobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (4-[123I]iodobutyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-[123I]iodobutyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-[123I]iodobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-[123I]iodobutyl)tri(pyrimidin-4-yl)phosphonium, (4-[123I]iodobutyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-[123I]iodobutyl)tri(pyridin-3-yl)phosphonium, (4-[124I]iodobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (4-[124I]iodobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (4-[124I]iodobutyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-[124I]iodobutyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-[124I]iodobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4- [76 Br] bromobutyl) diphenyl (1,2,3-triazin-4-yl) phosphonium, (4- [76 Br] bromobutyl) (phenyl) di (1,2,3-triazin-4-yl ) phosphonium, (4- [76 Br ] bromobutyl) tri (1,2,3-triazin-4-yl) phosphonium, (4- [76 Br] bromobutyl) diphenyl (pyrimidin-4-yl) phosphonium, (4- [76 Br] bromobutyl) (phenyl ) di (pyrimidin-4-yl) phosphonium, (4- [76 Br] bromobutyl) tri (pyrimidin-4-yl) phosphonium, (4- [76 Br] bromobutyl) (phenyl) di (pyridin-3-yl) phosphonium, (4- [76 Br] bromobutyl) tri (pyridin-3-yl) phosphonium, (4- [123 I] iodobutyl) diphenyl (1,2,3-triazin-4- yl) phosphonium, (4- [123 I] iodobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (4- [123 I] iodobutyl) tri (1,2,3-triazin -4-yl) phosphonium, (4- [ 123 I] iodobutyl) diphenyl (pyrimidin-4-yl) phosphonium, (4- [ 123 I] iodobutyl) - [123 I] iodobutyl) tri (pyrimidin-4-yl) phosphonium, (4- [123 I] iodobutyl) (phenyl) di (pyridin-3-yl) phosphonium, (4- [123 I] iodobutyl) tri ( pyridin-3-yl) phosphonium, (4- [ 124 ] iodobutyl) diphenyl (1,2,3-triazin- 124 I] iodobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (4- [124 I] iodobutyl) tri (1,2,3-triazin-4-yl) phosphonium, ( 4- [124 I] iodobutyl) diphenyl (pyrimidin-4-yl) phosphonium, (4- [124 I] iodobutyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4-[131I]iodobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (4-[131I]iodobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (4-[131I]iodobutyl)tri(1,2,3-triazin-4-yl)phosphonium, (4-[131I]iodobutyl)diphenyl(pyrimidin-4-yl)phosphonium, (4-[131I]iodobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (4-[131I]iodobutyl)tri(pyrimidin-4-yl)phosphonium, (4-[131I]iodobutyl)(phenyl)di(pyridin-3-yl)phosphonium, (4-[131I]iodobutyl)tri(pyridin-3-yl)phosphonium, (4- [131 I] iodobutyl) diphenyl (1,2,3-triazin-4-yl) phosphonium, (4- [131 I] iodobutyl) (phenyl) di (1,2,3-triazin-4-yl ) phosphonium, (4- [131 I ] iodobutyl) tri (1,2,3-triazin-4-yl) phosphonium, (4- [131 I] iodobutyl) diphenyl (pyrimidin-4-yl) phosphonium, (4- [131 I] iodobutyl) (phenyl ) di (pyrimidin-4-yl) phosphonium, (4- [131 I] iodobutyl) tri (pyrimidin-4-yl) phosphonium, (4- [131 I] iodobutyl) (phenyl) di (pyridin-3-yl) phosphonium, (4- [131 I] iodobutyl) tri (pyridin-3-yl) phosphonium,
(5-[18F]fluoropentyl)tripyridin-2-ylphosphonium,(5- [ 18 F] fluoropentyl) tripyridin-2-ylphosphonium,
(5-[18F]fluoropentyl)tripyridin-3-ylphosphonium,(5- [ 18 F] fluoropentyl) tripyridin-3-ylphosphonium,
(5-[18F]fluoropentyl)tripyridin-4-ylphosphonium,(5- [ 18 F] fluoropentyl) tripyridin-4-ylphosphonium,
(5-[18F]fluoropentyl)tris(4-(trifluoromethyl)phenyl)phosphonium,(5- [ 18 F] fluoropentyl) tris (4- (trifluoromethyl) phenyl) phosphonium,
(5-[18F]fluoropentyl)tripyridin-3-ylphosphonium,(5-[124I]iodopentyl)tri(pyrimidin-4-yl)phosphonium, (5-[124I]iodopentyl)(phenyl)di(pyridin-3-yl)phosphonium, (5-[124I]iodopentyl)tri(pyridin-3-yl)phosphonium, (5- [18 F] fluoropentyl) tripyridin-3-ylphosphonium, (5- [124 I] iodopentyl) tri (pyrimidin-4-yl) phosphonium, (5- [124 I] iodopentyl) (phenyl) di (pyridin- 3-yl) phosphonium, (5- [ 124 ] iodopentyl) tri (pyridin-3- yl) phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium, (2- (2- [ 18 F] fluoroethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)phenyldipyridin-3-ylphosphonium, (2- (2- [ 18 F] fluoroethoxy) ethyl) phenyl] pyridin-3-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-3-ylphosphonium, (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-3-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-4-ylphosphonium (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-4-ylphosphonium
(2-(2-[18F]fluoroethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium, (2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[18F]fluoroethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (2-(2-[18F]fluoroethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)tri(pyridin-3-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (2-(2-[76Br]bromoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)tri(pyridin-3-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (2-(2-[123I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)tri(pyridin-3-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (2-(2-[124I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)tri(pyridin-3-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium, (2-(2-[131I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium, 또는 (2- (2- [18 F] fluoroethoxy) ethyl) diphenyl (pyrimidin-4-yl) phosphonium, (2- (2- [18 F] fluoroethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium , (2- (2- [18 F ] fluoroethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- (2- [18 F] fluoroethoxy) ethyl) diphenyl (1,2,3- triazin-4-yl) phosphonium, (2- (2- [18 F] fluoroethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (2- (2- [18 F ] fluoroethoxy) ethyl) tri (1,2,3 -triazin-4-yl) phosphonium, (2- (2- [76 Br] bromoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium, (2- (2 - [76 Br] bromoethoxy) ethyl ) (phenyl) di (pyridin-3-yl) phosphonium, (2- (2- [76 Br] bromoethoxy) ethyl) tri (pyridin-3-yl) phosphonium, (2- ( 2- [76 Br] bromoethoxy) ethyl ) diphenyl (pyrimidin-4-yl) phosphonium, (2- (2- [76 Br] bromoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- (2- [76 Br] bromoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- (2- [76 Br] bromoethoxy) ethyl) diphenyl (1,2,3-triazin-4- yl) phosphonium, (2- (2- [18 F] fluoroethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (2- (2- [76 br] br omoethoxy) ethyl) tri (1,2,3- triazin-4-yl) phosphonium, (2- (2- [123 I] iodoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium, (2- (2- [123 I] iodoethoxy) ethyl) (phenyl) di (pyridin-3-yl) phosphonium, (2- (2- [123 I] iodoethoxy) ethyl) tri (pyridin-3-yl) phosphonium, (2- (2 - [123 I] iodoethoxy) ethyl ) diphenyl (pyrimidin-4-yl) phosphonium, (2- (2- [123 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- ( 2- [123 I] iodoethoxy) ethyl ) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- (2- [123 I] iodoethoxy) ethyl) diphenyl (1,2,3-triazin-4-yl ) phosphonium, (2- (2- [ 123 I] iodoethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (2- (2- [123 I] iodoethoxy) ethyl) tri (1,2,3-triazin-4- yl) phosphonium, (2- (2- [124 I] iodoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium, (2- (2- [124 I] iodoethoxy) ethyl) (phenyl) di (pyridin-3-yl) phosphonium, (2- (2- [124 I] iodoethoxy) ethyl) tri (pyridin-3-yl) phosphonium, (2- (2- [124 I ] iodoethoxy) ethyl) diphenyl (pyrimidin-4-yl) phosphonium, 2- (2- [ 124 I] iodoethoxy) ethyl) (2- (2- [124 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- (2- [124 I] iodoethoxy) ethyl) diphenyl (1,2,3-triazin -4-yl) phosphonium, (2- (2- [124 I] iodoethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (2- (2- [124 I] iodoethoxy) ethyl) tri (1,2,3- triazin-4-yl) phosphonium, (2- (2- [131 I] iodoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium, (2- (2- [131 I] iodoethoxy) ethyl) (phenyl) di (pyridin-3-yl) phosphonium, (2- (2- [131 I] iodoethoxy) ethyl) tri (pyridin-3-yl) phosphonium, (2- (2 - [131 I] iodoethoxy) ethyl ) diphenyl (pyrimidin-4-yl) phosphonium, (2- (2- [131 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- ( 2- [131 I] iodoethoxy) ethyl ) (phenyl) di (pyrimidin-4-yl) phosphonium, (2- (2- [131 I] iodoethoxy) ethyl) diphenyl (1,2,3-triazin-4-yl ) phosphonium, (2- (2- [ 131 I] iodoethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium, (2- (2- [131 I] iodoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium, or
(2-(2-(6-[18F]fluoronicotinamido)ethoxy)ethyl)diphenyl(pyridin-3-yl) phosphonium일 수 있다.(2- (2- (6- [ 18 F] fluoronicotinamido) ethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium.
본 발명의 다른 일 관점에 따르면, 상기 화합물 또는 그의 허용가능한 염의 R1이 118F, 76Br, 123I, 124I 및 131I로 구성되는 군으로부터 선택되는 하나 이상의 방사성 동위원소로 치환된, 방사성 화합물 또는 그의 허용가능한 염이 제공된다.According to another aspect of the invention, the compound or a acceptable salt thereof R 1 118 F, 76 Br, 123 I, substituted with one or more radioisotopes selected from the group consisting of 124 I and 131 I, radioactive A compound or an acceptable salt thereof is provided.
본 발명의 다른 일 관점에 따르면, 상기 화학식 I의 화합물 또는 그의 허용가능한 염의 R1 또는 상기 R1 내의 적어도 하나 이상의 수소가 118F, 76Br, 123I, 124I, 및 131I로 구성되는 군으로부터 선택되는 하나 이상의 방사성 동위원소로 치환하거나, 상기 방사성 동위원소를 포함하는 탄소수 2 내지 6의 할로알킬, 할로폴리에틸렌 옥사이드, 할로알킬 티올, 할로폴리에틸렌옥사이드 티올과 공유결합에 의해 연결하는 단계를 포함하는 방사성 화합물 또는 그의 허용가능한 염의 제조방법이 제공된다.According to another aspect of the invention, the group at least one hydrogen in the compound or a acceptable salt of the general formula I R 1 or the R 1 consists of 118 F, 76 Br, 123 I, 124 I, and 131 I Or a covalent bond with a haloalkyl, halopolyethylene oxide, haloalkylthiol or halopolyethylene oxide thiol having 2 to 6 carbon atoms containing the radioactive isotope, wherein the radioisotope is selected from the group consisting of A method of making a radioactive compound or an acceptable salt thereof is provided.
이때, 치환방법은 한정되지 않으며, 상황에 따라 당업자가 적절하게 선택할 수 있다는 것은 자명하다. 예컨대, 당업자는 상기 화학식 1의 화합물 또는 이의 허용 가능한 염에, 118F, 76Br, 123I, 124I, 및 131I 등을 가하여 R1의 치환기를 방사성 동위원소로 치환할 수 있다.At this time, the substitution method is not limited, and it is obvious that a person skilled in the art can appropriately select according to the situation. For example, one skilled in the art can substitute the substituent of R 1 with a radioisotope by adding 118 F, 76 Br, 123 I, 124 I, and 131 I to the compound of Formula 1 or an acceptable salt thereof.
선택적으로 상기 제조방법은 상기와 같은 치환방법 대신 하기와 같은 반응식으로 수행될 수 있다.Alternatively, the above production method can be carried out by the following reaction formula instead of the above substitution method.
(반응식 3).(Scheme 3).
본 발명의 다른 일 관점에 따르면, 하기 화학식 II의 구조를 갖는 화합물 및 방사성 동위 금속원소를 포함하는 방사성 금속 착물이 제공된다:According to another aspect of the present invention there is provided a radial metal complex comprising a compound having a structure of formula II and a radioisotope element:
(상기 식에서 X1은 O, S, N, 또는 C이고, X2 내지 X10은 각각 독립적으로 C 또는 N으로, 상기 X2 내지 X10는 독립적으로 C 또는 N이며, 상기 L1 및 L2는 각각 독립적으로 없거나 탄소수 1 내지 6인 알킬렌기, 알케닐렌기, 알키닐렌기, 탄소수 6 또는 10의 아릴렌기, 탄소수 2 내지 6의 알킬렌 옥사이드기 또는 그의 반복단위 2 내지 4의 중합체, 카르복실 에스테르기, 숙시니미딜기, 카르보닐기 및 
상기 방사성 금속 착물에 있어서, 상기 킬레이터는 NOTA(1,4,7-triazacyclononane-N,N',N''-triacetic acid), DOTA(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), TETA(1,4,8,11-tetraazacyclotetradecane-N',N",N"'-tetraacetic acid), DTPA(diethylenetriaminepentaacetic acid), EDTA(ethylenediamine tetraacetate), NTA(nitrilotriacetic acid) 또는 상기 킬레이터의 유도체일 수 있다. 단, 상기 방사성 금속 착물에서, R2 내지 R4가 모두 수소일 경우에는 상기 X2 내지 X10 중 적어도 하나 이상은 N이다.Wherein the chelator is selected from the group consisting of NOTA (1,4,7-triazacyclononane-N, N ', N "-triacetic acid), DOTA (1,4,7,10- tetraazacyclododecane- Tetraacetic acid), TETA (1,4,8,11-tetraazacyclotetradecane-N ', N'',N''- tetraacetic acid), DTPA (diethylenetriaminepentaacetic acid), EDTA (ethylenediamine tetraacetate), nitrilotriacetic acid ) Or a derivative of the chelator. In the above radioactive metal complex, when all of R 2 to R 4 are hydrogen, at least one of X 2 to X 10 is N.
상기 방사성 착물에 있어서, 상기 방사성 동위 금속원소는 44Sc, 64Cu, 66Cu, 67Ga, 68Ga, 71Ga, 115Ga, 89Y, 86Y, 90Y, 89Zr, 99mTc, 111In, 또는 177Lu일 수 있다.In the above radioactive complex, wherein the radioactive metallic element is 44 Sc, 64 Cu, 66 Cu , 67 Ga, 68 Ga, 71 Ga, 115 Ga, 89 Y, 86 Y, 90 Y, 89 Zr, 99m Tc, 111 In , Or 177 Lu.
본 발명의 다른 일 관점에 따르면, 상기 방사성 화합물 또는 그의 허용가능한 염 또는 상기 방사성 금속 착물을 유효성분으로 포함하는 양전자 방출 단층촬영(PET)용 조영제가 제공된다.According to another aspect of the present invention, there is provided a contrast agent for positron emission tomography (PET) comprising the radioactive compound or an acceptable salt thereof or the radioactive metal complex as an active ingredient.
실제 사용에 있어서, 본 발명의 일실시예에 따른 PET용 조영제는 통상적인 약제학적 조제 기술에 따른 약학적으로 허용되는 담체와 조합될 수 있다. 상기 담체는, 예를 들어 경구 또는 (정맥내 투여를 비롯한) 비경구 투여에 바람직한 제조에 따라 광범위하게 다양한 형태를 지닐 수 있다. For practical use, the contrast agent for PET according to one embodiment of the present invention may be combined with a pharmaceutically acceptable carrier according to conventional pharmaceutical preparation techniques. Such carriers may have a wide variety of forms depending on the preparation desired, for example, for oral or parenteral administration (including intravenous administration).
아울러, 본 발명의 일 실시예에 따른 조영제는 0.1 mg/kg 내지 1 g/kg의 용량으로 투여될 수 있으며, 더 바람직하게는 0.1 mg/kg 내지 500 mg/kg의 투여량으로 투여된다. 한편, 상기 투여량은 일간 또는 연간 허용되는 방사능 피폭양의 범위 내에서 환자의 나이, 성별 및 상태에 따라 적절히 조절될 수 있다. In addition, the contrast agent according to one embodiment of the present invention may be administered at a dose of 0.1 mg / kg to 1 g / kg, more preferably 0.1 mg / kg to 500 mg / kg. On the other hand, the dose can be appropriately adjusted according to the age, sex, and condition of the patient within the range of the amount of radiation exposure permitted for the day or the year.
본 발명의 일 실시예에 따른 조영제는 학학적으로 허용되는 담체를 비롯한 불활성 성분을 추가로 포함한다. 본 명세서에서 사용된 "학학적으로 허용된 담체"란 조성물, 구체적으로 의약 조성물의 활성 물질을 제외한 성분을 지칭하는 용어이다. 제약상 허용되는 담체의 예로는 결합제, 붕해제, 희석제, 충진제, 활택제, 가용화제 또는 유화제 및 염이 포함된다.The contrast agent according to one embodiment of the present invention further comprises an inert component, including a pharmaceutically acceptable carrier. As used herein, the term " pharmaceutically acceptable carrier " is a term referring to a composition, specifically a component other than the active ingredient of the pharmaceutical composition. Examples of pharmaceutically acceptable carriers include binders, disintegrants, diluents, fillers, lubricants, solubilizers or emulsifiers and salts.
상기 신규 조영제는 비경구 투여로 상기 개체에 투여될 수 있으며, 상기 비경구 투여는 정맥내 투여(intravenous injection), 복강내 투여(intraperitoneal injection), 근육내 투여(intramuscular injection), 또는 피하 투여(subcutaneous injection)일 수 있으나, 정맥내 투여가 가장 바람직하다.The new contrast agent may be administered to the subject by parenteral administration, and the parenteral administration may be by intravenous injection, intraperitoneal injection, intramuscular injection, or subcutaneous injection. injection, but intravenous administration is most preferred.
이하, 실시예 및 실험예를 통하여 본 발명을 더 상세히 설명한다. 그러나 본 발명은 이하에서 개시되는 실시예에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 수 있는 것으로, 이하의 실시예는 본 발명의 개시가 완전하도록 하며, 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이다. Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. It should be understood, however, that the invention is not limited to the disclosed embodiments, but may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, Is provided to fully inform the user.
실시예 1: 기준물질의 제조Example 1: Preparation of reference material
1-1: (5-플루오로펜틸)디페닐(피리딘-2-일)포스포니움 염의 제조1-1: Preparation of (5-fluoropentyl) diphenyl (pyridin-2-yl) phosphonium salt
0℃에서 정제된 피리딘 30 ㎖에 펜테인-1,5-디올 1.56 g과 4-메틸벤젠-1-설포닐 클로라이드 8.58 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.56 g of pentane-1,5-diol and 8.58 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, and the mixture was stirred at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product pentane-1,5-diylbis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g를 첨가하였다. 이후 환류 장치를 이용하여 4 시간 동안 가열한 후 증발 건조하고 혼합 이동상 (헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 5-플루오로펜틸 4-메틸벤젠술포네이트를 분리·정제하였다. Then 1.0 g of pentane-1,5-diylbis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. After heating for 4 hours using a reflux condenser, the mixture was evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give 5-fluoropentyl 4-methylbenzene The sulfonate was separated and purified.
최종적으로 5-플루오로펜틸 4-메틸벤젠술포네이트 1.0 g을 2-(디페닐포스피노)피리딘 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (5-플루오로펜틸)디페닐(피리딘-2-일)포스포니움 염을 실온에서 냉각시킨 후 준-정제 칼럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 5-fluoropentyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of 2- (diphenylphosphino) pyridine was dissolved, and then the mixture was heated again with a hot air stream. The synthesized (5-fluoropentyl) diphenyl (pyridin-2-yl) phosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, DMSO-d6): 1.50-1.70 (m, 6H), 2.27 (s, 3H), 3.56-3.62 (m, 2H), 4.33 (t, 1H), 4.43 (t, 1H), 7.10 (d, 2H), 7.47 (d, 2H), 7.73-7.91 (m, 11H), 7.96-7.99 (m, 1H), 8.16-8.21 (m, 1H), 9.00 (d, 1H) 1 H-NMR (300 MHz, DMSO-d 6): 1.50-1.70 (m, 6H), 2.27 (s, 3H), 3.56-3.62 (m, 2H), 4.33 (t, 1H), 4.43 (t, 1H), 7.00 (d, IH), 7.10 (d, 2H), 7.47 (d, 2H), 7.73-7.91 (m,
1-2: (2-(2-플루오로에톡시)에틸)디페닐(피리딘-2-일)포스포니움 염의 제조1-2: Preparation of (2- (2-fluoroethoxy) ethyl) diphenyl (pyridin-2-yl) phosphonium salt
0℃에서 정제된 피리딘 30 ㎖에 2,2'-옥시디에탄올 1.55 g과 4-메틸벤젠-1-설포닐 클로라이드 8.55 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 메틸렌 클로라이드(CH2Cl2)와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.55 g of 2,2'-oxydiethanol and 8.55 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, followed by stirring at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water. Pyridine was removed by using 80 ml of methylene chloride (CH 2 Cl 2 ) and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 Ml of water. The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g을 첨가하였다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발·건조하였고, 혼합 이동상(헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트를 분리·정제하였다. 1.0 g of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. The mixture was heated to reflux for 4 hours, evaporated to dryness, and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give the product 2- (2- Ethoxy) ethyl 4-methylbenzenesulfonate was isolated and purified.
최종적으로 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트 1.0 g을 2-(디페닐포스피노)피리딘 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (2-(2-플루오로에톡시)에틸)디페닐(피리딘-2-일)포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 2- (2-fluoroethoxy) ethyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of 2- (diphenylphosphino) pyridine was dissolved, and then the mixture was heated again with a hot air stream . The synthesized (2- (2-fluoroethoxy) ethyl) diphenyl (pyridin-2-yl) phosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 2.36 (s, 3H), 3.40 (m, 1H), 3.46 (m, 1H), 3.78-3.88 (m, 4H), 4.19 (m, 1H), 4.29 (m, 1H), 7.23 (m, 2H), 7.70-7.89 (m, 13H), 7.94-7.98 (m, 1H), 8.07-8.12 (m, 1H), 8.95-8.97 (m, 1H) 1 H-NMR (300 MHz, CD 3 OD): 2.36 (s, 3H), 3.40 (m, 1H), 3.46 1H), 8.95-8.97 (m, 1H), 7.29 (m, 2H)
1-3: (4-아미노부틸)디페닐(피리딘-2-일)포스포니움 염의 제조1-3: Preparation of (4-aminobutyl) diphenyl (pyridin-2-yl) phosphonium salt
터르트-부틸(4-히드록시부틸)카르바메이트 1.8 g을 메틸렌클로라이드 용매 하에서 4-메틸벤젠-1-설포닐 클로라이드 6.2 g과 반응시킨 후, 미반응 산물을 컬럼 그로마토그래피를 이용하여 제거한 후, 용매를 휘발시켜 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠설포네이트 4.2 g을 수득하였다.After reacting 1.8 g of tert-butyl (4-hydroxybutyl) carbamate with 6.2 g of 4-methylbenzene-1-sulfonyl chloride in a methylene chloride solvent, the unreacted product was removed by column chromatography Then, the solvent was evaporated to obtain 4.2 g of 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate.
이어 상기 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 1.0 g을 2-(디페닐포스피노)피리딘 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 170℃로 다시 가열하고 합성된 (4-(터르트-부톡시카르보닐아미노)부틸)디페닐(피리딘-2-일)포스포니움 염을 수득하였다.Then, 1.0 g of the 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of 2- (diphenylphosphino) pyridine was dissolved, C to obtain the synthesized (4- (tert-butoxycarbonylamino) butyl) diphenyl (pyridin-2-yl) phosphonium salt.
상기 (4-(터르트-부톡시카르보닐아미노)부틸)디페닐(피리딘-2-일)포스포니움 염을 산조건에서 반응시켜 (4-아미노부틸)디페닐(피리딘-2-일)포스포니움 염 0.6 g을 수득하였다.(4-aminobutyl) diphenyl (pyridin-2-yl) diphenyl (pyridin-2-yl) phosphonium salt was reacted with the above (4- (tert- 0.6 g of phosphonium salt was obtained.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 1.29-1.51 (m, 4H), 2.32 (s, 3H), 2.46-2.67 (m, 4H), 5.01 (s, 2H), 7.08 (d, 2H), 7.27 (d, 2H), 7.39-7.55 (m, 11H), 7.93-7.97 (m, 1H), 8.18-8.25 (m, 1H), 9.01-9.07 (m, 1H). 1 H-NMR (300 MHz, CD 3 OD): 1.29-1.51 (m, 4H), 2.32 (s, 3H), 2.46-2.67 (m, 4H), 5.01 (s, 2H), 7.08 (d, 2H ), 7.27 (d, 2H), 7.39-7.55 (m, 11H), 7.93-7.97 (m, 1H), 8.18-8.25 (m, 1H), 9.01-9.07 (m, 1H).
1-4: (5-플루오로펜틸)트리피리딘-2-일포스포니움 염의 제조1-4: Preparation of (5-fluoropentyl) tripyridin-2-ylphosphonium salt
0℃에서 정제된 피리딘 30 ㎖에 펜테인-1,5-디올 1.56 g과 4-메틸벤젠-1-설포닐 클로라이드 8.58 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.56 g of pentane-1,5-diol and 8.58 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, and the mixture was stirred at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product pentane-1,5-diylbis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g을 첨가하였다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발 건조하고 혼합 이동상(헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 5-플루오로펜틸 4-메틸벤젠술포네이트를 분리·정제하였다. Then 1.0 g of the pentane-1,5-diylbis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. After heating for 4 hours using a reflux condenser, the mixture was evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give 5-fluoropentyl 4-methylbenzene The sulfonate was separated and purified.
최종적으로 5-플루오로펜틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-2-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (5-플루오로펜틸)트리피리딘-2-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 5-fluoropentyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-2-yl) phosphine was dissolved, and then the mixture was heated again with a hot air. The synthesized (5-fluoropentyl) tripyridin-2-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 1.42-1.65 (m, 6H), 2.29 (s, 3H), 3.06-3.12 (m, 2H), 4.04 (t, 1H), 4.13 (t, 1H), 7.02 (d, 2H), 7.17 (d, 2H), 7.25-7.66 (m, 9H), 8.35-8.46 (m, 3H) 1 H-NMR (300 MHz, CD 3 OD): 1.42-1.65 (m, 6H), 2.29 (s, 3H), 3.06-3.12 (m, 2H), 4.04 (t, 1H), 4.13 (t, 1H ), 7.02 (d, 2H), 7.17 (d, 2H), 7.25-7.66 (m, 9H), 8.35-8.46
1-5: (2-(2-플루오로에톡시)에틸)트리피리딘-2-일포스포니움 염의 제조1-5: Preparation of (2- (2-fluoroethoxy) ethyl) tripyridin-2-ylphosphonium salt
0℃에서 정제된 피리딘 30 ㎖에 2,2'-옥시디에탄올 1.55 g과 4-메틸벤젠-1-설포닐 클로라이드 8.55 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.55 g of 2,2'-oxydiethanol and 8.55 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, followed by stirring at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g을 첨가하였다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발 건조 하고 혼합 이동상(헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트를 분리·정제하였다. 1.0 g of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. The mixture was then heated for 4 hours using a reflux condenser, then evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give the product 2- (2-fluoroethoxy ) Ethyl 4-methylbenzenesulfonate was separated and purified.
최종적으로 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-2-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (2-(2-플루오로에톡시)에틸)트리피리딘-2-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 2- (2-fluoroethoxy) ethyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-2-yl) phosphine was dissolved, Respectively. The synthesized (2- (2-fluoroethoxy) ethyl) tripyridin-2-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 2.32 (s, 3H), 2.75 (m, 2H), 3.35 (m, 2H), 3.47 (t, 1H), 3.55 (t, 1H), 4.08 (t, 1H), 4.15 (t, 1H), 7.21 (d, 2H), 7.30-7.66 (m, 11H), 8.34-8.46 (m, 3H) 1 H-NMR (300 MHz, CD 3 OD): 2.32 (s, 3H), 2.75 (m, 2H), 3.35 (m, 2H), 3.47 (t, 1H), 3.55 (t, 1H), 4.08 ( 2H), 7.30-7.66 (m, 11H), 8.34-8.46 (m, 3H)
1-6: (4-아미노부틸)디페닐(피리딘-2-일)포스포니움 염의 제조1-6 Preparation of (4-aminobutyl) diphenyl (pyridin-2-yl) phosphonium salt
터르트-부틸 (4-하이드록시부틸)카르바메이트 1.8 g을 메틸렌클로라이드 용매 하에서 4-메틸벤젠-1-설포닐 클로라이드 6.0 g과 반응시킨 후, 미반응산물을 컬럼 그로마토그래피를 이용하여 제거한 후, 용매를 휘발시켜 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 4.0 g을 수득하였다.After reacting 1.8 g of tert-butyl (4-hydroxybutyl) carbamate with 6.0 g of 4-methylbenzene-1-sulfonyl chloride in a methylene chloride solvent, the unreacted product was removed by column chromatography Then, the solvent was volatilized to obtain 4.0 g of 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate.
이어 상기 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-2-일)포스파인 1.2g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 170℃로 다시 가열하고 합성된 (4-(터르트-부톡시카르보닐아미노)부틸)트리피리딘-2-일포스포니움 염을 수득하였다.Then, 1.0 g of the 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-2-yl) And then heated again to 170 DEG C to obtain the synthesized (4- (tert-butoxycarbonylamino) butyl) tripyridin-2-ylphosphonium salt.
상기 (4-(터르트-부톡시카르보닐아미노)부틸)트리피리딘-2-일포스포니움 염을 산조건에서 반응시켜 (4-아미노부틸)트리피리딘-2-일포스포니움 염 0.54 g을 수득하였다.The above (4- (tert-butoxycarbonylamino) butyl) tripyridin-2-ylphosphonium salt was reacted under acidic condition to give 0.54 g of (4-aminobutyl) tripyridin-2-ylphosphonium salt ≪ / RTI >
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 1.23-1.47 (m, 4H), 2.30 (s, 3H), 2.42-2.55 (m, 4H), 5.05 (s, 2H), 7.10 (d, 2H), 7.31 (d, 2H), 7.40-7.65 (m, 9H), 8.31-8.49 (m, 3H). 1 H-NMR (300 MHz, CD 3 OD): 1.23-1.47 (m, 4H), 2.30 (s, 3H), 2.42-2.55 (m, 4H), 5.05 (s, 2H), 7.10 (d, 2H ), 7.31 (d, 2H), 7.40-7.65 (m, 9H), 8.31-8.49 (m, 3H).
1-7: (5-플루오로펜틸)트리피리딘-3-일포스포니움 염의 제조1-7: Preparation of (5-fluoropentyl) tripyridin-3-ylphosphonium salt
0 ℃에서 정제된 피리딘 30 ㎖에 펜테인-1,5-디올 1.56 g과 4-메틸벤젠-1-설포닐 클로라이드 8.58 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.56 g of pentane-1,5-diol and 8.58 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, and the mixture was stirred at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product pentane-1,5-diylbis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g 첨가 한다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발 건조 하고 혼합 이동상 (헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 5-플루오로펜틸 4-메틸벤젠술포네이트를 분리·정제하였다. Then 1.0 g of pentane-1,5-diylbis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. After heating for 4 hours using a reflux condenser, the mixture was evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give 5-fluoropentyl 4-methylbenzene The sulfonate was separated and purified.
최종적으로 5-플루오로펜틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-3-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (5-플루오로펜틸)트리피리딘-3-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 5-fluoropentyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-3-yl) phosphine was dissolved, and then the mixture was heated again with a hot air. The synthesized (5-fluoropentyl) tripyridin-3-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 1.32-1.54 (m, 6H), 2.27 (s, 3H), 2.68-2.87 (m, 2H), 4.03 (t, 1H), 4.13 (t, 1H), 7.10 (d, 2H), 7.23 (d, 2H), 7.43-7.66 (m, 6H), 8.35-8.56 (m, 6H) 1 H-NMR (300 MHz, CD 3 OD): 1.32-1.54 (m, 6H), 2.27 (s, 3H), 2.68-2.87 (m, 2H), 4.03 (t, 1H), 4.13 (t, 1H 2H), 7.43-7.66 (m, 6H), 8.35-8.56 (m, 6H)
1-8: (2-(2-플루오로에톡시)에틸)트리피리딘-3-일포스포니움 염의 제조1-8: Preparation of (2- (2-fluoroethoxy) ethyl) tripyridin-3-ylphosphonium salt
0℃에서 정제된 피리딘 30 ㎖에 2,2'-옥시디에탄올 1.55 g과 4-메틸벤젠-1-설포닐 클로라이드 8.55 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.55 g of 2,2'-oxydiethanol and 8.55 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, followed by stirring at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g을 첨가하였다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발·건조하고 혼합 이동상(헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트를 분리·정제하였다. 1.0 g of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. After heating for 4 hours using a reflux condenser, the mixture was evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) Ethoxy) ethyl 4-methylbenzenesulfonate was isolated and purified.
최종적으로 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-3-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (2-(2-플루오로에톡시)에틸)트리피리딘-3-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 2- (2-fluoroethoxy) ethyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-3-yl) phosphine was dissolved, Respectively. The synthesized (2- (2-fluoroethoxy) ethyl) tripyridin-3-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 2.26 (s, 3H), 2.65 (m, 2H), 3.33 (m, 2H), 3.45 (t, 1H), 3.57 (t, 1H), 4.05 (t, 1H), 4.25 (t, 1H), 7.19 (d, 2H), 7.34-7.78 (m, 8H), 8.29-8.51 (m, 6H) 1 H-NMR (300 MHz, CD 3 OD): 2.26 (s, 3H), 2.65 (m, 2H), 3.33 (m, 2H), 3.45 (t, 1H), 3.57 (t, 1H), 4.05 ( 2H), 7.34-7.78 (m, 8H), 8.29-8.51 (m, 6H)
1-9: (4-아미노부틸)트리피리딘-3-일포스포니움 염의 제조1-9: Preparation of (4-aminobutyl) tripyridin-3-ylphosphonium salt
터르트-부틸 (4-하이드록시부틸)카르바메이트 1.8 g을 메틸렌클로라이드 용매 하에서 4-메틸벤젠-1-설포닐 클로라이드 6.0 g과 반응시킨 후, 미반응산물을 컬럼 그로마토그래피를 이용하여 제거한 후, 용매를 휘발시켜 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 4.0 g을 수득하였다.After reacting 1.8 g of tert-butyl (4-hydroxybutyl) carbamate with 6.0 g of 4-methylbenzene-1-sulfonyl chloride in a methylene chloride solvent, the unreacted product was removed by column chromatography Then, the solvent was volatilized to obtain 4.0 g of 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate.
이어 상기 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-3-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 170℃로 다시 가열하고 합성된 (4-(터르트-부톡시카르보닐아미노)부틸)트리피리딘-3-일포스포니움 염을 수득하였다.Subsequently, 1.0 g of the 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-3-yl) And then heated again to 170 ° C to obtain the synthesized (4- (tert-butoxycarbonylamino) butyl) tripyridin-3-ylphosphonium salt.
상기 (4-(터르트-부톡시카르보닐아미노)부틸)트리피리딘-3-일포스포니움 염을 산조건에서 반응시켜 (4-아미노부틸)트리피리딘-3-일포스포니움 염 0.54 g을 수득하였다.The above (4- (tert-butoxycarbonylamino) butyl) tripyridin-3-ylphosphonium salt was reacted under acidic conditions to give 0.54 g of (4-aminobutyl) tripyridin-3-ylphosphonium salt ≪ / RTI >
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 1.25-1.46 (m, 4H), 2.28 (s, 3H), 2.52-2.65 (m, 4H), 5.07 (s, 2H), 7.08 (d, 2H), 7.26 (d, 2H), 7.35-7.77 (m, 6H), 8.33-8.51 (m, 6H) 1 H-NMR (300 MHz, CD 3 OD): 1.25-1.46 (m, 4H), 2.28 (s, 3H), 2.52-2.65 (m, 4H), 5.07 (s, 2H), 7.08 (d, 2H ), 7.26 (d, 2H), 7.35-7.77 (m, 6H), 8.33-8.51 (m, 6H)
1-10: (5-플루오로펜틸)트리피리딘-4-일포스포니움 염의 제조1-10: Preparation of (5-fluoropentyl) tripyridin-4-ylphosphonium salt
0 ℃에서 정제된 피리딘 30 ㎖에 펜테인-1,5-디올 1.56 g과 4-메틸벤젠-1-설포닐 클로라이드 8.58 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.56 g of pentane-1,5-diol and 8.58 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, and the mixture was stirred at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product pentane-1,5-diylbis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g을 첨가하였다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발 건조 하고 혼합 이동상 (헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 5-플루오로펜틸 4-메틸벤젠술포네이트를 분리·정제하였다. Then 1.0 g of the pentane-1,5-diylbis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. After heating for 4 hours using a reflux condenser, the mixture was evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give 5-fluoropentyl 4-methylbenzene The sulfonate was separated and purified.
최종적으로 5-플루오로펜틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-4-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (5-플루오로펜틸)트리피리딘-4-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 칼럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 5-fluoropentyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-4-yl) phosphine was dissolved, and then the mixture was heated again with a hot air. The synthesized (5-fluoropentyl) tripyridin-4-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 1.34-1.61 (m, 6H), 2.30 (s, 3H), 2.76-2.90 (m, 2H), 4.00 (t, 1H), 4.10 (t, 1H), 7.15 (d, 2H), 7.28 (d, 2H), 7.56-7.76 (m, 6H), 8.45-8.66 (m, 6H) 1 H-NMR (300 MHz, CD 3 OD): 1.34-1.61 (m, 6H), 2.30 (s, 3H), 2.76-2.90 (m, 2H), 4.00 (t, 1H), 4.10 (t, 1H ), 7.15 (d, 2H), 7.28 (d, 2H), 7.56-7.76 (m, 6H), 8.45-8.66
1-11: (2-(2-플루오로에톡시)에틸)트리피리딘-4-일포스포니움 염의 제조1-11: Preparation of (2- (2-fluoroethoxy) ethyl) tripyridin-4-ylphosphonium salt
0 ℃에서 정제된 피리딘 30 ㎖에 2,2'-옥시디에탄올 1.55 g과 4-메틸벤젠-1-설포닐 클로라이드 8.55 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.55 g of 2,2'-oxydiethanol and 8.55 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, followed by stirring at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g을 첨가하였다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발 건조 하고 혼합 이동상(헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트를 분리·정제하였다. 1.0 g of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. The mixture was then heated for 4 hours using a reflux condenser, then evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give the product 2- (2-fluoroethoxy ) Ethyl 4-methylbenzenesulfonate was separated and purified.
최종적으로 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-4-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (2-(2-플루오로에톡시)에틸)트리피리딘-4-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 2- (2-fluoroethoxy) ethyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-4-yl) phosphine was dissolved, Respectively. The synthesized (2- (2-fluoroethoxy) ethyl) tripyridin-4-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 2.28 (s, 3H), 2.67 (m, 2H), 3.43 (m, 2H), 3.47 (t, 1H), 3.53 (t, 1H), 4.18 (t, 1H), 4.25 (t, 1H), 7.21 (d, 2H), 7.30-7.66 (m, 8H), 8.44-8.67 (m, 6H) 1 H-NMR (300 MHz, CD 3 OD): 2.28 (s, 3H), 2.67 (m, 2H), 3.43 (m, 2H), 3.47 (t, 1H), 3.53 (t, 1H), 4.18 ( 2H), 7.30-7.66 (m, 8H), 8.44-8.67 (m, 6H)
1-12: (4-아미노부틸)트리피리딘-4-일포스포니움 염의 제조1-12: Preparation of (4-aminobutyl) tripyridin-4-ylphosphonium salt
터르트-부틸 (4-하이드록시부틸)카르바메이트 1.8 g을 메틸렌클로라이드 용매 하에서 4-메틸벤젠-1-설포닐 클로라이드 6.0 g과 반응시킨 후, 미반응산물을 컬럼 그로마토그래피를 이용하여 제거한 후, 용매를 휘발시켜 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 4.0 g을 수득하였다.After reacting 1.8 g of tert-butyl (4-hydroxybutyl) carbamate with 6.0 g of 4-methylbenzene-1-sulfonyl chloride in a methylene chloride solvent, the unreacted product was removed by column chromatography Then, the solvent was volatilized to obtain 4.0 g of 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate.
이어 상기 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 1.0 g을 트리(피리딘-4-일)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 170℃로 다시 가열하고 합성된 (4-(터르트-부톡시카르보닐아미노)부틸)트리피리딘-4-일포스포니움 염을 수득하였다.Then, 1.0 g of the 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tri (pyridin-4-yl) And then heated again to 170 DEG C to obtain the synthesized (4- (tert-butoxycarbonylamino) butyl) tripyridin-4-ylphosphonium salt.
상기 (4-(터르트-부톡시카르보닐아미노)부틸)트리피리딘-4-일포스포니움 염을 산조건에서 반응시켜 (4-아미노부틸)트리피리딘-4-일포스포니움 염 0.54 g을 수득하였다.The above (4- (tert-butoxycarbonylamino) butyl) tripyridin-4-ylphosphonium salt was reacted under acidic conditions to give 0.54 g of (4-aminobutyl) tripyridin-4-ylphosphonium salt ≪ / RTI >
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz,CD3OD): 1.30-1.52 (m, 4H), 2.25 (s, 3H), 2.51-2.68 (m, 4H), 5.10 (s, 2H), 7.10 (d, 2H), 7.30 (d, 2H), 7.48-7.75 (m, 6H), 8.29-8.48 (m, 6H) 1 H-NMR (300 MHz, CD 3 OD): 1.30-1.52 (m, 4H), 2.25 (s, 3H), 2.51-2.68 (m, 4H), 5.10 (s, 2H), 7.10 (d, 2H ), 7.30 (d, 2H), 7.48-7.75 (m, 6H), 8.29-8.48 (m, 6H)
1-13: (5-플루오로펜틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염의 제조1-13: Preparation of (5-fluoropentyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt
0 ℃에서 정제된 피리딘 30 ㎖에 펜테인-1,5-디올 1.56 g과 4-메틸벤젠-1-설포닐 클로라이드 8.58 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.56 g of pentane-1,5-diol and 8.58 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, and the mixture was stirred at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product pentane-1,5-diylbis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g 첨가 한다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발 건조 하고 혼합 이동상(헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 5-플루오로펜틸 4-메틸벤젠술포네이트를 분리·정제하였다. Then 1.0 g of pentane-1,5-diylbis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. After heating for 4 hours using a reflux condenser, the mixture was evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give 5-fluoropentyl 4-methylbenzene The sulfonate was separated and purified.
최종적으로 5-플루오로펜틸 4-메틸벤젠술포네이트 1.0 g을 트리스(4-(트리플루오로메틸)페닐)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (5-플루오로펜틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 5-fluoropentyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tris (4- (trifluoromethyl) phenyl) phosphine was dissolved, and then the mixture was heated again with a hot air stream. The synthesized (5-fluoropentyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz,CD3OD): 1.70-1.77 (m, 6H), 2.35 (s, 3H), 3.63-3.71 (m, 2H), 4.35 (t, 1H), 4.43 (t, 1H), 7.18 (d, 2H), 7.63 (d, 2H), 8.07-8.14 (m, 12H) 1 H-NMR (300 MHz, CD 3 OD): 1.70-1.77 (m, 6H), 2.35 (s, 3H), 3.63-3.71 (m, 2H), 4.35 (t, 1H), 4.43 (t, 1H ), 7.18 (d, 2H), 7.63 (d, 2H), 8.07-8.14 (m, 12H)
1-14: (2-(2-플루오로에톡시)에틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염의 제조1-14 Preparation of (2- (2-fluoroethoxy) ethyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt
0℃에서 정제된 피리딘 30 ㎖에 2,2'-옥시디에탄올 1.55 g과 4-메틸벤젠-1-설포닐 클로라이드 8.55 g을 첨가한 후 실온에서 2시간 동안 교반하였다. 2시간 교반 후 소량의 물을 사용하여 반응을 종결시키고 80 ㎖의 CH2Cl2와 1.0 M HCl 170 ㎖를 이용하여 피리딘을 제거한 후 추출한 CH2Cl2 층에 남아 있는 피리딘을 50 ㎖의 물을 이용하여 완전히 제거하였다. Na2SO4로 CH2Cl2 층의 수분을 제거하고 여과하였다. 여액을 증발 건조한 후 컬럼 크로마토그래피를 이용하여 생성물 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트)를 분리·정제하였다.1.55 g of 2,2'-oxydiethanol and 8.55 g of 4-methylbenzene-1-sulfonyl chloride were added to 30 ml of purified pyridine at 0 ° C, followed by stirring at room temperature for 2 hours. After stirring for 2 hours, the reaction was terminated by using a small amount of water, pyridine was removed by using 80 ml of CH 2 Cl 2 and 1.0 M HCl (170 ml), and pyridine remaining in the extracted CH 2 Cl 2 layer was extracted with 50 ml of water . The water of the CH 2 Cl 2 layer was removed with Na 2 SO 4 and filtered. The filtrate was evaporated to dryness, and the product 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was separated and purified by column chromatography.
이어 상기 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 1.0 g을 아세토나이트릴에 용해시키고 테트라부틸암모늄플루오라이드 트리하이드레이트 0.9 g을 첨가하였다. 이후 환류 장치를 이용하여 4시간 동안 가열한 후 증발 건조 하고 혼합 이동상(헥세인:메틸렌 클로라이드:아세톤=9:10:1)을 사용하여 컬럼 크로마토그래피로 생성물인 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트를 분리·정제하였다. 1.0 g of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) was dissolved in acetonitrile and 0.9 g of tetrabutylammonium fluoride trihydrate was added. The mixture was then heated for 4 hours using a reflux condenser, then evaporated to dryness and purified by column chromatography using a mixed mobile phase (hexane: methylene chloride: acetone = 9: 10: 1) to give the product 2- (2-fluoroethoxy ) Ethyl 4-methylbenzenesulfonate was separated and purified.
최종적으로 2-(2-플루오로에톡시)에틸 4-메틸벤젠술포네이트 1.0 g을 트리스(4-(트리플루오로메틸)페닐)포스파인 1.2 g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 열풍기로 다시 가열하였다. 합성된 (2-(2-플루오로에톡시)에틸)트리피리딘-4-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다. Finally, 1.0 g of 2- (2-fluoroethoxy) ethyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tris (4- (trifluoromethyl) phenyl) phosphine was dissolved, And then heated again with a hot air blower. The synthesized (2- (2-fluoroethoxy) ethyl) tripyridin-4-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 2.36 (s, 3H), 3.42-3.48 (m, 2H), 3.86 (d, 2H), 4.20 (d, 1H), 4.30 (d, 1H), 4.88 (s, 2H), 7.21 (d, 2H), 7.66 (d, 2H), 8.06-8.15 (m, 12H) 1 H-NMR (300 MHz, CD 3 OD): 2.36 (s, 3H), 3.42-3.48 (m, 2H), 3.86 (d, 2H), 4.20 (d, 1H), 4.30 (d, 1H), 2H), 7.66 (d, 2H), 8.06-8. 15 (m, 12H)
1-15: (4-아미노부틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염의 제조1-15 Preparation of (4-aminobutyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt
터르트-부틸(4-하이드록시부틸)카르바메이트 1.8 g을 메틸렌클로라이드 용매 하에서 4-메틸벤젠-1-설포닐 클로라이드 6.0 g과 반응시킨 후, 미반응산물을 컬럼 그로마토그래피를 이용하여 제거한 후, 용매를 휘발시켜 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 4.0 g을 수득하였다.After reacting 1.8 g of tert-butyl (4-hydroxybutyl) carbamate with 6.0 g of 4-methylbenzene-1-sulfonyl chloride in a methylene chloride solvent, the unreacted product was removed by column chromatography Then, the solvent was volatilized to obtain 4.0 g of 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate.
이어 상기 4-((터르트-부톡시카르보닐)아미노)부틸 4-메틸벤젠술포네이트 1.0 g을 트리스(4-(트리플루오로메틸)페닐)포스파인 1.2g이 용해된 5 ㎖의 톨루엔에 첨가한 후, 170℃로 다시 가열하고 합성된 (4-(터르트-부톡시카르보닐아미노)부틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염을 수득하였다.1.0 g of the 4 - ((tert-butoxycarbonyl) amino) butyl 4-methylbenzenesulfonate was added to 5 ml of toluene in which 1.2 g of tris (4- (trifluoromethyl) phenyl) After the addition, the mixture was heated again to 170 DEG C to obtain synthesized (4- (tert-butoxycarbonylamino) butyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt.
상기 (4-(터르트-부톡시카르보닐아미노)부틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염을 산조건에서 반응시켜 (4-아미노부틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염 0.48 g을 수득하였다.The reaction of (4- (tert-butoxycarbonylamino) butyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt with (4-aminobutyl) tris Fluoromethyl) phenyl) phosphonium salt were obtained.
1H-NMR 분석 결과는 하기와 같다: The results of 1 H-NMR analysis are as follows:
1H-NMR (300 MHz, CD3OD): 1.25-1.55 (m, 4H), 2.32 (s, 3H), 2.56-2.69 (m, 4H), 5.15 (s, 2H), 7.25 (d, 2H), 7.53 (d, 2H), 7.98-8.20 (m, 12H) 1 H-NMR (300 MHz, CD 3 OD): 1.25-1.55 (m, 4H), 2.32 (s, 3H), 2.56-2.69 (m, 4H), 5.15 (s, 2H), 7.25 (d, 2H ), 7.53 (d, 2H), 7.98-8. 20 (m, 12H)
실시예 2: 방사성 화합물을 제조의 제조Example 2: Preparation of radioactive compound
2-1: (5-[2-1: (5- [ 1818 F]플루오로펜틸)디페닐(피리딘-2-일)포스포니움 염의 제조F] fluoropentyl) diphenyl (pyridin-2-yl) phosphonium salt
상기 실시예 1-1에서 제조된 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 5-[18F]플루오로펜틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 2-(디페닐포스피노)피리딘 13 mg를 첨가 한 후 가열하여 (5-[18F]플루오로펜틸)디페닐(피리딘-2-일)포스포니움 염을 합성하였다. 합성된 (5-[18F]플루오로펜틸)디페닐(피리딘-2-일)포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였으며 이를 [18F]FDPP로 명명하였다.10 mg of pentane-1,5-diyl bis (4-methylbenzenesulfonate) prepared in Example 1-1 was reacted with a non-coated K 18 F in an acetonitrile solvent to obtain 5- [ 18 F] fluoro Pentyl 4 - methylbenzenesulfonate was synthesized and isolated using disposable cartridges. Then, 13 mg of 2- (diphenylphosphino) pyridine was added to the labeled compound and heated to synthesize (5- [ 18 F] fluoropentyl) diphenyl (pyridin-2-yl) phosphonium salt. The synthesized (5- [ 18 F] fluoropentyl) diphenyl (pyridin-2-yl) phosphonium salt was separated and purified using a quasi-purification column after cooling at room temperature and [ 18 F] FDPP Respectively.
2-2: (2-(2-[2-2: (2- (2- [ 1818 F]플루오로에톡시)에틸)디페닐(피리딘-2-일)포스포니움 염의 제조F] fluoroethoxy) ethyl) diphenyl (pyridin-2-yl) phosphonium salt
상기 실시예 1-2에서 제조된 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 2-(2-[18F]플루오로에톡시)에틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 2-(디페닐포스피노)피리딘 13 mg를 첨가한 후 가열하여 (2-(2-[18F]플루오로에톡시)에틸)디페닐(피리딘-2-일)포스포니움 염을 합성하였다. 합성된(2-(2-[18F]플루오로에톡시)에틸)디페닐(피리딘-2-일)포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였으며 이를 [18F]FEPP로 명명하였다.10 mg of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) prepared in Example 1-2 was reacted with silane coupling agent K 18 F in an acetonitrile solvent To synthesize 2- (2- [ 18 F] fluoroethoxy) ethyl 4-methylbenzenesulfonate, which was isolated using a disposable cartridge. Thereafter, 13 mg of 2- (diphenylphosphino) pyridine was added to the labeled compound, and the mixture was heated to obtain (2- ( 18 F) fluoroethoxy) ethyl) diphenyl (pyridin- Respectively. The synthesized (2- (2- [ 18 F] fluoroethoxy) ethyl) diphenyl (pyridin-2-yl) phosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column [ 18 F] FEPP.
2-3: (5-[2-3: (5- [ 1818 F]플루오로펜틸)트리피리딘-2-일포스포니움 염의 제조F] < / RTI > fluoropentyl) tripyridin-2-ylphosphonium salt
상기 실시예 1-1에서 제조된 펜테인-1,5-다이일비스(4-메틸벤젠설포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 (5-[18F]플루오로펜틸 4-메틸벤젠설포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리(피리딘-2-일)포스파인 13 mg를 첨가 한 후 가열하여 (5-[18F]플루오로펜틸)트리피리딘-2-일포스포니움 염을 합성하였다. 합성된 (5-[18F]플루오로펜틸)트리피리딘-2-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다.10 mg of pentane-1, 5-diyl bis (4-methylbenzenesulfonate) prepared in Example 1-1 was reacted with non-coated K 18 F in an acetonitrile solvent to obtain (5- [ 18 F] (Pyridin-2-yl) phosphine was added to the labeled compound, followed by heating to obtain (5- [ 18 Fluoropentyl) tripyridin-2-ylphosphonium salt was synthesized. The synthesized (5- [ 18 F] fluoropentyl) tripyridin-2-ylphosphonium salt was cooled to room temperature - Separation and purification using a purification column.
2-4: (2-(2-[2-4: (2- (2- [ 1818 F]플루오로에톡시)에틸)트리피리딘-2-일포스포니움 염의 제조F] fluoroethoxy) ethyl) tripyridin-2-ylphosphonium salt
상기 실시예 1-2에서 제조된 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 2-(2-[18F]플루오로에톡시)에틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리(피리딘-2-일)포스파인 13 mg를 첨가 한 후 가열하여 (2-(2-[18F]플루오로에톡시)에틸)트리피리딘-2-일포스포니움 염을 합성하였다. 합성된(2-(2-[18F]플루오로에톡시)에틸)트리피리딘-2-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다.10 mg of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) prepared in Example 1-2 was reacted with silane coupling agent K 18 F in an acetonitrile solvent To synthesize 2- (2- [ 18 F] fluoroethoxy) ethyl 4-methylbenzenesulfonate, which was isolated using a disposable cartridge. Thereafter, 13 mg of tri (pyridin-2-yl) phosphine was added to the labeled compound, and the mixture was heated to obtain (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-2-ylphosphonium salt Were synthesized. The synthesized (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-2-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
2-4: (5-[2-4: (5- [ 1818 F]플루오로펜틸)트리피리딘-3-일포스포니움 염의 제조F] < / RTI > fluoropentyl) tripyridin-3-ylphosphonium salt
상기 실시예 1-1에서 제조된 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 5-[18F]플루오로펜틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리(피리딘-3-일)포스파인 13 mg를 첨가 한 후 가열하여 (5-[18F]플루오로펜틸)트리피리딘-3-일포스포니움 염을 합성하였다. 합성된 (5-[18F]플루오로펜틸)트리피리딘-3-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다.10 mg of pentane-1,5-diyl bis (4-methylbenzenesulfonate) prepared in Example 1-1 was reacted with a non-coated K 18 F in an acetonitrile solvent to obtain 5- [ 18 F] fluoro Pentyl 4 - methylbenzenesulfonate was synthesized and isolated using disposable cartridges. Then, 13 mg of tri (pyridin-3-yl) phosphine was added to the labeled compound and heated to synthesize (5- [ 18 F] fluoropentyl) tripyridin-3-ylphosphonium salt. The synthesized (5- [ 18 F] fluoropentyl) tripyridin-3-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
2-5: (2-(2-[2-5: (2- (2- [ 1818 F]플루오로에톡시)에틸)트리피리딘-3-일포스포니움 염의 제조F] fluoroethoxy) ethyl) tripyridin-3-ylphosphonium salt
상기 실시예 1-2에서 제조된 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 2-(2-[18F]플루오로에톡시)에틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리(피리딘-3-일)포스파인 13 mg를 첨가 한 후 가열하여 (2-(2-[18F]플루오로에톡시)에틸)트리피리딘-3-일포스포니움 염을 합성하였다. 합성된(2-(2-[18F]플루오로에톡시)에틸)트리피리딘-3-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다.10 mg of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) prepared in Example 1-2 was reacted with silane coupling agent K 18 F in an acetonitrile solvent To synthesize 2- (2- [ 18 F] fluoroethoxy) ethyl 4-methylbenzenesulfonate, which was isolated using a disposable cartridge. Then, 13 mg of tri (pyridin-3-yl) phosphine was added to the labeled compound, and the mixture was heated to obtain (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-3-ylphosphonium salt Were synthesized. The synthesized (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-3-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
2-6: (5-[2-6: (5- [ 1818 F]플루오로펜틸)트리피리딘-4-일포스포니움 염의 제조F] < / RTI > fluoropentyl) tripyridin-4-ylphosphonium salt
상기 실시예 1-1에서 제조된 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 5-[18F]플루오로펜틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리(피리딘-4-일)포스파인 13 mg를 첨가 한 후 가열하여 (5-[18F]플루오로펜틸)트리피리딘-4-일포스포니움 염을 합성하였다. 합성된 (5-[18F]플루오로펜틸)트리피리딘-4-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 컬럼을 이용하여 분리·정제하였다.10 mg of pentane-1,5-diyl bis (4-methylbenzenesulfonate) prepared in Example 1-1 was reacted with a non-coated K 18 F in an acetonitrile solvent to obtain 5- [ 18 F] fluoro Pentyl 4 - methylbenzenesulfonate was synthesized and isolated using disposable cartridges. Thereafter, 13 mg of tri (pyridin-4-yl) phosphine was added to the labeled compound and heated to synthesize (5- [ 18 F] fluoropentyl) tripyridin-4-ylphosphonium salt. The synthesized (5- [ 18 F] fluoropentyl) tripyridin-4-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
2-7: (2-(2-[2-7: (2- (2- [ 1818 F]플루오로에톡시)에틸)트리피리딘-4-일포스포니움 염의 제조F] fluoroethoxy) ethyl) tripyridin-4-ylphosphonium salt
상기 실시예 1-2에서 제조된 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 2-(2-[18F]플루오로에톡시)에틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리(피리딘-4-일)포스파인 13 mg를 첨가 한 후 가열하여 (2-(2-[18F]플루오로에톡시)에틸)트리피리딘-4-일포스포니움 염을 합성하였다. 합성된(2-(2-[18F]플루오로에톡시)에틸)트리피리딘-4-일포스포니움 염을 실온에서 냉각시킨 후 준-정제 칼럼을 이용하여 분리·정제하였다.10 mg of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) prepared in Example 1-2 was reacted with silane coupling agent K 18 F in an acetonitrile solvent To synthesize 2- (2- [ 18 F] fluoroethoxy) ethyl 4-methylbenzenesulfonate, which was isolated using a disposable cartridge. Thereafter, 13 mg of tri (pyridin-4-yl) phosphine was added to the labeled compound and then heated to obtain (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-4-ylphosphonium salt Were synthesized. The synthesized (2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-4-ylphosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
2-8: (5-[2-8: (5- [ 1818 F]플루오로펜틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염의 제조F] fluoropentyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt
상기 실시예 1-1에서 제조된 펜테인-1,5-다이일 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 5-[18F]플루오로펜틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리스(4-(트리플루오로메틸)페닐)포스파인 13 mg를 첨가 한 후 가열하여 (5-[18F]플루오로펜틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염을 합성하였다. 합성된 (5-[18F]플루오로펜틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염을 실온에서 냉각시킨 후 준-정제 칼럼을 이용하여 분리·정제하였다.10 mg of pentane-1,5-diyl bis (4-methylbenzenesulfonate) prepared in Example 1-1 was reacted with a non-coated K 18 F in an acetonitrile solvent to obtain 5- [ 18 F] fluoro Pentyl 4 - methylbenzenesulfonate was synthesized and isolated using disposable cartridges. Thereafter, 13 mg of tris (4- (trifluoromethyl) phenyl) phosphine was added to the labeled compound, and the mixture was heated to obtain (5- [ 18 F] fluoropentyl) tris (4- Phosphonium salts were synthesized. The synthesized (5- [ 18 F] fluoropentyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt was cooled at room temperature and then separated and purified using a quasi-purification column.
2-9: (2-(2-[2-9: (2- (2- [ 1818 F]플루오로에톡시)에틸)트리스(4-(트리플루오로메틸)페닐)-F] fluoroethoxy) ethyl) tris (4- (trifluoromethyl) phenyl) -
포스포니움 염의 제조Preparation of phosphonium salt
상기 실시예 1-2에서 제조된 2,2'-옥시비스(에테인-2,1-다이일) 비스(4-메틸벤젠술포네이트) 10 mg을 아세토나이트릴 용매 하에서 무담채 K18F와 반응시켜 2-(2-[18F]플루오로에톡시)에틸 4-메틸벤젠술포네이트를 합성하였으며, 이를 일회용 카트리지를 이용하여 분리하였다. 그 후 표지 화합물에 트리스(4-(트리플루오로메틸)페닐)포스파인 13 mg를 첨가 한 후 가열하여 (2-(2-[18F]플루오로에톡시)에틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염을 합성하였다. 합성된(2-(2-[18F]플루오로에톡시)에틸)트리스(4-(트리플루오로메틸)페닐)포스포니움 염을 실온에서 냉각시킨 후 준-정제 칼럼을 이용하여 분리·정제하였다.10 mg of 2,2'-oxybis (ethane-2,1-diyl) bis (4-methylbenzenesulfonate) prepared in Example 1-2 was reacted with silane coupling agent K 18 F in an acetonitrile solvent To synthesize 2- (2- [ 18 F] fluoroethoxy) ethyl 4-methylbenzenesulfonate, which was isolated using a disposable cartridge. Thereafter, 13 mg of tris (4- (trifluoromethyl) phenyl) phosphine was added to the labeled compound, and the mixture was heated to obtain (2- (2- [ 18 F] fluoroethoxy) ethyl) Fluoromethyl) phenyl) phosphonium salt was synthesized. After cooling the synthesized (2- (2- [ 18 F] fluoroethoxy) ethyl) tris (4- (trifluoromethyl) phenyl) phosphonium salt at room temperature and separating using a quasi-purification column Lt; / RTI >
실험예 1: 방사성 화합물을 이용항 소동물 PET 조영Experimental Example 1: Animal animal PET imaging using a radioactive compound
본 발명자들은 상기 실시예 2-1 및 2-2에서 각각 제조된 방사성 화합물 [18F]FDPP 및 [18F]FEPP을 각각 200 μCi의 투여량으로 BALB/c 야생형 마우스에 꼬리정맥을 통해 정맥주사하고 30, 60분 시간이 경과한 후 소동물용 양전자 단층 촬영장치로 전신 영상을 촬영하였다. 대조군으로는 특허 제1172157호에서 합성된 (5-[18F]fluoropentyl)triphenylphosphonium 염([18F]FPTP)을 사용하였다.[ 18 F] FDPP and [ 18 F] FEPP prepared in Examples 2-1 and 2-2 described above were intravenously injected into the BALB / c wild-type mouse through the tail vein at a dose of 200 μCi, respectively After 30 and 60 minutes, whole body images were taken with a positron tomography system for small animals. As a control, 5- [ 18 F] fluoropentyl) triphenylphosphonium salt ([ 18 F] FPTP) synthesized in Japanese Patent No. 1172157 was used.
그 결과 도 1 내지 3에서 나타난 바와 같이, 본 발명의 일 실시예에 따른 방사성 화합물은 종래의 방사성 화합물인 [18F]FPTP에 비하여 심장에서의 신호 최대값이 큰폭으로 상승하였다. 도 1은 종래기술의 [18F]FPTP 투여 시 실험동물의 심장을 포함한 전신에 대한 PET 영상이고, 도 2 및 도 3은 각각 본 발명의 일 실시예에 따른 방사성 화합물인 [18F]FEPP 및 [18F]FDPP의 투여 이후 촬영한 PET 영상이다. 상기 결과는 본 발명의 일 실시예에 따른 방사성 화합물이 심장에서의 섭취율이 더 좋아졌음을 의미하는 것이다.As a result, as shown in FIGS. 1 to 3, the radioactive compound according to one embodiment of the present invention greatly increased the maximum signal value at the heart as compared with [ 18 F] FPTP, which is a conventional radioactive compound. FIG. 1 is a PET image of a whole body including the heart of an experimental animal when administered with [ 18 F] FPTP of the prior art, and FIGS. 2 and 3 are photographs of [ 18 F] FEPP and a radioactive compound according to an embodiment of the present invention, [ 18 F] PET images taken after administration of FDPP. The above results indicate that the radioactive compound according to one embodiment of the present invention has a better uptake rate at the heart.
더구나, 본 발명의 일 실시예에 따른 [18F]FEPP의 경우 [18F]FDPP와 비교시 갈비뼈의 윤곽이 거의 나타나지 않는 것으로 나타났는데, 이는 [18F]FEPP의 경우 뼈에서의 흡수율이 [18F]FDPP 보다 낮음을 의미하는 것이다. 이는 방사성 동위원소와 포스포니움염 사이에 존재하는 링커에 탄소 이외의 헤테로원자가 존재할 경우 심장에 대한 선택성이 더욱 향상됨을 의미하는 것이다.Further, was shown to be that if a [18 F] FEPP according to one embodiment of the present invention substantially the outline of the rib compared to [18 F] FDPP appear, which the absorption in the case of [18 F] FEPP bone [ 18 F] FDPP. This means that the presence of a heteroatom other than carbon in the linker existing between the radioactive isotope and the phosphonium salt further enhances the selectivity to the heart.
본 발명은 상술한 실시예 및 실험예를 통해 보다 상세히 설명되었다. 그러나 상기 실시예 및 실험예는 본 발명을 보다 완전히 설명하기 위한 것으로서, 본 발명의 보호범위가 상기 실시예 및 실험예로 제한되지 않음은 본 발명이 속한 기술분야의 통상의 기술을 가진자에게 자명하다고 할 것이다. 따라서, 본 발명의 실질적인 보호범위는 후술할 특허청구범위에 기재된 바에 정해진다.The present invention has been described in detail with reference to the above-described embodiments and experimental examples. It should be understood, however, that the invention is not to be limited to the details given herein, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. . Therefore, the scope of protection of the present invention is set forth in the following claims.
Claims (11)
(상기 식에서 X1은 O, S, NH, 또는 CH2이고, X2 내지 X10은 각각 독립적으로 C 또는 N으로, 상기 X2, X3, X5, X6, X8, 및 X9 중 적어도 하나 이상은 N이며, 상기 L1 및 L2는 각각 독립적으로 없거나 탄소수 1 내지 6인 알킬렌기, 알케닐렌기, 알키닐렌기, 탄소수 6 또는 10의 아릴렌기, 탄소수 2 내지 6의 알킬렌 옥사이드기 또는 그의 반복단위 2 내지 4의 중합체, 카르복실 에스테르기, 숙시니미딜기, 카르보닐기 및
Wherein X 1 is O, S, NH, or CH 2 and X 2 to X 10 are each independently C or N, and X 2 , X 3 , X 5 , X 6 , X 8 , and X 9 At least one of L 1 and L 2 is independently an alkylene group, an alkenylene group, an alkynylene group, an arylene group having 6 or 10 carbon atoms, an alkylene group having 2 to 6 carbon atoms A polymer of an oxide group or repeating units 2 to 4 thereof, a carboxylester group, a succinimidyl group, a carbonyl group,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-2-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-3-ylphosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)tripyridin-3-ylphosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)tri(pyridin-3-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)tri(pyridin-3-yl)phosphonium,
(4-(6-[124I]iodonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium,
(4-(6-[124I]iodonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-(6-[124I]iodonicotinamido)butyl)tri(pyridin-3-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)diphenyl(pyridin-3-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)tri(pyridin-3-yl)phosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[18F]fluoronicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[76Br]bromonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-(6-[123I]iodonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-(6-[124I]iodonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium,
(4-(6-[124I]iodonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[124I]iodonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)tri(pyrimidin-4-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)di(pyrimidin-4-yl)(1,2,3-triazin-4-yl)phosphonium,
(4-(6-[131I]iodonicotinamido)butyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-[18F]fluorobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(4-[18F]fluorobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(4-[18F]fluorobutyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-[18F]fluorobutyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-[18F]fluorobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-[18F]fluorobutyl)tri(pyrimidin-4-yl)phosphonium,
(4-[18F]fluorobutyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-[18F]fluorobutyl)tri(pyridin-3-yl)phosphonium,
(4-[18F]fluoropentyl)diphenyl(pyridin-2-yl)phosphonium,
(4-[18F]fluorobutyl)diphenyl(pyridin-3-yl)phosphonium,
(4-[76Br]bromobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(4-[76Br]bromobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(4-[76Br]bromobutyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-[76Br]bromobutyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-[76Br]bromobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-[76Br]bromobutyl)tri(pyrimidin-4-yl)phosphonium,
(4-[76Br]bromobutyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-[76Br]bromobutyl)tri(pyridin-3-yl)phosphonium,
(4-[123I]iodobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(4-[123I]iodobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(4-[123I]iodobutyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-[123I]iodobutyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-[123I]iodobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-[123I]iodobutyl)tri(pyrimidin-4-yl)phosphonium,
(4-[123I]iodobutyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-[123I]iodobutyl)tri(pyridin-3-yl)phosphonium,
(4-[124I]iodobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(4-[124I]iodobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(4-[124I]iodobutyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-[124I]iodobutyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-[124I]iodobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-[131I]iodobutyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(4-[131I]iodobutyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(4-[131I]iodobutyl)tri(1,2,3-triazin-4-yl)phosphonium,
(4-[131I]iodobutyl)diphenyl(pyrimidin-4-yl)phosphonium,
(4-[131I]iodobutyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(4-[131I]iodobutyl)tri(pyrimidin-4-yl)phosphonium,
(4-[131I]iodobutyl)(phenyl)di(pyridin-3-yl)phosphonium,
(4-[131I]iodobutyl)tri(pyridin-3-yl)phosphonium,
(5-[18F]fluoropentyl)tripyridin-2-ylphosphonium,
(5-[18F]fluoropentyl)tripyridin-3-ylphosphonium,
(5-[18F]fluoropentyl)tripyridin-3-ylphosphonium,
(5-[124I]iodopentyl)tri(pyrimidin-4-yl)phosphonium,
(5-[124I]iodopentyl)(phenyl)di(pyridin-3-yl)phosphonium,
(5-[124I]iodopentyl)tri(pyridin-3-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)phenyldipyridin-3-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-3-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)tri(pyridin-3-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[76Br]bromoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)tri(pyridin-3-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)tri(pyridin-3-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(pyridin-3-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)tri(pyridin-3-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)diphenyl(pyrimidin-4-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(pyrimidin-4-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)diphenyl(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)(phenyl)di(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium, 또는
(2-(2-(6-[18F]fluoronicotinamido)ethoxy)ethyl)diphenyl(pyridin-3-yl)phosphonium인, 방사성 화합물 또는 그의 허용가능한 염.The method of claim 3,
(2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-2-ylphosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-3-ylphosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) (phenyl) di (pyridin-3-yl) phosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) tripyridin-3-ylphosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium,
(4- (6- [ 76 Br] bromonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium,
(4- (6- [ 76 Br] bromonicotinamido) butyl) (phenyl) di (pyridin-3-yl) phosphonium,
(4- (6- [ 76 Br] bromonicotinamido) butyl) tri (pyridin-3-yl) phosphonium,
(4- (6- [ 123 ] iodonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium,
(4- (6- [ 123 I] iodonicotinamido) butyl) (phenyl) di (pyridin-3- yl) phosphonium,
(4- (6- [ 123 ] iodonicotinamido) butyl) tri (pyridin-3-yl) phosphonium,
(4- (6- [ 124 ] iodonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium,
(4- (6- [ 124 I] iodonicotinamido) butyl) (phenyl) di (pyridin-3- yl) phosphonium,
(4- (6- [ 124 ] iodonicotinamido) butyl) tri (pyridin-3-yl) phosphonium,
(4- (6- [131 I] iodonicotinamido) butyl) diphenyl (pyridin-3-yl) phosphonium,
(4- (6- [131 I] iodonicotinamido) butyl) (phenyl) di (pyridin-3-yl) phosphonium,
(4- (6- [131 I] iodonicotinamido) butyl) tri (pyridin-3-yl) phosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium,
(4- (6- [ 18 F] fluoronicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3-triazin-
(4- (6- [ 18 F] fluoronicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- (6- [ 76 Br] bromonicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- (6- [ 76 Br] bromonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- (6- [ 76 Br] bromonicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium,
(4- (6- [ 76 Br] bromonicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3-triazin-
(4- (6- [ 76 Br] bromonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- (6- [ 123 ] iodonicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- (6- [ 123 I] iodonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- (6- [123 I] iodonicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium,
(4- (6- [123 I] iodonicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3-triazin-4-yl) phosphonium,
(4- (6- [123 I] iodonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- (6- [ 123 ] iodonicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- (6- [ 123 I] iodonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- (6- [ 124 ] iodonicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium,
(4- (6- [ 124 ] iodonicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3-triazin-
(4- (6- [ 124 ] iodonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- (6- [131 I] iodonicotinamido) butyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- (6- [ 131 I] iodonicotinamido) butyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- (6- [131 I] iodonicotinamido) butyl) tri (pyrimidin-4-yl) phosphonium,
(4- (6- [131 I] iodonicotinamido) butyl) di (pyrimidin-4-yl) (1,2,3-triazin-4-yl) phosphonium,
(4- (6- [131 I] iodonicotinamido) butyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- [ 18 F] fluorobutyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(4- [ 18 F] fluorobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(4- [ 18 F] fluorobutyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- [ 18 F] fluorobutyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- [ 18 F] fluorobutyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- [ 18 F] fluorobutyl) tri (pyrimidin-4-yl) phosphonium,
(4- [ 18 F] fluorobutyl) (phenyl) di (pyridin-3-yl) phosphonium,
(4- [ 18 F] fluorobutyl) tri (pyridin-3-yl) phosphonium,
(4- [ 18 F] fluoropentyl) diphenyl (pyridin-2-yl) phosphonium,
(4- [ 18 F] fluorobutyl) diphenyl (pyridin-3-yl) phosphonium,
(4- [ 76 Br] bromobutyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(4- [ 76 Br] bromobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(4- [ 76 Br] bromobutyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- [ 76 Br] bromobutyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- [ 76 Br] bromobutyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- [ 76 Br] bromobutyl) tri (pyrimidin-4-yl) phosphonium,
(4- [ 76 Br] bromobutyl) (phenyl) di (pyridin-3-yl) phosphonium,
(4- [ 76 Br] bromobutyl) tri (pyridin-3-yl) phosphonium,
(4- [ 123 I] iodobutyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(4- [ 123 I] iodobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(4- [ 123 I] iodobutyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- [ 123 I] iodobutyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- [ 123 I] iodobutyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- [ 123 I] iodobutyl) tri (pyrimidin-4-yl) phosphonium,
(4- [ 123 I] iodobutyl) (phenyl) di (pyridin-3-yl) phosphonium,
(4- [ 123 I] iodobutyl) tri (pyridin-3-yl) phosphonium,
(4- [ 124 I] iodobutyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(4- [ 124 I] iodobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(4- [ 124 I] iodobutyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- [ 124 I] iodobutyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- [ 124 I] iodobutyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- [131 I] iodobutyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(4- [ 131 I] iodobutyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(4- [131 I] iodobutyl) tri (1,2,3-triazin-4-yl) phosphonium,
(4- [ 131 I] iodobutyl) diphenyl (pyrimidin-4-yl) phosphonium,
(4- [ 131 I] iodobutyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(4- [131 I] iodobutyl) tri (pyrimidin-4-yl) phosphonium,
(4- [ 131 I] iodobutyl) (phenyl) di (pyridin-3-yl) phosphonium,
(4- [131 I] iodobutyl) tri (pyridin-3-yl) phosphonium,
(5- [ 18 F] fluoropentyl) tripyridin-2-ylphosphonium,
(5- [ 18 F] fluoropentyl) tripyridin-3-ylphosphonium,
(5- [ 18 F] fluoropentyl) tripyridin-3-ylphosphonium,
(5- [ 124 I] iodopentyl) tri (pyrimidin-4-yl) phosphonium,
(5- [ 124 I] iodopentyl) (phenyl) di (pyridin-3-yl) phosphonium,
(5- [ 124 I] iodopentyl) tri (pyridin-3-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) phenyl] pyridin-3-ylphosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-3-ylphosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) diphenyl (pyrimidin-4-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) (phenyl) di (pyridin-3-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) tri (pyridin-3-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) diphenyl (pyrimidin-4-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 76 Br] bromoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 123 ] iodoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium,
(2- (2- [ 123 I] iodoethoxy) ethyl) (phenyl) di (pyridin-3-yl) phosphonium,
(2- (2- [123 I] iodoethoxy) ethyl) tri (pyridin-3-yl) phosphonium,
(2- (2- [ 123 ] iodoethoxy) ethyl) diphenyl (pyrimidin-4-yl) phosphonium,
(2- (2- [ 123 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 123 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 123 ] iodoethoxy) ethyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 123 I] iodoethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 123 ] iodoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 124 ] iodoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium,
(2- (2- [ 124 I] iodoethoxy) ethyl) (phenyl) di (pyridin-3-yl) phosphonium,
(2- (2- [ 124 ] iodoethoxy) ethyl) tri (pyridin-3-yl) phosphonium,
(2- (2- [ 124 ] iodoethoxy) ethyl) diphenyl (pyrimidin-4-yl) phosphonium,
(2- (2- [ 124 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 124 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 124 ] iodoethoxy) ethyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 124 I] iodoethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 124 ] iodoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 131 I] iodoethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium,
(2- (2- [ 131 I] iodoethoxy) ethyl) (phenyl) di (pyridin-3-yl) phosphonium,
(2- (2- [131 I] iodoethoxy) ethyl) tri (pyridin-3-yl) phosphonium,
(2- (2- [131 I] iodoethoxy) ethyl) diphenyl (pyrimidin-4-yl) phosphonium,
(2- (2- [ 131 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [ 131 I] iodoethoxy) ethyl) (phenyl) di (pyrimidin-4-yl) phosphonium,
(2- (2- [131 I] iodoethoxy) ethyl) diphenyl (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 131 I] iodoethoxy) ethyl) (phenyl) di (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 131 I] iodoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium, or
(2- (2- (6- [ 18 F] fluoronicotinamido) ethoxy) ethyl) diphenyl (pyridin-3-yl) phosphonium.
(상기 식에서 X1은 O, S, NH, 또는 CH2이고, X2 내지 X10은 각각 독립적으로 C 또는 N으로, 상기 X2, X3, X5, X6, X8, 및 X9 중 적어도 하나 이상은 N이며, 상기 L1 및 L2는 각각 독립적으로 없거나 탄소수 1 내지 6인 알킬렌기, 알케닐렌기, 알키닐렌기, 탄소수 6 또는 10의 아릴렌기, 탄소수 2 내지 6의 알킬렌 옥사이드기 또는 그의 반복단위 2 내지 4의 중합체, 카르복실 에스테르기, 숙시니미딜기, 카르보닐기 및
Wherein X 1 is O, S, NH, or CH 2 and X 2 to X 10 are each independently C or N, and X 2 , X 3 , X 5 , X 6 , X 8 , and X 9 At least one of L 1 and L 2 is independently an alkylene group, an alkenylene group, an alkynylene group, an arylene group having 6 or 10 carbon atoms, an alkylene group having 2 to 6 carbon atoms A polymer of an oxide group or repeating units 2 to 4 thereof, a carboxylester group, a succinimidyl group, a carbonyl group,
상기 방사성 동위 금속원소는 44Sc, 64Cu, 66Cu, 67Ga, 68Ga, 71Ga, 115Ga, 89Y, 86Y, 90Y, 89Zr, 99mTc, 111In, 또는 177Lu인, 방사성 금속 착물.The method according to claim 6,
Wherein the radioactive metallic element is 44 Sc, 64 Cu, 66 Cu , 67 Ga, 68 Ga, 71 Ga, 115 Ga, 89 Y, 86 Y, 90 Y, 89 Zr, 99m Tc, 111 In, or 177 Lu, Radioactive metal complex.
(상기 식에서, X2, X3, X5, X6, X8 및 X9는 각각 독립적으로 CH 또는 N이고, L1 및 L2는 각각 독립적으로 없거나 탄소수 1 내지 6인 알킬렌기, 알케닐렌기, 알키닐렌기, 탄소수 6 또는 10의 아릴렌기, 탄소수 2 내지 6의 알킬렌 옥사이드기 또는 그의 반복단위 2 내지 4의 중합체, 카르복실 에스테르기, 숙시니미딜기, 카르보닐기 및
Wherein X 2 , X 3 , X 5 , X 6 , X 8 and X 9 are each independently CH or N, L 1 and L 2 are each independently an alkylene group having 1 to 6 carbon atoms, An alkynylene group, an arylene group having 6 or 10 carbon atoms, an alkylene oxide group having 2 to 6 carbon atoms or a polymer of repeating units 2 to 4, a carboxylester group, a succinimidyl group, a carbonyl group,
(2-(2-[18F]fluoroethoxy)ethyl)tripyridin-4-ylphosphonium,
(2-(2-[18F]fluoroethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[123I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[124I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium,
(2-(2-[131I]iodoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium, 및
(2-(2-[76Br]bromoethoxy)ethyl)tri(1,2,3-triazin-4-yl)phosphonium로 구성되는 군으로부터 선택되는, 신규 화합물 또는 그의 허용가능한 염.11. The method of claim 10,
(2- (2- [ 18 F] fluoroethoxy) ethyl) tripyridin-4-ylphosphonium,
(2- (2- [ 18 F] fluoroethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 123 ] iodoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 124 ] iodoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium,
(2- (2- [ 131 I] iodoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium, and
(2- (2- [ 76 Br] bromoethoxy) ethyl) tri (1,2,3-triazin-4-yl) phosphonium.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170181493A KR101920902B1 (en) | 2017-12-27 | 2017-12-27 | A PET contrast compound for early diagnosis of cardiovascular diseases and use thereof |
| PCT/KR2018/002661 WO2019132117A1 (en) | 2017-12-27 | 2018-03-06 | Compound for pet imaging for early diagnosis of cardiovascular diseases and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170181493A KR101920902B1 (en) | 2017-12-27 | 2017-12-27 | A PET contrast compound for early diagnosis of cardiovascular diseases and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR101920902B1 true KR101920902B1 (en) | 2018-11-21 |
Family
ID=64602342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020170181493A Active KR101920902B1 (en) | 2017-12-27 | 2017-12-27 | A PET contrast compound for early diagnosis of cardiovascular diseases and use thereof |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR101920902B1 (en) |
| WO (1) | WO2019132117A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20230242558A1 (en) * | 2022-01-31 | 2023-08-03 | New Frontier Bio, Inc. | Nicotinate and nicotinamide riboside-based compounds and derivatives thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015075200A1 (en) * | 2013-11-22 | 2015-05-28 | Medical Research Council | Mitochondria-targeted dicarbonyl sequestering compounds |
| CN105153227A (en) | 2015-07-04 | 2015-12-16 | 河南中医学院 | A kind of [18F]-fluoromethyl triphenylphosphine salt and its preparation method and application |
| CN107325173A (en) * | 2016-04-28 | 2017-11-07 | 上海惠斯生物科技有限公司 | A kind of artificial antigen of 25(OH)VD 3, preparation method and application |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20050020755A (en) * | 2002-02-06 | 2005-03-04 | 더 존스 홉킨스 유니버시티 | Non-invasive diagnostic imaging technology for mitochondria using radiolabeled lipophilic salts |
| JP2014527969A (en) * | 2011-09-19 | 2014-10-23 | ジェンシア コーポレイション | Modified creatine compound |
-
2017
- 2017-12-27 KR KR1020170181493A patent/KR101920902B1/en active Active
-
2018
- 2018-03-06 WO PCT/KR2018/002661 patent/WO2019132117A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015075200A1 (en) * | 2013-11-22 | 2015-05-28 | Medical Research Council | Mitochondria-targeted dicarbonyl sequestering compounds |
| CN105153227A (en) | 2015-07-04 | 2015-12-16 | 河南中医学院 | A kind of [18F]-fluoromethyl triphenylphosphine salt and its preparation method and application |
| CN107325173A (en) * | 2016-04-28 | 2017-11-07 | 上海惠斯生物科技有限公司 | A kind of artificial antigen of 25(OH)VD 3, preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019132117A1 (en) | 2019-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7219497B2 (en) | PSMA binder and use thereof | |
| EP2170075B1 (en) | Labeled inhibitors of prostate specific membrane antigen (psma), biological evaluation, and use as imaging agents | |
| KR102223883B1 (en) | Compositions, methods, and systems for the synthesis and use of imaging agents | |
| CA3041113C (en) | Compositions, methods, and systems for the synthesis and use of imaging agents | |
| AU2018279007A1 (en) | Compositions, methods, and systems for the synthesis and use of imaging agents | |
| JP6661010B2 (en) | Peptide thiourea derivative, radioisotope-labeled compound containing the same, and pharmaceutical composition containing the same as active ingredient for treating or diagnosing prostate cancer | |
| KR101920902B1 (en) | A PET contrast compound for early diagnosis of cardiovascular diseases and use thereof | |
| US20170334804A1 (en) | F-18 labeled tracer and methods of manufacture | |
| KR102302065B1 (en) | A novel radioactive compound for treating melanoma and use thereof | |
| EP3216796B1 (en) | Phosphonium compound and production method therefor | |
| KR20180001250A (en) | A compound for PET imaging and use thereof | |
| US11504439B2 (en) | Radioactive compound for diagnosis of malignant melanoma and use thereof | |
| US8940273B2 (en) | Tricarbonyl complexes with tridentate chelators for myocardium imaging | |
| JPH0237345B2 (en) | ||
| JP2021536495A (en) | Contains radiolabeled compounds of quaternary ammonium salts of polycyclic aromatic amines, use of radiolabeled compounds in diagnostic methods of positron emission tomography, and radiolabeled compounds of quaternary ammonium salts of polycyclic aromatic amines. Pharmaceutical composition | |
| HK1182640B (en) | Compositions, methods and systems for the synthesis and use of imaging agents | |
| HK1182640A (en) | Compositions, methods and systems for the synthesis and use of imaging agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 20171227 |
|
| PA0201 | Request for examination | ||
| PA0302 | Request for accelerated examination |
Patent event date: 20171228 Patent event code: PA03022R01D Comment text: Request for Accelerated Examination Patent event date: 20171227 Patent event code: PA03021R01I Comment text: Patent Application |
|
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20180307 Patent event code: PE09021S01D |
|
| PE0902 | Notice of grounds for rejection |
Comment text: Final Notice of Reason for Refusal Patent event date: 20180920 Patent event code: PE09021S02D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20181112 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20181115 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20181116 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20211027 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20241015 Start annual number: 7 End annual number: 7 |