CN107353209B - 与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用 - Google Patents
与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用 Download PDFInfo
- Publication number
- CN107353209B CN107353209B CN201710474957.3A CN201710474957A CN107353209B CN 107353209 B CN107353209 B CN 107353209B CN 201710474957 A CN201710474957 A CN 201710474957A CN 107353209 B CN107353209 B CN 107353209B
- Authority
- CN
- China
- Prior art keywords
- compound
- 400mhz
- cdcl
- nmr
- imaging agent
- 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
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 208
- 239000012216 imaging agent Substances 0.000 claims abstract description 43
- 239000000126 substance Substances 0.000 claims abstract description 19
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
- 238000003745 diagnosis Methods 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 61
- -1 cyano, carboxyl Chemical group 0.000 claims description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- HKJBDZVNXYYHAK-UHFFFAOYSA-N CN(C1=CC=CC=C1)C.[N] Chemical compound CN(C1=CC=CC=C1)C.[N] HKJBDZVNXYYHAK-UHFFFAOYSA-N 0.000 claims description 23
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 15
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 238000002603 single-photon emission computed tomography Methods 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- SFDJOSRHYKHMOK-UHFFFAOYSA-N nitramide Chemical compound N[N+]([O-])=O SFDJOSRHYKHMOK-UHFFFAOYSA-N 0.000 claims 1
- 210000004556 brain Anatomy 0.000 abstract description 22
- 238000002372 labelling Methods 0.000 abstract description 4
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 207
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 204
- 230000015572 biosynthetic process Effects 0.000 description 107
- 238000003786 synthesis reaction Methods 0.000 description 107
- 238000005160 1H NMR spectroscopy Methods 0.000 description 102
- 238000000034 method Methods 0.000 description 95
- 239000000376 reactant Substances 0.000 description 89
- 239000007787 solid Substances 0.000 description 86
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 46
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 25
- 238000000605 extraction Methods 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- 238000000926 separation method Methods 0.000 description 19
- 235000019441 ethanol Nutrition 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000000843 powder Substances 0.000 description 17
- VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
- 229910052794 bromium Inorganic materials 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 12
- KPMVHELZNRNSMN-UHFFFAOYSA-N chembl1985849 Chemical compound N1=CC=C2NCCN21 KPMVHELZNRNSMN-UHFFFAOYSA-N 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 6
- 238000002600 positron emission tomography Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 5
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 229910052698 phosphorus Inorganic materials 0.000 description 5
- 239000011574 phosphorus Substances 0.000 description 5
- 238000011830 transgenic mouse model Methods 0.000 description 5
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 4
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- CGLRRIOHJAAOOU-UHFFFAOYSA-N [O-][N+](=O)C1=CC=C(OCCCCCCOC2=CC=CC=C2)C=C1 Chemical compound [O-][N+](=O)C1=CC=C(OCCCCCCOC2=CC=CC=C2)C=C1 CGLRRIOHJAAOOU-UHFFFAOYSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000002274 desiccant Substances 0.000 description 4
- 125000003963 dichloro group Chemical group Cl* 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000013399 early diagnosis Methods 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 230000036571 hydration Effects 0.000 description 4
- 238000006703 hydration reaction Methods 0.000 description 4
- 239000003068 molecular probe Substances 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 229910020889 NaBH3 Inorganic materials 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical group [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 3
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 3
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
- 210000001835 viscera Anatomy 0.000 description 3
- STBMZSJLFYGOJU-UHFFFAOYSA-N 1,1-dibromooctane Chemical compound CCCCCCCC(Br)Br STBMZSJLFYGOJU-UHFFFAOYSA-N 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
- SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 2
- HUTXVUPGARJNHM-UHFFFAOYSA-N 1-(2-chloroethoxy)ethanol Chemical compound CC(O)OCCCl HUTXVUPGARJNHM-UHFFFAOYSA-N 0.000 description 2
- PGNUVUUPCNUJRJ-UHFFFAOYSA-N 1-[2-(4-nitrophenoxy)ethyl]piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCN1CCNCC1 PGNUVUUPCNUJRJ-UHFFFAOYSA-N 0.000 description 2
- HMWCXMFAFZYXFL-UHFFFAOYSA-N 1-[6-(4-nitrophenoxy)hexyl]piperazine Chemical compound [N+](=O)([O-])C1=CC=C(OCCCCCCN2CCNCC2)C=C1 HMWCXMFAFZYXFL-UHFFFAOYSA-N 0.000 description 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 2
- REKIECQAAZCPIW-UHFFFAOYSA-N 4-[6-(4-chlorophenoxy)hexoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCCOC2=CC=C(C=C2)Cl REKIECQAAZCPIW-UHFFFAOYSA-N 0.000 description 2
- IKRBRRQGQXAWOR-UHFFFAOYSA-N 4-[6-(4-fluorophenoxy)hexoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCCOC2=CC=C(C=C2)F IKRBRRQGQXAWOR-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 238000012879 PET imaging Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 238000009206 nuclear medicine Methods 0.000 description 2
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- BOTNYLSAWDQNEX-UHFFFAOYSA-N phenoxymethylbenzene Chemical class C=1C=CC=CC=1COC1=CC=CC=C1 BOTNYLSAWDQNEX-UHFFFAOYSA-N 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- GTQHJCOHNAFHRE-UHFFFAOYSA-N 1,10-dibromodecane Chemical compound BrCCCCCCCCCCBr GTQHJCOHNAFHRE-UHFFFAOYSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 1
- LVWSZGCVEZRFBT-UHFFFAOYSA-N 1,7-dibromoheptane Chemical compound BrCCCCCCCBr LVWSZGCVEZRFBT-UHFFFAOYSA-N 0.000 description 1
- OBUUFRXYCKXCDL-UHFFFAOYSA-N 1-(10-bromodecoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCCCCCCCBr)C=C1 OBUUFRXYCKXCDL-UHFFFAOYSA-N 0.000 description 1
- HZEGDFQMXJLMIY-UHFFFAOYSA-N 1-(12-bromododecoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCCCCCCCCCBr)C=C1 HZEGDFQMXJLMIY-UHFFFAOYSA-N 0.000 description 1
- AHOFWSHLRKOJBS-UHFFFAOYSA-N 1-(2-bromoethoxy)-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1OCCBr AHOFWSHLRKOJBS-UHFFFAOYSA-N 0.000 description 1
- QBUSKXLDUNPEMZ-UHFFFAOYSA-N 1-(2-bromoethoxy)-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(OCCBr)=C1 QBUSKXLDUNPEMZ-UHFFFAOYSA-N 0.000 description 1
- WHZJAGORNSGMDU-UHFFFAOYSA-N 1-(2-bromoethoxy)-4-iodobenzene Chemical compound BrCCOC1=CC=C(I)C=C1 WHZJAGORNSGMDU-UHFFFAOYSA-N 0.000 description 1
- YQWCBDNNEZHPMA-UHFFFAOYSA-N 1-(2-bromoethoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCBr)C=C1 YQWCBDNNEZHPMA-UHFFFAOYSA-N 0.000 description 1
- LIBYGKUWXRBMPA-UHFFFAOYSA-N 1-(3-bromopropoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCBr)C=C1 LIBYGKUWXRBMPA-UHFFFAOYSA-N 0.000 description 1
- DBRBCFJUEVSKGZ-UHFFFAOYSA-N 1-(4-bromobutoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCBr)C=C1 DBRBCFJUEVSKGZ-UHFFFAOYSA-N 0.000 description 1
- BVSTUBWHFKRCJI-UHFFFAOYSA-N 1-(5-bromopentoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCCBr)C=C1 BVSTUBWHFKRCJI-UHFFFAOYSA-N 0.000 description 1
- OZGPUWICHIIELI-UHFFFAOYSA-N 1-(6-bromohexoxy)-4-iodobenzene Chemical compound BrCCCCCCOC1=CC=C(I)C=C1 OZGPUWICHIIELI-UHFFFAOYSA-N 0.000 description 1
- HWAIAEBLYDVAIW-UHFFFAOYSA-N 1-(6-bromohexoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCCCBr)C=C1 HWAIAEBLYDVAIW-UHFFFAOYSA-N 0.000 description 1
- WWQAQSAZKMEGJG-UHFFFAOYSA-N 1-(7-bromoheptoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCCCCBr)C=C1 WWQAQSAZKMEGJG-UHFFFAOYSA-N 0.000 description 1
- LZLYKMANGJCWHY-UHFFFAOYSA-N 1-(8-bromooctoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCCCCCBr)C=C1 LZLYKMANGJCWHY-UHFFFAOYSA-N 0.000 description 1
- XDCLTJPQTHRKJK-UHFFFAOYSA-N 1-[10-(4-iodophenoxy)decoxy]-4-nitrobenzene Chemical compound [O-][N+](=O)c1ccc(OCCCCCCCCCCOc2ccc(I)cc2)cc1 XDCLTJPQTHRKJK-UHFFFAOYSA-N 0.000 description 1
- NKHYVWOSQYWDBT-UHFFFAOYSA-N 1-[12-(4-iodophenoxy)dodecoxy]-4-nitrobenzene Chemical compound IC1=CC=C(C=C1)OCCCCCCCCCCCCOC1=CC=C(C=C1)[N+](=O)[O-] NKHYVWOSQYWDBT-UHFFFAOYSA-N 0.000 description 1
- UJSBDRNPLDBTRZ-UHFFFAOYSA-N 1-[2-(2-chloroethoxy)ethoxy]ethanol Chemical compound CC(O)OCCOCCCl UJSBDRNPLDBTRZ-UHFFFAOYSA-N 0.000 description 1
- WOEYCFHIKSKQFO-UHFFFAOYSA-N 1-[2-(4-bromophenoxy)ethoxy]-4-nitrobenzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCOC1=CC=C(Br)C=C1 WOEYCFHIKSKQFO-UHFFFAOYSA-N 0.000 description 1
- UNMSFRKQMKTDPO-UHFFFAOYSA-N 1-[2-(4-chlorophenoxy)ethoxy]-4-nitrobenzene Chemical compound [O-][N+](=O)c1ccc(OCCOc2ccc(Cl)cc2)cc1 UNMSFRKQMKTDPO-UHFFFAOYSA-N 0.000 description 1
- KEZZMESIBKWBHL-UHFFFAOYSA-N 1-[2-(4-fluorophenoxy)ethoxy]-4-nitrobenzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCOC1=CC=C(F)C=C1 KEZZMESIBKWBHL-UHFFFAOYSA-N 0.000 description 1
- ACWATNXHNVJEMZ-UHFFFAOYSA-N 1-[2-(4-iodophenoxy)ethoxy]-2-nitrobenzene Chemical compound C1=CC=C(C(=C1)[N+](=O)[O-])OCCOC2=CC=C(C=C2)I ACWATNXHNVJEMZ-UHFFFAOYSA-N 0.000 description 1
- UJCPPNBZLWCBMB-UHFFFAOYSA-N 1-[2-(4-iodophenoxy)ethoxy]-3-nitrobenzene Chemical compound C1=CC(=CC(=C1)OCCOC2=CC=C(C=C2)I)[N+](=O)[O-] UJCPPNBZLWCBMB-UHFFFAOYSA-N 0.000 description 1
- XMZSDTTZWOHFGE-UHFFFAOYSA-N 1-[2-(4-iodophenoxy)ethoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCOC2=CC=C(C=C2)I XMZSDTTZWOHFGE-UHFFFAOYSA-N 0.000 description 1
- ZAQUZNYDEPZLFA-UHFFFAOYSA-N 1-[2-(4-iodophenoxy)ethyl]-4-[2-(4-nitrophenoxy)ethyl]piperazine Chemical compound IC1=CC=C(OCCN2CCN(CC2)CCOC2=CC=C(C=C2)[N+](=O)[O-])C=C1 ZAQUZNYDEPZLFA-UHFFFAOYSA-N 0.000 description 1
- GZVWAWAMTRNWSN-UHFFFAOYSA-N 1-[2-[2-(4-iodophenoxy)ethoxy]ethoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCOCCOC2=CC=C(C=C2)I GZVWAWAMTRNWSN-UHFFFAOYSA-N 0.000 description 1
- BJGCFXUKAABGMQ-UHFFFAOYSA-N 1-[3-(4-iodophenoxy)propoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCOC2=CC=C(C=C2)I BJGCFXUKAABGMQ-UHFFFAOYSA-N 0.000 description 1
- GNYJTHFQZTYMTM-UHFFFAOYSA-N 1-[4-(4-iodophenoxy)butoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCCOC2=CC=C(C=C2)I GNYJTHFQZTYMTM-UHFFFAOYSA-N 0.000 description 1
- GGQUOYYRBNCANL-UHFFFAOYSA-N 1-[5-(4-iodophenoxy)pentoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCCCOC2=CC=C(C=C2)I GGQUOYYRBNCANL-UHFFFAOYSA-N 0.000 description 1
- FPLYKUZQGDQANM-UHFFFAOYSA-N 1-[6-(4-bromophenoxy)hexoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCCCCOC2=CC=C(C=C2)Br FPLYKUZQGDQANM-UHFFFAOYSA-N 0.000 description 1
- NXASCYNEZXPQSB-UHFFFAOYSA-N 1-[6-(4-chlorophenoxy)hexoxy]-4-nitrobenzene Chemical compound ClC1=CC=C(OCCCCCCOC2=CC=C(C=C2)[N+](=O)[O-])C=C1 NXASCYNEZXPQSB-UHFFFAOYSA-N 0.000 description 1
- CULQGOFNDSMJOA-UHFFFAOYSA-N 1-[6-(4-fluorophenoxy)hexoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCCCCOC2=CC=C(C=C2)F CULQGOFNDSMJOA-UHFFFAOYSA-N 0.000 description 1
- CXEQXHXCFYXZAD-UHFFFAOYSA-N 1-[6-(4-iodophenoxy)hexoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCCCCOC2=CC=C(C=C2)I CXEQXHXCFYXZAD-UHFFFAOYSA-N 0.000 description 1
- YDICLCJFVQQGEC-UHFFFAOYSA-N 1-[6-(4-iodophenoxy)hexyl]-4-[2-(4-nitrophenoxy)hexyl]piperazine Chemical compound CCCCC(CN1CCN(CC1)CCCCCCOC2=CC=C(C=C2)I)OC3=CC=C(C=C3)[N+](=O)[O-] YDICLCJFVQQGEC-UHFFFAOYSA-N 0.000 description 1
- SXLDHTIYWMUNSI-UHFFFAOYSA-N 1-[7-(4-iodophenoxy)heptoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCCCCCOC2=CC=C(C=C2)I SXLDHTIYWMUNSI-UHFFFAOYSA-N 0.000 description 1
- URFNDUVECWWNMM-UHFFFAOYSA-N 1-[8-(4-iodophenoxy)octoxy]-4-nitrobenzene Chemical compound C1=CC(=CC=C1[N+](=O)[O-])OCCCCCCCCOC2=CC=C(C=C2)I URFNDUVECWWNMM-UHFFFAOYSA-N 0.000 description 1
- QNBGAUAHPKUOQY-UHFFFAOYSA-N 1-bromo-4-[2-(4-iodophenoxy)ethoxy]benzene Chemical compound C1=CC(Br)=CC=C1OCCOC1=CC=C(I)C=C1 QNBGAUAHPKUOQY-UHFFFAOYSA-N 0.000 description 1
- BATHOOFERVHTDY-UHFFFAOYSA-N 1-bromo-4-[6-(4-iodophenoxy)hexoxy]benzene Chemical compound C1=CC(=CC=C1OCCCCCCOC2=CC=C(C=C2)I)Br BATHOOFERVHTDY-UHFFFAOYSA-N 0.000 description 1
- FHPBKFATHBOBHK-UHFFFAOYSA-N 1-chloro-4-[2-(4-iodophenoxy)ethoxy]benzene Chemical compound C1=CC(=CC=C1OCCOC2=CC=C(C=C2)I)Cl FHPBKFATHBOBHK-UHFFFAOYSA-N 0.000 description 1
- CEBFOJALJWYHBA-UHFFFAOYSA-N 1-chloro-4-[6-(4-iodophenoxy)hexoxy]benzene Chemical compound C1=CC(=CC=C1OCCCCCCOC2=CC=C(C=C2)I)Cl CEBFOJALJWYHBA-UHFFFAOYSA-N 0.000 description 1
- OXLWSLIBIRBHRI-UHFFFAOYSA-N 1-fluoro-4-[2-(4-iodophenoxy)ethoxy]benzene Chemical compound C1=CC(=CC=C1OCCOC2=CC=C(C=C2)I)F OXLWSLIBIRBHRI-UHFFFAOYSA-N 0.000 description 1
- ZDPYYFXMAILRHD-UHFFFAOYSA-N 1-fluoro-4-[6-(4-iodophenoxy)hexoxy]benzene Chemical compound C1=CC(=CC=C1OCCCCCCOC2=CC=C(C=C2)I)F ZDPYYFXMAILRHD-UHFFFAOYSA-N 0.000 description 1
- LKTFMSXZPSPYEN-UHFFFAOYSA-N 1-iodo-2-[2-(4-nitrophenoxy)ethoxy]benzene Chemical compound C1=CC=C(C(=C1)OCCOC2=CC=C(C=C2)[N+](=O)[O-])I LKTFMSXZPSPYEN-UHFFFAOYSA-N 0.000 description 1
- JIOVBEAKDVMJQQ-UHFFFAOYSA-N 1-iodo-3-[2-(4-nitrophenoxy)ethoxy]benzene Chemical compound C1=CC(=CC(=C1)I)OCCOC2=CC=C(C=C2)[N+](=O)[O-] JIOVBEAKDVMJQQ-UHFFFAOYSA-N 0.000 description 1
- HXPWHRNDZMLZKQ-UHFFFAOYSA-N 1-iodo-4-[2-(4-iodophenoxy)ethoxy]benzene Chemical compound C1=CC(I)=CC=C1OCCOC1=CC=C(I)C=C1 HXPWHRNDZMLZKQ-UHFFFAOYSA-N 0.000 description 1
- IFSQLKPUROEPJF-UHFFFAOYSA-N 1-iodo-4-[2-(4-methoxyphenoxy)ethoxy]benzene Chemical compound C1=CC(OC)=CC=C1OCCOC1=CC=C(I)C=C1 IFSQLKPUROEPJF-UHFFFAOYSA-N 0.000 description 1
- VSQBPQTXIVESLQ-UHFFFAOYSA-N 1-iodo-4-[6-(4-iodophenoxy)hexoxy]benzene Chemical compound C1=CC(I)=CC=C1OCCCCCCOC1=CC=C(I)C=C1 VSQBPQTXIVESLQ-UHFFFAOYSA-N 0.000 description 1
- OUNDNWMJSZWYKY-UHFFFAOYSA-N 1-iodo-4-[6-(4-methoxyphenoxy)hexoxy]benzene Chemical compound IC1=CC=C(C=C1)OCCCCCCOC1=CC=C(C=C1)OC OUNDNWMJSZWYKY-UHFFFAOYSA-N 0.000 description 1
- AVLGCENMLNBEIO-UHFFFAOYSA-N 1-iodocyclohexa-2,4-dien-1-ol Chemical compound OC1(I)CC=CC=C1 AVLGCENMLNBEIO-UHFFFAOYSA-N 0.000 description 1
- AVOSADBWMXBHGB-UHFFFAOYSA-N 1-nitro-4-(4-phenoxybutoxy)benzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCCCOC1=CC=CC=C1 AVOSADBWMXBHGB-UHFFFAOYSA-N 0.000 description 1
- FDOQVQRUWMLROM-UHFFFAOYSA-N 1-nitro-4-(5-phenoxypentoxy)benzene Chemical compound [N+](=O)([O-])C1=CC=C(OCCCCCOC2=CC=CC=C2)C=C1 FDOQVQRUWMLROM-UHFFFAOYSA-N 0.000 description 1
- XLDIQJWQKGEYRY-UHFFFAOYSA-N 1-tert-butyl-4-[2-(4-iodophenoxy)ethoxy]benzene Chemical compound CC(C)(C)C1=CC=C(C=C1)OCCOC2=CC=C(C=C2)I XLDIQJWQKGEYRY-UHFFFAOYSA-N 0.000 description 1
- WCPKXEDMGLKCGN-UHFFFAOYSA-N 1-tert-butyl-4-[6-(4-iodophenoxy)hexoxy]benzene Chemical compound C(C)(C)(C)C1=CC=C(C=C1)OCCCCCCOC1=CC=C(C=C1)I WCPKXEDMGLKCGN-UHFFFAOYSA-N 0.000 description 1
- MUSRQKJMKFUVBI-UHFFFAOYSA-N 2-[2-(4-iodophenoxy)ethoxy]-N-methylaniline Chemical compound CNC1=CC=CC=C1OCCOC2=CC=C(C=C2)I MUSRQKJMKFUVBI-UHFFFAOYSA-N 0.000 description 1
- XRHSQUQQDFZDGT-UHFFFAOYSA-N 2-[2-(4-iodophenoxy)ethoxy]aniline Chemical compound NC1=CC=CC=C1OCCOC1=CC=C(I)C=C1 XRHSQUQQDFZDGT-UHFFFAOYSA-N 0.000 description 1
- JEQVAGWIQNXLOE-UHFFFAOYSA-N 2-[2-(4-nitrophenoxy)ethoxy]ethanol Chemical compound OCCOCCOC1=CC=C([N+]([O-])=O)C=C1 JEQVAGWIQNXLOE-UHFFFAOYSA-N 0.000 description 1
- HHMZBDBWIQZVMN-UHFFFAOYSA-N 2-[2-[2-(4-nitrophenoxy)ethoxy]ethoxy]ethanol Chemical compound OCCOCCOCCOC1=CC=C([N+]([O-])=O)C=C1 HHMZBDBWIQZVMN-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 229940093475 2-ethoxyethanol Drugs 0.000 description 1
- KQDJTBPASNJQFQ-UHFFFAOYSA-N 2-iodophenol Chemical compound OC1=CC=CC=C1I KQDJTBPASNJQFQ-UHFFFAOYSA-N 0.000 description 1
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
- XBHOUXSGHYZCNH-UHFFFAOYSA-N 2-phenyl-1,3-benzothiazole Chemical class C1=CC=CC=C1C1=NC2=CC=CC=C2S1 XBHOUXSGHYZCNH-UHFFFAOYSA-N 0.000 description 1
- XARSQZSLMFZZDX-UHFFFAOYSA-N 3-[2-(4-iodophenoxy)ethoxy]-N,N-dimethylaniline Chemical compound IC1=CC=C(OCCOC=2C=C(N(C)C)C=CC=2)C=C1 XARSQZSLMFZZDX-UHFFFAOYSA-N 0.000 description 1
- BJCLESAZVKIPSK-UHFFFAOYSA-N 3-[2-(4-iodophenoxy)ethoxy]aniline Chemical compound NC1=CC=CC(OCCOC=2C=CC(I)=CC=2)=C1 BJCLESAZVKIPSK-UHFFFAOYSA-N 0.000 description 1
- FXTKWBZFNQHAAO-UHFFFAOYSA-N 3-iodophenol Chemical compound OC1=CC=CC(I)=C1 FXTKWBZFNQHAAO-UHFFFAOYSA-N 0.000 description 1
- RTZZCYNQPHTPPL-UHFFFAOYSA-N 3-nitrophenol Chemical compound OC1=CC=CC([N+]([O-])=O)=C1 RTZZCYNQPHTPPL-UHFFFAOYSA-N 0.000 description 1
- SIJLYRDVTMMSIP-UHFFFAOYSA-N 4-Bromo-1-butanol Chemical compound OCCCCBr SIJLYRDVTMMSIP-UHFFFAOYSA-N 0.000 description 1
- MWTDYLPOPLUYNP-UHFFFAOYSA-N 4-[10-(4-iodophenoxy)decoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCCCCCCOC2=CC=C(C=C2)I MWTDYLPOPLUYNP-UHFFFAOYSA-N 0.000 description 1
- MXOIKIDYZWKPMN-UHFFFAOYSA-N 4-[10-(4-iodophenoxy)decoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCCCCCCOC2=CC=C(C=C2)I MXOIKIDYZWKPMN-UHFFFAOYSA-N 0.000 description 1
- VWALOJDMKKOTDI-UHFFFAOYSA-N 4-[12-(4-iodophenoxy)dodecoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCCCCCCCCOC2=CC=C(C=C2)I VWALOJDMKKOTDI-UHFFFAOYSA-N 0.000 description 1
- RYGJOACYJFYIPX-UHFFFAOYSA-N 4-[12-(4-iodophenoxy)dodecoxy]aniline Chemical compound IC1=CC=C(OCCCCCCCCCCCCOC2=CC=C(N)C=C2)C=C1 RYGJOACYJFYIPX-UHFFFAOYSA-N 0.000 description 1
- RYUVXEHZAMRLSH-UHFFFAOYSA-N 4-[2-(2-iodophenoxy)ethoxy]-N,N-dimethylaniline Chemical compound IC1=C(OCCOC2=CC=C(N(C)C)C=C2)C=CC=C1 RYUVXEHZAMRLSH-UHFFFAOYSA-N 0.000 description 1
- BDEWFRMQAXALOA-UHFFFAOYSA-N 4-[2-(2-iodophenoxy)ethoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCOC1=CC=CC=C1I BDEWFRMQAXALOA-UHFFFAOYSA-N 0.000 description 1
- NHFIZIWIMTWZGW-UHFFFAOYSA-N 4-[2-(3-iodophenoxy)ethoxy]-N,N-dimethylaniline Chemical compound IC=1C=C(OCCOC2=CC=C(N(C)C)C=C2)C=CC=1 NHFIZIWIMTWZGW-UHFFFAOYSA-N 0.000 description 1
- QCKKZOXLTAYRNE-UHFFFAOYSA-N 4-[2-(3-iodophenoxy)ethoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCOC1=CC=CC(I)=C1 QCKKZOXLTAYRNE-UHFFFAOYSA-N 0.000 description 1
- DHEIDMFVXWRLRU-UHFFFAOYSA-N 4-[2-(4-bromophenoxy)ethoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCOC1=CC=C(Br)C=C1 DHEIDMFVXWRLRU-UHFFFAOYSA-N 0.000 description 1
- VSDZFKXZWZADII-UHFFFAOYSA-N 4-[2-(4-chlorophenoxy)ethoxy]-N,N-dimethylaniline Chemical compound ClC1=CC=C(OCCOC2=CC=C(N(C)C)C=C2)C=C1 VSDZFKXZWZADII-UHFFFAOYSA-N 0.000 description 1
- UTNUGUXNYQSMFR-UHFFFAOYSA-N 4-[2-(4-chlorophenoxy)ethoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCOC1=CC=C(Cl)C=C1 UTNUGUXNYQSMFR-UHFFFAOYSA-N 0.000 description 1
- XXPXKSQMWCLUDB-UHFFFAOYSA-N 4-[2-(4-fluorophenoxy)ethoxy]-N,N-dimethylaniline Chemical compound FC1=CC=C(OCCOC2=CC=C(N(C)C)C=C2)C=C1 XXPXKSQMWCLUDB-UHFFFAOYSA-N 0.000 description 1
- KNFNJDGLCVUSIA-UHFFFAOYSA-N 4-[2-(4-fluorophenoxy)ethoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCOC1=CC=C(F)C=C1 KNFNJDGLCVUSIA-UHFFFAOYSA-N 0.000 description 1
- KNRQQTLXHVXTCQ-UHFFFAOYSA-N 4-[2-(4-iodophenoxy)ethoxy]-N,N-dimethylaniline Chemical compound IC1=CC=C(OCCOC2=CC=C(N(C)C)C=C2)C=C1 KNRQQTLXHVXTCQ-UHFFFAOYSA-N 0.000 description 1
- BVRCNRYECDIFGI-UHFFFAOYSA-N 4-[2-(4-iodophenoxy)ethoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCOC1=CC=C(I)C=C1 BVRCNRYECDIFGI-UHFFFAOYSA-N 0.000 description 1
- HWJDXLPSNKHILD-UHFFFAOYSA-N 4-[2-[2-(4-iodophenoxy)ethoxy]ethoxy]aniline Chemical compound IC1=CC=C(OCCOCCOC2=CC=C(N)C=C2)C=C1 HWJDXLPSNKHILD-UHFFFAOYSA-N 0.000 description 1
- HBMDZUQNRLVHNP-UHFFFAOYSA-N 4-[2-[2-[2-(4-iodophenoxy)ethoxy]ethoxy]ethoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCOCCOCCOC2=CC=C(C=C2)I HBMDZUQNRLVHNP-UHFFFAOYSA-N 0.000 description 1
- ZEGJWZBCFBDZDG-UHFFFAOYSA-N 4-[2-[2-[2-(4-iodophenoxy)ethoxy]ethoxy]ethoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCOCCOCCOC2=CC=C(C=C2)I ZEGJWZBCFBDZDG-UHFFFAOYSA-N 0.000 description 1
- AEXNURIHFONYNB-UHFFFAOYSA-N 4-[2-[4-[2-(4-iodophenoxy)ethyl]piperazin-1-yl]ethoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCN2CCN(CC2)CCOC3=CC=C(C=C3)I AEXNURIHFONYNB-UHFFFAOYSA-N 0.000 description 1
- AXCGUOWDKYGAKQ-UHFFFAOYSA-N 4-[2-[4-[2-(4-iodophenoxy)ethyl]piperazin-1-yl]ethoxy]aniline Chemical compound C1CN(CCN1CCOC2=CC=C(C=C2)N)CCOC3=CC=C(C=C3)I AXCGUOWDKYGAKQ-UHFFFAOYSA-N 0.000 description 1
- BWSVRDCKNKSCDG-UHFFFAOYSA-N 4-[3-(4-iodophenoxy)propoxy]aniline Chemical compound C1=CC(N)=CC=C1OCCCOC1=CC=C(I)C=C1 BWSVRDCKNKSCDG-UHFFFAOYSA-N 0.000 description 1
- PBHIJJRJXVAVEK-UHFFFAOYSA-N 4-[4-(4-iodophenoxy)butoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCOC2=CC=C(C=C2)I PBHIJJRJXVAVEK-UHFFFAOYSA-N 0.000 description 1
- YLJHEFZNKGBXNK-UHFFFAOYSA-N 4-[4-(4-iodophenoxy)butoxy]aniline Chemical compound IC1=CC=C(OCCCCOC2=CC=C(N)C=C2)C=C1 YLJHEFZNKGBXNK-UHFFFAOYSA-N 0.000 description 1
- HXWHNXDJJSGYFJ-UHFFFAOYSA-N 4-[5-(4-iodophenoxy)pentoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCOC2=CC=C(C=C2)I HXWHNXDJJSGYFJ-UHFFFAOYSA-N 0.000 description 1
- HEFUFPUOOGLUCP-UHFFFAOYSA-N 4-[5-(4-iodophenoxy)pentoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCOC2=CC=C(C=C2)I HEFUFPUOOGLUCP-UHFFFAOYSA-N 0.000 description 1
- QISFEJQLIAIAQQ-UHFFFAOYSA-N 4-[6-(4-bromophenoxy)hexoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCCOC2=CC=C(C=C2)Br QISFEJQLIAIAQQ-UHFFFAOYSA-N 0.000 description 1
- ZEXRWQQHEJERPI-UHFFFAOYSA-N 4-[6-(4-chlorophenoxy)hexoxy]-N,N-dimethylaniline Chemical compound ClC1=CC=C(OCCCCCCOC2=CC=C(C=C2)N(C)C)C=C1 ZEXRWQQHEJERPI-UHFFFAOYSA-N 0.000 description 1
- QIFWTVWWZABDDZ-UHFFFAOYSA-N 4-[6-(4-fluorophenoxy)hexoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCCOC2=CC=C(C=C2)F QIFWTVWWZABDDZ-UHFFFAOYSA-N 0.000 description 1
- MMTQMYRQAJWIOP-UHFFFAOYSA-N 4-[6-(4-iodophenoxy)hexoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCCOC2=CC=C(C=C2)I MMTQMYRQAJWIOP-UHFFFAOYSA-N 0.000 description 1
- BCDLCVYATYPCJW-UHFFFAOYSA-N 4-[6-(4-iodophenoxy)hexoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCCOC2=CC=C(C=C2)I BCDLCVYATYPCJW-UHFFFAOYSA-N 0.000 description 1
- RVBGIQRWFVLRIF-UHFFFAOYSA-N 4-[6-[4-[6-(4-iodophenoxy)hexyl]piperazin-1-yl]hexoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCCN2CCN(CC2)CCCCCCOC3=CC=C(C=C3)I RVBGIQRWFVLRIF-UHFFFAOYSA-N 0.000 description 1
- NKLNHRHREOMMAA-UHFFFAOYSA-N 4-[7-(4-iodophenoxy)heptoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCCCOC2=CC=C(C=C2)I NKLNHRHREOMMAA-UHFFFAOYSA-N 0.000 description 1
- LWEAKADFKWXQQE-UHFFFAOYSA-N 4-[7-(4-iodophenoxy)heptoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCCCOC2=CC=C(C=C2)I LWEAKADFKWXQQE-UHFFFAOYSA-N 0.000 description 1
- YAVWWGYAEYYKBZ-UHFFFAOYSA-N 4-[8-(4-iodophenoxy)octoxy]-N,N-dimethylaniline Chemical compound CN(C)C1=CC=C(C=C1)OCCCCCCCCOC2=CC=C(C=C2)I YAVWWGYAEYYKBZ-UHFFFAOYSA-N 0.000 description 1
- FTVKHBJFPNJULQ-UHFFFAOYSA-N 4-[8-(4-iodophenoxy)octoxy]aniline Chemical compound C1=CC(=CC=C1N)OCCCCCCCCOC2=CC=C(C=C2)I FTVKHBJFPNJULQ-UHFFFAOYSA-N 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- IFLIAOLVZGBFFQ-UHFFFAOYSA-N N,N-dimethyl-4-[2-(4-tributylstannylphenoxy)ethoxy]aniline Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C=C1)OCCOC2=CC=C(C=C2)N(C)C IFLIAOLVZGBFFQ-UHFFFAOYSA-N 0.000 description 1
- YCIGATKKSUIVQR-UHFFFAOYSA-N N,N-dimethyl-4-[2-[2-(4-tributylstannylphenoxy)ethoxy]ethoxy]aniline Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C=C1)OCCOCCOC2=CC=C(C=C2)N(C)C YCIGATKKSUIVQR-UHFFFAOYSA-N 0.000 description 1
- DZDCXWOSLPZQLY-UHFFFAOYSA-N N,N-dimethyl-4-[6-(4-tributylstannylphenoxy)hexoxy]aniline Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C=C1)OCCCCCCOC2=CC=C(C=C2)N(C)C DZDCXWOSLPZQLY-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- VQUQOGWOGHMFSX-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C(OCCCCCCCCCCCCOC2=CC=CC=C2)C=C1 Chemical compound [N+](=O)([O-])C1=CC=C(OCCCCCCCCCCCCOC2=CC=CC=C2)C=C1 VQUQOGWOGHMFSX-UHFFFAOYSA-N 0.000 description 1
- PJQBBLOMKBNQNM-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C(OCCCCCCCCOC2=CC=CC=C2)C=C1 Chemical compound [N+](=O)([O-])C1=CC=C(OCCCCCCCCOC2=CC=CC=C2)C=C1 PJQBBLOMKBNQNM-UHFFFAOYSA-N 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005253 cladding Methods 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- NCWZOASIUQVOFA-FWZJPQCDSA-N florbetaben ((18)F) Chemical compound C1=CC(NC)=CC=C1\C=C\C1=CC=C(OCCOCCOCC[18F])C=C1 NCWZOASIUQVOFA-FWZJPQCDSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000036301 sexual development Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 230000000192 social effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/35—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/36—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
- C07C205/37—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- 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
- C07B59/001—Acyclic or carbocyclic compounds
-
- 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
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/84—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/24—Preparation of ethers by reactions not forming ether-oxygen bonds by elimination of halogens, e.g. elimination of HCl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/205—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
- C07C43/2055—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring containing more than one ether bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds
- C07F7/2208—Compounds having tin linked only to carbon, hydrogen and/or halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一类与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用，该类分子被放射性核素标记后作为Aβ斑块显像剂用于阿尔兹海默症的诊断，其结构式如下所示；此类分子的化学结构不同于现有技术所公开的化合物，属于诊断阿尔茨海默症的全新分子；经过放射性核素标记后得到的Aβ斑块显像剂，体内稳定性好，脂溶性低、脑清除速率快，具有巨大的应用前景和市场价值。
Description
技术领域
本发明涉及放射性药物化学和临床核医学技术领域，具体地说，涉及一类与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用，
背景技术
阿尔茨海默症(Alzheimer's Disease，AD)是一种进行性发展的致死性神经退行性疾病，临床表现为认知和记忆功能下降，日常生活能力减退，并伴有各种神经精神症状和行为障碍。AD多发于老年人群，统计资料显示，全球目前有3600万人患有AD,而且每隔二十年AD病患翻两倍，即到2030年将有6600万人遭受AD的折磨，而到2050年，这一数字将达到11500万。目前我国正在快速步入老龄化社会，AD已成为继肿瘤、心脏病和中风之后，严重威胁老年人身心健康的主要疾病。可见，AD的防治工作任务艰巨，研究AD的早期诊断方法及治疗药物具有极其重要社会意义和实际价值。研究表明，AD脑内沉积在神经细胞外的老年斑(SPs)和神经细胞内的神经纤维缠结(NFTs)是AD的两大主要病理特征。利用脑内的Aβ斑块为靶点，开发与之具有高亲和性和选择性的分子探针，通过单光子计算机扫描(SPECT)或正电子发射断层扫描(PET)等核医学影像技术，可以无创伤的从分子水平上早期诊断AD。
在过去的研究里，用于核医学PET显像的Aβ斑块显像剂发展迅速，通过对硫磺素-T(ThT)和刚果红(CR)这两种染料进行修饰，已经有不少分子进入了临床试验阶段。如2-苯基苯并噻唑类的代表化合物[11C]PIB是目前使用最为广泛的Aβ斑块显像剂，它的类似物[18F]GE-067获得美国FDA批准；二苯乙烯衍生物[18F]AV-45、[18F]BAY94-9172也获得美国FDA批准。然而，用于SPECT显像的Aβ斑块显像剂还没有获得突破性进展，其中123I标记的2-苯基咪唑并吡啶衍生物[123I]IMPY是第一个进入临床阶段的SPECT显像剂，但由于其体内稳定性差而宣告失败。纵观以往发展的Aβ斑块分子探针，均具有共轭的平面结构，而我组最近研究表明柔性结构的苯基苄基醚类衍生物与Aβ斑块具有高亲和性，有发展为Aβ斑块显像剂的潜力。在此基础上，试图进一步增加分子柔性，从而得到一系列二苯氧基柔性分子。该类分子是一类全新的与脑内Aβ斑块具有高亲和力的化合物，对其进行放射性核素标记，可以得到一种能够用于AD的早期诊断的Aβ斑块显像剂，势必将会有巨大的应用前景和经济价值。同时，具有不同柔性linker二苯氧基柔性分子化合物与Aβ蛋白结合模式的探究为继续开发新型柔性结构Aβ斑块分子探针的研究奠定理论基础。
发明内容
本发明的目的之一在于，提供一类二苯氧基柔性分子化合物。该类化合物与AD病人脑内Aβ斑块具有高亲和力，属于诊断和治疗AD的全新化合物。
本发明的另一目的在于，提供所述二苯氧基柔性分子化合物的制备方法。
本发明的另一目的在于，提供一种利用所述二苯氧基柔性分子化合物制备得到的Aβ斑块显像剂。
本发明的另一目的在于，提供所述Aβ斑块显像剂在诊断淀粉样病变疾病的药物中的应用，包括AD的早期诊断。
为了实现上述目的，本发明提供的二苯氧基柔性分子化合物，其结构式如下所示：
其中，化合物(Ⅰ)，n为1–11的整数，R1为I或NMe2,R2为氢、卤素、羟基、巯基、烷氧基、烷基、硝基、氨基、烷氨基、氰基、羧基、-Sn(烷基)3、-(OCH2CH2)m-F(m为1-3的整数)；化合物(Ⅱ)，n为2–5的整数，R1为NMe2，R2为I或-(OCH2CH2)m-F(m为1-3的整数)；化合物(III)，n为1–5的整数，R1为NMe2，R2为I或-(OCH2CH2)m-F(m为1-3的整数)。
其中，Me表示甲基。
本发明提供的二苯氧基柔性分子化合物，进一步地，其结构式如式(I)所示：
其中，n为1–11的整数，R1为I或NMe2，R2为氢、卤素、羟基、巯基、烷氧基、烷基、硝基、氨基、烷氨基、氰基、羧基、-Sn(Bu)3、-(OCH2CH2)m-F(m为1-3的整数)，R1和R2均为邻位、间位或对位取代基。
进一步，优选地，n＝2或6，R1和R2分别为：
本发明提供的二苯氧基柔性分子化合物，进一步地，其结构式如式(Ⅱ)所示：
其中，n为2–5的整数，R1为NMe2，R2为I、-Sn(Bu)3、(OCH2CH2)m-F(m为1-3的整数)。
本发明提供的二苯氧基柔性分子化合物，进一步地，其结构式如式(III)所示：
其中，n为2–5的整数，R1为NMe2，R2为I或-(OCH2CH2)m-F(m为1-3的整数)。
本发明提供的上述任意一项二苯氧基柔性分子化合物，进一步地，当其中含有氟原子时，F为18F或19F；当其中含有碘原子时，I为123I、124I、125I、127I或131I；当其中含有甲基、甲氧基、N-甲氨基或二甲氨基时，-CH3为-11CH3、-OCH3为-O11CH3、-NHCH3为-NH11CH3或-N(CH3)2为-N(11CH3)2或-N(CH3)(11CH3)。
更进一步地，当F为18F或I为124I时，得到的二苯氧基柔性分子化合物可作为Aβ斑块显像剂，尤其作为PET类Aβ斑块显像剂。
更进一步地，当-CH3为-11CH3、-OCH3为-O11CH3、-NHCH3为-NH11CH3或-N(CH3)2为-N(11CH3)2或-N(CH3)(11CH3)时，得到的二苯氧基柔性分子化合物可作为Aβ斑块显像剂，尤其作为PET类Aβ斑块显像剂。
更进一步地，当I为125I，123I或131I时，得到的二苯氧基柔性分子化合物可作为Aβ斑块显像剂，尤其作为SPECT类Aβ斑块显像剂。
本发明所述二苯氧基柔性分子化合物(I)，可按照下述反应方程式制备所述化合物：
其中，R1、R2、n与式(I)所示化合物具有相应的定义。
其制备方法包括以下步骤(以n为2，R1为p-NMe2，R2为p-I为例，其他均采用类似方法制备)：
(1)将化合物对硝基苯酚(1396.0mg,10.0mmol)、化合物1,2-二溴乙烷(3758.2mg,20.0mmol)和K2CO3(4142.8mg,30.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末中间体(Ⅴ-a)。
(2)将化合物(Ⅴ-a)(738.2mg,3.0mmol)、化合物4-碘苯酚(660.1mg,3.0mmol)和K2CO3(1242.8mg,9.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末中间体(Ⅰ-a)。
(3)将化合物(Ⅰ-a)(385.2mg,1.0mmol)和二水合二氯亚锡(902.8mg,4.0mmol)溶于适量乙醇中，向溶液中滴加5mL浓盐酸，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，抽滤，除去干燥剂，旋蒸，除去溶剂，即得中间体(Ⅰ-b)。
(4)将化合物(Ⅰ-b)(269.6mg,0.7mmol)和多聚甲醛(210.2mg,7.0mmol)溶于适量冰醋酸中，在冰浴条件下，向溶液中缓慢分批加入氰基硼氢化钠(219.9mg,3.5mmol)，室温反应过夜，反应结束后，向溶液中加入氨水调pH至弱碱性，CH2Cl2萃取，MgSO4干燥，柱色谱分离得白色粉末的终产物(Ⅰ-c)。
本发明所述二苯氧基柔性分子化合物(Ⅱ)，可按照下述反应方程式制备所述化合物：
其中，R1、R2、n与式(Ⅱ)所示化合物具有相应的定义。
其制备方法包括以下步骤(以n为2，R1为NMe2，R2为I为例，其他均采用类似方法制备)：
(1)将化合物对硝基苯酚(1396.0mg,10.0mmol)、化合物2-氯乙氧基乙醇(1246.2mg,10.0mmol)和K2CO3(4142.8mg,30.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色蜡状中间体。将该中间体(1136.5mg,5.0mmol)和对甲苯磺酰氯(1143.8mg,6.0mmol)溶于适量的无水二氯甲烷中，再向溶液中滴加5mL的三乙胺，室温反应6h，旋蒸，除掉溶剂，柱色谱分离得淡黄色粉末的中间体(Ⅶ-a)。
(2)将化合物(Ⅶ-a)(1144.2mg,3.0mmol)、化合物4-碘苯酚(660.1mg,3.0mmol)和K2CO3(1242.8mg,9.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末中间体(Ⅱ-a)。
(3)将化合物(Ⅱ-a)(429.2mg,1.0mmol)和二水合二氯亚锡(902.8mg,4.0mmol)溶于适量乙醇中，向溶液中滴加5mL浓盐酸，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，抽滤，除去干燥剂，旋蒸，除去溶剂，即得中间体(Ⅱ-b)。
(4)将化合物(Ⅱ-b)(360.0mg,0.9mmol)和多聚甲醛(270.9mg,9.0mmol)溶于适量冰醋酸中，冰浴下，向溶液中缓慢分批加入氰基硼氢化钠(282.9mg,4.5mmol)，室温反应过夜，反应结束后，向溶液中加入氨水调pH至弱碱性，CH2Cl2萃取，MgSO4干燥，柱色谱分离得白色粉末的终产物(Ⅱ-c)。
本发明所述二苯氧基柔性分子化合物(III)，可按照下述反应方程式制备所述化合物：
其中，R1、R2、n与式(III)所示化合物具有相应的定义。
其制备方法包括以下步骤(以n为2，R1为NMe2，R2为I为例，其他均采用类似方法制备)：
(1)取3mL溴化氢溶液(40％)加入溶有化合物哌嗪(516.8mg,6.0mmol)的乙醇溶液中，然后将溶有化合物(Ⅴ-a)(738.2mg,3.0mmol)的乙醇溶液加入上述溶液中，90℃回流反应48h，反应结束后，旋蒸，除去溶剂，加水酸化(10％HCl,pH＝5-6)，CH2Cl2洗涤，收集水相，碱化(50％NaOH,pH>9),CH2Cl2萃取，得到黄色固体中间体(VIII-a)。
(2)将化合物(VIII-a)(152.9mg,0.6mmol)、化合物1-(2-溴乙醇)-4-碘苯(199.0mg,0.6mmol)和K2CO3(248.8mg,1.8mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末中间体(III-a)。
(3)III-b，III-c的合成方法同Ⅱ-b，Ⅱ-c的合成。
本发明还提供利用所述二苯氧基柔性分子化合物制备得到的Aβ斑块显像剂。
其中，当上述任意一项二苯氧基柔性分子化合物中含有氟原子时，制备得到含有放射性核素18F的化合物，即作为Aβ斑块显像剂，尤其作为PET类Aβ斑块显像剂。
或者，当上述任意一项二苯氧基柔性分子化合物中含有碘原子时，制备得到含有放射性核素124I的化合物，即作为Aβ斑块显像剂，尤其作为PET类Aβ斑块显像剂。
或者，当上述任意一项二苯氧基柔性分子化合物中含有甲基、甲氧基、N-甲氨基或二甲氨基时，制备得到含有放射性核素11C(-11CH3、-O11CH3、-NH11CH3、-N(11CH3)2或-N(CH3)(11CH3))的化合物，即作为Aβ斑块显像剂，尤其作为PET类Aβ斑块显像剂。
或者，当上述任意一项二苯氧基柔性分子化合物中含有碘原子时，制备得到含有放射性核素123I、125I或131I的化合物，即作为Aβ斑块显像剂，尤其作为SPECT类Aβ斑块显像剂。
其中，所述Aβ斑块显像剂为单光子或正电子Aβ斑块显像剂。
其中，所述Aβ斑块显像剂可用于PET显像或SPECT显像。
本发明提供的Aβ斑块显像剂可用于AD中淀粉样病变的早期诊断。
本发明还提供所述二苯氧基柔性分子化合物或所述Aβ斑块显像剂在制备和治疗诊断淀粉样病变疾病(包括阿尔茨海默症)的药物中的应用。
本发明首次公开了一类全新结构的二苯氧基柔性分子化合物化合物，体外竞争结合实验表明，该类分子与Aβ1-42聚集体的亲和力很高；体外放射自显影实验表明I-125的该类分子可以特异性地与AD人脑切片或AD转基因小鼠脑内的Aβ斑块结合；正常小鼠体内生物分布实验表明，部分I-125标记的显像剂具有初始脑摄取高，清除快的优点；有望成为一种新的用于临床显像的单光子Aβ斑块显像剂。
本发明提供一类全新的与AD病人脑内Aβ斑块具有高亲和力的苯基苄基醚衍生物，化学结构不同于现有技术所公开的化合物，尤其是硫磺素-T和刚果红，属于诊断和治疗阿尔茨海默症的全新化合物；利用该化合物制备的Aβ斑块显像剂，体内稳定性好，具有巨大的应用前景和市场价值。同时，具有不同柔性linker二苯氧基柔性分子化合物与Aβ蛋白结合模式的探究，为继续开发新型柔性结构Aβ斑块分子探针的研究奠定理论基础。
附图说明
图1和图2为本发明实施例1中碘代化合物(Ⅰ)的合成反应路线。
图3为本发明实施例2中碘代化合物(Ⅱ)合成反应路线。
图4为本发明实施例3中碘代化合物(III)合成反应路线。
图5为本发明实施例4中部分二苯氧基柔性分子与AD转基因小鼠及AD病人脑切片中的斑块结合的放射自显影实验结果。
具体实施方式
以下实施例用于说明本发明，但不用来限制本发明的范围。若未特别指明，实施例中所用的技术手段为本领域技术人员所熟知的常规手段，所用原料均为市售商品。
实施例1：碘代化合物(Ⅰ)的合成
合成反应路线如图1，图2所示，本实施例中的化合物编号均与该图反应路线中的编号统一。
在图1所示的合成路线中，试剂与条件如下：(a)1，n-二溴烷烃(n＝2-11)，K2CO3,DMF,90℃；(b)n-碘苯酚(n＝2,3或4)，K2CO3,DMF,90℃；(c)SnCl2·2H2O,EtOH,HCl,回流；(d)(CH2O)n,NaBH3CN,HAc,室温(e)(Bu3Sn)2,(PPh3)4Pd,甲苯,Et3N,回流；(f)[125I]NaI,HCl(1M),H2O2(3％)。
在图2所示的合成路线中，试剂与条件如下：(a)1，n-二溴烷烃(n＝2，6)，K2CO3,丙酮,90℃；(b)4-R-苯酚(R＝OCH3,F,Cl,Br,I,t-Bu)，K2CO3,DMF,90℃。
1)1-(2-溴乙醇基)-4-硝基苯(1-(2-bromoethoxy)-4-nitrobenzene，化合物1.1)的合成
将对硝基苯酚(1396.0mg,10.0mmol)、1,2-二溴乙烷(3758.2mg,20.0mmol)和K2CO3(4142.8mg,30.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末1.1。1H NMR(400MHz,CDCl3)δ8.22(d,J＝8.9Hz,2H),6.98(d,J＝9.1Hz,2H),4.39(t,J＝6.1Hz,2H),3.68(t,J＝6.1Hz,2H).
2)1-(2-溴乙醇基)-2-硝基苯(1-(2-bromoethoxy)-2-nitrobenzene，化合物1.1a)的合成
按照化合物1.1)的方法制备(反应物用邻硝基苯酚代替对硝基苯酚)，得到淡黄色固体1.1a。1H NMR(400MHz,CDCl3)δ7.84(dd,J＝8.3,1.7Hz,1H),7.54(td,J＝8.5,1.7Hz,1H),7.12–7.06(m,2H),4.42(t,J＝6.5Hz,2H),3.68(t,J＝6.5Hz,2H).
3)1-(2-溴乙醇基)-3-硝基苯(1-(2-bromoethoxy)-3-nitrobenzene，化合物1.1b)的合成
按照化合物1.1)的方法制备(反应物用间硝基苯酚代替对硝基苯酚)，得到淡黄色固体1.1b。1H NMR(400MHz,CDCl3)δ7.88(ddd,J＝8.1,2.1,0.8Hz,1H),7.76(t,J＝2.3Hz,1H),7.47(t,J＝8.2Hz,1H),7.27(ddd,J＝8.1,2.1,0.8Hz,1H),4.39(t,J＝6.1Hz,2H),3.69(t,J＝6.1Hz,2H).
4)1-(3-溴丙醇基)-4-硝基苯(1-(3-bromopropoxy)-4-nitrobenzene，化合物1.2)的合成
按照化合物1.1)的方法制备(反应物用1,3-二溴丙烷代替1,2-二溴乙烷)，得到淡黄色固体1.2。1H NMR(400MHz,CDCl3)δ8.21(d,J＝9.1Hz,2H),6.97(d,J＝9.1Hz,2H),4.22(t,J＝5.8Hz,2H),3.61(t,J＝6.2Hz,2H),2.39–2.36(m,2H).
5)1-(4-溴丁醇基)-4-硝基苯(1-(4-bromobutoxy)-4-nitrobenzene，化合物1.3)的合成
按照化合物1.1)的方法制备(反应物用1,4-二溴丁烷代替1,2-二溴乙烷)，得到淡黄色固体1.3。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.1Hz,2H),6.95(d,J＝9.1Hz,2H),4.10(t,J＝5.8Hz,2H),3.50(t,J＝6.2Hz,2H),2.10–1.99(m,4H).
6)1-(5-溴戊醇基)-4-硝基苯(1-((5-bromopentyl)oxy)-4-nitrobenzene，化合物1.4)的合成
按照化合物1.1)的方法制备(反应物用1,5-二溴戊烷代替1,2-二溴乙烷)，得到淡黄色固体1.4。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.1Hz,2H),6.94(d,J＝9.1Hz,2H),4.07(t,J＝6.2Hz,2H),3.47–3.40(m,2H),1.99–1.83(m,4H),1.69–1.59(m,2H).
7)1-(6-溴己醇基)-4-硝基苯(1-((6-bromohexyl)oxy)-4-nitrobenzene，化合物1.5)的合成
按照化合物1.1)的方法制备(反应物用1,6-二溴己烷代替1,2-二溴乙烷)，得到淡黄色固体1.5。1H NMR(400MHz,CDCl3)δ8.20(d,J＝8.9Hz,2H),6.94(d,J＝8.9Hz,2H),4.06(t,J＝6.2Hz,1H),3.45–3.40(m,2H),1.91–1.85(m,4H),1.54–1.48(m,4H).
8)1-(7-溴庚醇基)-4-硝基苯(1-((7-bromoheptyl)oxy)-4-nitrobenzene，化合物1.6)的合成
按照化合物1.1)的方法制备(反应物用1,7-二溴庚烷代替1,2-二溴乙烷)，得到淡黄色固体1.6。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),8.19(d,J＝9.2Hz,2H),4.05(t,J＝6.4Hz,2H),3.42(t,J＝6.4Hz,2H),1.90–1.80(m,4H),1.49–1.43(m,4H),1.42–1.35(m,2H).
9)1-(8-溴辛醇基)-4-硝基苯(1-((8-bromooctyl)oxy)-4-nitrobenzene，化合物1.7)的合成
按照化合物1.1)的方法制备(反应物用1,8-二溴辛烷代替1,2-二溴乙烷)，得到淡黄色固体1.7。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),6.94(d,J＝9.2Hz,2H),4.05(t,J＝6.5Hz,2H),3.41(t,J＝6.8Hz,2H),1.87–1.79(m,4H),1.49–1.44(m,4H),1.44–1.36(m,4H).
10)1-(10-溴癸醇基)-4-硝基苯(1-((10-bromodecyl)oxy)-4-nitrobenzene，化合物1.9)的合成
按照化合物1.1)的方法制备(反应物用1,10-二溴癸烷代替1,2-二溴乙烷)，得到淡黄色固体1.9。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),6.94(d,J＝9.2Hz,2H),4.05(t,J＝6.5Hz,1H),3.41(t,J＝6.8Hz,1H),1.89–1.78(m,4H),1.48–1.40(m,4H),1.40–1.32(m,8H).
11)1-(12-溴十二醇基)-4-硝基苯(1-((12-bromododecyl)oxy)-4-nitrobenzene，化合物1.11)的合成
按照化合物1.1)的方法制备(反应物用1,12-二溴辛烷代替1,2-二溴乙烷)，得到淡黄色固体1.11。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),6.94(d,J＝9.3Hz,2H),4.04(t,J＝6.5Hz,2H),3.40(t,J＝6.8,2H),1.89–1.78(m,4H),1.50–1.39(m,4H),1.29(s,12H).
12)1-碘-4-(2-(4-硝基苯氧基)乙氧基)苯(1-iodo-4-(2-(4-nitrophenoxy)ethoxy)benzene,化合
物1.12)的合成
将化合物1.1(738.2mg,3.0mmol)、4-碘苯酚(660.1mg,3.0mmol)和K2CO3(1242.8mg,9.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末。1H NMR(400MHz,CDCl3)δ8.23(d,J＝9.0Hz,2H),7.59(d,J＝8.6Hz,2H),7.01(d,J＝9.1Hz,2H),6.73(d,J＝8.7Hz,2H),4.41(s,2H),4.33(s,2H).
13)1-(2-(4-碘苯氧基)乙氧基)-2-硝基苯(1-(2-(4-iodophenoxy)ethoxy)-2-nitrobenzene,化合
物1.12a)的合成
按照化合物1.12)的方法制备(反应物用1.1a代替1.1)，得到淡黄色固体1.12a。1HNMR(400MHz,CDCl3)δ7.84(dd,J＝8.1,1.7Hz,1H),7.57(d,J＝9.0Hz,2H),7.55–7.52(m,1H),7.16(dd,J＝8.4,0.8Hz,1H),7.10–7.06(m,1H),6.73(d,J＝9.0Hz,2H),4.47–4.44(m,2H),4.35–4.33(m,2H).
14)1-(2-(4-碘苯氧基)乙氧基)-3-硝基苯(1-(2-(4-iodophenoxy)ethoxy)-3-nitrobenzene,化合
物1.12b)的合成
按照化合物1.12)的方法制备(反应物用1.1b代替1.1)，得到淡黄色固体1.12b。1HNMR(400MHz,CDCl3)δ7.86(ddd,J＝8.1,2.1,0.8Hz,1H),7.80(t,J＝2.3Hz,1H),7.58(d,J＝9.0Hz,2H),7.45(t,J＝8.2Hz,1H),7.28(ddd,J＝8.5,2.6,0.9Hz,1H),6.73(d,J＝9.0Hz,2H),4.41–4.39(m,2H),4.34–4.32(m,2H).
15)1-碘-2-(2-(4-硝基苯氧基)乙氧基)苯(1-iodo-2-(2-(4-nitrophenoxy)ethoxy)benzene,化合物
1.12c)的合成
按照化合物1.12)的方法制备(反应物用1-碘苯酚代替4-碘苯酚)，得到淡黄色固体1.12c。1H NMR(400MHz,CDCl3)δ8.22(dt,J＝9.28,3.4Hz,2H),7.79(dd,J＝7.8,1.6Hz,1H),7.32(ddd,J＝8.2,7.5,1.6Hz,1H),7.06(dt,J＝9.24,3.4Hz,2H),6.90(dd,J＝8.2,1.3Hz,1H),6.76(td,J＝7.6,1.3Hz,1H),4.53–4.47(m,2H),4.41(dd,J＝5.8,3.7Hz,2H).
16)1-碘-3-(2-(4-硝基苯氧基)乙氧基)苯(1-iodo-3-(2-(4-nitrophenoxy)ethoxy)benzene,化合物
1.12d)的合成
按照化合物1.12)的方法制备(反应物用3-碘苯酚代替4-碘苯酚)，得到淡黄色固体1.12d。1H NMR(400MHz,CDCl3)δ8.23(d,J＝9.3Hz,2H),7.34–7.30(m,2H),7.04–7.00(m,3H),6.93–6.90(m,1H),4.42–4.39(m,1H),4.36–4.33(m,1H).
17)1-氟-4-(2-(4-硝基苯氧基)乙氧基)苯(1-fluoro-4-(2-(4-nitrophenoxy)ethoxy)benzene,化合
物1.12e)的合成
按照化合物1.12)的方法制备(反应物用4-氟苯酚代替4-碘苯酚)，得到淡黄色固体1.12e。1H NMR(400MHz,CDCl3)δ8.23(d,J＝9.3Hz,2H),7.03–6.98(m,4H),6.91–6.87(m,2H),4.42–4.40(m,2H),4.34–4.32(m,2H).
18)1-氯-4-(2-(4-硝基苯氧基)乙氧基)苯(1-chloro-4-(2-(4-nitrophenoxy)ethoxy)benzene,化合
物1.12f)的合成
按照化合物1.12)的方法制备(反应物用4-氯苯酚代替4-碘苯酚)，得到淡黄色固体1.12f。1H NMR(400MHz,CDCl3)δ8.22(d,J＝9.3Hz,2H),7.26(d,J＝9.0Hz,2H),7.02(d,J＝9.3Hz,2H),6.88(d,J＝9.0Hz,2H),4.43–4.39(m,2H),4.36–4.32(m,2H).
19)1-溴-4-(2-(4-硝基苯氧基)乙氧基)苯(1-bromo-4-(2-(4-nitrophenoxy)ethoxy)benzene,化合
物1.12g)的合成
按照化合物1.12)的方法制备(反应物用4-溴苯酚代替4-碘苯酚)，得到淡黄色固体1.12g。1H NMR(400MHz,CDCl3)δ8.22(d,J＝9.0Hz,2H),7.40(d,J＝8.7Hz,2H),7.01(d,J＝9.1Hz,2H),6.83(d,J＝8.6Hz,2H),4.41–4.40(m,2H),4.34–4.33(m,2H).
20)1-碘-4-(3-(4-硝基苯氧基)丙氧基)苯(1-iodo-4-(3-(4-nitrophenoxy)propoxy)benzene,化合
物1.13)的合成
按照化合物1.12)的方法制备(反应物用化合物1.2代替化合物1.1)，得到淡黄色固体1.13。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.2Hz,2H),7.55(d,J＝8.8Hz,2H),6.94(d,J＝9.2Hz,2H),6.67(d,J＝8.8Hz,2H),4.12(d,J＝5.7Hz,2H),4.01(d,J＝5.8Hz,2H),2.32–2.27(m,2H).
21)1-碘-4-(4-(4-硝基苯氧基)丁氧基)苯(1-iodo-4-(4-(4-nitrophenoxy)butoxy)benzene,化合物
1.14)的合成
按照化合物1.12)的方法制备(反应物用化合物1.3代替化合物1.1)，得到淡黄色固体1.14。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.2Hz,2H),7.55(d,J＝8.8Hz,2H),6.94(d,J＝9.2Hz,2H),6.67(d,J＝8.8Hz,2H),4.13(d,J＝5.7Hz,2H),4.01(d,J＝5.8Hz,2H),1.99(s,4H).
22)1-碘-4-(5-(4-硝基苯氧基)戊氧基)苯(1-iodo-4-((5-(4-nitrophenoxy)pentyl)oxy)benzene,化
合物1.15)的合成
按照化合物1.12)的方法制备(反应物用化合物1.4代替化合物1.1)，得到淡黄色固体1.15。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),7.55(d,J＝8.8Hz,2H),6.94(d,J＝9.2Hz,2H),6.67(d,J＝8.8Hz,2H),4.08(d,J＝6.3Hz,2H),3.96(d,J＝6.3Hz,2H),1.94–1.83(m,4H),1.70–1.62(m,2H).
23)1-碘-4-(6-(4-硝基苯氧基)己氧基)苯(1-iodo-4-((6-(4-nitrophenoxy)hexyl)oxy)benzene,化
合物1.16)的合成
按照化合物1.12)的方法制备(反应物用化合物1.5代替化合物1.1)，得到淡黄色固体1.16。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),7.53(d,J＝8.8Hz,2H),6.93(d,J＝9.2Hz,2H),6.66(d,J＝8.8Hz,2H),4.06(t,J＝6.4Hz,1H),3.93(t,J＝6.4Hz,1H),1.87–1.80(m,4H),1.56–1.53(m,4H).
24)1-氟-4-(6-(4-硝基苯氧基)己氧基)苯(1-fluoro-4-((6-(4-nitrophenoxy)hexyl)oxy)benzene,化
合物1.16a)的合成
按照化合物1.12)的方法制备(反应物用化合物4-氟苯酚代替4-碘苯酚)，得到淡黄色固体1.16a。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.3Hz,2H),7.22(d,J＝9.0Hz,2H),6.94(d,J＝9.3Hz,2H),6.81(d,J＝9.0Hz,2H),4.06(t,J＝6.4Hz,2H),3.94(t,J＝6.4Hz,2H),1.88–1.78(m,4H),1.57–1.53(m,4H).
25)1-氯-4-(6-(4-硝基苯氧基)己氧基)苯(1-chloro-4-((6-(4-nitrophenoxy)hexyl)oxy)benzene,化
合物1.16b)的合成
按照化合物1.12)的方法制备(反应物用化合物4-氯苯酚代替4-碘苯酚)，得到淡黄色固体1.16b。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.3Hz,2H),6.98–6.93(m,4H),6.85–6.79(m,2H),4.06(t,J＝6.4Hz,2H),3.93(t,J＝6.4Hz,2H),1.88–1.78(m,4H),1.57–1.54(m,4H).
26)1-溴-4-(6-(4-硝基苯氧基)己氧基)苯(1-bromo-4-((6-(4-nitrophenoxy)hexyl)oxy)benzene,化
合物1.16b)的合成
按照化合物1.12)的方法制备(反应物用化合物4-溴苯酚代替4-碘苯酚)，得到淡黄色固体1.16c。1H NMR(400MHz,CDCl3)δ8.19(dd,J＝9.3,2.2Hz,2H),7.39–7.33(m,2H),6.97–6.91(m,2H),6.77(dd,J＝8.9,2.1Hz,2H),4.06(t,J＝6.4Hz,2H),3.94(t,J＝6.3Hz,2H),1.93–1.77(m,4H),1.56–1.53(m,4H).
27)1-碘-4-(7-(4-硝基苯氧基)庚氧基)苯(1-iodo-4-((7-(4-nitrophenoxy)heptyl)oxy)benzene,化
合物1.17)的合成
按照化合物1.12)的方法制备(反应物用化合物1.6代替化合物1.1)，得到淡黄色固体1.17。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),7.54(d,J＝8.9Hz,2H),6.93(d,J＝9.2Hz,2H),6.66(d,J＝8.8Hz,2H),4.05(t,J＝6.5Hz,1H),3.92(t,J＝6.5Hz,1H),1.87–1.76(m,4H),1.51–1.43(m,6H).
28)1-碘-4-(8-(4-硝基苯氧基)辛氧基)苯(1-iodo-4-((8-(4-nitrophenoxy)octyl)oxy)benzene,化
合物1.18)的合成
按照化合物1.12)的方法制备(反应物用化合物1.7代替化合物1.1)，得到淡黄色固体1.18。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,1H),7.54(d,J＝8.9Hz,1H),6.94(d,J＝9.3Hz,1H),6.67(d,J＝8.9Hz,1H),4.04(t,J＝6.5Hz,1H),3.91(t,J＝6.5Hz,1H),1.86–1.74(m,4H),1.50–1.43(m,4H),1.41–1.38(m,4H).
29)1-碘-4-(10-(4-硝基苯氧基)葵氧基)苯(1-iodo-4-((10-(4-nitrophenoxy)decyl)oxy)benzene,化
合物1.20)的合成
按照化合物1.12)的方法制备(反应物用化合物1.9代替化合物1.1)，得到淡黄色固体1.20。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.2Hz,2H),7.54(d,J＝8.9Hz,2H),6.94(d,J＝9.3Hz,2H),6.67(d,J＝8.9Hz,2H),4.04(t,J＝6.5Hz,2H),3.91(t,J＝6.5Hz,2H),1.89–1.73(m,4H),1.51–1.39(m,4H),1.33(s,8H).
30)1-碘-4-(12-(4-硝基苯氧基)十二烷氧基)苯
(1-iodo-4-((12-(4-nitrophenoxy)dodecyl)oxy)benzene,化合物1.22)的合成
按照化合物1.12)的方法制备(反应物用化合物1.11代替化合物1.1)，得到淡黄色固体1.22。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.3Hz,2H),7.53(d,J＝8.9Hz,2H),6.94(d,J＝9.3Hz,2H),6.67(d,J＝9.0Hz,2H),4.04(t,J＝6.5Hz,2H),3.91(t,J＝6.5Hz,2H),1.87–1.71(m,4H),1.52–1.38(m,4H),1.29(s,12H).
31)4-(2-(4-碘苯氧基)乙氧基)苯胺(4-(2-(4-iodophenoxy)ethoxy)aniline,化合物1.23)的合成
将化合物1.12)(385.2mg,1.0mmol)和二水合二氯亚锡(902.8mg,4.0mmol)溶于适量乙醇中，向溶液中滴加5mL浓盐酸，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，抽滤，除去干燥剂，旋蒸，除去溶剂，即得化合物1.23。1H NMR(400MHz,CDCl3)δ7.56(dd,J＝8.8,2.8Hz,2H),6.79(d,J＝8.9Hz,2H),6.73(d,J＝8.6Hz,2H),6.64(d,J＝8.6Hz,2H),4.24(s,4H),3.44(s,2H).
32)2-(2-(4-碘苯氧基)乙氧基)苯胺(2-(2-(4-iodophenoxy)ethoxy)aniline,化合物1.23a)的合成
按照化合物1.23)的方法制备(反应物用化合物1.12a代替化合物1.12)，得到淡黄色固体1.23a.1H NMR(400MHz,CDCl3)δ7.57(d,J＝9.0Hz,2H),6.83–6.81(m,2H),6.74–6.71(m,4H),4.34–4.28(m,4H),3.79(s,2H).
33)3-(2-(4-碘苯氧基)乙氧基)苯胺(3-(2-(4-iodophenoxy)ethoxy)aniline,化合物1.23b)的合成
按照化合物1.23)的方法制备(反应物用化合物1.12b代替化合物1.12)，得到淡黄色固体1.23b.1H NMR(400MHz,CDCl3)δ7.56(d,J＝9.0Hz,2H),7.07(t,J＝8.0Hz,1H),6.73(d,J＝9.0Hz,2H),6.37–6.30(m,2H),6.28(t,J＝2.2Hz,1H),4.27(s,4H),3.68(s,2H).
34)4-(2-(2-碘苯氧基)乙氧基)苯胺(4-(2-(2-iodophenoxy)ethoxy)aniline,化合物1.23c)的合成
按照化合物1.23)的方法制备(反应物用化合物1.12c代替化合物1.12)，得到淡黄色固体1.23c.1H NMR(400MHz,CDCl3)δ7.76(d,J＝7.8Hz,2H),7.28(m,1H),6.86(m,3H),6.72(m,3H),4.33(s,4H).
35)4-(2-(3-碘苯氧基)乙氧基)苯胺(4-(2-(3-iodophenoxy)ethoxy)aniline,化合物1.23d)的合成
按照化合物1.23)的方法制备(反应物用化合物1.12d代替化合物1.12)，得到淡黄色固体1.23d.1H NMR(400MHz,CDCl3)δ7.30–7.29(m,2H),6.98(t,J＝8.0Hz,1H),6.93–6.90(m,1H),6.79(d,J＝8.9Hz,2H),6.65(d,J＝8.8Hz,2H),4.24(s,4H).
36)4-(2-(4-氟苯氧基)乙氧基)苯胺(4-(2-(4-fluorophenoxy)ethoxy)aniline,化合物1.23e)的合成
按照化合物1.23)的方法制备(反应物用化合物1.12e代替化合物1.12)，得到淡黄色固体1.23e.1H NMR(400MHz,CDCl3)δ6.98(t,J＝8.0Hz,2H),6.90(s,1H),6.80(d,J＝7.7Hz,2H),6.65(d,J＝7.6Hz,2H),4.24(s,4H),3.47(s,2H).
37)4-(2-(4-氯苯氧基)乙氧基)苯胺(4-(2-(4-chlorophenoxy)ethoxy)aniline,化合物1.23f)的合成
按照化合物1.23)的方法制备(反应物用化合物1.12f代替化合物1.12)，得到淡黄色固体1.23f.1H NMR(400MHz,CDCl3)δ7.24(d,J＝9.0Hz,2H),6.88(d,J＝9.0Hz,2H),6.79(d,J＝8.8Hz,2H),6.65(d,J＝8.8Hz,2H),4.25(s,4H),3.45(s,2H).
38)4-(2-(4-溴苯氧基)乙氧基)苯胺(4-(2-(4-bromophenoxy)ethoxy)aniline,化合物1.23f)的合成
按照化合物1.23)的方法制备(反应物用化合物1.12g代替化合物1.12)，得到淡黄色固体1.23g.1H NMR(400MHz,CDCl3)δ7.30(d,J＝7.5Hz,2H),6.95(d,J＝7.9Hz,2H),6.80(d,J＝8.3Hz,2H),6.64(d,J＝8.4Hz,2H),4.27(s,4H),3.42(s,2H).
39)4-(3-(4-碘苯氧基)丙氧基)苯胺(4-(3-(4-iodophenoxy)propoxy)aniline,化合物1.24)的合成
按照化合物1.23)的方法制备(反应物用化合物1.13代替化合物1.12)，得到淡黄色固体1.24。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.0Hz,2H),6.76(d,J＝8.9Hz,2H),6.70(d,J＝8.9Hz,2H),6.68(d,J＝8.9Hz,2H),4.11(t,J＝6.2Hz,2H),4.07(t,J＝6.1Hz,2H),2.24–2.18(m,2H).
40)4-(4-(4-碘苯氧基)丁氧基)苯胺(4-(4-(4-iodophenoxy)butoxy)aniline,化合物1.25)的合成
按照化合物1.23)的方法制备(反应物用化合物1.14代替化合物1.12)，得到淡黄色固体1.25。1H NMR(400MHz,CDCl3)δ7.54(dd,J＝8.9,2.2Hz,2H),6.74(d,J＝8.8Hz,2H),6.67(d,J＝8.7Hz,2H),6.64(d,J＝8.7Hz,2H),3.98–3.95(m,4H),3.48(s,2H),1.93–1.84(m,4H).
41)4-(5-(4-碘苯氧基)戊氧基)苯胺(4-((5-(4-iodophenoxy)pentyl)oxy)aniline,化合物1.26)的合成
按照化合物1.23)的方法制备(反应物用化合物1.15代替化合物1.12)，得到淡黄色固体1.26。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.9Hz,2H),6.73(d,J＝8.7Hz,2H),6.66(d,J＝8.9Hz,1H),6.63(d,J＝8.7Hz,2H),3.95–3.89(m,4H),3.41(s,2H),1.88–1.77(m,4H),1.65–1.58(m,2H).
42)4-(6-(4-碘苯氧基)己氧基)苯胺(4-((6-(4-iodophenoxy)hexyl)oxy)aniline,化合物1.27)的合成
按照化合物1.23)的方法制备(反应物用化合物1.16代替化合物1.12)，得到淡黄色固体1.27。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.9Hz,2H),6.73(d,J＝8.7Hz,2H),6.66(d,J＝8.9Hz,1H),6.63(d,J＝8.7Hz,2H),3.93–3.87(m,4H),3.51(s,2H),1.83–1.74(m,4H),1.55–1.49(m,4H).
43)4-(6-(4-氟苯氧基)己氧基)苯胺(4-((6-(4-fluorophenoxy)hexyl)oxy)aniline,化合物1.27a)的合成
按照化合物1.23)的方法制备(反应物用化合物1.16a代替化合物1.12)，得到淡黄色固体1.27a。1H NMR(400MHz,CDCl3)δ6.98–6.94(m,2H),6.85–6.80(m,2H),6.74(d,J＝8.8Hz,2H),6.65(d,J＝8.8Hz,2H),3.93–3.88(m,4H),1.81–1.75(m,4H),1.54–1.50(m,4H).
44)4-(6-(4-氯苯氧基)己氧基)苯胺(4-((6-(4-chlorophenoxy)hexyl)oxy)aniline,化合物1.27b)的合成
按照化合物1.23)的方法制备(反应物用化合物1.16b代替化合物1.12)，得到淡黄色固体1.27b。1H NMR(400MHz,CDCl3)δ6.99–6.93(m,2H),6.85–6.79(m,2H),6.74(d,J＝8.7Hz,2H),6.65(d,J＝8.7Hz,2H),3.93–3.88(m,4H),1.80–1.75(m,4H),1.54–1.50(m,4H).
45)4-(6-(4-溴苯氧基)己氧基)苯胺(4-((6-(4-bromophenoxy)hexyl)oxy)aniline,化合物1.27c)的合成
按照化合物1.23)的方法制备(反应物用化合物1.16c代替化合物1.12)，得到淡黄色固体1.27c。1H NMR(400MHz,CDCl3)δ7.36(d,J＝7.7Hz,1H),7.29(d,J＝1.6Hz,1H),6.90(d,J＝8.2Hz,1H),6.78–6.73(m,3H),6.64(d,J＝8.7Hz,2H),3.98–3.88(m,4H),3.31(s,2H),1.83–1.76(m,4H),1.53–1.50(m,4H).
46)4-(7-(4-碘苯氧基)庚氧基)苯胺(4-((7-(4-iodophenoxy)heptyl)oxy)aniline,化合物1.28)的合成
按照化合物1.23)的方法制备(反应物用化合物1.17代替化合物1.12)，得到淡黄色固体1.28。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.7Hz,2H),6.73(d,J＝8.8Hz,2H),6.66(d,J＝8.8Hz,2H),6.63(d,J＝8.8Hz,2H),3.92–3.86(m,4H),3.40(s,2H),1.77–1.71(m,4H),1.51–1.35(m,6H).
47)4-(8-(4-碘苯氧基)辛氧基)苯胺(4-((8-(4-iodophenoxy)octyl)oxy)aniline,化合物1.29)的合成
按照化合物1.23)的方法制备(反应物用化合物1.18代替化合物1.12)，得到淡黄色固体1.29。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),6.74(d,J＝8.8Hz,2H),6.67(d,J＝8.9Hz,2H),6.64(d,J＝8.8Hz,2H),3.92–3.86(m,4H),3.51(s,2H),1.80–1.70(m,4H),1.48–1.43(m,4H),1.42–1.36(m,4H).
48)4-(10-(4-碘苯氧基)葵氧基)苯胺(4-((10-(4-iodophenoxy)decyl)oxy)aniline,化合物1.31)的合成
按照化合物1.23)的方法制备(反应物用化合物1.20代替化合物1.12)，得到淡黄色固体1.31。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.9Hz,2H),6.74(d,J＝8.8Hz,2H),6.67(d,J＝9.0Hz,2H),6.63(d,J＝8.8Hz,2H),3.92–3.86(m,4H),3.41(s,2H),1.79–1.70(m,4H),1.46–1.40(m,4H),1.32(m,8H).
49)4-(12-(4-碘苯氧基)十二烷氧基)苯胺(4-((12-(4-iodophenoxy)dodecyl)oxy)aniline,化合物1.33)的合成
按照化合物1.23)的方法制备(反应物用化合物1.22代替化合物1.12)，得到淡黄色固体1.33。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.8Hz,2H),6.74(d,J＝8.6Hz,2H),6.67(d,J＝8.9Hz,2H),6.64(d,J＝8.6Hz,2H),3.92–3.86(m,4H),1.79–1.70(m,4H),1.43–1.39(m,4H),1.28(s,12H).
50)4-(2-(4-碘苯氧基)乙氧基)-氮，氮-二甲苯胺(4-(2-(4-iodophenoxy)ethoxy)-N,N-dimethylaniline,化合物1.34)的合成
将化合物1.23(269.6mg,0.7mmol)和多聚甲醛(210.2mg,7.0mmol)溶于适量冰醋酸中，在冰浴条件下，向溶液中缓慢分批加入氰基硼氢化钠(219.9mg,3.5mmol)，室温反应过夜，反应结束后，向溶液中加入氨水调pH至弱碱性，CH2Cl2萃取，MgSO4干燥，柱色谱分离得白色粉末的终产物1.34。1H NMR(400MHz,CDCl3)δ7.56(d,J＝8.9Hz,2H),7.02–6.82(m,4H),6.73(d,J＝8.9Hz,2H),4.26(s,4H),2.91(s,6H).
51)2-(2-(4-碘苯氧基)乙氧基)-氮-甲苯胺(2-(2-(4-iodophenoxy)ethoxy)-N-methylaniline,化合物1.34a)的合成
按照化合物1.34)的方法制备(反应物用化合物1.23a代替化合物1.23)，得到白色固体1.34a。52)3-(2-(4-碘苯氧基)乙氧基)-氮，氮-二甲苯胺(3-(2-(4-iodophenoxy)ethoxy)-N,N-dimethylaniline,化合物1.34b)的合成
按照化合物1.34)的方法制备(反应物用化合物1.23b代替化合物1.23)，得到白色固体1.34b。1H NMR(400MHz,CDCl3)δ7.56(d,J＝9.0Hz,2H),7.16(t,J＝8.0Hz,1H),6.73(d,J＝9.0Hz,2H),6.39(d,J＝6.5Hz,1H),6.33(s,2H),4.33–4.30(m,2H),4.29–4.26(m,2H),2.94(s,6H).
53)4-(2-(2-碘苯氧基)乙氧基)-氮，氮-二甲苯胺(4-(2-(2-iodophenoxy)ethoxy)-N,N-dimethylaniline,化合物1.34c)的合成
按照化合物1.34)的方法制备(反应物用化合物1.23c代替化合物1.23)，得到白色固体1.34c。1H NMR(400MHz,CDCl3)δ7.78(dd,J＝7.8,1.6Hz,1H),7.30(td,J＝8.2,1.6Hz,1H),6.94(d,J＝9.0Hz,2H),6.89(dd,J＝8.2,1.3Hz,1H),6.82–6.69(m,3H),4.34(s,4H),2.89(s,6H).
54)4-(2-(3-碘苯氧基)乙氧基)-氮，氮-二甲苯胺(4-(2-(3-iodophenoxy)ethoxy)-N,N-dimethylaniline,化合物1.34d)的合成
按照化合物1.34)的方法制备(反应物用化合物1.23d代替化合物1.23)，得到白色固体1.34d。1H NMR(400MHz,CDCl3)δ7.31–7.29(m,2H),7.01(t,J＝8.1Hz,1H),6.93–6.89(m,3H),6.75(s,2H),4.26(s,4H),2.89(s,6H).
55)4-(2-(4-氟苯氧基)乙氧基)-氮，氮-二甲苯胺(4-(2-(4-fluorophenoxy)ethoxy)-N,N-dimethylaniline,化合物1.34e)的合成
按照化合物1.34)的方法制备(反应物用化合物1.23e代替化合物1.23)，得到白色固体1.34e。1H NMR(400MHz,CDCl3)δ7.02–6.95(m,2H),6.94–6.86(m,4H),6.77(s,2H),4.26(s,4H),2.90(s,6H).
56)4-(2-(4-氯苯氧基)乙氧基)-氮，氮-二甲苯胺(4-(2-(4-chlorophenoxy)ethoxy)-N,N-dimethylaniline,化合物1.34f)的合成
按照化合物1.34)的方法制备(反应物用化合物1.23f代替化合物1.23)，得到白色固体1.34f。1H NMR(400MHz,CDCl3)δ7.24(d,J＝9.0Hz,2H),6.91–6.86(m,4H),6.76(s,2H),4.26(s,4H),2.89(s,6H).
57)4-(2-(4-溴苯氧基)乙氧基)-氮，氮-二甲苯胺(4-(2-(4-bromophenoxy)ethoxy)-N,N-dimethylaniline(化合物1.34g)的合成
按照化合物1.34)的方法制备(反应物用化合物1.23g代替化合物1.23)，得到白色固体1.34g。1H NMR(400MHz,CDCl3)δ7.31–7.27(m,2H),6.98–6.90(m,6H),4.29(s,4H),2.90(s,6H).
58)4-(3-(4-碘苯氧基)丙氧基)-氮，氮-二甲苯胺(4-(3-(4-iodophenoxy)propoxy)-N,N-dimethylaniline(化合物1.35)的合成
按照化合物1.34)的方法制备(反应物用化合物1.24代替化合物1.23)，得到白色固体1.35。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),6.85(d,J＝8.7Hz,2H),6.75(s,2H),6.69(d,J＝8.9Hz,2H),4.13–4.08(m,4H),2.88(s,6H),2.26–2.17(m,2H).
59)4-(4-(4-碘苯氧基)丁氧基)-氮，氮-二甲苯胺(4-(4-(4-iodophenoxy)butoxy)-N,N-dimethylaniline,化合物1.36)的合成
按照化合物1.34)的方法制备(反应物用化合物1.25代替化合物1.23)，得到白色固体1.36。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),6.84(d,J＝8.5Hz,2H),6.78(s,2H),6.67(d,J＝8.9Hz,2H),4.00–3.96(m,4H),2.89(s,6H),1.97–1.90(m,4H).
60)4-(5-(4-碘苯氧基)戊氧基)-氮，氮-二甲苯胺(4-((5-(4-iodophenoxy)pentyl)oxy)-N,N-dimethylaniline,化合物1.37)的合成
按照化合物1.34)的方法制备(反应物用化合物1.26代替化合物1.23)，得到白色固体1.37。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),6.84(d,J＝8.5Hz,2H),6.76(s,2H),6.67(d,J＝8.9Hz,2H),3.96–3.92(m,4H),2.88(s,6H),1.86–1.79(m,4H),1.66–1.60(m,2H).
61)4-(6-(4-碘苯氧基)己氧基)-氮，氮-二甲苯胺(4-((6-(4-iodophenoxy)hexyl)oxy)-N,N-dimethylaniline,化合物1.38)的合成
按照化合物1.34)的方法制备(反应物用化合物1.27代替化合物1.23)，得到白色固体1.38。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.0Hz,2H),6.83(d,J＝9.0Hz,2H),6.75(s,2H),6.66(d,J＝8.9Hz,2H),3.94–3.90(m,4H),2.87(s,6H),1.81–1.74(m,4H),1.53–1.50(m,4H).
62)4-(6-(4-氟苯氧基)己氧基)-氮，氮-二甲苯胺(4-((6-(4-fluorophenoxy)hexyl)oxy)-N,N-dimethylaniline,化合物1.38a)的合成
按照化合物1.34)的方法制备(反应物用化合物1.27a代替化合物1.23)，得到白色固体1.38a。1H NMR(400MHz,CDCl3)δ6.98–6.94(m,2H),6.85–6.77(m,6H),3.92(t,J＝6.5Hz,4H),2.87(s,6H),1.80–1.75(m,4H),1.56–1.49(m,4H).
63)4-(6-(4-氯苯氧基)己氧基)-氮，氮-二甲苯胺(4-((6-(4-chlorophenoxy)hexyl)oxy)-N,N-dimethylaniline,化合物1.38b)的合成
按照化合物1.34)的方法制备(反应物用化合物1.27b代替化合物1.23)，得到白色固体1.38b。1H NMR(400MHz,CDCl3)δ7.22(d,J＝8.9Hz,2H),6.85–6.79(m,4H),6.77–6.70(m,2H),3.94–3.90(m,4H),2.87(s,6H),1.82–1.74(m,4H),1.54–1.50(m,4H).
64)4-(6-(4-溴苯氧基)己氧基)-氮，氮-二甲苯胺(4-((6-(4-bromophenoxy)hexyl)oxy)-N,N-dimethylaniline(化合物1.38c)的合成
按照化合物1.34)的方法制备(反应物用化合物1.27c代替化合物1.23)，得到白色固体1.38c。1H NMR(400MHz,CDCl3)δ7.35(d,J＝9.0Hz,1H),7.29–7.27(m,1H),6.94–6.83(m,4H),6.77(d,J＝9.0Hz,2H),3.98–8.91(m,4H),2.88(s,6H),1.81–1.78(m,4H),1.55–1.50(m,4H).
65)4-(7-(4-碘苯氧基)庚氧基)-氮，氮-二甲苯胺(4-((7-(4-iodophenoxy)heptyl)oxy)-N,N-dimethylaniline,化合物1.39)的合成
按照化合物1.34)的方法制备(反应物用化合物1.28代替化合物1.23)，得到白色固体1.39。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.9Hz,2H),6.83(d,J＝8.8Hz,2H),6.75(s,2H),6.66(d,J＝8.9Hz,2H),3.93–3.89(m,4H),2.87(s,6H),1.79–1.74(m,4H),1.49–1.41(m,6H).
66)4-(8-(4-碘苯氧基)辛氧基)-氮，氮-二甲苯胺(4-((8-(4-iodophenoxy)octyl)oxy)-N,N-dimethylaniline,化合物1.40)的合成
按照化合物1.34)的方法制备(反应物用化合物1.29代替化合物1.23)，得到白色固体1.40。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.9Hz,2H),6.84(d,J＝8.2Hz,2H),6.76(s,2H),6.66(d,J＝8.9Hz,2H),3.91(t,J＝6.5Hz,4H),2.89(s,6H),1.80–1.72(m,4H),1.47–1.43(m,4H),1.39–1.37(m,4H).
67)4-(10-(4-碘苯氧基)葵氧基)-氮，氮-二甲苯胺(4-((10-(4-iodophenoxy)decyl)oxy)-N,N-dimethylaniline,化合物1.42)的合成
按照化合物1.34)的方法制备(反应物用化合物1.31代替化合物1.23)，得到白色固体1.42。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.9Hz,2H),6.84(d,J＝8.9Hz,2H),6.78(s,2H),6.67(d,J＝8.9Hz,2H),3.92–3.88(m,4H),2.87(s,6H),1.79–1.71(m,4H),1.45–1.40(m,4H),,1.32(s,8H).
68)4-(12-(4-碘苯氧基)十二烷氧基)-氮，氮-二甲苯胺(4-((12-(4-iodophenoxy)dodecyl)oxy)-N,N-dimethylaniline,化合物1.44)的合成
按照化合物1.34)的方法制备(反应物用化合物1.33代替化合物1.23)，得到白色固体1.44。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.9Hz,2H),6.84(d,J＝9.1Hz,2H),6.75(d,J＝8.0Hz,2H),6.67(d,J＝8.9Hz,2H),3.92–3.88(m,4H),2.86(s,6H),1.78–1.71(m,4H),1.45–1.38(m,4H),1.35–1.28(m,12H).
69)氮，氮-二甲基-4-(2-(4-(三叔丁基锡)苯氧基)乙氧基)苯胺(N,N-dimethyl-4-(2-(4-(tributylstannyl)phenoxy)ethoxy)aniline,化合物1.45)的合成
将化合物1.34(93.8mg,0.24mmol)、六正丁基二锡(417.7mg,0.72mmol)和四(三苯基磷)钯(23.1mg,0.02mmol)溶于10mL甲苯中(含1mL三乙胺)，回流搅拌反应过夜。减压除去溶剂，残余物经硅胶柱层析分离(石油醚/乙酸乙酯＝15/1)得无色油状化合物1.45(67.5mg,51.5％)。1H NMR(400MHz,CDCl3)δ7.36(d,J＝8.4Hz,2H),6.94(d,J＝8.5Hz,2H),6.90(d,J＝9.1Hz,2H),6.77(d,J＝8.7Hz,2H),4.28(t,J＝2.7Hz,4H),2.88(s,6H),1.57–1.50(m,6H),1.37–1.30(m,12H),0.88(t,J＝7.3Hz,9H).
70)氮，氮-二甲基-4-(6-(4-(三叔丁基锡)苯氧基)乙氧基)苯胺(N,N-dimethyl-4-((6-(4-(tributylstannyl)phenoxy)hexyl)oxy)aniline,化合物1.46)的合成按照化合物1.45)的方法制备(反应物用化合物1.38代替化合物1.34)，得到无色油状化合物1.46。1HNMR(400MHz,CDCl3)δ7.35(d,J＝8.5Hz,2H),6.89(d,J＝8.5Hz,2H),6.84(d,J＝9.0Hz,2H),7.76–7.74(m,2H),3.96(t,J＝6.5Hz,2H),3.91(t,J＝6.5Hz,2H),2.87(s,6H),1.84–1.76(m,4H),1.56–1.49(m,10H),1.37–1.28(m,6H),1.06–0.98(m,6H),0.88(t,J＝7.3Hz,9H).
71)1-(2-溴乙氧基)-4-碘苯(1-(2-bromoethoxy)-4-iodobenzene,化合物2.1)的合成
将对碘苯酚(5000.0mg,22.7mmol)、1,2-二溴乙烷(12800.0mg,68.2mmol)和K2CO3(4700.0mg,34.1mmol)溶于适量丙酮中，90℃回流反应24h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得白色粉末2.1。1H NMR(400MHz,CDCl3)δ7.57(d,J＝9.0Hz,2H),6.69(d,J＝9.0Hz,2H),4.26(t,J＝6.2Hz,2H),3.62(t,J＝6.2Hz,2H).
72)1-(6-溴乙氧基)-4-碘苯(1-((6-bromohexyl)oxy)-4-iodobenzene,化合物2.2)的合成
按照化合物2.1)的方法制备(反应物用1,6-二溴己烷代替1,2-二溴乙烷)，得到白色固体化合物2.2。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.0Hz,2H),6.67(d,J＝9.0Hz,2H),3.91(t,J＝6.6Hz,2H),1.79–1.72(m,2H),1.48–1.40(m,2H),1.37–1.29(m,4H),0.90(t,J＝7.0Hz,2H).
73)1-碘-4-(2-(4-甲氧基苯氧基)乙氧基)苯(1-iodo-4-(2-(4-methoxyphenoxy)ethoxy)benzene,化合物2.3a)的合成
将化合物2.1(738.2mg,3.0mmol)、4-甲氧基苯酚(660.1mg,3.0mmol)和K2CO3(1242.8mg,9.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，重结晶得白色晶体2.3a。1H NMR(400MHz,CDCl3)δ7.56(d,J＝8.9Hz,2H),6.90–6.83(m,4H),6.73(d,J＝8.9Hz,2H),4.26(s,4H),3.78(s,3H).
74)1-碘-4-(6-(4-甲氧基苯氧基)己氧基)苯(1-iodo-4-((6-(4-methoxyphenoxy)hexyl)oxy)benzene,
化合物2.3b)的合成
按照化合物2.3a)的方法制备(反应物用化合物2.2代替化合物2.1)，得到白色固体化合物2.3b。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),6.83(s,4H),6.67(d,J＝8.9Hz,2H),3.92(t,J＝6.4,4H),3.77(s,3H),1.83–1.76(m,4H),1.54–1.50(m,4H).
75)1-氟-4-(2-(4-碘苯氧基)乙氧基)苯(1-fluoro-4-(2-(4-iodophenoxy)ethoxy)benzene,化合物2.4a)的合成
按照化合物2.3a)的方法制备(反应物用4-氟苯酚代替4-甲氧基苯酚)，得到白色固体化合物2.4a。1H NMR(400MHz,CDCl3)δ7.57(d,J＝9.0Hz,2H),6.98–6.95(m,2H),6.91–6.87(m,2H),6.73(d,J＝9.0Hz,2H),4.27(s,4H).
76)1-氟-4-(6-(4-碘苯氧基)乙氧基)苯(1-fluoro-4-((6-(4-iodophenoxy)hexyl)oxy)benzene(化合物2.4b)的合成
按照化合物2.3a)的方法制备(反应物用4-氟苯酚代替4-甲氧基苯酚，化合物2.2代替化合物2.1)，得到白色固体化合物2.4b。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),6.98–6.94(m,2H),6.83–6.80(m,1H),6.67(d,J＝8.9Hz,2H),3.93(t,J＝6.4,2H),3.92(t,J＝6.4,2H),1.81–1.79(m,2H),1.54–1.51(m,2H).
77)1-氯-4-(2-(4-碘苯氧基)乙氧基)苯(1-chloro-4-(2-(4-iodophenoxy)ethoxy)benzene,化合物2.5a)的合成
按照化合物2.3a)的方法制备(反应物用化合物4-氯苯酚代替化合物4-甲氧基苯酚)，得到白色固体化合物2.5a。1H NMR(400MHz,CDCl3)δ7.57(d,J＝9.0Hz,2H),7.25(d,J＝9.0Hz,2H),6.87(d,J＝9.0Hz,2H),6.73(d,J＝9.0Hz,2H),4.28(s,4H).
78)1-氯-4-(6-(4-碘苯氧基)乙氧基)苯(1-chloro-4-((6-(4-iodophenoxy)hexyl)oxy)benzene,化合物2.5b)的合成
按照化合物2.3a)的方法制备(反应物用4-氯苯酚代替4-甲氧基苯酚，化合物2.2代替化合物2.1)，得到白色固体化合物2.5b。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),7.22(d,J＝9.0Hz,2H),6.81(d,J＝9.0Hz,2H),6.67(d,J＝8.9Hz,2H),3.93(t,J＝6.4,2H),3.92(t,J＝6.4,2H),1.82–1.77(m,4H),1.54–1.50(m,4H).
79)1-溴-4-(2-(4-碘苯氧基)乙氧基)苯(1-bromo-4-(2-(4-iodophenoxy)ethoxy)benzene,化合物2.6a)的合成
按照化合物2.3a)的方法制备(反应物用4-溴苯酚代替4-甲氧基苯酚)，得到白色固体化合物2.6a。1H NMR(400MHz,CDCl3)δ7.57(d,J＝9.0Hz,1H),7.39(d,J＝9.0Hz,1H),6.82(d,J＝9.1Hz,1H),6.72(d,J＝9.0Hz,1H),4.27(s,2H).
80)1-溴-4-(6-(4-碘苯氧基)乙氧基)苯(1-bromo-4-((6-(4-iodophenoxy)hexyl)oxy)benzene,化合物2.6b)的合成
按照化合物2.3a)的方法制备(反应物用4-溴苯酚代替4-甲氧基苯酚，化合物2.2代替化合物2.1)，得到白色固体化合物2.6b。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),7.36(d,J＝9.0Hz,2H),6.76(d,J＝9.0Hz,2H),6.66(d,J＝8.9Hz,2H),3.92(t,J＝6.4Hz,4H),1.83–1.77(m,4H),1.54–1.50(m,4H).
81)1,2-二(4-碘苯氧基)乙烷(1,2-bis(4-iodophenoxy)ethane,化合物2.7a)的合成
按照化合物2.3a)的方法制备(反应物用4-碘苯酚代替4-甲氧基苯酚)，得到白色固体化合物2.7a。1H NMR(400MHz,CDCl3)δ7.57(d,J＝9.0Hz,4H),6.72(d,J＝9.0Hz,4H),4.27(s,4H).
82)1,6-二(4-碘苯氧基)己烷(1,6-bis(4-iodophenoxy)hexane,化合物2.7b)的合成
按照化合物2.3a)的方法制备(反应物用4-溴苯酚代替4-甲氧基苯酚，化合物2.2代替化合物2.1)，得到白色固体化合物2.6b。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.0Hz,2H),6.66(d,J＝8.9Hz,2H),3.92(t,J＝6.4Hz,4H),1.81–1.77(m,4H),1.53–1.50(m,4H).
83)1-叔丁基-4-(2-(4-碘苯氧基)乙氧基)苯(1-(tert-butyl)-4-(2-(4-iodophenoxy)ethoxy)benzene,化合物2.8a)的合成
按照化合物2.3a)的方法制备(反应物用4-叔丁基苯酚代替4-甲氧基苯酚)，得到白色固体化合物2.8a。1H NMR(400MHz,CDCl3)δ7.56(d,J＝9.0Hz,2H),7.31(d,J＝8.9Hz,2H),6.88(d,J＝8.9Hz,2H),6.73(d,J＝9.0Hz,2H),4.31–4.26(m,4H),1.30(s,9H).
84)1-叔丁基-4-(6-(4-碘苯氧基)己氧基)苯(1-(tert-butyl)-4-((6-(4-iodophenoxy)hexyl)oxy)benzene,化合物2.8b)的合成
按照化合物2.3a)的方法制备(反应物用4-叔丁基苯酚代替4-甲氧基苯酚，化合物2.2代替化合物2.1)，得到白色固体化合物2.6b。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.9Hz,2H),7.29(d,J＝8.8Hz,2H),6.83(d,J＝8.8Hz,2H),6.67(d,J＝8.9Hz,2H),3.95(t,J＝6.4Hz,2H),3.92(t,J＝6.4Hz,2H),1.83–1.77(m,4H),1.54–1.51(m,4H),1.30(s,9H).
实施例2：碘代化合物(Ⅱ)的合成
合成反应路线如图3所示，本实施例中的化合物编号均与该图反应路线中的编号统一。
在图3所示的合成路线中，试剂与条件如下：(a)(n＝1-4)，K2CO3,DMF,90℃；(b)TsCl,Et3N,CH2Cl2,0℃–室温；(c)4-碘苯酚，K2CO3,DMF,90℃；(d)SnCl2·2H2O,EtOH,HCl,回流；(e)(CH2O)n,NaBH3CN,HAc,室温(f)(Bu3Sn)2,(PPh3)4Pd,甲苯,Et3N,回流；(g)[125I]NaI,HCl(1M),H2O2(3％)。
1)2-(2-(4-硝基苯氧基)乙氧基)乙醇(2-(2-(4-nitrophenoxy)ethoxy)ethan-1-ol,化合物3.1)
的合成
将对硝基苯酚(1396.0mg,10.0mmol)、2-氯乙氧基乙醇(1246.2mg,10.0mmol)和K2CO3(4142.8mg,30.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色蜡状固体3.1。1H NMR(400MHz,CDCl3)δ8.21(d,J＝9.2Hz,2H),6.99(d,J＝9.2Hz,2H),4.25–4.23(m,2H),3.92–3.90(m,2H),3.79–3.78(m,2H),3.70–3.68(m,2H),1.96(s,1H).
2)2-(2-(2-(4-硝基苯氧基)乙氧基)乙氧基)乙醇
(2-(2-(2-(4-nitrophenoxy)ethoxy)ethoxy)ethan-1-ol,化合物3.2)的合成
按照化合物3.1)的方法制备(反应物用2-(2-(2-氯乙氧基)乙氧基乙醇代替2-氯乙氧基乙醇)，得到淡黄色蜡状固体3.2。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.1Hz,2H),6.99(d,J＝9.2Hz,2H),4.27–4.19(m,2H),3.95–3.87(m,2H),3.79–3.67(m,6H),3.66–3.59(m,2H),2.46(s,1H).
3)2-(2-(4-硝基苯氧基)乙氧基)乙基-4-甲苯磺酸盐2-(2-(4-nitrophenoxy)ethoxy)ethyl
4-methylbenzenesulfonate,化合物3.5)的合成
将3.1(1136.5mg,5.0mmol)和对甲苯磺酰氯(1143.8mg,6.0mmol)溶于适量的无水二氯甲烷中，再向溶液中滴加5mL的三乙胺，室温反应6h，旋蒸，除掉溶剂，柱色谱分离得淡黄色粉末3.5。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.3Hz,2H),7.79(d,J＝8.3Hz,2H),7.32(d,J＝8.0Hz,2H),6.96(d,J＝9.3Hz,2H),4.21–4.15(m,2H),3.86–3.83(m,2H),3.79–3.76(m,2H),3.67–3.63(m,2H),2.43(s,3H).
4)2-(2-(2-(4-硝基苯氧基)乙氧基)乙氧基)乙基-4-甲苯磺酸盐(2-(2-(2-(4-nitrophenoxy)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate,化合物3.6)的合成
按照化合物3.5)的方法制备(反应物用化合物3.2代替化合物3.1)，得到淡黄色粉末3.6。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.3Hz,2H),7.80(d,J＝8.3Hz,2H),7.34(d,J＝8.0Hz,2H),6.98(d,J＝9.3Hz,2H),4.23–4.20(m,2H),4.17–4.15(m,2H),3.89–3.87(m,2H),3.69–3.67(m,4H),3.64–3.62(m,2H),2.44(s,3H).
5)1-碘-4-(2-(2-(4-硝基苯氧基)乙氧基)乙氧基)苯(1-iodo-4-(2-(2-(4-nitrophenoxy)ethoxy)ethoxy)benzene,化合物3.9)的合成
将化合物3.5(1144.2mg,3.0mmol)、4-碘苯酚(660.1mg,3.0mmol)和K2CO3(1242.8mg,9.0mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末粉末3.9。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.3Hz,2H),7.54(d,J＝9.0Hz,2H),6.97(d,J＝9.3Hz,2H),6.69(d,J＝9.0Hz,2H),4.25–4.23(m,2H),4.13–4.11(m,2H),3.97–3.94(m,2H),3.93–3.91(m,2H).
6)1-碘-4-(2-(2-(2-(4-硝基苯氧基)乙氧基)乙氧基)乙氧基)苯1-iodo-4-(2-(2-(2-(4-nitrophenoxy)ethoxy)ethoxy)ethoxy)benzene,化合物3.10)的合成
按照化合物3.9)的方法制备(反应物用化合物3.6代替化合物3.5)，得到淡黄色粉末3.10。1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.3Hz,2H),7.53(d,J＝9.0Hz,2H),6.96(d,J＝9.3Hz,2H),6.68(d,J＝9.0Hz,2H),4.21–4.19(m,2H),4.10–4.08(m,2H),3.90–3.88(m,2H),3.86–3.83(m,2H),3.74(s,4H).
7)4-(2-(2-(4-碘苯氧基)乙氧基)乙氧基)苯胺(4-(2-(2-(4-iodophenoxy)ethoxy)ethoxy)aniline,化合物3.13)的合成
将化合物3.9(429.2mg,1.0mmol)和二水合二氯亚锡(902.8mg,4.0mmol)溶于适量乙醇中，向溶液中滴加5mL浓盐酸，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，抽滤，除去干燥剂，旋蒸，除去溶剂，即得白色油状物3.13。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.0Hz,2H),6.76(d,J＝8.8Hz,2H),6.70(d,J＝9.0Hz,2H),6.63(d,J＝8.8Hz,2H),4.12–4.06(m,4H),3.93–3.85(m,4H).
8)4-(2-(2-(2-(4-碘苯氧基)乙氧基)乙氧基)乙氧基)苯胺(4-(2-(2-(2-(4-iodophenoxy)ethoxy)ethoxy)ethoxy)aniline,化合物3.14)的合成
按照化合物3.13)的方法制备(反应物用化合物3.10代替化合物3.9)，得到白色油状物3.14。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.0Hz,2H),6.75(d,J＝8.8Hz,2H),6.69(d,J＝9.0Hz,2H),6.62(d,J＝8.8Hz,2H),4.09–4.03(m,4H),3.85–3.82(m,4H),3.74(s,4H),3.41(s,2H).
9)4-(2-(2-(4-碘苯氧基)乙氧基)乙氧基)-氮，氮-二甲苯胺4-(2-(2-(4-iodophenoxy)ethoxy)ethoxy)-N,N-dimethylaniline,化合物3.17)的合成
将化合物3.13(360.0mg,0.9mmol)和多聚甲醛(270.9mg,9.0mmol)溶于适量冰醋酸中，冰浴下，向溶液中缓慢分批加入氰基硼氢化钠(282.9mg,4.5mmol)，室温反应过夜，反应结束后，向溶液中加入氨水调pH至弱碱性，CH2Cl2萃取，MgSO4干燥，柱色谱分离得白色粉末的终产物3.17。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.0Hz,2H),6.86(d,J＝9.1Hz,2H),6.76–6.68(m,4H),4.12–4.09(m,4H),3.90–3.87(m,4H),2.87(s,6H).
10)4-(2-(2-(2-(4-碘苯氧基)乙氧基)乙氧基)乙氧基)-氮，氮-二甲苯胺(4-(2-(2-(2-(4-iodophenoxy)ethoxy)ethoxy)ethoxy)-N,N-dimethylaniline,化合物3.18)的合成
按照化合物3.17)的方法制备(反应物用化合物3.14代替化合物3.13)，得到白色粉末3.18。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.0Hz,2H),6.85(d,J＝9.1Hz,2H),6.75–6.65(m,4H),4.09–4.06(m,4H),3.86–3.81(m,4H),3.74(s,4H),2.87(s,6H).
11)氮，氮-二甲基-4-(2-(2-(4-(三叔丁基锡)苯氧基)乙氧基)乙氧基)苯胺(N,N-dimethyl-4-(2-(2-(4-(tributylstannyl)phenoxy)ethoxy)ethoxy)aniline,化合物3.21)的合成
按照化合物1.45)的方法制备(反应物用化合物3.17代替化合物1.34)，得到无色油状化合物3.21。1H NMR(400MHz,CDCl3)δ7.35(d,J＝8.4Hz,2H),6.92(d,J＝8.4Hz,2H),6.88(d,J＝9.1Hz,2H),6.80(d,J＝7.1Hz,2H),4.18–4.14(m,2H),4.13–4.09(m,2H),3.94–3.87(m,4H),2.88(s,6H),4.18–4.14(m,6H),4.18–4.14(m,12H),0.88(t,J＝7.3Hz,9H).
实施例3：碘代化合物(III)的合成
合成反应路线如图4所示，本实施例中的化合物编号均与该图反应路线中的编号统一。
在图3所示的合成路线中，试剂与条件如下：(a)溴化氢溶液(40％)，哌嗪,1-(n-溴R烷氧基)-4-硝基苯，乙醇,90℃；(b)4-碘苯酚，K2CO3,DMF,90℃；(c)SnCl2·2H2O,EtOH,HCl,回流；(d)(CH2O)n,NaBH3CN,HAc,室温。
1)1-(2-(4-硝基苯氧基)乙基)哌嗪(1-(2-(4-nitrophenoxy)ethyl)piperazine,化合物4.2)的合成
取3mL溴化氢溶液(40％)加入溶有哌嗪(516.8mg,6.0mmol)的乙醇溶液中，然后将溶有化合物1-(2-溴乙氧基)-4-硝基苯(738.2mg,3.0mmol)的乙醇溶液加入上述溶液中，90℃回流反应48h，反应结束后，旋蒸，除去溶剂，加水酸化(10％HCl,pH＝5-6)，CH2Cl2洗涤，收集水相，碱化(50％NaOH,pH>9),CH2Cl2萃取，得到黄色固体4.2。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.3Hz,2H),6.97(d,J＝9.3Hz,2H),4.20(t,J＝5.8Hz,2H),2.97–2.93(m,4H),2.84(t,J＝5.8Hz,2H),2.59(s,4H),2.45(s,1H).
2)1-(6-(4-硝基苯氧基)己基)哌嗪(1-(6-(4-nitrophenoxy)hexyl)piperazine,化合物4.6)的合成
按照化合物4.2)的方法制备(反应物用1-(6-溴己氧基)-4-硝基苯代替1-(2-溴乙氧基)-4-硝基苯)，得到黄色固体4.6。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.2Hz,2H),6.94(d,J＝9.2Hz,2H),5.75(s,1H),4.05(t,J＝6.4Hz,2H),3.12–3.10(m,4H),2.66–2.64(m,4H),2.43–2.39(m,2H),1.86–1.79(m,2H),1.57–1.46(m,4H),1.42–1.34(m,2H).
3)1-(2-(4-碘苯氧基)乙基)-4-(2-(4-硝基苯氧基)乙基)哌嗪
(1-(2-(4-iodophenoxy)ethyl)-4-(2-(4-nitrophenoxy)ethyl)piperazine,化合物4.8)的合成
将化合物4.2(152.9mg,0.6mmol)、1-(2-溴乙氧基)-4-碘苯(199.0mg,0.6mmol)和K2CO3(248.8mg,1.8mmol)溶于适量DMF中，90℃回流反应4h,反应结束后，旋蒸，除去溶剂，CH2Cl2萃取，MgSO4干燥，柱色谱分离得淡黄色粉末4.8。1H NMR(400MHz,CDCl3)δ8.21(d,J＝9.2Hz,2H),7.56(d,J＝8.9Hz,2H),6.96(d,J＝9.2Hz,2H),6.70(d,J＝9.0Hz,2H),4.44–4.41(m,2H),4.19–4.14(m,4H),3.50(s,4H),2.85(s,2H),2.53(s,4H).
4)1-(6-(4-碘苯氧基)己基)-4-(6-(4-硝基苯氧基)己基)哌嗪(1-(6-(4-iodophenoxy)hexyl)-4-(2-(4-nitrophenoxy)hexyl)piperazine,化合物4.12)的合成
按照化合物4.8)的方法制备(反应物用化合物4.3代替4.2，1-(6-溴己氧基)-4-碘苯代替1-(2-溴乙氧基)-4-碘苯)，得到黄色固体4.12。1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.3Hz,2H),7.54(d,J＝9.0Hz,2H),6.93(d,J＝9.3Hz,2H),6.66(d,J＝9.0Hz,2H),4.04(t,J＝6.4Hz,2H),3.91(t,J＝6.4Hz,2H),2.57(s,8H),2.51(s,4H),1.86–1.80(m,2H),1.79–1.73(m,2H),1.69–1.56(m,4H),1.54–1.43(m,4H),1.40–1.33(m,4H).
5)4-(2-(4-(2-(4-碘苯氧基)乙基)哌嗪-1-基)乙氧基)苯胺(4-(2-(4-(2-(4-iodophenoxy)ethyl)piperazin-1-yl)ethoxy)aniline,化合物4.14)的合成
按照化合物3.13)的方法制备(反应物用化合物4.8代替3.9)，得到黄色固体4.14。1H NMR(400MHz,CDCl3)δ7.56(d,J＝9.0Hz,2H),6.73(d,J＝8.8Hz,2H),6.69(d,J＝8.9Hz,0H),6.63(d,J＝8.9Hz,2H),4.44–4.42(m,2H),4.25–4.11(m,4H),3.79–3.56(m,4H),3.11–2.64(m,6H).
6)4-(6-(4-(6-(4-碘苯氧基)己基)哌嗪-1-基)己氧基)苯胺4-((6-(4-(6-(4-iodophenoxy)hexyl)piperazin-1-yl)hexyl)oxy)aniline,化合物4.18)的合成
按照化合物3.13)的方法制备(反应物用化合物4.12代替3.9)，得到黄色固体4.14。1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.7Hz,2H),6.73(d,J＝8.7Hz,2H),6.67–6.62(m,4H),3.92–3.5(m,4H),3.41(s,2H),2.51(s,8H),2.36–2.32(m,4H),1.80–1.70(m,4H),1.57–1.42(m,8H),1.39–1.34(m,4H).
7)4-(2-(4-(2-(4-碘苯氧基)乙基)哌嗪-1-基)乙氧基)-氮，氮-二甲苯胺(4-(2-(4-(2-(4-iodophenoxy)ethyl)piperazin-1-yl)ethoxy)-N,N-dimethylaniline,化合物4.20)的合成
按照化合物3.17)的方法制备(反应物用化合物4.14代替3.13)，得到黄色固体4.20。1H NMR(400MHz,CDCl3)δ7.56(d,J＝8.9Hz,2H),6.84(d,J＝9.1Hz,2H),6.79–6.74(m,2H),6.70(d,J＝8.9Hz,2H),4.44–4.41(m,2H),4.16–4.10(m,4H),3.58(s,4H),2.87(s,8H),2.62(s,4H).
8)4-(6-(4-(6-(4-碘苯氧基)己基)哌嗪-1-基)己氧基)-氮，氮-二甲苯胺(4-((6-(4-(6-(4-iodophenoxy)hexyl)piperazin-1-yl)hexyl)oxy)-N,N-dimethylaniline,化合物4.24)的合成
按照化合物3.17)的方法制备(反应物用化合物4.18代替3.13)，得到黄色固体4.24。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.0Hz,2H),6.83(d,J＝9.2Hz,2H),6.73(d,J＝9.2Hz,2H),6.66(d,J＝9.0Hz,2H),3.92–3.88(m,4H),2.86(s,6H),2.53(s,8H),2.42–2.32(s,4H),1.80–1.71(m,4H),1.57–1.50(m,4H),1.48–1.43(m,4H),1.39–1.32(m,4H).
实施例4：125I标记配体的制备
一、实验步骤
化合物[125I]1.34、[125I]1.38和[125I]3.17的制备
合成反应路线见图1，称取0.1mg各相应锡前体(分别为化合物1.45、1.46和3.21)于玻璃反应瓶中，加入100μL乙醇溶解，再依次加入1μL[125]NaI溶液(200μCi，2200Ci/mmol)，100μL 1M盐酸和50μL H2O2水溶液(3％)。密闭后室温下反应15min，加入20μL饱和亚硫酸氢钠溶液终止反应，适量NaHCO3调节至中性。反应液经HPLC分离，[125I]1.34的分离条件：Venusil MP C18反向柱(5μm,4.6×250mm)；CH3CN:H2O＝85％:15％；流速1.0mL/min。[125I]1.38的分离条件为：Venusil MP C18反向柱(5μm,4.6×250mm)；CH3CN:H2O＝80％:20％；流速1.0mL/min。[125I]3.17的分离条件为：Venusil MP C18反向柱(5μm,4.6×250mm)；CH3CN:H2O＝70％:30％；流速1.0mL/min。并通过HPLC分析125I标记配体与参比化合物的保留时间。所得125I标记配体置于-20℃下储存待用。
二、实验结果
125I标记配体由经典的锡卤交换法制备。[125I]1.34、[125I]1.38和[125I]3.17的标记率依次为95.9％、98.1％和98.1％。经HPLC分离纯化后，放射性化学纯度都大于95％，且与稳定碘代配体的保留时间一致(表1)。
表1 125I标记配体及其稳定配体的保留时间和纯度
实验例1：生物评价
一、化合物1.34～1.44，2.3a～2.8b，3.17，3.18，4.20，4.24，IMPY与Aβ1-42聚集体体外竞争结合实验(Ki测定)
使一定浓度的Aβ1-42聚集体蛋白与一定浓度的放射性配基[125I]IMPY发生结合反应，反应***中同时加入不同浓度的待测化合物(分别制备的化合物1.34～1.44，2.3a～2.8b，3.17，3.18，4.20和4.24)以及IMPY与[125I]IMPY发生竞争反应，平衡后分离复合物通过测定放射性来计算抑制常数(Ki)。
1、实验步骤
(1)配制10％乙醇溶液4L；
(2)放射配基[125I]IMPY按照已有方法制备；将[125I]IMPY配制成100000cpm/100μL的水溶液；
(3)将待测化合物配制成10-3至10-9mol/L连续稀释的乙醇溶液；
(4)受体Aβ1-42蛋白按照已有方法制备。将其稀释成约30nM的水溶液；
(5)在12mm×75mm高硼硅玻璃管中分别加入100μL不同浓度待测化合物溶液和100μL[125I]IMPY溶液、700μL PBS及100μL Aβ1-42溶液。用封口膜封好，涡旋；
(6)在37℃恒温水浴中振荡孵育3h；
(7)多头细胞收集器收集反应液，用10％乙醇溶液冲洗三遍，每次3mL；
(8)用γ计数仪测量计数；
(9)数据处理。
2、实验结果
由竞争结合实验得到的半抑制常数(IC50)以及进一步根据公式计算出的抑制常数Ki见表2。
表2稳定配体的抑制常数Ki值
通过上述的竞争结合实验可知，本发明的部分化合物具有与Aβ1-42聚集体较高的亲和力，比已知化合物IMPY和PIB要高。
实验例2：放射自显影实验
分别使一定浓度的[125I]1.34和[125I]3.17与AD转基因小鼠及AD病人脑切片中的斑块结合后，通过磷屏曝光，然后用储磷屏***分析图像。
1、实验步骤
(1)预处理AD转基因小鼠脑切片和AD人脑切片；
(2)分别在AD转基因小鼠脑切片或AD人脑切片上覆盖5μCi的125I标记的化合物溶液100μL，室温下孵育60分钟；
(3)用40％乙醇溶液冲洗3分钟；
(4)晾干后，保鲜膜包覆置于磷屏下曝光3h，用储磷屏***分析图像。
2、实验结果
实验结果如图5所示，充分说明本发明的化合物被放射性核素标记后，可以作为脑Aβ斑块的显像剂，在临床诊断中具有潜在的应用前景。
图5显示：[125I]1.34和[125I]3.17分别在AD人脑切片(A和G)，91岁，女性；转基因鼠脑切片(C和I)，APPswe/PSEN1，22月；正常鼠脑切片(E和K)，C57BL6(22月)的放射自显影结果。相同切片经过硫磺素-S染色加以对照，其中，B和H与A和G对应；D和J与C和I对应；F和L与E和K对应。
实验例3：正常小鼠体内生物分布实验
通过体内分布实验研究了[125I]1.34、[125I]1.38和[125I]3.17在小鼠体内的药代动力学性质，特别是初始脑摄取和脑清除情况。
1、实验步骤
将5-10μCi标记化合物(100μL生理盐水溶液，含5％乙醇)由尾静脉注射入正常小鼠(ICR，雄性，20-22g，5周龄)体内(n＝5)，分别于注射后2分钟、10分钟、30分钟和60分钟将其断头处死，解剖取出相关脏器，测量湿重及放射性计数。数据表示为脏器中放射性百分剂量(％ID/organ)和每克脏器中放射性百分剂量(％ID/g)。
2、实验结果
实验结果如表3所示，本发明所述的[125I]1.34可以顺利的通过血脑屏障，2分钟时脑部摄取达到峰值且在正常小鼠脑部清除很快，2分钟与60分钟脑摄取比值达到约为7。而化合物[125I]1.38和[125I]3.17的2分钟初始脑部摄取值较低，脑清除速率较低。
表3[125I]1.34、[125I]1.38及[125I]3.17在正常小鼠体内生物分布结果a
a表示为％ID/g，n＝4-5
b表示为％ID/organ(器官)
虽然，上文中已经用一般性说明及具体实施方案对本发明作了详尽的描述，但在本发明基础上，可以对之作一些修改或改进，这对本领域技术人员而言是显而易见的。因此，在不偏离本发明精神的基础上所做的这些修改或改进，均属于本发明要求保护的范围。
Claims (8)
1.二苯氧基柔性分子化合物，其特征在于，所述化合物为4-(2-(2-(4-碘苯氧基)乙氧基)乙氧基)-氮，氮-二甲苯胺或4-(2-(2-(2-(4-碘苯氧基)乙氧基)乙氧基)乙氧基)-氮，氮-二甲苯胺；
所述碘为123I、124I、125I、127I或131I。
2.二苯氧基柔性分子化合物，其特征在于，化合物的结构式如下：
其中，n为2–5的整数，R1为NMe2，R2为I或-(OCH2CH2)m-F，其中m为1-3的整数；当化合物中含有氟原子时，F为18F或19F；当化合物中含有碘原子时，I为123I、124I、125I、127I或131I；当化合物中含有-N(CH3)2时，-N(CH3)2为-N(11CH3)2。
3.权利要求2所述化合物的制备方法，按照下述反应方程式制备所述化合物：
其中，R1、R2、n与权利要求2中式(Ⅲ)所示化合物具有相应的定义。
4.利用权利要求1或2所述化合物制备得到的Aβ斑块显像剂，其特征在于，当所述化合物中含有氟原子时，制备得到含有放射性核素18F的化合物，作为Aβ斑块显像剂；或者，
当所述化合物中含有碘原子时，制备得到含有放射性核素124I的化合物，作为Aβ斑块显像剂；或者，
当所述化合物中含有二甲氨基时，制备得到含有放射性核素11C的化合物，作为Aβ斑块显像剂；或者，
当所述化合物中含有碘原子时，制备得到含有放射性核素123I、125I或131I的化合物，作为Aβ斑块显像剂。
5.根据权利要求4所述的Aβ斑块显像剂，其特征在于，当所述化合物中含有氟原子时，制备得到含有放射性核素18F的化合物，作为PET类Aβ斑块显像剂；或者，
当所述化合物中含有碘原子时，制备得到含有放射性核素124I的化合物，作为PET类Aβ斑块显像剂；或者，
当所述化合物中含有二甲氨基时，制备得到含有放射性核素11C的化合物，作为PET类Aβ斑块显像剂；或者，
当所述化合物中含有碘原子时，制备得到含有放射性核素123I、125I或131I的化合物，作为SPECT类Aβ斑块显像剂。
6.权利要求1或2所述化合物或权利要求4或5所述Aβ斑块显像剂在制备用于治疗或诊断阿尔茨海默症的药物中的应用。
7.二苯氧基柔性分子化合物在制备用于治疗或诊断阿尔茨海默症的药物中的应用；
所述二苯氧基柔性分子化合物的结构如下：
其中，n为1–11的整数，R1为I或NMe2，R2为氢、卤素、羟基、巯基、烷氧基、烷基、硝基、氨基、烷氨基、氰基、羧基、-Sn(Bu)3、-(OCH2CH2)m-F，其中m为1-3的整数，R1和R2均为邻位、间位或对位取代基；当化合物中含有氟原子时，F为18F或19F；当化合物中含有碘原子时，I为123I、124I、125I、127I或131I；当化合物中含有-CH3或-N(CH3)2时，-CH3为-11CH3、-N(CH3)2为-N(11CH3)2。
8.根据权利要求7所述的应用，其特征在于，所述二苯氧基柔性分子化合物的结构中，n＝2或6，R1和R2分别为：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710474957.3A CN107353209B (zh) | 2017-06-21 | 2017-06-21 | 与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710474957.3A CN107353209B (zh) | 2017-06-21 | 2017-06-21 | 与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107353209A CN107353209A (zh) | 2017-11-17 |
| CN107353209B true CN107353209B (zh) | 2019-07-19 |
Family
ID=60272322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710474957.3A Active CN107353209B (zh) | 2017-06-21 | 2017-06-21 | 与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107353209B (zh) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2007326395B2 (en) * | 2006-12-01 | 2012-10-11 | Msd K.K. | Novel phenyl-isoxazol-3-ol derivative |
| CN103724207B (zh) * | 2013-12-20 | 2016-07-06 | 北京智博高科生物技术有限公司 | 苯基苄基醚类衍生物及其制备方法和应用 |
-
2017
- 2017-06-21 CN CN201710474957.3A patent/CN107353209B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107353209A (zh) | 2017-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2526655T3 (es) | Derivados de estilbeno y su uso para la unión y la visualización de placas amiloides | |
| CN103724207B (zh) | 苯基苄基醚类衍生物及其制备方法和应用 | |
| Ono et al. | Novel chalcones as probes for in vivo imaging of β-amyloid plaques in Alzheimer’s brains | |
| US9238631B2 (en) | Radiolabeled amino acids for diagnostic imaging | |
| US7858072B2 (en) | Stilbene derivatives and their use for binding and imaging amyloid plaques | |
| US20110158907A1 (en) | Diphenyl-heteroaryl derivatives and their use for binding and imaging amyloid plaques | |
| JP2009532349A (ja) | スチリルピリジン誘導体及びアミロイド斑を結合させ画像化するためのその使用 | |
| KR100745445B1 (ko) | 종양 영상화 화합물 | |
| CN107353209B (zh) | 与Aβ斑块具有高亲和力的二苯氧基柔性分子及其制备方法和应用 | |
| Ono et al. | Synthesis and characterization of styrylchromone derivatives as β-amyloid imaging agents | |
| Watanabe et al. | Synthesis and biological evaluation of radioiodinated 2, 5-diphenyl-1, 3, 4-oxadiazoles for detecting β-amyloid plaques in the brain | |
| Zheng et al. | Syntheses and evaluation of fluorinated benzothiazole anilines as potential tracers for β-amyloid plaques in Alzheimer's disease | |
| CN103497217A (zh) | 与Aβ斑块具有高亲和力的2-芳基苯并噻唑类化合物、其制备方法及应用 | |
| KR102031652B1 (ko) | 전이체 단백질 과발현 관련 질환의 양성자방출단층촬영 방사성추적자, 형광영상 진단 및 광역학 치료를 위한 전이체 단백질 표적 리간드 및 이의 제조방법 | |
| Auzeloux et al. | A potential melanoma tracer: synthesis, radiolabeling, and biodistribution in mice of a new nitridotechnetium bis (aminothiol) derivative pharmacomodulated by a N-(diethylaminoethyl) benzamide | |
| WO2000066537A1 (en) | Spect imaging agents for serotonin transporters | |
| CA2811688A1 (en) | Choline analogs as radiotracer | |
| Lin et al. | Preparation and biological evaluation of a technetium-99m labeled 4-nitroimidazole derivative for imaging tumor hypoxia | |
| Mukherjee et al. | Development of N-[3-(2′, 4′-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropargylamine (18F-fluoroclorgyline) as a potential PET radiotracer for monoamine oxidase-A | |
| CN109438265B (zh) | 一种与棕色脂肪组织具有亲和力的化合物及其制备方法和应用 | |
| CN107337681A (zh) | 一种超氧阴离子探针及其制备方法和应用 | |
| Fernandes et al. | Synthesis and biological evaluation of silylated mixed-ligand 99mTc complexes with the [PNS/S] donor atom set | |
| US8372379B2 (en) | Technetium-99m (I) tricarbonyl complexes with tridentate chelators for myocardium imaging | |
| EP3581565A1 (en) | Phenyl benzyl ether derivative and preparation method and application thereof | |
| Büyükkaya et al. | PREPARATION OF SOME PYRIDYL-SUBSTITUTED SCHIFF BASES AND THEIR LABELLING WITH Tc-99m |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |