JP2004231647A - フェニルオキシアニリン誘導体 - Google Patents
フェニルオキシアニリン誘導体 Download PDFInfo
- Publication number
- JP2004231647A JP2004231647A JP2004001691A JP2004001691A JP2004231647A JP 2004231647 A JP2004231647 A JP 2004231647A JP 2004001691 A JP2004001691 A JP 2004001691A JP 2004001691 A JP2004001691 A JP 2004001691A JP 2004231647 A JP2004231647 A JP 2004231647A
- Authority
- JP
- Japan
- Prior art keywords
- daa1106
- alkyl group
- atom
- group
- halogen atom
- 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.)
- Pending
Links
- GYNAVKULVOETAD-UHFFFAOYSA-N n-phenoxyaniline Chemical class C=1C=CC=CC=1NOC1=CC=CC=C1 GYNAVKULVOETAD-UHFFFAOYSA-N 0.000 title claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 125000005843 halogen group Chemical group 0.000 claims abstract description 19
- 239000003446 ligand Substances 0.000 claims abstract description 11
- 102000004300 GABA-A Receptors Human genes 0.000 claims abstract description 7
- 108090000839 GABA-A Receptors Proteins 0.000 claims abstract description 7
- 230000002093 peripheral effect Effects 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 3
- 239000001257 hydrogen Substances 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- DCRZYADKQRHHSF-UHFFFAOYSA-N daa-1106 Chemical compound COC1=CC=C(OC)C(CN(C(C)=O)C=2C(=CC=C(F)C=2)OC=2C=CC=CC=2)=C1 DCRZYADKQRHHSF-UHFFFAOYSA-N 0.000 description 52
- NZVKWLWAFUSDQE-UHFFFAOYSA-N n-[[2-(2-fluoroethoxy)-5-methoxyphenyl]methyl]-n-(5-fluoro-2-phenoxyphenyl)acetamide Chemical compound COC1=CC=C(OCCF)C(CN(C(C)=O)C=2C(=CC=C(F)C=2)OC=2C=CC=CC=2)=C1 NZVKWLWAFUSDQE-UHFFFAOYSA-N 0.000 description 16
- RAVIZVQZGXBOQO-UHFFFAOYSA-N PK-11195 Chemical compound N=1C(C(=O)N(C)C(C)CC)=CC2=CC=CC=C2C=1C1=CC=CC=C1Cl RAVIZVQZGXBOQO-UHFFFAOYSA-N 0.000 description 13
- -1 5-fluoroheptyl group Chemical group 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 229940049706 benzodiazepine Drugs 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 2
- 0 CC(C)(C=C1)C=CC(OC2=CC(C)(*)C=CC=C2)=C1N(C)C(*)=O Chemical compound CC(C)(C=C1)C=CC(OC2=CC(C)(*)C=CC=C2)=C1N(C)C(*)=O 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 235000010724 Wisteria floribunda Nutrition 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000013399 early diagnosis Methods 0.000 description 2
- XGVXNTVBGYLJIR-UHFFFAOYSA-N fluoroiodomethane Chemical compound FCI XGVXNTVBGYLJIR-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical group CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- BQGMMFZDQBVDCE-UHFFFAOYSA-N n-(5-fluoro-2-phenoxyphenyl)-n-[(2-hydroxy-5-methoxyphenyl)methyl]acetamide Chemical compound COC1=CC=C(O)C(CN(C(C)=O)C=2C(=CC=C(F)C=2)OC=2C=CC=CC=2)=C1 BQGMMFZDQBVDCE-UHFFFAOYSA-N 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- KENPFZUYYWVXNW-UHFFFAOYSA-N 2-bromoethyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OCCBr KENPFZUYYWVXNW-UHFFFAOYSA-N 0.000 description 1
- XNRDLSNSMTUXBV-UHFFFAOYSA-N 2-fluoroethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCF)C=C1 XNRDLSNSMTUXBV-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000020358 Learning disease Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-BJUDXGSMSA-N fluorine-18 atom Chemical compound [18F] YCKRFDGAMUMZLT-BJUDXGSMSA-N 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- NZVKWLWAFUSDQE-FNNGWQQSSA-N n-[[2-(2-fluoranylethoxy)-5-methoxyphenyl]methyl]-n-(5-fluoro-2-phenoxyphenyl)acetamide Chemical compound COC1=CC=C(OCC[18F])C(CN(C(C)=O)C=2C(=CC=C(F)C=2)OC=2C=CC=CC=2)=C1 NZVKWLWAFUSDQE-FNNGWQQSSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl 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])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
炭素数1〜10のアルキル基とは直鎖状又は分枝状のアルキル基を意味し、例えばメチル基、エチル基、n−プロピル基、イソプロピル基、n−ブチル基、n−ヘプチル基などが挙げられる。
ハロゲン原子で置換された炭素数1〜10のアルキル基とはハロゲン原子の1〜3個で水素原子が置換された直鎖状又は分枝状のアルキル基を意味し、好ましくはフッ素原子又はヨウ素原子で置換されたアルキル基である。それらとしては、例えばフルオロメチル基、2−フルオロエチル基、2−ヨウ化エチル基、5−フルオロヘプチル基、6−ブロモヘキシル基などが挙げられる。ハロゲン原子で置換された炭素数1〜5のアルキル基とはハロゲン原子の1〜3個で水素原子が置換された直鎖状又は分枝状のアルキル基を意味し、好ましくはフッ素原子又はヨウ素原子で置換されたアルキル基である。それらとしては、例えばフルオロメチル基、2−フルオロエチル基、2−ヨウ化エチル基、5−フルオロヘプチル基などが挙げられる。
実施例1
N−(2−フルオロメチル−5−メトキシベンジル)−N−(5−フルオロ−2−フェノキシフェニル)アセタミド(以下FMDAA1106)の製造
N−(2−ヒドロキシ−5−メトキシベンジル)−N−(5−フルオロ−2−フェノキシフェニル)アセタミド(以下DAA1123)(18mg)をN,N−ジメチルホルムアミド(DMF 1.0mL)に溶解させた溶液に油性水素化ナトリウム(60%)5.1mgを加えて0℃で攪拌した後、フルオロメチルヨーダイド(FCH2I)10mgを加えて、さらに0℃で1時間攪拌した。反応液に水を加えて酢酸エチルにて抽出し、有機層を飽和食塩水にて洗浄後、無水硫酸マグネシウムにて乾燥した。溶媒を減圧下留去して得た粗生成物をシリカゲルカラムクロマトグラフィー(クロロホルム:ヘキサン:酢酸エチル=1:3:1にて溶出)にて精製し、表記の化合物16mgを得た。
融点 71〜72℃
N−(2−[18F]フルオロメチル−5−メトキシベンジル)−N−(5−フルオロ−2−フェノキシフェニル)アセタミド(以下[18F]FMDAA1106)の製造
[18F]フッ素([18F]F)は20atom%H2 18Oを用い、18MeVプロトンの照射によって生産された。照射後、[18F]F-をターゲットから回収し、Dowex 1-X8アニオン交換樹脂により[18O]H2Oから分離した後、Kryptofix 2.2.2.(25mg)を含有したアセトニトリル(CH3CN 1.5mL)と混合した後、照射室から合成セルに移送した。合成セルで[18F]Fを乾燥したのち、130℃でジヨードメタン(CH2I2)を反応容器に注入した。注入と同時にヘリウムガスによって生成した[18F]F CH2IをDAA1123 1mgと水素化ナトリウム(6.8μL,0.5g/20mL)のDMF(300mL)溶液にバブリングした。バブリングが2分以内で終了し、混合物を室温で10分間放置後、反応混合物を逆相セミ分離HPLC(YMCJ'sphere ODS-H80カラム,10mmID×250mm)に注入した。移動相がCH3CN/H2O(6/4)で、流速が6mL/minで[18F]FMDAA1106のフラクションを取得した。本フラクションに対し、減圧下で溶媒を除去し、生理食塩水(10mL)に溶解し、0.22μm ミリポアフィルターを通過し、[18F]FMDAA1106(110MBq,n=3)を最終製剤として得ることができた。(照射条件:15min,15μA)。なお、合成時間が照射終了時から約45分間を要した。
N−[2−(2−フルオロ)エチル−5−メトキシベンジル]−N−(5−フルオロ−2−フェノキシフェニル)アセタミド(以下FEDAA1106)の製造
実施例1と同様な操作により、フルオロメチルヨーダイド(FCH2I)に代わり1−フルオロ−2−トシロキシエタン(FCH2CH2OTs)を用い表記の化合物20mgを得た。
融点 54〜56℃
N−[2−(2−[18F]フルオロ)エチル−5−メトキシベンジル]−N−(5−フルオロ−2−フェノキシフェニル)アセタミド(以下[18F]FEDAA1106)の製造
実施例2と同様な操作により、ジヨードメタン(CH2I2)の代わりに2−ブロモエチルトリフレート(BrCH2CH2OTf)を用い表記の化合物を得た。
Sihver, S.らのJ. Pharmacol. Exp. Ther. 1999, 290, 917.及びZhang, M.-RらのNucl.Med. Biol. 2002, 29, 469.に記載の従来法により、インビトロにおけるPBRに対する親和性を調べた。
1. [11C]DAA1106(1 nM)
2. [11C]DAA1106(1 nM) + DAA1106(0.1 nM)
3. [11C]DAA1106(1 nM) + DAA1106(0.33 nM)
4. [11C]DAA1106(1 nM) + DAA1106(1 nM)
5. [11C]DAA1106(1 nM) + DAA1106(3.3 nM)
6. [11C]DAA1106(1 nM) + DAA1106(10 nM)
7. [11C]DAA1106(1 nM) + DAA1106(33 nM)
8. [11C]DAA1106(1 nM) + DAA1106(100 nM)
9. [11C]DAA1106(1 nM) + DAA1106(1μM)
10. [11C]DAA1106(1 nM) + DAA1106(10μM)
12. [11C]DAA1106(1 nM) + PK 11195 (0.33 nM)
13. [11C]DAA1106(1 nM) + PK 11195(1 nM)
14. [11C]DAA1106(1 nM) + PK 11195(3.3 nM)
15. [11C]DAA1106(1 nM) + PK 11195(10 nM)
16. [11C]DAA1106(1 nM) + PK 11195(33 nM)
17. [11C]DAA1106(1 nM) + PK 11195(100 nM)
18. [11C]DAA1106(1 nM) + PK 11195(1μM)
19. [11C]DAA1106(1 nM) + PK 11195(10μM)
21. [11C]DAA1106(1 nM) + FMDAA1106(0.33 nM)
22. [11C]DAA1106(1 nM) + FMDAA1106(1 nM)
23. [11C]DAA1106(1 nM) + FMDAA1106(3.3 nM)
24. [11C]DAA1106(1 nM) + FMDAA1106(10 nM)
25. [11C]DAA1106(1 nM) + FMDAA1106(33 nM)
26. [11C]DAA1106(1 nM) + FMDAA1106(100 nM)
27. [11C]DAA1106(1 nM) + FMDAA1106(1μM)
28. [11C]DAA1106(1 nM) + FMDAA1106(10μM)
30. [11C]DAA1106(1 nM) + FEDAA1106(0.33 nM)
31. [11C]DAA1106(1 nM) + FEDAA1106(1 nM)
32. [11C]DAA1106(1 nM) + FEDAA1106(3.3 nM)
33. [11C]DAA1106(1 nM) + FEDAA1106(10 nM)
34. [11C]DAA1106(1 nM) + FEDAA1106(33 nM)
35. [11C]DAA1106(1 nM) + FEDAA1106(100 nM)
36. [11C]DAA1106(1 nM) + FEDAA1106(1μM)
37. [11C]DAA1106(1 nM) + FEDAA1106(10μM)
Claims (4)
- ハロゲン原子がフッ素原子、ヨウ素原子又は臭素原子である請求項1又は2記載のフェニルオキシアニリン誘導体又はその放射性同位体。
- 請求項1〜3のいずれか記載のフェニルオキシアニリン誘導体又はその放射性同位体の末梢性ベンゾジアゼピン受容体標識リガンドとしての利用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004001691A JP2004231647A (ja) | 2003-01-10 | 2004-01-07 | フェニルオキシアニリン誘導体 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003004251 | 2003-01-10 | ||
JP2004001691A JP2004231647A (ja) | 2003-01-10 | 2004-01-07 | フェニルオキシアニリン誘導体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2004231647A true JP2004231647A (ja) | 2004-08-19 |
JP2004231647A5 JP2004231647A5 (ja) | 2007-02-22 |
Family
ID=32964672
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004001691A Pending JP2004231647A (ja) | 2003-01-10 | 2004-01-07 | フェニルオキシアニリン誘導体 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP2004231647A (ja) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009515940A (ja) * | 2005-11-18 | 2009-04-16 | ハマースミス・イメイネット・リミテッド | 末梢ベンゾジアゼピンレセプター(pbr)親和性を有するインビボイメージング剤としての四環式インドール誘導体 |
JP2009537457A (ja) * | 2006-05-19 | 2009-10-29 | ザ・ユニバーシティ・オブ・シドニー | 輸送タンパク質(18kDa)のためのリガンドとしての2−アリールピラゾロ[l,5−α]ピリミジン−3−イルアセトアミド誘導体 |
JP2009298725A (ja) * | 2008-06-12 | 2009-12-24 | Natl Inst Of Radiological Sciences | 蛍光標識フェニルオキシアニリン誘導体及び蛍光標識プローブ |
JP2010521651A (ja) * | 2007-03-12 | 2010-06-24 | 独立行政法人放射線医学総合研究所 | 脳内のアミロイド関連神経炎症の画像化 |
JP2011529929A (ja) * | 2008-08-06 | 2011-12-15 | バイエル ファーマ アクチエンゲゼルシャフト | 診断用造影及び医薬的処置のための末梢ベンゾジアゼピン受容体のリガンドとしてのdaa−ピリジン |
JP2012504581A (ja) * | 2008-10-02 | 2012-02-23 | ジーイー・ヘルスケア・リミテッド | 神経炎症のイメージング |
JP2016531155A (ja) * | 2013-09-13 | 2016-10-06 | バイオ イメージング コリア シーオー.,エルティーディー. | [18f]フルオロメチル基が導入された脳神経炎症標的陽子放出断層撮影放射性追跡子、これらの合成及びそれを用いた生物学的結果の評価方法。 |
-
2004
- 2004-01-07 JP JP2004001691A patent/JP2004231647A/ja active Pending
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009515940A (ja) * | 2005-11-18 | 2009-04-16 | ハマースミス・イメイネット・リミテッド | 末梢ベンゾジアゼピンレセプター(pbr)親和性を有するインビボイメージング剤としての四環式インドール誘導体 |
JP2009537457A (ja) * | 2006-05-19 | 2009-10-29 | ザ・ユニバーシティ・オブ・シドニー | 輸送タンパク質(18kDa)のためのリガンドとしての2−アリールピラゾロ[l,5−α]ピリミジン−3−イルアセトアミド誘導体 |
JP2010521651A (ja) * | 2007-03-12 | 2010-06-24 | 独立行政法人放射線医学総合研究所 | 脳内のアミロイド関連神経炎症の画像化 |
JP2009298725A (ja) * | 2008-06-12 | 2009-12-24 | Natl Inst Of Radiological Sciences | 蛍光標識フェニルオキシアニリン誘導体及び蛍光標識プローブ |
JP2011529929A (ja) * | 2008-08-06 | 2011-12-15 | バイエル ファーマ アクチエンゲゼルシャフト | 診断用造影及び医薬的処置のための末梢ベンゾジアゼピン受容体のリガンドとしてのdaa−ピリジン |
JP2012504581A (ja) * | 2008-10-02 | 2012-02-23 | ジーイー・ヘルスケア・リミテッド | 神経炎症のイメージング |
JP2016531155A (ja) * | 2013-09-13 | 2016-10-06 | バイオ イメージング コリア シーオー.,エルティーディー. | [18f]フルオロメチル基が導入された脳神経炎症標的陽子放出断層撮影放射性追跡子、これらの合成及びそれを用いた生物学的結果の評価方法。 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Zhang et al. | [18F] FMDAA1106 and [18F] FEDAA1106: two positron-emitter labeled ligands for peripheral benzodiazepine receptor (PBR) | |
CA2715390A1 (en) | Imaging agents for detecting neurological dysfunction | |
Prasad et al. | Synthesis of fluorinated analogues of sphingosine-1-phosphate antagonists as potential radiotracers for molecular imaging using positron emission tomography | |
CN101835728A (zh) | 用于中枢神经系统疾病或肿瘤的成像、诊断和/或治疗的化合物 | |
US6870069B2 (en) | Phenyloxyaniline derivatives | |
CN109400645A (zh) | 一种磷酸衍生物及制备方法和用途 | |
WO2018218696A1 (zh) | α7烟碱型乙酰胆碱受体的配体化合物及其应用 | |
JP2004231647A (ja) | フェニルオキシアニリン誘導体 | |
Majo et al. | Synthesis and in vivo evaluation of [18F] 2-(4-(4-(2-(2-fluoroethoxy) phenyl) piperazin-1-yl) butyl)-4-methyl-1, 2, 4-triazine-3, 5 (2H, 4H)-dione ([18F] FECUMI-101) as an imaging probe for 5-HT1A receptor agonist in nonhuman primates | |
Maisonial et al. | Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for central σ1 receptors and comparison with fluoroalkyl homologs | |
JP2002525325A (ja) | 放射標識化ニューロキニン−1受容体拮抗薬 | |
USRE43688E1 (en) | Compositions and methods related to serotonin 5-HT1A receptors | |
Wang et al. | Synthesis and biological evaluation of 18F labeled fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives for sigma-1 receptor imaging | |
Sorger et al. | A new 18F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter | |
Zhang et al. | Synthesis and evaluation of 3-(4-chlorobenzyl)-8-[11C] methoxy-1, 2, 3, 4-tetrahydrochromeno [3, 4-c] pyridin-5-one: a PET tracer for imaging sigma1 receptors | |
Modemann et al. | Development of high-affinity fluorinated ligands for cannabinoid subtype 2 receptor, and in vitro evaluation of a radioactive tracer for imaging | |
CN112469701A (zh) | Tspo结合剂 | |
Leston et al. | Is pineal melatonin released in the third ventricle in humans? A study in movement disorders | |
Santschi et al. | Synthesis of 2‐[18F] Fluoro‐2‐deoxyisosorbide 5‐mononitrate and Assessment of Its in vivo Biodistribution as Determined by Dynamic Positron Emission Tomography (PET) | |
Zhu et al. | An improved preparation of [18F] FPBM: a potential serotonin transporter (SERT) imaging agent | |
CN105593210B (zh) | 用于体内成像的咔唑化合物 | |
JP2006506319A (ja) | 5−ht受容体リガンドとしてのピリジニルオキシ誘導体 | |
EP4286390A1 (en) | Heterocyclic amide derivative, preparation method therefor, and application thereof | |
Bdair et al. | Radiosynthesis and in vivo evaluation of four positron emission tomography tracer candidates for imaging of melatonin receptors | |
KR20230034222A (ko) | 헌팅틴 단백질의 이미징을 위한 헤테로사이클릭 화합물 및 이미징제 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061228 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061228 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20070919 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20070919 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20071126 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20071203 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090318 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090515 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090520 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090807 |