JPH0832681B2 - 2-Yododobutyrophenone derivative and process for producing the same - Google Patents
2-Yododobutyrophenone derivative and process for producing the sameInfo
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- JPH0832681B2 JPH0832681B2 JP61193485A JP19348586A JPH0832681B2 JP H0832681 B2 JPH0832681 B2 JP H0832681B2 JP 61193485 A JP61193485 A JP 61193485A JP 19348586 A JP19348586 A JP 19348586A JP H0832681 B2 JPH0832681 B2 JP H0832681B2
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Description
【発明の詳細な説明】 本発明は、一般式（Ｉ） 〔式中、Ｘは放射性または非放射性ヨウ素原子を表わ
し、Ｒは一般式 で示される置換基を表わす。ここで、R1は水素原子、ハ
ロゲン原子、低級アルキル基、低級ハロアルキル基また
は低級アルコキシ基を表わし、R2は水素原子または低級
アルキル基を表わし、点線部分は単結合または二重結合
を表わす。〕 で示される新規な放射性または非放射性２−ヨードブチ
ロフェノン誘導体（以下、本発明化合物と称す）および
その製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention has the general formula (I) [In the formula, X represents a radioactive or non-radioactive iodine atom, and R represents a general formula. Represents a substituent represented by. Here, R 1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group or a lower alkoxy group, R 2 represents a hydrogen atom or a lower alkyl group, and the dotted line portion represents a single bond or a double bond. ] A novel radioactive or non-radioactive 2-iodobutyrophenone derivative represented by the following (hereinafter referred to as the compound of the present invention) and a method for producing the same.
一般式（Ｉ）で示される放射性の本発明化合物は文献
未記載の新規化合物であり、ドーパミン受容体に対して
高い親和性を有しており、ドーパミン受容体の核医学診
断薬として、また放射性医薬品として極めて有用なもの
である。The radioactive compound of the present invention represented by the general formula (I) is a novel compound not described in the literature, has a high affinity for the dopamine receptor, and is used as a nuclear medicine diagnostic agent for the dopamine receptor and also as a radioactive compound. It is extremely useful as a medicine.
近年、脳の病的状態（たとえばパーキンソン病や精神
分裂病等）においてドーパミン受容体の量が正常人に比
べて変化することが見出され、ドーパミン受容体と諸種
の脳の疾患との関係が医学、薬学の分野において注目さ
れてきている。In recent years, it has been found that the amount of dopamine receptors changes in pathological conditions of the brain (such as Parkinson's disease and schizophrenia) as compared with those in normal people, and the relationship between dopamine receptors and various brain diseases is related. It has been drawing attention in the fields of medicine and pharmacy.
このような状況を背景としてドーパミン受容体を標的
とする核医学診断薬、放射性医薬品の出現が強く臨まれ
ている。Against this background, the emergence of nuclear medicine diagnostic agents and radiopharmaceuticals targeting dopamine receptors is strongly anticipated.
本発明者らは、放射性のヨウ素を分子内に持つドーパ
ミン受容体指向性診断薬、放射性医薬品を目標に研究を
行い、前記一般式（Ｉ）で示される放射性の本発明化合
物がドーパミン受容体に対して高い親和性を有し、特異
的にそれと結合することを見出した。また、放射性の本
発明化合物は、脳への移行性が比較的高く、ドーパミン
受容体指向性の放射性診断薬、放射性医薬品として優れ
た性質を有する。The present inventors have conducted research aiming at a dopamine receptor-directed diagnostic agent having a radioactive iodine molecule in the molecule, and a radiopharmaceutical, and the radioactive compound of the present invention represented by the general formula (I) has been identified as a dopamine receptor. It has been found to have a high affinity for and specifically bind to it. Further, the radioactive compound of the present invention has relatively high migration to the brain, and has excellent properties as a dopamine receptor-directed radiological diagnostic agent and radiopharmaceutical.
したがって、放射性の本発明化合物を用いればヒトま
たは動物の脳およびその他の臓器、組織のドーパミン受
容体の存在を非侵襲的に検出できるばかりか、受容体の
量の変化を動的に測定することも可能となり、脳の疾患
等の核医学診断および治療に極めて有用である。また乳
癌等の癌とドーパミン受容体との関連性からこの方面へ
の応用においても有用である。Therefore, by using the radioactive compound of the present invention, the presence of dopamine receptors in human or animal brain and other organs and tissues can be detected non-invasively, and changes in the amount of receptors can be dynamically measured. It is also very useful for nuclear medicine diagnosis and treatment of brain diseases and the like. It is also useful in applications in this direction due to the relationship between cancers such as breast cancer and dopamine receptors.
また、一般式（Ｉ）で示される非放射性の本発明化合
物もドーパミン受容体に対して高い親和性を有すること
から、中枢神経抑制作用、抗アドレナリン作用、自律神
経作用などを示し、精神病治療剤、鎮痛剤、降圧剤、精
神安定剤、トランキライザーとして有用である。Further, since the non-radioactive compound of the present invention represented by the general formula (I) also has a high affinity for dopamine receptors, it exhibits central nervous system depressant action, anti-adrenergic action, autonomic nerve action, etc. It is useful as an analgesic, antihypertensive, tranquilizer, and tranquilizer.
以下に本発明化合物の製造法について説明する。 The production method of the compound of the present invention is described below.
前記一般式（Ｉ）で示される本発明化合物は、放射性
または非放射性ヨウ素化合物の一般的合成法により製造
できるが、たとえば以下に示す方法Ａあるいは方法Ｂに
従って製造することができる。The compound of the present invention represented by the general formula (I) can be produced by a general method for synthesizing a radioactive or non-radioactive iodine compound, and can be produced, for example, according to the following method A or method B.
一般式（II） 〔式中、Ｒは前記と同一の意味を表わす。〕 で示される２−アミノブチロフェノン誘導体を、適当な
溶媒中、例えばテトラヒドロフラン、ジオキサンまたは
アセトニトリル等の溶媒中、希硫酸または希塩酸等の存
在下、亜硝酸アルカリ金属塩と反応させ、一般式（II
I） 〔式中、Ｒは前記と同一の意味を表わし、Y-はハロゲン
イオンまたは式HSO4 -で示される陰イオンを表わす。〕 で示されるジアゾニウム塩を形成させる。次いで一般式
（III）で示されるジアゾニウム塩を放射性または非放
射性ヨウ素金属塩と反応させることにより前記一般式
（Ｉ）で示される本発明化合物を得る。本反応は−５〜
30℃の範囲で実施される。General formula (II) [In the formula, R represents the same meaning as described above. ] The 2-aminobutyrophenone derivative represented by the formula (II) is reacted with an alkali metal nitrite in a suitable solvent, for example, a solvent such as tetrahydrofuran, dioxane or acetonitrile in the presence of dilute sulfuric acid or dilute hydrochloric acid to give a compound of the general formula (II
I) [In the formula, R represents the same meaning as described above, and Y − represents a halogen ion or an anion represented by the formula HSO 4 − . ] The diazonium salt shown by these is formed. Then, the diazonium salt represented by the general formula (III) is reacted with a radioactive or non-radioactive iodine metal salt to obtain the compound of the present invention represented by the general formula (I). This reaction is -5
It is carried out in the range of 30 ° C.
得られた化合物は、必要に応じ薄層クロマトグラフィ
ー（TLC）または高速液体クロマトグラフィー（HPLC）
等の一般的方法により精製することもできる。The obtained compound can be used for thin layer chromatography (TLC) or high performance liquid chromatography (HPLC).
It can also be purified by a general method such as.
一般式（IV） 〔式中、Ｚはハロゲン原子を表わし、Ｒは前記と同一の
意味を表わす。〕 で示される２−ハロゲノブチロフェノン誘導体を適当な
溶媒中、例えばアセトニトリル、ジメチルホルムアミ
ド、エチレングリコール、エチレングリコールのエーテ
ル誘導体、ジエチレングリコールのエーテル誘導体また
は水等の溶媒中、50〜180℃の反応温度で放射性または
非放射性ヨウ素金属塩と交換反応を行う。得られた化合
物は必要に応じTLCまたはHPLC等の一般的方法により精
製することもできる。General formula (IV) [In the formula, Z represents a halogen atom, and R represents the same meaning as described above. ] In a solvent such as acetonitrile, dimethylformamide, ethylene glycol, ether derivative of ethylene glycol, ether derivative of diethylene glycol or water in a suitable solvent, the 2-halogenobutyrophenone derivative represented by Alternatively, an exchange reaction is performed with a non-radioactive iodine metal salt. The obtained compound can be purified by a general method such as TLC or HPLC, if necessary.
本発明において放射性のヨウ素原子としては、例えば
Ｉ−123,I−125,I−131,I−132などが挙げられ、好まし
くはＩ−123である。放射性ヨウ素金属塩とは上記放射
性ヨウ素の金属塩を意味し、その化学形は放射性I-イオ
ンを与えるものであればよいが、好ましくは例えばヨウ
化ナトリウム、ヨウ化カリウム、ヨウ化リチウムのよう
なアルカリ金属塩である。一般式（III）におけるハロ
ゲンイオンとしては、例えば塩素、臭素、ヨウ素等の陰
イオンが挙げられ、一般式（IV）におけるハロゲン原子
としては、例えばフッ素原子、塩素原子、臭素原子、ヨ
ウ素原子が挙げられる。Examples of the radioactive iodine atom in the present invention include I-123, I-125, I-131, and I-132, and I-123 is preferable. The radioactive iodine metal salt means a metal salt of radioactive iodine described above, and its chemical form may be one which gives a radioactive I − ion, but is preferably sodium iodide, potassium iodide, lithium iodide, etc. It is an alkali metal salt. Examples of the halogen ion in the general formula (III) include anions such as chlorine, bromine and iodine, and examples of the halogen atom in the general formula (IV) include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. To be
以下に実施例および参考例を挙げて本発明をさらに具
体的に説明する。Hereinafter, the present invention will be described more specifically with reference to Examples and Reference Examples.
実施例１ ４′−フルオロ−２′−ヨード−４−（４−ハイドロ
キシ−４−ｐ−クロロフェニルピペリジノ）ブチルフェ
ノン（２−ヨードハロペリドール）の製造 ２−アミノハロペリドール（391mg）を2N−塩酸およ
びアセトニトリルに懸濁し、氷冷下、亜硝酸ナトリウム
（95mg）の水溶液を滴下した。５℃以下で30分間撹拌
し、生じたジアゾニウム塩に氷冷下、ヨウ化カリウム
（166mg）の水溶液を滴下した。滴下後、同温度で1.5時
間撹拌した。反応後、アルカリ性とし溶液（クロロホル
ム）で抽出し、溶媒を留去して、粗生成物を得た。この
ものをシリカゲルカラムクロマトグラフィーにより精製
し、２−ヨードハロペリドール（401mg）を得た。Example 1 Preparation of 4'-fluoro-2'-iodo-4- (4-hydroxy-4-p-chlorophenylpiperidino) butylphenone (2-iodohaloperidol) 2-aminohaloperidol (391 mg) was added to 2N-hydrochloric acid. And suspended in acetonitrile, and an aqueous solution of sodium nitrite (95 mg) was added dropwise under ice cooling. The mixture was stirred at 5 ° C or lower for 30 minutes, and an aqueous solution of potassium iodide (166 mg) was added dropwise to the resulting diazonium salt under ice cooling. After dropping, the mixture was stirred at the same temperature for 1.5 hours. After the reaction, the mixture was made alkaline and extracted with a solution (chloroform), and the solvent was distilled off to obtain a crude product. This was purified by silica gel column chromatography to obtain 2-iodohaloperidol (401 mg).
融点:120〜125℃ IR（ヌジョール）cm-1： 1690（Ｃ＝Ｏ）1 H−NMR（CDCl3）δ（ppm）： 1.50−3.00（15H,m,メチレン,OH）4.72（2H,s,−HN−CH
2N）6.90−7.80（7H,m,ベンゼン環Ｈ） マススペクトル（70eV）m/e: 501/508〔M+〕， 224/226 実施例２ １−〔１−｛４−（ｐ−フルオロ−ｏ−ヨードフェニ
ル）−４−オキソブチル｝ピペリジン−４−イル〕−２
−ベンズイミダリゾリノン（２−ヨードベンペリドー
ル）の製造 ２−アミノベンペリドール（170mg）を2N−塩酸およ
びアセトニトリルに懸濁し、氷冷下、亜硝酸ナトリウム
（44mg）の水溶液を滴下した。５℃以下で30分間撹拌
し、生じたジアゾニウム塩に氷冷下、ヨウ化カリウム
（344mg）の水溶液を滴下した。滴下後、同温度で２時
間撹拌した。反応後、アルカリ性とし、溶媒（クロロホ
ルム）にて抽出した。溶媒を留去して、粗生成物を得
た。このものをシリカゲルカラムクロマトグラフィーに
より精製し、２−ヨードベンペリドール（153mg）を得
た。Melting point: 120 to 125 ° C. IR (nujol) cm −1 : 1690 (C═O) 1 H-NMR (CDCl 3 ) δ (ppm): 1.50-3.00 (15H, m, methylene, OH) 4.72 (2H, s , -HN-CH
2 N) 6.90-7.80 (7H, m, benzene ring H) mass spectrum (70 eV) m / e: 501/508 [M + ], 224/226 Example 2 1- [1- {4- (p-fluoro -O-iodophenyl) -4-oxobutyl} piperidin-4-yl] -2
-Preparation of benzimidazolidinone (2-iodobenperidol) 2-aminobenperidol (170 mg) was suspended in 2N-hydrochloric acid and acetonitrile, and an aqueous solution of sodium nitrite (44 mg) was added dropwise under ice cooling. . The mixture was stirred at 5 ° C or lower for 30 minutes, and an aqueous solution of potassium iodide (344 mg) was added dropwise to the resulting diazonium salt under ice cooling. After the dropping, the mixture was stirred at the same temperature for 2 hours. After the reaction, the mixture was made alkaline and extracted with a solvent (chloroform). The solvent was distilled off to obtain a crude product. This product was purified by silica gel column chromatography to obtain 2-iodobenperidol (153 mg).
融点:157〜161℃ IR(CHCl3)cm-1： 1700（Ｃ＝Ｏ）1 H−NMR（CDCl3）δ（ppm）： 1.60−3.10（15H,m,メチレン，）4.40（1H,bs,NH）7.00
−8.10（7H,m,ベンゼン環Ｈ） マススペクトル（70eV）m/e: 489（M+−H2O） HPLC（カラム：リクロソルブRP−18,4×25mm）:9.83m
in 溶媒：水−エタノール−アセトニトリル−トリエチルア
ミン＝（820/1680/340/1） 保持時間:9.83分 実施例３ 〔125I〕−４′−フルオロ−２′−ヨード−（４−ハ
イドロキシ−４−ｐ−クロロフェニルピペリジノ）ブチ
ロフェノン（〔125I〕−２−ヨードハロペリドール）の
製造 ２−アミノハロペリドール（40μｇ）を用い2N−硫酸
および亜硝酸ナトリウムを用いて調製したジアゾニウム
塩に氷冷下、Na125I（2mCi）を実施例１と同様に反応さ
せ、得られた粗生成物をHPLC（カラム：リクロソルブ
RP−18）を用いて精製し、〔125I〕−２−ヨードハロペ
リドール（1.4mCi）を得た。本品はTLCおよびHPLCのRf
値が実施例１で得られた標品と一致した。 Mp: 157~161 ℃ IR (CHCl 3) cm -1: 1700 (C = O) 1 H-NMR (CDCl 3) δ (ppm): 1.60-3.10 (15H, m, methylene,) 4.40 (1H, bs , NH) 7.00
-8.10 (7H, m, benzene ring H) mass spectrum (70eV) m / e: 489 (M + -H 2 O) HPLC ( Column: LiChrosolv® RP-18,4 × 25mm): 9.83m
in solvent: water-ethanol-acetonitrile-triethylamine = (820/1680/340/1) retention time: 9.83 minutes Example 3 [ 125I ] -4'-fluoro-2'-iodo- (4-hydroxy-4- Preparation of p-chlorophenylpiperidino) butyrophenone ([ 125 I] -2-iodohaloperidol) Diaminonium salt prepared using 2-aminohaloperidol (40 μg) with 2N-sulfuric acid and sodium nitrite under ice cooling under Na cooling 125 I (2 mCi) was reacted in the same manner as in Example 1, and the obtained crude product was subjected to HPLC (column: lyclosolve).
It was purified using RP-18) to obtain [ 125 I] -2-iodohaloperidol (1.4 mCi). This product is Rf of TLC and HPLC
The value was in agreement with the standard product obtained in Example 1.
実施例４ 交換法による〔125I〕−２−ヨードハロペリドールの
製造 実施例１の方法で合成した、２−ヨードハロペリドー
ル（３μｇ）にジメチルホルムアミド（10μｌ）、Na
125I（2.2mCi）を加え、さらに微量の0.1N硫酸を加え、
加熱した。反応後、粗生成物をHPLCにて精製し、
〔125I〕−２−ヨードハロペリドール（0.9mCi）を得
た。本品はTLC、HPLCのRf値が実施例１で得られた標品
と一致した。Example 4 Production of [ 125 I] -2-iodohaloperidol by Exchange Method 2-iodohaloperidol (3 μg) synthesized by the method of Example 1 was added to dimethylformamide (10 μl) and Na.
125 I (2.2 mCi) was added, and a trace amount of 0.1 N sulfuric acid was added,
Heated. After the reaction, the crude product was purified by HPLC,
[ 125 I] -2-iodohaloperidol (0.9 mCi) was obtained. This product had the same TLC and HPLC Rf values as the standard product obtained in Example 1.
実施例５ 〔125I〕−１−〔１−｛４−（ｐ−フルオロ−ｏ−ヨ
ードフェニル）−４−オキソブチル｝ピペリジン−４−
イル〕−２−ベンズイミダゾリノン（〔125I〕−２−ヨ
ードベンペリドール）の製造 ２−アミノベンペリドール（50μｇ）を用い、2N−硫
酸および亜硝酸ナトリウムを用いて調製したジアゾニウ
ム塩に氷冷下、Na125I（2mCi）を実施例２と同様に反応
させ、得られた粗生成物をHPLC（カラム：リクロソルブ
RP−18）を用い精製し、〔125I〕−２−ヨードベンペ
リドール（1.35mCi）を得た。本品のTLCにおけるRf値お
よびHPLCにおける保持時間は実施例２で得られた標品と
一致した。Example 5 [ 125 I] -1- [1- {4- (p-fluoro-o-iodophenyl) -4-oxobutyl} piperidine-4-
Preparation of [2] -benzimidazolinone ([ 125 I] -2-iodobenperidol) 2-aminobenzperidol (50 μg) was used to prepare a diazonium salt prepared with 2N-sulfuric acid and sodium nitrite. Under ice cooling, Na 125 I (2 mCi) was reacted in the same manner as in Example 2, and the obtained crude product was subjected to HPLC (column: liclosolve).
RP-18) was used for purification to obtain [ 125 I] -2-iodobenperidol (1.35 mCi). The Rf value of this product by TLC and the retention time by HPLC were in agreement with those of the standard product obtained in Example 2.
実施例６ 交換法による〔125I〕−２−ヨードベンペリドールの
製造 実施例２の方法で合成した２−ヨードベンペリドール
（５μｇ）にジメチルホルムアミド（10μｌ）、Na125I
（2.0mCi）を加え、微量の0.1N硫酸を加えた後、加熱し
た。反応後、粗生成物をHPLCにて精製し、〔125I〕−２
−ヨードベンペリドール（1.2mCi）を得た。本品はTL
C、HPLCにおいて実施例２で得られた標品と一致した。Example 6 Production of [ 125 I] -2-iodobeneperidol by Exchange Method 2-Iodobeneperidol (5 μg) synthesized by the method of Example 2 was added to dimethylformamide (10 μl) and Na 125 I.
(2.0 mCi) was added, and a trace amount of 0.1 N sulfuric acid was added, followed by heating. After the reaction, the crude product was purified by HPLC, and [ 125 I] -2
-Iodobenperidol (1.2 mCi) was obtained. This product is TL
In C and HPLC, it was in agreement with the standard product obtained in Example 2.
参考例１ ４′−フルオロ−２′−ブロモ−４−（４−ハイドロ
キシ−４−ｐ−クロロフェニルピペリジノ）ブチロフェ
ノン（２−ブロモハロペリドール）の製造 ２−アミノハロペリドール（390mg）をアセトニトリ
ル−水混合液に懸濁し、１−ナフタレンスルホン酸（11
30mg）を加え、氷冷下、亜硝酸ナトリウム（95mg）の水
溶液を滴下した。５℃以下で１時間撹拌し、生じたジア
ゾニウム塩の結晶を濾取した。結晶をアセトニトリル−
臭化水素水混合液にに溶解後、銅粉（5mg）を加えて３
時間撹拌した。反応後、溶媒（クロロホルム）で抽出
し、酸およびアルカリで洗浄後、溶媒を留去して、粗生
成物を得た。このものをシリカゲルカラムクロマトグラ
フィーにより精製し、２−ブロモハロペリドール（205m
g）を得た。Reference Example 1 Preparation of 4'-fluoro-2'-bromo-4- (4-hydroxy-4-p-chlorophenylpiperidino) butyrophenone (2-bromohaloperidol) 2-aminohaloperidol (390 mg) was mixed with acetonitrile-water. 1-naphthalenesulfonic acid (11
30 mg) was added, and an aqueous solution of sodium nitrite (95 mg) was added dropwise under ice cooling. The mixture was stirred at 5 ° C or lower for 1 hour, and the resulting diazonium salt crystal was collected by filtration. Acetonitrile-
After dissolving in a mixture of hydrogen bromide and copper powder (5 mg), add 3
Stirred for hours. After the reaction, the product was extracted with a solvent (chloroform), washed with an acid and an alkali, and then the solvent was distilled off to obtain a crude product. This product was purified by silica gel column chromatography to give 2-bromohaloperidol (205m
g) was obtained.
融点:93.5〜95.5℃ IR（CHCl3）cm-1： 1690（Ｃ＝Ｏ）1 H−NMR（CDCl3）δ（ppm）： 1.60−3.10（15H,m,メチレン,OH）,6.90−7.60（7H,m,
ベンゼン環Ｈ） マススペクトル（70eV）m/e: 453,455,457〔M+〕Melting point: 93.5-95.5 ° C IR (CHCl 3 ) cm -1 : 1690 (C = O) 1 H-NMR (CDCl 3 ) δ (ppm): 1.60-3.10 (15H, m, methylene, OH), 6.90-7.60 (7H, m,
Benzene ring H) Mass spectrum (70eV) m / e: 453,455,457 [M + ]
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 米国特許3907812（ＵＳ，Ａ) 米国特許3799932（ＵＳ，Ａ) Ｊ．Ｌａｂｅｌｌｅｄ Ｃｏｍｐｄ．Ｒ ａｄｉｏｐｈａｒｍ．，ｖｏｌ．16，ｎ ｏ．３（1979），ｐｐ．407−414 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References US Patent 3907812 (US, A) US Patent 3799932 (US, A) Labeled Compd. R adiopharm. , Vol. 16, no. 3 (1979), pp. 407-414
Claims (4)
ロゲン原子、低級アルキル基、低級ハロアルキル基また
は低級アルコキシ基を表わし、R2は水素原子または低級
アルキル基を表わし、点線部分は単結合または二重結合
を表わす。〕 で示される放射性２−ヨードブチロフェノン誘導体。1. A general formula (I) [In the formula, X represents a radioactive iodine atom, and R represents a general formula. Represents a substituent represented by. Here, R 1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group or a lower alkoxy group, R 2 represents a hydrogen atom or a lower alkyl group, and the dotted line portion represents a single bond or a double bond. ] The radioactive 2-iodobutyrophenone derivative shown by these.
−123,I−125,I−131またはＩ−132である特許請求の範
囲第１項に記載の放射性２−ヨードブチロフェノン誘導
体。2. In the above general formula (I), the substituent X is I
The radioactive 2-iodobutyrophenone derivative according to claim 1, which is -123, I-125, I-131 or I-132.
ロゲン原子、低級アルキル基、低級ハロアルキル基また
は低級アルコキシ基を表わし、R2は水素原子または低級
アルキル基を表わし、点線部分は単結合または二重結合
を表わす。〕 で示される２−アミノブチロフェノン誘導体をジアゾ化
して得られる一般式（III） 〔式中、Ｒは前記と同一の意味を表わし、Y-はハロゲン
イオンまたは式HSO4 -で示される陰イオンを表わす。〕 で示されるジアゾ化合物に放射性金属ヨウ化物を反応さ
せることを特徴とする一般式（Ｉ） 〔式中、Ｘは放射性ヨウ素原子を表わし、Ｒは前記と同
一の意味を表わす。〕 で示される放射性２−ヨードブチロフェノン誘導体の製
造方法。3. General formula (II) [Wherein R is a general formula Represents a substituent represented by. Here, R 1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group or a lower alkoxy group, R 2 represents a hydrogen atom or a lower alkyl group, and the dotted line portion represents a single bond or a double bond. ] The general formula (III) obtained by diazotizing the 2-aminobutyrophenone derivative represented by [In the formula, R represents the same meaning as described above, and Y − represents a halogen ion or an anion represented by the formula HSO 4 − . ] The general formula (I) characterized by reacting a diazo compound represented by [In the formula, X represents a radioactive iodine atom, and R represents the same meaning as described above. ] The manufacturing method of the radioactive 2-iodobutyrophenone derivative shown by these.
ロゲン原子、低級アルキル基、低級ハロアルキル基また
は低級アルコキシ基を表わし、R2は水素原子または低級
アルキル基を表わし、点線部分は単結合または二重結合
を表わす。〕 で示される２−ハロゲノブチロフェノン誘導体に放射性
金属ヨウ化物を反応させることを特徴とする一般式
（Ｉ） 〔式中、Ｘは放射性ヨウ素原子を表わし、Ｒは前記と同
一の意味を表わす。〕 で示される放射性２−ヨードブチロフェノン誘導体の製
造方法。4. A general formula (IV) [In the formula, Z represents a halogen atom, and R is a general formula. Represents a substituent represented by. Here, R 1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group or a lower alkoxy group, R 2 represents a hydrogen atom or a lower alkyl group, and the dotted line portion represents a single bond or a double bond. ] The 2-halogenobutyrophenone derivative shown by these is made to react with a radioactive metal iodide, General formula (I) characterized by the above-mentioned. [In the formula, X represents a radioactive iodine atom, and R represents the same meaning as described above. ] The manufacturing method of the radioactive 2-iodobutyrophenone derivative shown by these.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18453385 | 1985-08-22 | ||
| JP60-184533 | 1985-08-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62123170A JPS62123170A (en) | 1987-06-04 |
| JPH0832681B2 true JPH0832681B2 (en) | 1996-03-29 |
Family
ID=16154862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61193485A Expired - Fee Related JPH0832681B2 (en) | 1985-08-22 | 1986-08-19 | 2-Yododobutyrophenone derivative and process for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0832681B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19952146A1 (en) * | 1999-10-29 | 2001-06-07 | Boehringer Ingelheim Pharma | Arylalkanes, arylalkenes and aryl-azaalkanes, medicaments containing these compounds and process for their preparation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3799932A (en) | 1970-03-20 | 1974-03-26 | Sumitomo Chemical Co | Gamma-piperidinobutyrophenones |
| US3907812A (en) | 1969-07-16 | 1975-09-23 | Sumitomo Chemical Co | Butyrophenone derivatives |
-
1986
- 1986-08-19 JP JP61193485A patent/JPH0832681B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3907812A (en) | 1969-07-16 | 1975-09-23 | Sumitomo Chemical Co | Butyrophenone derivatives |
| US3799932A (en) | 1970-03-20 | 1974-03-26 | Sumitomo Chemical Co | Gamma-piperidinobutyrophenones |
Non-Patent Citations (1)
| Title |
|---|
| Ｊ．ＬａｂｅｌｌｅｄＣｏｍｐｄ．Ｒａｄｉｏｐｈａｒｍ．，ｖｏｌ．１６，ｎｏ．３（１９７９），ｐｐ．４０７−４１４ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62123170A (en) | 1987-06-04 |
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