JPH06329646A - Spin-labeled triglyceride compound - Google Patents
Spin-labeled triglyceride compoundInfo
- Publication number
- JPH06329646A JPH06329646A JP5118288A JP11828893A JPH06329646A JP H06329646 A JPH06329646 A JP H06329646A JP 5118288 A JP5118288 A JP 5118288A JP 11828893 A JP11828893 A JP 11828893A JP H06329646 A JPH06329646 A JP H06329646A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- spin
- electron spin
- spin resonance
- 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
- -1 triglyceride compound Chemical class 0.000 title claims abstract description 10
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 10
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- 235000021314 Palmitic acid Nutrition 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 abstract description 22
- 238000004435 EPR spectroscopy Methods 0.000 abstract description 9
- 238000005259 measurement Methods 0.000 abstract description 9
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 abstract description 6
- 238000001727 in vivo Methods 0.000 abstract description 4
- 238000009833 condensation Methods 0.000 abstract description 3
- 230000005494 condensation Effects 0.000 abstract description 3
- 238000002372 labelling Methods 0.000 abstract description 3
- 238000004458 analytical method Methods 0.000 abstract description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000001362 electron spin resonance spectrum Methods 0.000 description 16
- 238000000034 method Methods 0.000 description 14
- 238000012937 correction Methods 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000005291 magnetic effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DRAWQKGUORNASA-CLFAGFIQSA-N 1,3-dioleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)COC(=O)CCCCCCC\C=C/CCCCCCCC DRAWQKGUORNASA-CLFAGFIQSA-N 0.000 description 1
- YNCPXBIZAPNQIJ-UHFFFAOYSA-N 1h-imidazole;sodium Chemical compound [Na].C1=CNC=N1 YNCPXBIZAPNQIJ-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- DRAWQKGUORNASA-UHFFFAOYSA-N Anticancer Glycerol Ester PMV70P691-119 Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCC=CCCCCCCCC DRAWQKGUORNASA-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([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])[H] 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、スピンラベル化トリグ
リセライド化合物に関する。更に詳しくは、電子スピン
共鳴装置により検出を可能とするものである。FIELD OF THE INVENTION The present invention relates to spin-labeled triglyceride compounds. More specifically, it can be detected by an electron spin resonance device.
【０００２】[0002]
【従来の技術】生体膜などへの電子スピン共鳴の応用と
してスピンラベル法がある。この手法は安定な常磁性分
子をプローブとして、人為的に分子構造内に取り込ませ
ることにより電子スピン共鳴測定を可能にし、そのスペ
クトルから磁気共鳴固有の情報を得ようとするものであ
る。従って、スピントラップ法などによる系中のラジカ
ル種そのものの検出とは異なり、既知のラジカル種のス
ペクトルの解析から分子のおかれた環境の物性を知る手
段として用いられている。2. Description of the Related Art There is a spin label method as an application of electron spin resonance to a biological membrane. This method makes it possible to measure electron spin resonance by artificially incorporating it into the molecular structure using a stable paramagnetic molecule as a probe, and obtain information specific to magnetic resonance from the spectrum. Therefore, unlike the detection of the radical species themselves in the system by the spin trap method or the like, it is used as a means of knowing the physical properties of the environment in which the molecule is placed by analyzing the spectra of known radical species.
【０００３】従来、生体におけるトリグリセライドの研
究は数多くなされてきた。その研究は、その本来の複雑
さのためもあって、種々のアプローチからの取り組みが
為されている。しかし、本発明のようにトリグリセライ
ドにスピンラベルした化合物を用い、電子スピン共鳴に
よりその生体内挙動を追跡した報告は知られていない。Conventionally, many studies on triglycerides in living bodies have been made. Due to its inherent complexity, the research has been approached from various approaches. However, there is no report of tracking the in-vivo behavior by electron spin resonance using a compound spin-labeled with triglyceride as in the present invention.
【０００４】[0004]
【発明が解決しようとする課題】これら従来の方法は、
主として生体膜などの膜脂質の研究において応用される
ことが多かったが、新しいスピンラベル剤の開発と装置
の改良によりタンパク質、酵素などの研究分野において
も重要な研究手段の一つとなりつつある。These conventional methods are as follows.
Although it was often applied mainly to the study of membrane lipids such as biological membranes, it is becoming one of the important research tools in the field of proteins and enzymes due to the development of new spin labeling agents and the improvement of the equipment.
【０００５】トリグリセライドの生体内分布の研究は放
射ラベルを施して研究した例はあるが、組織分布を測定
するには臓器を摘出しなければならないために同一の個
体で経時的に測定することは出来なかった。Although there has been an example of studying the biodistribution of triglyceride by applying a radiolabel, it is necessary to take out an organ in order to measure the tissue distribution, and therefore it is not possible to measure it in the same individual over time. I could not do it.
【課題を解決するための手段】本発明者らは、トリグリ
セライドにスピンラベルを結合することにより、電子ス
ピン共鳴装置でトリグリセライドの存在状態をスペクト
ルとして検出することが可能になることを見いだし、本
発明を完成した。The present inventors have found that the presence of triglyceride can be detected as a spectrum in an electron spin resonance apparatus by binding a spin label to triglyceride, and the present invention has been found. Was completed.
【０００６】すなわち、本発明は式（Ｉ） ［式中、Ｒ1は、オレイン酸またはパルミチン酸を示
し、Ｒ2は、式（ＩＩ）That is, the present invention has the formula (I) [In the formula, R1Indicates oleic acid or palmitic acid
And R2Is of formula (II)
【０００７】 [0007]
【０００８】（式中、ｍは０から１０のアラビア数字を
示し、ｎは１から５のアラビア数字を示す。）を示
す。］で表されるスピンラベル化トリグリセライド化合
物および式（ＩＩＩ） ［式中、Ｒ1は、オレイン酸またはパルミチン酸を示
し、Ｒ2は、式（ＩＩ）を示す。］で表されるスピンラ
ベル化トリグリセライド化合物である。(Where m is an Arabic numeral from 0 to 10)
Where n is an Arabic numeral from 1 to 5. )
You ] The spin-labeled triglyceride compound represented by
And formula (III) [In the formula, R1Indicates oleic acid or palmitic acid
And R2Represents formula (II). ] Spinra represented by
It is a belled triglyceride compound.
【０００９】本発明化合物は、例えば以下の（ａ）ある
いは（ｂ）で示す方法によって合成できる。 （ａ）式（ＩＶ）を Ｒ2ＯＨ ・・・・（ＩＶ） ［式中、Ｒ2は、前記と同意義である。］ Ｎ，Ｎ´―カルボニルジイミダゾールなどの縮合剤存在
下、式（ＶＩＩ）と ［式中、Ｒ1は、前記と同意義である。］ ジクロロメタンなどの有機溶媒で縮合し式（Ｉ）で表さ
れる化合物を得る。 （ｂ）式（ＩＶ）をＮ，Ｎ´―カルボニルジイミダゾー
ルなどの縮合剤存在下、式（ＶＩ）と ［式中、Ｒ1は、オレイン酸またはパルミチン酸を示
す。］ ジクロロメタンなどの有機溶媒で縮合し式（ＩＩＩ）で
表される化合物を得る。The compound of the present invention is, for example, the following (a):
Or can be synthesized by the method shown in (b). (A) R in the formula (IV)2OH ... (IV) [wherein R2Is as defined above. ] Condensing agent such as N, N'-carbonyldiimidazole present
Below, with formula (VII)[In the formula, R1Is as defined above. ] Condensed with an organic solvent such as dichloromethane and represented by formula (I)
To obtain the compound. (B) Formula (IV) is converted into N, N′-carbonyldiimidazo
With a formula (VI) in the presence of a condensing agent such as [In the formula, R1Indicates oleic acid or palmitic acid
You ] In formula (III) by condensation with an organic solvent such as dichloromethane
The compound represented is obtained.
【００１０】[0010]
【発明の効果】本発明化合物を、生体内に投与し、その
体内分布を電子スピン共鳴により測定する場合、無侵襲
解析のために生体にストレスを与えることなく経時的に
トリグリセライドの体内分布を測定することができる。EFFECT OF THE INVENTION When the compound of the present invention is administered in vivo and the distribution in the body is measured by electron spin resonance, the distribution of triglyceride in the body is measured over time without stress on the body for non-invasive analysis. can do.
【００１１】[0011]
【実施例】以下実施例及び試験例を挙げ、本発明を具体
的に説明する。EXAMPLES The present invention will be specifically described with reference to the following examples and test examples.
【００１２】実施例１［１，３―ジオレオイル―（２）
―１２ＳＬＳ―ＴＧ（12-Spine Labeled stealic acid
=12-doxyl-stearic acid)の合成］ １２―ドキシル―ステアリン酸 ３４９ｍｇ（０．９ｍ
Ｍ）とＮ，Ｎ´―カルボニルジイミダゾール（ＣＤＩ）
１７５ｍｇ（１．０８ｍＭ）に乾燥ジクロロメタン５
ｍｌを入れて室温にて１時間攪拌した。この反応液に
１，３―ジオレイン４００ｍｇ（０．６４ｍＭ）を乾燥
ジクロロメタンに溶解し入れ、さらにイミダゾールナト
リウム（Ｉｍ―Ｎａ）のジメチルスルホキシド（ＤＭＳ
Ｏ）溶液０．７ｍｌ（０．７ｍＭ）〔水素化ナトリウム
（６０％）８０ｍｇとイミダゾール２００ｍｇをＤＭＳ
Ｏ ２ｍｌ中 １時間反応させて調製したもの〕及び無
水ピリジン０．３ｍｌを加え、室温で３時間反応させ
た。反応終了後、１ＮＨＣｌで中和し減圧濃縮した。得
られた濃縮物をヘキサンに溶かし、同溶媒で処理したシ
リカゲル４０ｇカラムに付し、ヘキサン、ヘキサン―エ
ーテル混液（９５：５）、ヘキサン―エーテル混液
（９：１）の溶媒系で順次溶出した。得られた溶出液を
薄層クロマトグラフィー〔展開溶媒：石油エーテル：エ
ーテル：酢酸（８０：３０：１）〕で検索し、目的画分
を集め、減圧濃縮乾燥し、本品１６２．７ｍｇ（収率；
２０％）を得た。Example 1 [1,3-dioleoyl- (2)
-12SLS-TG (12-Spine Labeled stealic acid
= 12-doxyl-stearic acid)] 12-doxyl-stearic acid 349 mg (0.9 m
M) and N, N'-carbonyldiimidazole (CDI)
175 mg (1.08 mM) to dry dichloromethane 5
After adding ml, the mixture was stirred at room temperature for 1 hour. To this reaction solution, 400 mg (0.64 mM) of 1,3-diolein was dissolved in dry dichloromethane, and dimethyl sulfoxide (DMS) of imidazole sodium (Im-Na) was further added.
O) solution 0.7 ml (0.7 mM) [sodium hydride (60%) 80 mg and imidazole 200 mg DMS
O 2 ml prepared by reacting for 1 hour] and 0.3 ml of anhydrous pyridine were added and reacted at room temperature for 3 hours. After completion of the reaction, the mixture was neutralized with 1N HCl and concentrated under reduced pressure. The obtained concentrate was dissolved in hexane and applied to a 40 g column of silica gel treated with the same solvent, and eluted sequentially with a solvent system of hexane, a hexane-ether mixed solution (95: 5), and a hexane-ether mixed solution (9: 1). . The obtained eluate was searched for by thin layer chromatography [developing solvent: petroleum ether: ether: acetic acid (80: 30: 1)], the target fractions were collected, concentrated under reduced pressure and dried, and 162.7 mg of this product (yield rate;
20%).
【００１３】本品は薄層クロマトグラフィー〔シリカゲ
ルプレート Ｆ２５４（メルク社製）、展開溶媒：ヘキ
サン：エーテル（８５：１５）、検出試薬；ヨウ素、紫
外線照射〕上、単一のスポットを示した。This product showed a single spot on thin layer chromatography [silica gel plate F254 (manufactured by Merck), developing solvent: hexane: ether (85:15), detection reagent: iodine, UV irradiation].
【００１４】実施例２［１，２―パルミトイル―（３）
―１２ＳＬＳ―ＴＧの合成］ １２―ドキシル―ステアリン酸 ８０ｍｇ（０．２ｍ
Ｍ）とＣＤＩに乾燥ジクロロメタン５ｍｌを入れて室温
にて１時間反応した。Example 2 [1,2-palmitoyl- (3)
Synthesis of -12SLS-TG] 12-doxyl-stearic acid 80 mg (0.2 m
M) and CDI were mixed with 5 ml of dry dichloromethane and reacted at room temperature for 1 hour.
【００１５】次いで、この反応液に１，２―パルミチン
９２ｍｇ（０．１６ｍＭ）を入れ、さらにＩｍ―Ｎａ
のＤＭＳＯ溶液０．１６ｍｌ（０．１６ｍＭ）及び無水
ピリジン０．１ｍｌを加え、室温で３時間反応させた。
終了後、実施例１と同様にシリカゲルカラムクロマトグ
ラフィーにて精製し、本品４１．２ｍｇ（２５．９％）
を得た。Next, 92 mg (0.16 mM) of 1,2-palmitin was added to this reaction solution, and Im-Na was added.
DMSO solution 0.16 ml (0.16 mM) and anhydrous pyridine 0.1 ml were added and reacted at room temperature for 3 hours.
After the completion, the product was purified by silica gel column chromatography in the same manner as in Example 1 to give 41.2 mg (25.9%) of this product.
Got
【００１６】尚、本品はＴＬＣ上、単一のスポットを示
した。This product showed a single spot on TLC.
【００１７】試験例１ 実施例１で得られた下式（ＶＩＩ）で表される化合物式Test Example 1 Compound formula represented by the following formula (VII) obtained in Example 1
【００１８】 [0018]
【００１９】０．１ｍｍｏｌを１ｍｌのクロロホルムに
溶解したときの電子スピン共鳴スペクトルを図１に示
す。 測定条件：電子スピン共鳴装置：ＲＥＩＸ・Ｘ―バンド
（日本電子製） マイクロ波出力 ５ｍＷ 測定温度 室温 外部磁場 ３３６．３±５ｍＴ 掃引時間 ２分 磁場変調 １００ｋＨｚ・０．１２５ｋＨｚ 時定数 ０．０３秒FIG. 1 shows the electron spin resonance spectrum when 0.1 mmol was dissolved in 1 ml of chloroform. Measurement conditions: electron spin resonance device: REIX X-band (made by JEOL) Microwave output 5 mW Measurement temperature room temperature External magnetic field 336.3 ± 5 mT Sweep time 2 minutes Magnetic field modulation 100 kHz / 0.125 kHz Time constant 0.03 seconds
【００２０】試験例２ 実施例１で得られた式（ＶＩＩ）で表される化合物０．
６μｍｏｌを１ｍｌのクロロホルムに溶解したときの電
子スピン共鳴スペクトルを図２に示した。測定条件は試
験例１と同様。Test Example 2 The compound of the formula (VII) obtained in Example 1
The electron spin resonance spectrum when 6 μmol was dissolved in 1 ml of chloroform is shown in FIG. The measurement conditions are the same as in Test Example 1.
【００２１】試験例３ 実施例１で得られた式（ＶＩＩ）で表される化合物０．
６μｍｏｌを１ｍｌの精製水に分散したときの電子スピ
ン共鳴スペクトルを図３に示した。測定条件は試験例１
と同様。Test Example 3 The compound of the formula (VII) obtained in Example 1
The electron spin resonance spectrum when 6 μmol was dispersed in 1 ml of purified water is shown in FIG. Measurement conditions are Test Example 1
same as.
【００２２】試験例４ 実施例１で得られた式（ＶＩＩ）で表される化合物１μ
ｍｏｌを１ｍｌのｐＨ７．４リン酸緩衝液に加え、牛血
清アルブミンを４％になるように加えたときの電子スピ
ン共鳴スペクトルを図４に示した。測定条件は試験例１
と同様。Test Example 4 1 μm of the compound represented by the formula (VII) obtained in Example 1
The electron spin resonance spectrum when mol was added to 1 ml of pH 7.4 phosphate buffer and bovine serum albumin was added to 4% is shown in FIG. Measurement conditions are Test Example 1
same as.
【００２３】試験例４ 実施例２で得られた下式（ＶＩＩＩ）で表される化合物Test Example 4 Compound of the following formula (VIII) obtained in Example 2
【００２４】 [0024]
【００２５】０．１ｍｍｏｌを１ｍｌのクロロホルムに
溶解したときの電子スピン共鳴スペクトルを図５に示
す。FIG. 5 shows the electron spin resonance spectrum when 0.1 mmol was dissolved in 1 ml of chloroform.
【００２６】試験例５ 実施例２で得られた式（ＶＩＩＩ）で表される化合物
０．６μｍｏｌを１ｍｌのクロロホルムに溶解したとき
の電子スピン共鳴スペクトルを図６に示した。測定条件
は試験例１と同様。Test Example 5 FIG. 6 shows an electron spin resonance spectrum when 0.6 μmol of the compound represented by the formula (VIII) obtained in Example 2 was dissolved in 1 ml of chloroform. The measurement conditions are the same as in Test Example 1.
【００２７】試験例６ 実施例２で得られた式（ＶＩＩＩ）で表される化合物
０．６μｍｏｌを１ｍｌの精製水に分散したときの電子
スピン共鳴スペクトルを図７に示した。測定条件は試験
例１と同様。Test Example 6 FIG. 7 shows an electron spin resonance spectrum when 0.6 μmol of the compound represented by the formula (VIII) obtained in Example 2 was dispersed in 1 ml of purified water. The measurement conditions are the same as in Test Example 1.
【００２８】試験例７ 実施例２で得られた式（ＶＩＩＩ）で表される化合物１
μｍｏｌを１ｍｌのｐＨ７．４リン酸緩衝液に加え、牛
血清アルブミンを４％になるように加えたときの電子ス
ピン共鳴スペクトルを図８に示した。測定条件は試験例
１と同様。Test Example 7 Compound 1 represented by the formula (VIII) obtained in Example 2
FIG. 8 shows the electron spin resonance spectrum when μmol was added to 1 ml of pH 7.4 phosphate buffer and bovine serum albumin was added to 4%. The measurement conditions are the same as in Test Example 1.
【図１】試験例１の電子スピン共鳴スペクトル図FIG. 1 is an electron spin resonance spectrum diagram of Test Example 1.
【図２】試験例２の電子スピン共鳴スペクトル図FIG. 2 is an electron spin resonance spectrum diagram of Test Example 2.
【図３】試験例３の電子スピン共鳴スペクトル図FIG. 3 is an electron spin resonance spectrum diagram of Test Example 3.
【図４】試験例４の電子スピン共鳴スペクトル図FIG. 4 is an electron spin resonance spectrum diagram of Test Example 4.
【図５】試験例５の電子スピン共鳴スペクトル図FIG. 5 is an electron spin resonance spectrum diagram of Test Example 5.
【図６】試験例６の電子スピン共鳴スペクトル図FIG. 6 is an electron spin resonance spectrum diagram of Test Example 6.
【図７】試験例７の電子スピン共鳴スペクトル図FIG. 7 is an electron spin resonance spectrum diagram of Test Example 7.
【図８】試験例８の電子スピン共鳴スペクトル図FIG. 8 is an electron spin resonance spectrum diagram of Test Example 8.
【手続補正書】[Procedure amendment]
【提出日】平成５年５月２１日[Submission date] May 21, 1993
【手続補正１】[Procedure Amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】特許請求の範囲[Name of item to be amended] Claims
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【特許請求の範囲】[Claims]
【手続補正２】[Procedure Amendment 2]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】０００６[Correction target item name] 0006
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【０００６】すなわち、本発明は式（Ｉ） ［式中、Ｒ1は、オレイル基またはパルミトイル基を示
し、Ｒ2は、式（ＩＩ）That is, the present invention has the formula (I) [In the formula, R 1 represents an oleyl group or a palmitoyl group , and R 2 represents a compound represented by the formula (II).
【手続補正３】[Procedure 3]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】０００８[Correction target item name] 0008
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【０００８】（式中、ｍは０から１０のアラビア数字を
示し、ｎは１から５のアラビア数字を示す。）を示
す。］で表されるスピンラベル化トリグリセライド化合
物および式（ＩＩＩ） ［式中、Ｒ1は、オレイル基またはパルミトイル基を示
し、Ｒ2は、式（ＩＩ）を示す。］で表されるスピンラ
ベル化トリグリセライド化合物である。(Where m is an Arabic numeral from 0 to 10)
Where n is an Arabic numeral from 1 to 5. )
You ] The spin-labeled triglyceride compound represented by
And formula (III) [In the formula, R1IsOleyl groupOrPalmitoyl groupShows
And R2Represents formula (II). ] Spinra represented by
It is a belled triglyceride compound.
【手続補正４】[Procedure amendment 4]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】０００９[Correction target item name] 0009
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【０００９】本発明化合物は、例えば以下の（ａ）ある
いは（ｂ）で示す方法によって合成できる。 （ａ）式（ＩＶ）を Ｒ2ＯＨ ・・・・（ＩＶ） ［式中、Ｒ2は、前記と同意義である。］ Ｎ，Ｎ´―カルボニルジイミダゾールなどの縮合剤存在
下、式（ＶＩＩ）と ［式中、Ｒ1は、前記と同意義である。］ ジクロロメタンなどの有機溶媒で縮合し式（Ｉ）で表さ
れる化合物を得る。 （ｂ）式（ＩＶ）をＮ，Ｎ´―カルボニルジイミダゾー
ルなどの縮合剤存在下、式（ＶＩ）と ［式中、Ｒ1は、オレイル基またはパルミトイル基を示
す。］ジクロロメタンなどの有機溶媒で縮合し式（ＩＩ
Ｉ）で表される化合物を得る。The compound of the present invention is, for example, the following (a):
Or can be synthesized by the method shown in (b). (A) R in the formula (IV)2OH ... (IV) [wherein R2Is as defined above. ] Condensing agent such as N, N'-carbonyldiimidazole present
Below, with formula (VII)[In the formula, R1Is as defined above. ] Condensed with an organic solvent such as dichloromethane and represented by formula (I)
To obtain the compound. (B) Formula (IV) is converted into N, N′-carbonyldiimidazo
With a formula (VI) in the presence of a condensing agent such as [In the formula, R1IsOleyl groupOrPalmitoyl groupShows
You ] The compound of the formula (II
A compound of formula I) is obtained.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 狩野 明 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 (72)発明者 那須 貞子 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 (72)発明者 林 英文 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Akira Kano 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Sadako Nasu 3-2-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Hidefumi Hayashi 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd.
Claims (2)
し、Ｒ2は、式 （式中、ｍは０から１０のアラビア数字を示し、ｎは１
から５のアラビア数字を示す。）を示す。］で表される
スピンラベル化トリグリセライド化合物。1. A formula [In the formula, R1Indicates oleic acid or palmitic acid
And R2Is the expression(In the formula, m is an Arabic numeral from 0 to 10, and n is 1
Arabic numerals from 5 to 5 are shown. ) Is shown. ]]
Spin-labeled triglyceride compound.
し、Ｒ2は、式 （式中、ｍは０から１０のアラビア数字を示し、ｎは１
から５のアラビア数字を示す。）を示す。］で表される
スピンラベル化トリグリセライド化合物。2. A formula [In the formula, R1Indicates oleic acid or palmitic acid
And R2Is the expression(In the formula, m is an Arabic numeral from 0 to 10, and n is 1
Arabic numerals from 5 to 5 are shown. ) Is shown. ]]
Spin-labeled triglyceride compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5118288A JPH06329646A (en) | 1993-05-20 | 1993-05-20 | Spin-labeled triglyceride compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5118288A JPH06329646A (en) | 1993-05-20 | 1993-05-20 | Spin-labeled triglyceride compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06329646A true JPH06329646A (en) | 1994-11-29 |
Family
ID=14732966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5118288A Pending JPH06329646A (en) | 1993-05-20 | 1993-05-20 | Spin-labeled triglyceride compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06329646A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003525456A (en) * | 2000-02-28 | 2003-08-26 | エーヴェー ハンデルス−ウント コンスルティンク ゲゼルシャフト ミット ベシュレンクテル ハフツング | Methods for ESR spectroscopic detection of changes in albumin transport properties in albumin-containing samples, spectrometers for performing said methods, and use of said methods for diagnostic purposes and management of albumin-containing formulations |
-
1993
- 1993-05-20 JP JP5118288A patent/JPH06329646A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003525456A (en) * | 2000-02-28 | 2003-08-26 | エーヴェー ハンデルス−ウント コンスルティンク ゲゼルシャフト ミット ベシュレンクテル ハフツング | Methods for ESR spectroscopic detection of changes in albumin transport properties in albumin-containing samples, spectrometers for performing said methods, and use of said methods for diagnostic purposes and management of albumin-containing formulations |
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