JPH0581594B2 - - Google Patents
Info
- Publication number
- JPH0581594B2 JPH0581594B2 JP63054331A JP5433188A JPH0581594B2 JP H0581594 B2 JPH0581594 B2 JP H0581594B2 JP 63054331 A JP63054331 A JP 63054331A JP 5433188 A JP5433188 A JP 5433188A JP H0581594 B2 JPH0581594 B2 JP H0581594B2
- Authority
- JP
- Japan
- Prior art keywords
- fluorouracil
- formula
- film
- carbon atoms
- didecyl
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 24
- -1 N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide Chemical compound 0.000 claims description 16
- 239000012528 membrane Substances 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000005265 dialkylamine group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims 1
- 239000010408 film Substances 0.000 description 28
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical group FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229960002949 fluorouracil Drugs 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000005192 partition Methods 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- GMTCPFCMAHMEMT-UHFFFAOYSA-N n-decyldecan-1-amine Chemical compound CCCCCCCCCCNCCCCCCCCCC GMTCPFCMAHMEMT-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KYSXOUNBTJWDIW-UHFFFAOYSA-N 3-(5-fluoro-2,4-dioxopyrimidin-1-yl)propanoic acid Chemical compound OC(=O)CCN1C=C(F)C(=O)NC1=O KYSXOUNBTJWDIW-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は５−フルオロウラシル基を有する化合
物のLangmuir−Blodgett膜に関する。
（従来の技術）
最近、Langmuir−Blodgett膜（以下LB膜と
いう）の研究が盛んである。これは従来の化学で
は、一つの分子の構造や性質に関心が向けられて
いたのに対し、LB法を用いると、きちんとした
一定の配向、配列をもつ分子集団が作成でき、分
子集合体の構造や性質の研究が行えるようになつ
たためである。その結果、今まで手をつけること
ができなかつた生体モデル膜、分子素子、超薄膜
レジストなどの分子レベルでの研究が可能とな
り、大きな発展が期待されている。（本発明にお
いてLB膜とは単分子膜、LB膜、単分子層膜のつ
みかさね、すなわちLB累積膜の総称である。）
一方、代謝拮抗剤である５−フツ化ウラシル
（以下5FUと略す）は強い制癌剤として知られて
いるが、同時に強い副作用がありその毒性を軽減
し、その持続性を増加させることが重要な課題と
なつている。
（発明が解決すべき問題点）
本発明者は、これらの問題点に鑑み、鋭意研究
を重ねた結果、5FU基を有する化合物のLB膜化
に成功し、本発明を完成するに到つた。
すなわち、本発明の目的は、第１に5FU基を有
するLB膜化が可能な化合物を提供することであ
り、第２に5FU基を有するLB膜を提供すること
であり、第３に抗腫瘍活性を有するLB膜を提供
することである。
本願の各発明の構成は下記の(1)〜(6)で示され
る。
(1) 一般式
【化】
（こゝでR1はＨまたは飽和もしくは不飽和の
炭素数１〜10のアルキル基、R2，R3は同種もし
くは異種の炭素数１〜20のアルキル基を示す。）
で表わされる化合物。
(2) 式
【化】
で表わされるＮ，Ｎ−ジデシル−３−（５−フル
オロウラシル−１−イル）プロピオンアミドであ
る(1)項記載の化合物。
(3) 一般式
【化】
で表わされる化合物と一般式
【化】
で表わされるジアルキルアミンとを反応させるこ
とを特徴とする
【化】
で表わされる化合物の製造法。
（こゝで、R2，R3は同種もしくは異種の炭素
数１〜20のアルキル基、R1はＨまたは飽和もし
くは不飽和の炭素数１〜10のアルキル基、R4は
ハロゲンもしくは
【式】
(4) ３−（５−フルオロウラシル−１−イル）プ
ロピオノイルオキシコハク酸イミドと、ジ−ｎ
−デシルアミンとを反応させ、Ｎ，Ｎ−ジデシ
ル−３−（５−フルオロウラシル−１−イル）
プロピオンアミドを合成する(3)項記載の製造
法。
(5) 一般式
【化】
（こゝでR1はＨまたは飽和もしくは不飽和の
炭素数１〜10のアルキル基、R2，R3は同種もし
くは異種の炭素数１〜20のアルキル基を示す。）
で表わされる化合物からなることを特徴とする
Langmuir−Blodgett膜。
(6) 式
【化】
で表わされるＮ，Ｎ−ジデシル−３−（５−フル
オロウラシル−１−イル）プロピオンアミドから
なる(5)項記載のLangmuir−Blodgett膜。
本発明の化合物の合成法の具体的な一例を説明
する。
５−フルオロウラシルとエチルアクリレートの
エタノール中でのMichel反応によりえられた１
−β−エチルプロピオノイレート−５−フルオロ
ウラシルを加水分解後、DCCの存在下、Ｎ−ヒ
ドロキシスクシンイミドと反応させることによ
り、３−（５−フルオロウラシル−１−イル）プ
ロピオノイルオキシスクシンイミドを合成し、そ
れをジ−ｎ−デシルアミンと反応させＮ，Ｎ−ジ
デシル−３−（５−フルオロウラシル−１−イル）
プロピオンアミドを得ることができる。これらの
合成ルートを式で表すとつぎのとおりである。
【化】
【化】
（こゝでDCCはジシクロヘキシルカルボジイ
ミド、DMFはジメチルホルムアミドを表す。）
(3)，(4)項に係る本発明の製造法における反応温
度は０〜100℃、好ましい反応条件としては10〜
50℃である。反応時間は限定しないが長時間が好
ましい。反応に使用する溶媒は特に限定しない
が、ジメチルホルムアミド、テトラヒドロフラ
ン、クロロホルムなどが好ましい。
（本発明の効果）
本発明の化合物は、従来存在しなかつた新規な
化合物であり、Ｐ−388の増殖を阻害し、代謝拮
抗剤として使用できる。また、本発明の化合物は
LB膜化が可能であり、またそのLB膜の表面積と
表面圧の関係を示すπ−Ａ曲線は、従来の一般的
なπ−Ａ曲線にみられる限界点が１ケ所のものと
著しく異なる限界点を２つもつ特徴を示す。
本発明の５−FU基を有する化合物のLB膜化
は、リポソーム形成を可能とし、５−FUの毒性
の軽減、薬物を標的組織にのみ作用させるミサイ
ル療法などが可能となる。
以下、実施例にて、本発明を説明する。
実施例におけるLB膜の作成、表面圧と表面積
の関係を示すπ−Ａ曲線の測定はLAUDA社の
Film Balance Measuring装置タイプFW（以下
LB膜測定装置という）を使用した。
実施例 １
Ｎ，Ｎ−ジデシル−３−（５−フルオロウラシ
ル−１−イル）プロピオンアミドの合成
ジ−ｎ−デシルアミン0.1731ｇに対して等モル
の１−β−カルボキシエチル−５−フルオロウラ
シル0.1741ｇを各々10mlのDMFに溶解させてナ
ス形フラスコ内で混合した。２日間室温で放置し
た後減圧下で濃縮した。そこへエタノールを加え
て攪拌しガラスフイルターでろ過して残さを乾燥
させＮ，Ｎ−ジデシル−３−（５−フルオロウラ
シル−１−イル）プロピオンアミドを得た。
得られた化合物の物性値は、1H−NMR
（CDCl3）：δ7.72（ｄ，1H，CH），4.01（ｔ，2H，
CH2CH2），3.15（ｔ，4H，2CH2），2.73（ｔ，
2H，CH2 CH2 ），1.26（ｓ，32H，２（CH2）8），
0.88（ｍ，6H，2CH3）であつた。
得られた化合物はいづれもＰ−388の増殖を阻
害した。
実施例 ２
LB膜測定装置を使用し、つぎの条件でLB膜を
作つた。
Ｎ，Ｎ−ジデシル−３−（５−フルオロウラシ
ル−１−イル）プロピオンアミドの0.001ｇをク
ロロホルム７mlに溶かし、その約15滴を水温12.3
℃の水面に滴下する。その後クロロホルムが蒸発
して水面上が安定するまで放置しＮ，Ｎ−ジデシ
ル−３−（５−フルオロウラシル−１−イル）プ
ロピオンアミドの単分子膜いわゆるLB膜を得た。
この単分子膜に所定の方法で一定の圧力（25ダ
イン／cm2）を加え、表面圧が一定になつたところ
で所定のシリコン基板を垂直浸漬法によつて以下
作動させ、レコーダーによりＹ−Depositionの
LB累積膜が得られたことを確認した。（図４参
照）
また、自動エリプソメーターを用いてこのLB
膜の膜厚を測定した。10層、20層、40層の各層に
対して測定し、その平均値は15〜16Å／１層であ
つた。
実施例 ３
Ｎ，Ｎ−ジデシル−３−（５−フルオロウラシ
ル−１−イル）プロピオンアミドの0.001ｇをク
ロロホルム７mlに溶かし、前記LB膜の作成と同
様にしてその１滴を水面に滴下し、溶媒を蒸発さ
せてLB膜を作成した。LB膜測定装置の可動仕切
り（moveable barrier）を固定仕切りの方へ向
かつて押してLB膜を圧縮して、LB膜の専有する
表面積を狭め固定仕切りに及ぼす表面圧の変化を
レコーダーに記録してπ−Ａ曲線を得た。水温
6.2℃、12.3℃、21.5℃、32.2℃で行なつた結果が
図１である。
実施例の結果をくわしく説明するとつぎのとお
りである。
実施例の本発明の化合物は次式で示され、偽親
水基と疎水基からなる。
【化】
これを図２のＣで表わすと、図１にπ−Ａ曲線
のＢの状態は図３のＢで表わされ、図１のＡの状
態は図３のＡで表わすことができる。
更に詳しく説明すると本発明の化合物のπ−Ａ
曲線は図１で示されるごとく限界点（膜破壊点）
がＡとＢの２ケ所表れる。これは一般的な直鎖型
π−Ａ曲線にみられる限界が１ケ所のものと著し
く異なることである。
この現象は膜状態の変性が著しい圧力変化を伴
う不連続であることを示唆している。つまり、分
子の構造が平板状（コイン形）の5FUのその上に
２本鎖が立つているため、最初の限界点〔図１の
Ｂ〕では図３のＢのようにいわば水の上にコイン
が浮くような形になつていると考えられる。さら
に圧力を加えると、２本鎖と5FU部分の接点が親
水性でないことも考慮すると図３のＡのようにコ
インが、水面上で立つ要領で、膜状態が変化する
ため圧力が急に上がるものと考えることができ
る。 DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a Langmuir-Blodgett membrane of a compound having a 5-fluorouracil group. (Prior Art) Recently, research on Langmuir-Blodgett films (hereinafter referred to as LB films) has been active. This is because conventional chemistry focuses on the structure and properties of a single molecule, but using the LB method, it is possible to create a group of molecules with a fixed orientation and arrangement. This is because it has become possible to study its structure and properties. As a result, it has become possible to conduct research at the molecular level on biological model membranes, molecular devices, and ultra-thin film resists, which were previously inaccessible, and great advances are expected. (LB film in the present invention is a general term for monomolecular film, LB film, stack of monomolecular layer films, that is, LB cumulative film.) On the other hand, 5-uracil fluoride (hereinafter abbreviated as 5FU), which is an antimetabolite, Although it is known as a strong anticancer agent, it also has strong side effects, and it is important to reduce its toxicity and increase its sustainability. (Problems to be Solved by the Invention) In view of these problems, the present inventor has conducted extensive research, and as a result has succeeded in forming an LB film from a compound having a 5FU group, and has completed the present invention. That is, the purpose of the present invention is, firstly, to provide a compound having a 5FU group that can be formed into an LB film, secondly to provide an LB film having a 5FU group, and thirdly to provide an antitumor compound. The object of the present invention is to provide an active LB membrane. The configurations of each invention of the present application are shown in (1) to (6) below. (1) General formula [Formula] (where R 1 is H or a saturated or unsaturated alkyl group having 1 to 10 carbon atoms, and R 2 and R 3 are the same or different alkyl groups having 1 to 20 carbon atoms. show.)
A compound represented by (2) The compound according to item (1), which is N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide represented by the formula: (3) A method for producing a compound represented by the general formula [Chemical formula], which comprises reacting a compound represented by the general formula [Chemical formula] with a dialkylamine represented by the general formula [Chemical formula]. (Here, R 2 and R 3 are the same or different alkyl groups having 1 to 20 carbon atoms, R 1 is H or a saturated or unsaturated alkyl group having 1 to 10 carbon atoms, and R 4 is a halogen or ] (4) 3-(5-fluorouracil-1-yl)propionoyloxysuccinimide and di-n
-N,N-didecyl-3-(5-fluorouracil-1-yl)
The manufacturing method described in (3) for synthesizing propionamide. ( 5 ) General formula show.)
characterized by consisting of a compound represented by
Langmuir−Blodgett membrane. (6) The Langmuir-Blodgett membrane according to item (5), comprising N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide represented by the formula: A specific example of the method for synthesizing the compound of the present invention will be explained. 1 obtained by Michel reaction of 5-fluorouracil and ethyl acrylate in ethanol
- Synthesis of 3-(5-fluorouracil-1-yl)propionoyloxysuccinimide by hydrolyzing β-ethylpropionoylate-5-fluorouracil and reacting it with N-hydroxysuccinimide in the presence of DCC. and reacted with di-n-decylamine to obtain N,N-didecyl-3-(5-fluorouracil-1-yl).
Propionamide can be obtained. These synthesis routes are expressed as follows. [C] [C] (Here, DCC represents dicyclohexylcarbodiimide and DMF represents dimethylformamide.) The reaction temperature in the production method of the present invention related to items (3) and (4) is 0 to 100°C, preferred reaction conditions. As for 10~
It is 50℃. The reaction time is not limited, but a long time is preferred. The solvent used in the reaction is not particularly limited, but dimethylformamide, tetrahydrofuran, chloroform, etc. are preferred. (Effect of the present invention) The compound of the present invention is a novel compound that has not existed before, inhibits the proliferation of P-388, and can be used as an antimetabolite. Moreover, the compound of the present invention
It is possible to form an LB film, and the π-A curve that shows the relationship between the surface area and surface pressure of the LB film has a limit that is significantly different from the conventional general π-A curve, which has one limit point. Indicates a feature with two points. LB membrane formation of the compound having a 5-FU group of the present invention enables liposome formation, which reduces the toxicity of 5-FU and enables missile therapy in which the drug acts only on target tissues. The present invention will be explained below with reference to Examples. In the examples, the preparation of the LB film and the measurement of the π-A curve showing the relationship between surface pressure and surface area were carried out using LAUDA's
Film Balance Measuring equipment type FW (hereinafter
A LB film measuring device) was used. Example 1 Synthesis of N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide Equimole of 0.1741 g of 1-β-carboxyethyl-5-fluorouracil was added to 0.1731 g of di-n-decylamine. Each was dissolved in 10 ml of DMF and mixed in an eggplant-shaped flask. After being left at room temperature for 2 days, it was concentrated under reduced pressure. Ethanol was added thereto, stirred, filtered through a glass filter, and the residue was dried to obtain N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide. The physical properties of the obtained compound are as follows: 1 H-NMR
(CDCl 3 ): δ7.72 (d, 1H, CH), 4.01 (t, 2H,
CH 2 CH 2 ), 3.15 (t, 4H, 2CH 2 ), 2.73 (t,
2H, CH 2 CH 2 ), 1.26(s, 32H, 2(CH 2 ) 8 ),
It was 0.88 (m, 6H, 2CH 3 ). All of the obtained compounds inhibited the proliferation of P-388. Example 2 Using an LB film measuring device, an LB film was produced under the following conditions. Dissolve 0.001 g of N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide in 7 ml of chloroform, and add about 15 drops of it to water at a temperature of 12.3
Drop onto the water surface at °C. Thereafter, the mixture was allowed to stand until the chloroform evaporated and the surface of the water became stable, yielding a monomolecular film of N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide, a so-called LB film. A constant pressure (25 dynes/cm 2 ) is applied to this monomolecular film by a prescribed method, and when the surface pressure becomes constant, a prescribed silicon substrate is operated by a vertical immersion method, and Y-Deposition is performed using a recorder. of
It was confirmed that an LB cumulative film was obtained. (See Figure 4) In addition, this LB was measured using an automatic ellipsometer.
The film thickness of the film was measured. Measurements were made for each of 10, 20, and 40 layers, and the average value was 15 to 16 Å/layer. Example 3 0.001 g of N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide was dissolved in 7 ml of chloroform, and one drop of it was dropped onto the water surface in the same manner as in the preparation of the LB film, and the solvent was removed. was evaporated to create an LB film. Push the movable barrier of the LB film measuring device toward the fixed partition to compress the LB film, narrowing the surface area occupied by the LB film, and recording the change in surface pressure on the fixed partition on a recorder. -A curve was obtained. water temperature
Figure 1 shows the results obtained at 6.2°C, 12.3°C, 21.5°C, and 32.2°C. The results of the examples will be explained in detail as follows. The compounds of the present invention in Examples are represented by the following formula and consist of a pseudohydrophilic group and a hydrophobic group. [C] If this is represented by C in Figure 2, the state B of the π-A curve in Figure 1 can be represented by B in Figure 3, and the state A in Figure 1 can be represented by A in Figure 3. . To explain in more detail, π-A of the compound of the present invention
The curve is at the breaking point (membrane breakdown point) as shown in Figure 1.
appears in two places, A and B. This is significantly different from a single limit seen in a general linear π-A curve. This phenomenon suggests that the denaturation of the membrane state is discontinuous with significant pressure changes. In other words, since the double strands stand on top of 5FU, which has a flat (coin-shaped) molecular structure, at the first breaking point [B in Figure 1], it is on top of water, as shown in B in Figure 3. It is thought that the coin is shaped like a floating coin. When further pressure is applied, considering that the contact point between the two strands and the 5FU part is not hydrophilic, the pressure suddenly increases as the membrane state changes, as shown in A in Figure 3, just like a coin standing on the water surface. It can be thought of as a thing.
図１はＮ，Ｎ−ジデシル−３−（５−フルオロ
ウラシル−１−イル）プロピオンアミドの、温度
(a)6.2℃，(b)12.3℃，(c)21.5℃，(d)32.2℃における
π−Ａ曲線を示しＡ，Ｂは２ケ所の限界点を示
す。図２はＮ，Ｎ−ジデシル−３−（５−フルオ
ロウラシル−１−イル）プロピオンアミドを例と
する本発明化合物の模型図ｃを示しａは偽親水
基、ｂは疎水基を示す。図３のＡは図１における
Ａの状態、Ｂは図１におけるＢの状態を示し、ｃ
はＮ，Ｎ−ジデシル−３−（５−フルオロウラシ
ル−イル）プロピオンアミド、ｄは空気、ｅは
水、ｆは加動仕切り、ｇは固定仕切りを示す。図
４のｈはシリコン基板、ｃ，ｅは図３と同様であ
り、矢印は基板の動く方向を示す。
Figure 1 shows the temperature of N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide.
The π-A curves are shown at (a) 6.2℃, (b) 12.3℃, (c) 21.5℃, and (d) 32.2℃. A and B indicate the two limit points. FIG. 2 shows a schematic diagram c of the compound of the present invention, taking N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide as an example, in which a represents a pseudohydrophilic group and b represents a hydrophobic group. A in FIG. 3 shows the state of A in FIG. 1, B shows the state of B in FIG. 1, and c
is N,N-didecyl-3-(5-fluorouracil-yl)propionamide, d is air, e is water, f is a movable partition, and g is a fixed partition. In FIG. 4, h is a silicon substrate, c and e are the same as in FIG. 3, and arrows indicate the direction in which the substrate moves.
Claims (1)
炭素数１〜10のアルキル基、R2，R3は同種もし
くは異種の炭素数１〜20のアルキル基を示す。）
で表わされる化合物。 ２ 式 【式】 で表わされるＮ，Ｎ−ジデシル−３−（５−フル
オロウラシル−１−イル）プロピオンアミドであ
る請求項１記載の化合物。 ３ 一般式 【式】 で表わされる化合物と一般式 【式】 で表わされるジアルキルアミンとを反応させるこ
とを特徴とする。 【式】 で表わされる化合物の製造法。 （ここで、R2，R3は同種もしくは異種の炭素
数１〜20のアルキル基、R1はＨまたは飽和もし
くは不飽和の炭素数１〜10のアルキル基、R4は
ハロゲンもしくは 【式】基を示す。 ４ ３−（５−フルオロウラシル−１−イル）プ
ロピオノイルオキシコハク酸イミドと、ジ−ｎ−
デシルアミンとを反応させ、Ｎ，Ｎ−ジデシル−
３−（５−フルオロウラシル−１−イル）プロピ
オンアミドを合成する請求項３記載の製造法。 ５ 一般式 【化】 （ここでR1はＨまたは飽和もしくは不飽和の
炭素数１〜10のアルキル基、R2，R3は同種もし
くは異種の炭素数１〜20のアルキル基を示す。） で表わされる化合物からなることを特徴とする
Langmuir−Blodgett膜。 ６ 式 【化】 で表わされるＮ，Ｎ−ジデシル−３−（５−フル
オロウラシル−１−イル）プロピオンアミドから
なる請求項５記載のLangmuir−Blodgett膜。[Claims] 1 General formula [Formula] (where R 1 is H or a saturated or unsaturated alkyl group having 1 to 10 carbon atoms, R 2 and R 3 are the same or different groups having 1 to 20 carbon atoms) (Indicates an alkyl group.)
A compound represented by 2. The compound according to claim 1, which is N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide represented by the formula: 3 It is characterized by reacting a compound represented by the general formula [Formula] with a dialkylamine represented by the general formula [Formula]. A method for producing a compound represented by the formula: (Here, R 2 and R 3 are the same or different alkyl groups having 1 to 20 carbon atoms, R 1 is H or a saturated or unsaturated alkyl group having 1 to 10 carbon atoms, and R 4 is a halogen or [Formula] 4 3-(5-fluorouracil-1-yl)propionoyloxysuccinimide and di-n-
By reacting with decylamine, N,N-didecyl-
4. The method according to claim 3, wherein 3-(5-fluorouracil-1-yl)propionamide is synthesized. 5 General formula: (Here, R 1 is H or a saturated or unsaturated alkyl group having 1 to 10 carbon atoms, and R 2 and R 3 are the same or different alkyl groups having 1 to 20 carbon atoms.) characterized by consisting of a compound represented by
Langmuir−Blodgett membrane. 6. The Langmuir-Blodgett membrane according to claim 5, comprising N,N-didecyl-3-(5-fluorouracil-1-yl)propionamide represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63054331A JPH01226876A (en) | 1988-03-08 | 1988-03-08 | Compound having 5-fluorouracil group and lb membrane thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63054331A JPH01226876A (en) | 1988-03-08 | 1988-03-08 | Compound having 5-fluorouracil group and lb membrane thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01226876A JPH01226876A (en) | 1989-09-11 |
| JPH0581594B2 true JPH0581594B2 (en) | 1993-11-15 |
Family
ID=12967612
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63054331A Granted JPH01226876A (en) | 1988-03-08 | 1988-03-08 | Compound having 5-fluorouracil group and lb membrane thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01226876A (en) |
-
1988
- 1988-03-08 JP JP63054331A patent/JPH01226876A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01226876A (en) | 1989-09-11 |
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