JPS6350337B2 - - Google Patents
Info
- Publication number
- JPS6350337B2 JPS6350337B2 JP59265444A JP26544484A JPS6350337B2 JP S6350337 B2 JPS6350337 B2 JP S6350337B2 JP 59265444 A JP59265444 A JP 59265444A JP 26544484 A JP26544484 A JP 26544484A JP S6350337 B2 JPS6350337 B2 JP S6350337B2
- Authority
- JP
- Japan
- Prior art keywords
- present
- dihydroxy
- shikonin
- naphthoquinone
- compound
- 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
Links
- 150000004585 5,8-dihydroxy-1,4-naphthoquinones Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- NEZONWMXZKDMKF-JTQLQIEISA-N Alkannin Chemical compound C1=CC(O)=C2C(=O)C([C@@H](O)CC=C(C)C)=CC(=O)C2=C1O NEZONWMXZKDMKF-JTQLQIEISA-N 0.000 description 8
- 241001071917 Lithospermum Species 0.000 description 8
- UNNKKUDWEASWDN-UHFFFAOYSA-N alkannin Natural products CC(=CCC(O)c1cc(O)c2C(=O)C=CC(=O)c2c1O)C UNNKKUDWEASWDN-UHFFFAOYSA-N 0.000 description 8
- 239000003146 anticoagulant agent Substances 0.000 description 6
- 229960004676 antithrombotic agent Drugs 0.000 description 5
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910021536 Zeolite Inorganic materials 0.000 description 3
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 239000010457 zeolite Substances 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229930192627 Naphthoquinone Natural products 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 150000002791 naphthoquinones Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NEZONWMXZKDMKF-UHFFFAOYSA-N C.I. Natural Red 20 Chemical compound C1=CC(O)=C2C(=O)C(C(O)CC=C(C)C)=CC(=O)C2=C1O NEZONWMXZKDMKF-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010050661 Platelet aggregation inhibition Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- WNFXUXZJJKTDOZ-HNNXBMFYSA-N [(1s)-1-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] acetate Chemical compound C1=CC(O)=C2C(=O)C([C@@H](OC(C)=O)CC=C(C)C)=CC(=O)C2=C1O WNFXUXZJJKTDOZ-HNNXBMFYSA-N 0.000 description 1
- DLBQFLWCDFTEQG-UHFFFAOYSA-N [1-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] propanoate Chemical compound C1=CC(O)=C2C(=O)C(C(CC=C(C)C)OC(=O)CC)=CC(=O)C2=C1O DLBQFLWCDFTEQG-UHFFFAOYSA-N 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl 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])([H])[H] 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- WNFXUXZJJKTDOZ-UHFFFAOYSA-N shikonin acetate Natural products C1=CC(O)=C2C(=O)C(C(OC(C)=O)CC=C(C)C)=CC(=O)C2=C1O WNFXUXZJJKTDOZ-UHFFFAOYSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000002948 undecyl 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])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
〔産業上の利用分野〕
本発明は抗血栓剤として有用な新規５，８−ジ
ヒドロキシ−１，４−ナフトキノン誘導体に関す
る。
〔従来の技術〕
５，８−ジヒドロキシ−１，４−ナフトキノン
誘導体として、２−（１−ヒドロキシ−４−メチ
ル−３−ペンテン−１−イル）−５，８−ジヒド
ロキシ−１，４−ナフトキノン（シコニン）や２
−（１−アセトキシ−４−メチル−３−ペンテン
−１−イル）−５，８−ジヒドロキシ−１，４−
ナフトキノン（アセチルシコニン）など多くの化
合物が知られ、例えば薬学雑誌Vol92、525
（1972）、生薬雑誌Vol27、31（1973）、日本薬理学
雑誌Vol73、193（1977）、Chem.Pharm.Bull.、
Vol25、2392（1977）などにおいて抗腫瘍活性を
はじめとするある種の薬理活性について研究され
ている。
しかし本発明の如き５，８−ジヒドロキシ−
１，４−ナフトキノン誘導体、および該誘導体の
もつ血小板凝集抑制作用、すなわち抗血栓剤とし
ての有用性については全く明らかにされていな
い。
〔発明の効果〕
本発明者らは、５，８−ジヒドロキシ−１，４
−ナフトキノン誘導体について研究を進めるう
ち、本発明の化合物が新規でかつ抗血栓剤として
の有用性を有することを見い出し、本発明を完成
することができた。
〔発明の概要〕
本発明は一般式〔〕
（式中、Ｒは炭素数６ないし12のアルキル基であ
る。以下同じ。）で表わされる新規５，８−ジヒ
ドロキシ−１，４−ナフトキノン誘導体を提供す
るものである。
〔本発明の化合物〕
本発明の化合物は一般式〔〕で表わされるも
のであるが、式中のＲとしては、例えばヘキシル
基、ヘプチル基、オクチル基、ノニル基、デシル
基、ウンデシル基、ドデシル基であり、これらは
直鎖状のほか、各種分枝状のものであつてもよ
い。これらアルキル基の中では炭素数が６ないし
11の直鎖状のものが好ましい。
本発明の好ましい化合物を次表に示す。
[Industrial Field of Application] The present invention relates to novel 5,8-dihydroxy-1,4-naphthoquinone derivatives useful as antithrombotic agents. [Prior art] As a 5,8-dihydroxy-1,4-naphthoquinone derivative, 2-(1-hydroxy-4-methyl-3-penten-1-yl)-5,8-dihydroxy-1,4-naphthoquinone (shikonin) and 2
-(1-acetoxy-4-methyl-3-penten-1-yl)-5,8-dihydroxy-1,4-
Many compounds such as naphthoquinone (acetylshikonin) are known, for example, Pharmaceutical Journal Vol. 92, 525.
(1972), Herbal Medicine Journal Vol. 27, 31 (1973), Japanese Pharmacological Journal Vol. 73, 193 (1977), Chem.Pharm.Bull.
Vol. 25, 2392 (1977) and other publications have studied certain pharmacological activities including antitumor activity. However, as in the present invention, 5,8-dihydroxy-
1,4-naphthoquinone derivatives and their anti-platelet aggregation activity, that is, their usefulness as antithrombotic agents, have not been clarified at all. [Effect of the invention] The present inventors have discovered that 5,8-dihydroxy-1,4
-While conducting research on naphthoquinone derivatives, it was discovered that the compound of the present invention is novel and useful as an antithrombotic agent, and the present invention was completed. [Summary of the invention] The present invention is based on the general formula [] (In the formula, R is an alkyl group having 6 to 12 carbon atoms. The same applies hereinafter.) A novel 5,8-dihydroxy-1,4-naphthoquinone derivative is provided. [Compound of the present invention] The compound of the present invention is represented by the general formula [ ], and R in the formula is, for example, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl group, a dodecyl group. These groups may be linear or various branched. Among these alkyl groups, the number of carbon atoms is 6 or more.
11 linear chains are preferred. Preferred compounds of the invention are shown in the table below.
本発明の化合物は西独特許公開公報
Offenlegungs−shrift）2831786に記載の方法に
準じてシコニンより誘導できるほか、同じくシコ
ニンより下記の方法によつても製造することがで
きる。
すなわち、シコニンと酸ハロゲン化物RCOX
（Ｒは前記と同じであり、Ｘはハロゲン、とくに
好ましくは塩素を表わす。）をゼオライト（とく
に商品名「モレキユラシーブ」）で知られる合成
ゼオライトが好ましい。）の存在下に反応させる
ことにより容易に得ることができる。この場合の
溶媒としては反応に不活性なもの、例えばベンゼ
ン、トルエン、キシレンの如き芳香族炭化水素、
塩化メチレン、クロロホルム、テトラクロロエタ
ンの如きハロゲン化炭化水素、エチルエーテル、
プロピルエーテル、テトラヒドロフラン、ジオキ
サンの如きエーテル、酢酸エチル、酢酸プロピル
の如きエステルを使用することができ、これらの
中では酢酸エチルが好ましい。
好ましい触媒たる合成ゼオライトはHClを吸収
し、シコニンを吸収しない孔径を有するもので、
市販モレキユラシーブの4Aタイプ、5Aタイプ、
13Xタイプなどを使用することができる。
反応条件としては、酸ハロゲン化物をシコニン
に対し0.5ないし10倍モル、好ましくは１ないし
５倍モル、モレキユラシーブをシコニン１ｇに対
し0.5ないし５ｇ用い、通常シコニンを濃度が
0.02ないし0.3モル／となるよう溶媒中で、反
応温度０ないし100℃、好ましくは20ないし70℃
にて１ないし100時間、好ましくは２ないし30時
間反応させる。
反応後は常法により目的物を分離・精製すれば
よい。
〔本発明の化合物の有用性〕
本発明の化合物は前述のように血小板の凝集を
抑制する活性を有するので、抗血栓剤として用い
ることができる。これは後述の試験例で明らかで
ある。
〔実施例〕
以下、実施例によつて本発明を具体的に説明す
る。
参考例
２−（１−プロピオニルオキシ−４−メチル−
３−ペンテン−１−イル）−５，８−ジヒドロ
キシ−１，４−ナフトキノン
シコニン432mgを無水の酢酸エチル25mlに溶解
し、これに塩化プロピオニル278mgとモレキユラ
ーシーブ4A1.8ｇを加え、時々振りまぜながら３
日間放置した。酢酸エチルと未反応の塩化プロピ
オニルを減圧下で留去し、残つた赤色の粘稠な油
状物を薄層クロマトグラフイーで分離して赤色結
晶を得た。
赤色油状物
収 率：67％
質量分析：344（M+）
1H−核磁気共鳴スペクトル（ppm、重クロロホ
ルム、TMS基準）
1.15（3H、ｔ、Ｊ＝６Hz）；1.59（3H、ｓ）；
1.88（3H、ｓ）；2.3〜2.54（4H、ｍ）；5.10（1H、
ｔ、Ｊ＝６Hz）；6.02（1H、ｔ、Ｊ＝５Hz）；
6.97（1H、ｓ）；7.18（2H、ｓ）；12.38（1H、
ｓ）、12.54（1H、ｓ）
実施例 １〜２
参考例と同様にして以下の化合物を得た。
The compound of the present invention is disclosed in the West German Patent Publication No.
In addition to being derived from shikonin according to the method described in J. Offenlegungs-shrift 2831786, it can also be produced from shikonin by the method described below. i.e. shikonin and acid halide RCOX
(R is the same as above, and X represents a halogen, particularly preferably chlorine.) Synthetic zeolite known as zeolite (especially under the trade name "Molecular Sieve") is preferred. ) can be easily obtained by reacting in the presence of In this case, the solvent is inert to the reaction, such as aromatic hydrocarbons such as benzene, toluene, xylene, etc.
halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloroethane, ethyl ether,
Ethers such as propyl ether, tetrahydrofuran, dioxane, and esters such as ethyl acetate and propyl acetate can be used, of which ethyl acetate is preferred. The preferred catalyst, synthetic zeolite, has a pore size that absorbs HCl but not shikonin;
Commercially available Molecule Sieve 4A type, 5A type,
13X type etc. can be used. As for the reaction conditions, the acid halide is used at 0.5 to 10 times the mole of shikonin, preferably 1 to 5 times the mole, and 0.5 to 5 g of molecular sieve is used per 1 g of shikonin.
in a solvent such that the concentration is 0.02 to 0.3 mol/reaction temperature 0 to 100°C, preferably 20 to 70°C
The reaction is carried out for 1 to 100 hours, preferably for 2 to 30 hours. After the reaction, the target product may be separated and purified by conventional methods. [Utility of the compound of the present invention] As described above, the compound of the present invention has the activity of inhibiting platelet aggregation, and therefore can be used as an antithrombotic agent. This is clear from the test examples described below. [Example] Hereinafter, the present invention will be specifically explained with reference to Examples. Reference example 2-(1-propionyloxy-4-methyl-
3-penten-1-yl)-5,8-dihydroxy-1,4-naphthoquinone Dissolve 432 mg of shikonin in 25 ml of anhydrous ethyl acetate, add 278 mg of propionyl chloride and 1.8 g of molecular sieve 4A, and shake occasionally. While stirring 3
I left it for days. Ethyl acetate and unreacted propionyl chloride were distilled off under reduced pressure, and the remaining red viscous oil was separated by thin layer chromatography to obtain red crystals. Red oil yield: 67% Mass spectrometry: 344 (M + ) 1 H-nuclear magnetic resonance spectrum (ppm, deuterochloroform, TMS standard) 1.15 (3H, t, J = 6Hz); 1.59 (3H, s);
1.88 (3H, s); 2.3~2.54 (4H, m); 5.10 (1H,
t, J=6Hz); 6.02 (1H, t, J=5Hz);
6.97 (1H, s); 7.18 (2H, s); 12.38 (1H,
s), 12.54 (1H, s) Examples 1-2 The following compounds were obtained in the same manner as in Reference Examples.
【表】【table】
実施例１によつてえられた化合物を用いてウサ
ギ血液の血小板によるBorn〔Nature194、927
（1962）〕、MichalおよびBorn〔Nature231、220
〔1971）〕の方法に準じて血小板凝集抑制作用の試
験を行つたところ、血小板凝集阻害は、ADPが
53％、コラーゲンが83％であつた。
この結果から本発明の化合物はADPおよびコ
ラーゲンによつて誘起される血小板の凝集を抑制
し、抗血栓剤として有用なことが明らかである。
Born using rabbit blood platelets using the compound obtained in Example 1 [Nature 194, 927
(1962)], Michal and Born [Nature 231 , 220
[1971], we conducted a test for platelet aggregation inhibition, and found that ADP inhibited platelet aggregation.
53% and collagen 83%. From these results, it is clear that the compounds of the present invention inhibit platelet aggregation induced by ADP and collagen, and are useful as antithrombotic agents.
Claims (1)
る。） で表わされる５，８−ジヒドロキシ−１，４−ナ
フトキノン誘導体。[Claims] 1. General formula [] (In the formula, R is an alkyl group having 6 to 12 carbon atoms.) A 5,8-dihydroxy-1,4-naphthoquinone derivative represented by the following formula.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26544484A JPS61143334A (en) | 1984-12-18 | 1984-12-18 | 5,8-dehydroxy-1,4-naphthoquinone derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26544484A JPS61143334A (en) | 1984-12-18 | 1984-12-18 | 5,8-dehydroxy-1,4-naphthoquinone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61143334A JPS61143334A (en) | 1986-07-01 |
| JPS6350337B2 true JPS6350337B2 (en) | 1988-10-07 |
Family
ID=17417233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP26544484A Granted JPS61143334A (en) | 1984-12-18 | 1984-12-18 | 5,8-dehydroxy-1,4-naphthoquinone derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61143334A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0180791B1 (en) * | 1995-07-24 | 1999-05-15 | 김용옥 | 6-substituted-5,8-dioxy-1,4-naphthoquinone derivative, its preparation process and the usage as anticancer drug |
| GB0117326D0 (en) * | 2001-07-16 | 2001-09-05 | Univ Aberdeen | Napthoquinone-type inhibitors of protein aggregation |
| JP4272515B2 (en) | 2001-07-27 | 2009-06-03 | 株式会社アドバンテスト | Phase correction circuit |
| DE10234398B4 (en) * | 2002-07-23 | 2006-07-27 | Ls-Medcap Gmbh | An implantable medical device coating composition and method of coating such device and its use |
-
1984
- 1984-12-18 JP JP26544484A patent/JPS61143334A/en active Granted
Non-Patent Citations (1)
| Title |
|---|
| J.PRAKT.CHEM=1982 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61143334A (en) | 1986-07-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2556722B2 (en) | Novel sulfonamide compound | |
| JPS6350337B2 (en) | ||
| US5395985A (en) | Compound and separating agent | |
| JPS6035347B2 (en) | Synthesis method of α-tocopherol | |
| US3418345A (en) | Halonitroanilides | |
| EP0076600A1 (en) | Anthranilic acid esters | |
| US3231590A (en) | N?-(6, 8-dichlorooctanoyl)-l-lysine | |
| US4661625A (en) | Synthesis and purification of d-propoxyphene hydrochloride | |
| US5599949A (en) | Bisphenol derivative and its manufacturing method | |
| JPH0665212A (en) | Pyrazine derivative and its production | |
| JPS6111956B2 (en) | ||
| IL99378A (en) | Synthesis of monhaloalkanoyl-ferrocenes | |
| JPH0129177B2 (en) | ||
| JPS5888361A (en) | 3-amino-1,4-bis(alkoxycarbonyl)maleimide compound and its preparation | |
| JPS6345380B2 (en) | ||
| LU87900A1 (en) | NOVEL DERIVATIVES OF 5-PHENYL-1H-PYRAZOLE-4-PROPIONIC ACID, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS | |
| KR0129789B1 (en) | N-alloy-c-(n-methylanilino)imidoyl chloride derivatives and the process of production thereof | |
| JPS59216841A (en) | Agent for optical resolution | |
| US2629734A (en) | N-oxyalkyl-p-aminobenzoyl glutamates | |
| JP3655311B2 (en) | Method for producing phthalide compound | |
| JPH062721B2 (en) | Novel N, N, N ', N'-tetracyclohexyl-dicarboxylic acid diamide | |
| JPS63258828A (en) | Production of high-purity alpha-hydroxyketone | |
| HUT75713A (en) | Process for producing 5-aryl-2,4-dialkyl-3h-1,2,4-triazol-3-thion derivatives | |
| JPH02129133A (en) | Production of alpha,alpha-dichloro-diphenylmethanes | |
| JPS5916879A (en) | Production of n-substituted imidazole |