JPS637187B2 - - Google Patents
Info
- Publication number
- JPS637187B2 JPS637187B2 JP8609480A JP8609480A JPS637187B2 JP S637187 B2 JPS637187 B2 JP S637187B2 JP 8609480 A JP8609480 A JP 8609480A JP 8609480 A JP8609480 A JP 8609480A JP S637187 B2 JPS637187 B2 JP S637187B2
- Authority
- JP
- Japan
- Prior art keywords
- diethenyl
- tetramethyl
- methoxycarbonylethyl
- porphynatogermanium
- germanium
- 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
- 229910052732 germanium Inorganic materials 0.000 claims description 14
- -1 2 -methoxycarbonylethyl Chemical group 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 8
- KSFOVUSSGSKXFI-GAQDCDSVSA-N CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O Chemical compound CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O KSFOVUSSGSKXFI-GAQDCDSVSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 230000005976 liver dysfunction Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229950003776 protoporphyrin Drugs 0.000 description 3
- IEXRMSFAVATTJX-UHFFFAOYSA-N tetrachlorogermane Chemical compound Cl[Ge](Cl)(Cl)Cl IEXRMSFAVATTJX-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- LQBPATQBTSBIIH-UHFFFAOYSA-N methyl 3-[8,13-bis(ethenyl)-18-(3-methoxy-3-oxopropyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoate Chemical compound N1C(C=C2C(=C(C=C)C(=CC=3C(=C(CCC(=O)OC)C(=C4)N=3)C)N2)C)=C(C=C)C(C)=C1C=C1C(C)=C(CCC(=O)OC)C4=N1 LQBPATQBTSBIIH-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- VJHDVMPJLLGYBL-UHFFFAOYSA-N tetrabromogermane Chemical compound Br[Ge](Br)(Br)Br VJHDVMPJLLGYBL-UHFFFAOYSA-N 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 208000007348 Experimental Liver Cirrhosis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 201000001352 cholecystitis Diseases 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 150000002291 germanium compounds Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000011133 lead Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
【発明の詳細な説明】
本発明は多彩な薬理作用を有する新規なプロト
ポルフイリンジメチルエステルゲルマニウム錯体
およびその製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel protoporphyrin dimethyl ester germanium complex having various pharmacological actions and a method for producing the same.
さらに詳しくは、本発明は
一般式
（式中Ｙはハロゲン原子または水酸基を表わす）
で示されるビス置換−７・12−ジエテニル−３・
８・13・17−テトラメチル−２・18−ジ（２−メ
トキシカルボニルエチル）ポルフイナトゲルマニ
ウム（）、および
で示される７・12−ジエテニル−３・８・13・17
−テトラメチル−21H・23H−ポルフイン−２・
18−ジプロピオン酸ジメチルエステルとハロゲン
化ゲルマニウムを反応させて
一般式
（式中Ｘはハロゲン原子を表わす）で示されるビ
スハロゲノ−７・12−ジエテニル−３・８・13・
17−テトラメチル−２・18−ジ（２−メトキシカ
ルボニルエチル）ポルフイナトゲルマニウム
（）を得、これを加水分解し、ビスハイドロキ
シ−７・12−ジエテニル−３・８・13・17−テト
ラメチル−２・18−ジ（２−メトキシカルボニル
エチル）ポルフイナトゲルマニウム（）を製造
する方法である。 More specifically, the present invention relates to the general formula (In the formula, Y represents a halogen atom or a hydroxyl group)
Bis-substituted-7,12-diethenyl-3, represented by
8,13,17-tetramethyl-2,18-di(2-methoxycarbonylethyl)porphynatogermanium (), and 7,12-diethenyl-3,8,13,17
-tetramethyl-21H・23H-porphin-2・
By reacting 18-dipropionate dimethyl ester and germanium halide, the general formula Bishalogeno-7,12-diethenyl-3,8,13, represented by (in the formula, X represents a halogen atom)
17-tetramethyl-2,18-di(2-methoxycarbonylethyl)porphynatogermanium () was obtained and hydrolyzed to give bishydroxy-7,12-diethenyl-3,8,13,17-tetramethyl This is a method for producing -2,18-di(2-methoxycarbonylethyl)porphynatogermanium ().
プロトポルフイリンには肝機能障害改善作用、
酸化触媒能、肝機能、窒素代謝などの増進作用あ
るいは網内系機能に好ましい影響を与え、さらに
実験的肝硬変症の抑制作用、抗炎症作用ならびに
抗アレルギー作用等のあることが知られている。 Protoporphyrin has the effect of improving liver dysfunction,
It is known to have a positive effect on the oxidation catalytic ability, liver function, nitrogen metabolism, etc., or on the reticuloendothelial system function, and also to have an inhibitory effect on experimental liver cirrhosis, an anti-inflammatory effect, and an anti-allergic effect.
現在までに知られているプロトポルフイリンの
錯体としては、鉄、コバルト、ニツケル、鉛、亜
鉛、銅、スズ、カドミウムおよびその他の金属類
との錯体が知られているが、半金属であるゲルマ
ニウムとの錯体はいまだ知られておらず、特にゲ
ルマニウム２価との錯体は存在しても非常に不安
定であろうと推測されるにすぎなかつた
〔Schaffer、A.M.、Gouterman、M.、Theoret.
Chim.Acta.、18.1（1970）〕。 Protoporphyrin complexes known to date include complexes with iron, cobalt, nickel, lead, zinc, copper, tin, cadmium, and other metals; Complexes with germanium are still unknown, and complexes with divalent germanium, even if they exist, are only speculated to be extremely unstable [Schaffer, AM, Gouterman, M., Theoret.
Chim. Acta., 18.1 (1970)].
しかしながら本発明者らは鋭意研究の結果、プ
ロトポルフイリン誘導体を用いてゲルマニウム錯
体の合成に成功し本発明を完成した。 However, as a result of intensive research, the present inventors succeeded in synthesizing a germanium complex using a protoporphyrin derivative and completed the present invention.
すなわち本発明化合物である一般式(3)のビスハ
ロゲノ−７・12−ジエテニル−３・８・13・17−
テトラメチル−２・18−ジ（２−メトキシカルボ
ニルエチル）ポルフイナトゲルマニウム（）
は、原料化合物のプロトポルフイリンジメチルエ
ステル体、すなわち式(2)の７・12−ジエテニル−
３・８・13・17−テトラメチル−21H・23H−ポ
ルフイン−２・18−ジプロピオン酸ジメチルエス
テルとハロゲン化ゲルマニウムとを通常、溶媒中
で数時間から十数時間、高温で反応させることに
より得られる。 That is, bishalogeno-7,12-diethenyl-3,8,13,17- of the general formula (3) which is the compound of the present invention
Tetramethyl-2,18-di(2-methoxycarbonylethyl)porphynatogermanium ()
is the protoporphyrin dimethyl ester of the starting compound, i.e. 7,12-diethenyl- of formula (2)
By reacting 3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropionic acid dimethyl ester and germanium halide at high temperature, usually in a solvent for several hours to more than ten hours. can get.
この場合使用される溶媒としてはピロール、ピ
リジン、ピリミジン、ピラジン、ピリダジン、フ
エノール、ナフトール、キノリン、イソキノリ
ン、インドール等が挙げられるが、特に原料のプ
ロトポルフイリンジメチルエステル体の溶解性お
よび反応温度などを考慮して、ピリジン、キノリ
ンが好んで使用される。 Examples of solvents used in this case include pyrrole, pyridine, pyrimidine, pyrazine, pyridazine, phenol, naphthol, quinoline, isoquinoline, indole, etc. In view of this, pyridine and quinoline are preferably used.
反応は通常、耐圧反応容器中で行なわれるが、
反応時間と反応温度は使用する溶媒等により特に
限定されないが、たとえばピリジン中では４〜５
時間、180℃に加熱すると反応は進行する。 The reaction is usually carried out in a pressure-resistant reaction vessel, but
The reaction time and reaction temperature are not particularly limited depending on the solvent used, but for example, in pyridine, 4 to 5
The reaction proceeds when heated to 180°C for an hour.
試薬として用いるゲルマニウム化合物は、通
常、四塩化ゲルマニウム、四臭化ゲルマニウムの
ようなハロゲン化ゲルマニウムが用いられる。原
料化合物(2)と試薬であるハロゲン化ゲルマニウム
との混合割合は特に限定されないが、通常、原料
化合物(2)１モルに対してやや過剰の３〜８モルの
ハロゲン化ゲルマニウムが使用される。一方、
式
で示される水酸基で置換されたビスハイドロキシ
−７・12−ジエテニル−３・８・13・17−テトラ
メチル−２・18−ジ（２−メトキシカルボニルエ
チル）ポルフイナトゲルマニウム（）は、プロ
トポルフイリンから合成することが困難であつた
が、本発明化合物であるビスハロゲノ−７・12−
ジエテニル−３・８・13・17−テトラメチル−
２・18−ジ（２−メトキシカルボニルエチル）ポ
ルフイナトゲルマニウム（）(3)を加水分解する
ことにより得られるが特にクロロホルムとメタノ
ールとの100対１混合溶液を展開溶媒として用い、
シリカゲルカラムクロマトグラムで処理すること
によりジハロゲン原子が容易に水酸基と置換する
ことを見い出し、目的とする水酸基の入つたプロ
トポルフイリン誘導体のゲルマニウム錯体を合成
することができた。 As the germanium compound used as a reagent, germanium halides such as germanium tetrachloride and germanium tetrabromide are usually used. The mixing ratio of the raw material compound (2) and the reagent germanium halide is not particularly limited, but usually 3 to 8 moles of germanium halide is used, which is slightly in excess of 1 mole of the raw material compound (2). On the other hand, Eq. Bishydroxy-7,12-diethenyl-3,8,13,17-tetramethyl-2,18-di(2-methoxycarbonylethyl)porphynatogermanium () substituted with the hydroxyl group represented by is protoporphyrin. However, the compound of the present invention, bishalogeno-7,12-
Diethenyl-3,8,13,17-tetramethyl-
It is obtained by hydrolyzing 2,18-di(2-methoxycarbonylethyl)porphynatogermanium () (3), and in particular, a 100:1 mixed solution of chloroform and methanol is used as the developing solvent.
We found that dihalogen atoms can be easily substituted with hydroxyl groups by treatment with silica gel column chromatography, and were able to synthesize the desired germanium complex of protoporphyrin derivatives containing hydroxyl groups.
このようにして得た、
一般式
（式中Ｙはハロゲン原子または水酸基を表わす）
で示されるビス置換−７・12−ジエテニル−３・
８・13・17−テトラメチル−２・18−ジ（２−メ
トキシカルボニルエチル）ポルフイナトゲルマニ
ウム（）は新規化合物で種々のすぐれた薬理作
用を有しており、医薬品として極めて有用であ
る。 The general formula obtained in this way (In the formula, Y represents a halogen atom or a hydroxyl group)
Bis-substituted-7,12-diethenyl-3, represented by
8,13,17-tetramethyl-2,18-di(2-methoxycarbonylethyl)porphynatogermanium () is a new compound that has various excellent pharmacological actions and is extremely useful as a pharmaceutical.
たとえば本発明化合物(1)は先に挙げたプロトポ
ルフイリンの有する薬理作用をいずれも保持して
おり、さらに注目すべきはすぐれた制癌作用を有
していることである。そのため肝機能障害の治療
のみならず癌の治療にも有用であることが期待さ
れる。 For example, the compound (1) of the present invention retains all of the pharmacological actions of protoporphyrin mentioned above, and what is more noteworthy is that it has excellent anticancer action. Therefore, it is expected to be useful not only for the treatment of liver dysfunction but also for the treatment of cancer.
本物質を医薬として投与する場合、錠剤、カプ
セル剤、散剤、顆粒剤などとして経口的に用いら
れるほか、注射剤、坐剤、ペレツトなどとして非
経口的に投与することができる。胆石、胆のう炎
に伴う肝機能障害の治療剤として用いる場合は、
成人１人につき通常１日30mg〜500mgを経口的ま
たは非経口的に投与することができる。 When administering this substance as a medicine, it can be administered orally in the form of tablets, capsules, powders, granules, etc., or parenterally in the form of injections, suppositories, pellets, etc. When used as a treatment for liver dysfunction associated with gallstones and cholecystitis,
Usually 30 mg to 500 mg per adult per day can be administered orally or parenterally.
以下に実施例を記載して本発明をより具体的に
説明する。 EXAMPLES The present invention will be described in more detail with reference to Examples below.
実施例 １
ビスクロロ−７・12−ジエテニル−３・８・
13・17−テトラメチル−２・18−ジ（２−メト
キシカルボニルエチル）ポルフイナトゲルマニ
ウム（）
７・12−ジエテニル−３・８・13・17−テトラ
メチル−21H・23H−ポルフイン−２・18−ジプ
ロピオン酸ジメチルエステル590mg（1.0ミリモ
ル）をピリジン20mlに溶解した溶液を内容量200
mlの耐圧反応容器にいれ、これに四塩化ゲルマニ
ウム１ｇ（4.6ミリモル）を添加した後、密閉し
て180℃で4.5時間加熱撹拌する。冷却後析出する
不溶物を去し、液を減圧下で濃縮乾固する。
残留物をクロロホルム20mlに溶解しアルミナ
（ウエルム製）30ｇのカラムに吸着させた後、ク
ロロホルム200mlで溶出する。赤褐色の溶出液を
過し、減圧下で濃縮乾固するとビスクロロ−
７・12−ジエテニル−３・８・13・17−テトラメ
チル−２・18−ジ（２−メトキシカルボニルエチ
ル）ポルフイナトゲルマニウム（）の黒紫色粉
末結晶350mg（0.48ミリモル）を得る。Example 1 Bischloro-7.12-diethenyl-3.8.
13,17-tetramethyl-2,18-di(2-methoxycarbonylethyl)porphynatogermanium () 7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphin-2,18 - A solution of 590 mg (1.0 mmol) of dipropionate dimethyl ester dissolved in 20 ml of pyridine was added to a volume of 200
ml of pressure-resistant reaction vessel, and after adding 1 g (4.6 mmol) of germanium tetrachloride thereto, the mixture is sealed and heated and stirred at 180°C for 4.5 hours. After cooling, the precipitated insoluble matter is removed, and the liquid is concentrated to dryness under reduced pressure.
The residue was dissolved in 20 ml of chloroform and adsorbed on a 30 g column of alumina (manufactured by Wellm), followed by elution with 200 ml of chloroform. The reddish brown eluate was filtered and concentrated to dryness under reduced pressure to give bischloro-
350 mg (0.48 mmol) of black-purple powder crystals of 7,12-diethenyl-3,8,13,17-tetramethyl-2,18-di(2-methoxycarbonylethyl)porphynatogermanium () are obtained.
融点 205℃から分解
ゲルマニウム含有率（原子吸光法）
理論値（％）9.91
実験値（％）10.30
可視部吸収極大（クロロホルム中で測定）
419nｍ 542nｍ 579nｍ
赤外吸収スペクトル 添付図面の第１図に示す通
り。Melting point Decomposed from 205℃ Germanium content (atomic absorption method) Theoretical value (%) 9.91 Experimental value (%) 10.30 Visible absorption maximum (measured in chloroform) 419 nm 542 nm 579 nm Infrared absorption spectrum Shown in Figure 1 of the attached drawings street.
核磁気共鳴スペクトル 添付図面の第２図に示す
通り。Nuclear magnetic resonance spectrum As shown in Figure 2 of the attached drawings.
実施例 ２
ビスブロモ−７・12−ジエテニル−３・８・
13・17−テトラメチル−２・18−ジ（2′−メト
キシカルボニルエチル）ポルフイナトゲルマニ
ウム（）
実施例１の方法に従い、四塩化ゲルマニウムの
代りに四臭化ゲルマニウムを用いることにより、
ビスブロモ−７・12−ジエテニル−３・８・13・
17−テトラメチル−２・18−ジ（2′−メトキシカ
ルボニルエチル）ポルフイナトゲルマニウム
（）の黒紫色の粉末結晶（収率52％）を得る。Example 2 Bisbromo-7.12-diethenyl-3.8.
13,17-tetramethyl-2,18-di(2'-methoxycarbonylethyl)porphynatogermanium () By following the method of Example 1 and using germanium tetrabromide in place of germanium tetrachloride,
Bisbromo-7.12-diethenyl-3.8.13.
Black-purple powder crystals (yield 52%) of 17-tetramethyl-2,18-di(2'-methoxycarbonylethyl)porphynatogermanium () are obtained.
融点 208℃から分解
ゲルマニウム含有率（原子吸光法）
理論値（％）8.84
実験値（％）8.95
実施例 ３
ビスハイドロキシ−７・12−ジエテニル−３・
８・13・17−テトラメチル−２・18−ジ（2′−
メトキシカルボニルエチル）ポルフイナトゲル
マニウム（）
実施例１で得られたビスクロロ−７・12−ジエ
テニル−３・８・13・17−テトラメチル−２・18
−ジ（2′−メトキシカルボニルエチル）ポルフイ
ナトゲルマニウム（）0.7ｇ（0.96ミリモル）
をクロロホルム20mlに溶解し、シリカゲルカラム
に吸着させた後、クロロホルムとメタノールの
100対１の混合溶媒２を用いて溶出すると赤紫
色の溶出液を得る。これを過して減圧下で濃縮
乾固するとビスハイドロキシ−７・12−ジエテニ
ル−３・８・13・17−テトラメチル−２・18−ジ
（2′−メトキシカルボニルエチル）ポルフイナト
ゲルマニウム（）の黒紫色粉末結晶0.6ｇ
（0.87ミリモル）が得られる。Melting point Decomposed from 208℃ Germanium content (atomic absorption method) Theoretical value (%) 8.84 Experimental value (%) 8.95 Example 3 Bishydroxy-7・12-diethenyl-3・
8,13,17-tetramethyl-2,18-di(2'-
methoxycarbonylethyl) porphynatogermanium () Bischloro-7,12-diethenyl-3,8,13,17-tetramethyl-2,18 obtained in Example 1
-di(2'-methoxycarbonylethyl)porphynatogermanium () 0.7g (0.96 mmol)
was dissolved in 20 ml of chloroform, adsorbed on a silica gel column, and then mixed with chloroform and methanol.
Elution using a 100:1 mixed solvent 2 gives a reddish-purple eluate. After filtering and concentrating to dryness under reduced pressure, bishydroxy-7,12-diethenyl-3,8,13,17-tetramethyl-2,18-di(2'-methoxycarbonylethyl)porphynatogermanium () 0.6g of black-purple powder crystals
(0.87 mmol) is obtained.
融点 210℃から分解 ゲルマニウム含有率（原子吸光法） 理論値（％）10.44 実験値（％）9.81 可視部吸収極大（クロロホルム中で測定） 419nｍ 542nｍ 579nｍ 赤外吸収スペクトル 添付図面の第３図の通り 核磁気共鳴スペクトル 添付図面の第４図の通りDecomposes from melting point 210℃ Germanium content (atomic absorption method) Theoretical value (%) 10.44 Experimental value (%) 9.81 Visible absorption maximum (measured in chloroform) 419nm 542nm 579nm Infrared absorption spectrum As shown in Figure 3 of the attached drawings Nuclear magnetic resonance spectrum As shown in Figure 4 of the attached drawings
第１図はビクロロ−７・12−ジエテニル−３・
８・13・17−テトラメチル−２・18−ジ（2′−メ
トキシカルボニルエチル）ポルフイナトゲルマニ
ウム（）の赤外吸収スペクトル（KBr法）、第
２図はその核磁気共鳴スペクトル〔重クロロホル
ム中で測定、内部標準としてテトラメチルシラン
（TMS）を使用する〕を示す。第３図はビスハイ
ドロキシ−７・12−ジエテニル−３・８・13・17
−テトラメチル−２・18−ジ（2′−メトキシカル
ボニルエチル）ポルフイナトゲルマニウム（）
の赤外吸収スペクトル（KBr法）、第４図はその
核磁気共鳴スペクトル（重クロロホルム中で測
定）を示す。
Figure 1 shows bichloro-7.12-diethenyl-3.
Infrared absorption spectrum (KBr method) of 8,13,17-tetramethyl-2,18-di(2'-methoxycarbonylethyl)porphynatogermanium (). Figure 2 shows its nuclear magnetic resonance spectrum [in deuterium chloroform]. measured using tetramethylsilane (TMS) as an internal standard]. Figure 3 shows bishydroxy-7,12-diethenyl-3,8,13,17
-Tetramethyl-2,18-di(2'-methoxycarbonylethyl)porphinatogermanium ()
Figure 4 shows its infrared absorption spectrum (KBr method) and its nuclear magnetic resonance spectrum (measured in deuterated chloroform).
Claims (1)
で示されるビス置換−７・12−ジエテニル−３・
８・13・17−テトラメチル−２・18−ジ（２−メ
トキシカルボニルエチル）ポルフイナトゲルマニ
ウム（）。 ２ 式 で示される７・12−ジエテニル−３・８・13・17
−テトラメチル−21H・23H−ポルフイン−２・
18−ジプロピオン酸ジメチルエステルとハロゲン
化ゲルマニウムとを反応させて、ビスハロゲノ−
７・12−ジエテニル−３・８・13・17−テトラメ
チル−２・18−ジ（２−メトキシカルボニルエチ
ル）ポルフイナトゲルマニウム（）を得、これ
を加水分解することを特徴とするビスハイドロキ
シ−７・12−ジエテニル−３・８・13・17−テト
ラメチル−２・18−ジ（２−メトキシカルボニル
エチル）ポルフイナトゲルマニウム（）の製造
法。[Claims] 1. General formula (In the formula, Y represents a halogen atom or a hydroxyl group)
Bis-substituted-7,12-diethenyl-3, represented by
8,13,17-tetramethyl-2,18-di( 2 -methoxycarbonylethyl)porphynatogermanium (). 2 formulas 7,12-diethenyl-3,8,13,17
-tetramethyl-21H・23H-porphin-2・
By reacting dimethyl 18-dipropionate with germanium halide, bishalogeno-
7,12-diethenyl-3,8,13,17-tetramethyl-2,18-di( 2 -methoxycarbonylethyl)porphynatogermanium () is obtained, and this is hydrolyzed. A method for producing 7,12-diethenyl-3,8,13,17-tetramethyl-2,18-di( 2 -methoxycarbonylethyl)porphynatogermanium ().
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8609480A JPS5711985A (en) | 1980-06-24 | 1980-06-24 | Protoporphyrin dimethyl ester germanium complex and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8609480A JPS5711985A (en) | 1980-06-24 | 1980-06-24 | Protoporphyrin dimethyl ester germanium complex and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5711985A JPS5711985A (en) | 1982-01-21 |
| JPS637187B2 true JPS637187B2 (en) | 1988-02-15 |
Family
ID=13877114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8609480A Granted JPS5711985A (en) | 1980-06-24 | 1980-06-24 | Protoporphyrin dimethyl ester germanium complex and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5711985A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0615545B2 (en) * | 1984-10-01 | 1994-03-02 | 東洋薄荷工業株式会社 | Metal pheophobide derivatives and metal porphyrin derivatives |
| JPH0714942B2 (en) * | 1986-03-03 | 1995-02-22 | 浜理薬品工業株式会社 | Porphyrin derivative |
| JP2520735B2 (en) * | 1988-07-14 | 1996-07-31 | 東洋薄荷工業株式会社 | Porphyrin derivative |
| EP1145713A4 (en) * | 1999-01-12 | 2003-08-06 | Kyowa Hakko Kogyo Kk | Telomerase inhibitors |
-
1980
- 1980-06-24 JP JP8609480A patent/JPS5711985A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5711985A (en) | 1982-01-21 |
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