JPS5933292A - Organogermanium compound - Google Patents
Organogermanium compoundInfo
- Publication number
- JPS5933292A JPS5933292A JP57143198A JP14319882A JPS5933292A JP S5933292 A JPS5933292 A JP S5933292A JP 57143198 A JP57143198 A JP 57143198A JP 14319882 A JP14319882 A JP 14319882A JP S5933292 A JPS5933292 A JP S5933292A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- lower alkyl
- present
- group
- 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.)
- Granted
Links
- -1 Organogermanium compound Chemical class 0.000 title claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 18
- 150000002148 esters Chemical class 0.000 abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 abstract description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 3
- VWHUZNBSDQCMRD-UHFFFAOYSA-N 3-trichlorogermylpropanoyl chloride Chemical compound ClC(=O)CC[Ge](Cl)(Cl)Cl VWHUZNBSDQCMRD-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003213 activating effect Effects 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 230000001900 immune effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 150000002291 germanium compounds Chemical class 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229910052732 germanium Inorganic materials 0.000 description 3
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- MWYJZGOBCALGKK-UHFFFAOYSA-N [Ge].C(=O)(O)OC(=O)O Chemical compound [Ge].C(=O)(O)OC(=O)O MWYJZGOBCALGKK-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000004020 conductor Substances 0.000 description 2
- 229940093626 germanium sesquioxide Drugs 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- XEABSBMNTNXEJM-UHFFFAOYSA-N propagermanium Chemical compound OC(=O)CC[Ge](=O)O[Ge](=O)CCC(O)=O XEABSBMNTNXEJM-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- IQULGZQMMPRBLA-UHFFFAOYSA-N 2-carboxyethylgermanium Chemical compound OC(=O)CC[Ge] IQULGZQMMPRBLA-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- GIEAINOVPLDQPT-UHFFFAOYSA-N ethylgermanium Chemical compound CC[Ge] GIEAINOVPLDQPT-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940035339 tri-chlor Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は新規なＷｔ進全有する有機ゲルマニウム化合物
に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an organic germanium compound having a novel Wt concentration.
炭素の同族体であるゲルマニウム（Ｇθ）は、同シ〈炭
素の同族体であるシリコン（Ｓｌ）と同様に半導体効果
金有するという特殊′註から、古くエフ物理学や無機化
学の分野で研究の対象となっているものであるが、近年
になってゲルマニウムの有機化合物に関する研究やその
成芽の発表が活発に行なわれる工うＫなった。Germanium (Gθ), a homolog of carbon, has long been the subject of research in the fields of F-physics and inorganic chemistry because of its special property of having a semiconductor effect like silicon (Sl), a homolog of carbon. In recent years, research on organic compounds of germanium and presentations on their germination have become active.
而して、従来公知の有機ゲルマニウム化合物としては、
以下に示す如くトリクロルゲルミルブロピオノｖ／ｓｈ
体（Ｉｔ） 、カルボキシエテルゲルマニウムセスキオ
キサイド計導体（ト）やパンアミノフェニルゲルマニウ
ムセスキオキサイド誘導体面等があり、それらのうちに
は好ましい薬理特性ケ示すとされているものもある。Therefore, conventionally known organic germanium compounds include:
Trichlorgel milbropiono v/sh as shown below
These include carboxyethergermanium sesquioxide conductors (It), carboxyether germanium sesquioxide conductors (I), and panaminophenylgermanium sesquioxide derivatives, some of which are said to exhibit favorable pharmacological properties.
即ち、式（ＩＩＩ）で表わされる化合物中のカルボキシ
エチルゲルマニウムセスキ刈ギサイド
（ＧθＣＴＴｚＣＨ，Ｃｏｏ）（）ｔ０３は優ｊ、た抗
腫瘍作用やインターフェロン誘起作用を示（７，又２式
動で表わされる化合物は抗炎症作用や免疫賦活作用ケ示
すとされているのである。That is, carboxyethylgermanium sesquigicide (GθCTTzCH,Coo)()t03 in the compound represented by formula (III) exhibits significant antitumor and interferon-inducing effects (7, and is also represented by the formula 2). The compound is said to exhibit anti-inflammatory and immunostimulatory effects.
然し乍ら、土肥化合物（Ｉ）乃至動はいずれもゲルマニ
ウム原子にブロビオノ酸残基やパラアミノフェニルＸ：
等生体になじみにぐい基が結合しているので、とｔ′１
．に生体になじみ易い基金導入すること≠；できｊば、
吸収速度や生体内利用率等においてｇ＃九た有機ゲルマ
ニウム化合物を得ることができると考えられる。However, Doi Compound (I) has a brobionoic acid residue or para-aminophenyl X on the germanium atom.
Since the group is bonded to the living body, and t′1
．． If possible, introduce a fund that is compatible with living organisms.
It is believed that it is possible to obtain an organic germanium compound with a g# of 9 in terms of absorption rate, bioavailability, etc.
本発明の発明者は、上述した事情全背景として鋭意研究
の結果、アミノ酸構造を導入することに成卸し、本発明
を守成させたもので１本発明有機ゲルマニウム化合物は
１式
式中、Ｒ３は水酸基又はＯ−低級アルキル基、＆は水素
原子、供級アルキル基又汀ベンジ＋卑：ｉＲｉ＋Ｒ４σ
水素原子又は＃糾アルキル基金そｎ、 −ｒ ７”ｌ示
すで表わされることを特徴とするものである。The inventor of the present invention, as a result of intensive research against the background of all the above-mentioned circumstances, has decided to introduce an amino acid structure, and the present invention has been adhered to.1 The organic germanium compound of the present invention has the following formula: Hydroxyl group or O-lower alkyl group, & is a hydrogen atom, donor alkyl group or benzene+base: iRi+R4σ
It is characterized by being represented by a hydrogen atom or an alkyl group, -r 7"l.
以下、本発明の詳細な説明する。The present invention will be explained in detail below.
Ｏ。O.
ヲ
ＯＯＨ
Ｈ−Ｃ−ＮＨが結合したもので、エテルゲルマニラムセ
スキオキサイド構造の部分は前記公知化合物の−である
カルボキシエチルゲルマニウムセスキオキサイドと共通
するケルマニウムー酸素結合を有していて、肖該化合物
と同様に抗腫瘍作用やインターフェロン誘起作用等の薬
理作用をもたらすと考えられ、一方アミノ酸構造の部分
は、アミノ酸が、タンパク省の構成分子として、又、タ
ンパク質が酵累にエフ分解さｎて単独で１体内に広（分
布しているものであるから生体に対して極めてなじみ易
く０本発明化合物の吸収速度や生体内利用率を高めるこ
とが期待される。WOOOH H-C-NH is bonded, and the ether gel maniram sesquioxide structure part has a kermanium-oxygen bond in common with carboxyethylgermanium sesquioxide, which is the - of the above-mentioned known compound, and is similar to the corresponding compound. Similarly, it is thought to bring about pharmacological effects such as antitumor effects and interferon-inducing effects.On the other hand, the amino acid structure part shows that amino acids act as constituent molecules of proteinaceous proteins, and that proteins are degraded by enzymes and used alone. Since it is widely distributed in the body, it is extremely compatible with the living body and is expected to increase the absorption rate and bioavailability of the compound of the present invention.
本発明化合物中の買換）−；中、Ｒ１は水酸基又はメト
キシ基、エトギシ基等の〇−低級アルキル基。In the compounds of the present invention, R1 is a hydroxyl group or a 〇-lower alkyl group such as a methoxy group or an ethoxy group.
Ｒ２は水素原子又はメチル基、エチル基、イソプロピル
基、イソブチル基等の低級アルキル基若しくはベンジル
基、１え、及び＆は水素原子又はメチル基。R2 is a hydrogen atom or a lower alkyl group such as a methyl group, an ethyl group, an isopropyl group, an isobutyl group, or a benzyl group, and 1e and & are a hydrogen atom or a methyl group.
エチル基等の低級アルキル基をそれぞれ示すものであり
、従って本発明化合物には例えば以下に示すような有機
ゲルマニウム仕合物が句含される。Each represents a lower alkyl group such as an ethyl group, and therefore, the compounds of the present invention include, for example, organic germanium compounds as shown below.
尚５本発明化合物はゲルマニウム−酸素結合全分子間に
有する巨大分子化合物であるから。Note that the compound of the present invention is a macromolecular compound having germanium-oxygen bonds between all molecules.
又は。Or.
のＩうに表わしても良い。It may also be expressed as I.
而して、以トの様な特徴ケ有する本発明化合物は、例え
は次のような方法で製造することができる。The compound of the present invention having the characteristics described below can be produced, for example, by the following method.
即ち１例えば本発明化合物（Ｔ）中、Ｒ，＝ Ｏ−Ｃ，
Ｔ（、。That is, 1 For example, in the compound (T) of the present invention, R,=OC,
T(,.
Ｒａ −’ ＣＨ，−Ｃ３Ｈ５、Ｒ３＝ Ｒ４” Ｈの
もの（Ｔ−ａ’）’（ｒｒ得るには、アミノ酸の−１，
ｔｌであるフェニルアラニン１のカルボキシル基全エス
テル化してエステル体２とし、該エステル体２にトリク
ロルゲルミルプロピオニルクロライド３を反応させてト
リクロル体４を得、該トリフルル体４全加水分解するの
である。Ra −' CH, -C3H5, R3=R4''H's(T-a')' (To obtain rr, -1 of the amino acid,
The carboxyl group of phenylalanine 1, which is tl, is completely esterified to form ester 2, the ester 2 is reacted with trichlorogermylpropionyl chloride 3 to obtain trichlor 4, and the trifluor 4 is completely hydrolyzed.
ＣＩ（、−Ｃ６Ｈａ ＣＬＣＪ（ｓ
２
ＣトＬＣＩＩＨａ
このように１２で得られた本発明化合物は、ゲルマニウ
ム−酸Ｘ’ 結合’（ｒ 持つエチルゲルマニウムセス
キオキサイド構造と生体に対して極めてんじみ易いアミ
ノ酸構造とを併有しているので、吸収速度や生体内利用
率が公知の有機ゲルマニウム化合物Ｘｖ向−ヒし、そｎ
、に基き薬理活ｌ註も同士することが期待され、事実本
発明化合物（■）中Ｒ＋ ＝ ０−Ｃｙ Ｈａ 。CI(, -C6Ha CLCJ(s 2 C to LCIIHa) The compound of the present invention thus obtained in 12 has an ethylgermanium sesquioxide structure with a germanium-acid structure, its absorption rate and bioavailability are comparable to known organic germanium compounds Xv.
It is expected that the pharmacological activities will be similar based on , and in fact, R+ = 0-Cy Ha in the compound of the present invention (■).
Ｒ７” ＣＨｙ Ｃ６Ｈ５、Ｒａ ＝ Ｒ４＝ Ｈの
もの（Ｔ −ａ） にマウスに移殖し、た腫瘍細胞に
対し、抗腫瘍体用のあるとさｎているカルボキシエテル
ゲルマニウムセスキオキ→ｔイド（Ｇ４ＣＨ２ＣＪＬ
Ｃ０ＯＨ）ｔ Ｏｓ エリ少量で優ｎた抑制率を示し
た。R7" CHy C6H5, Ra = R4 = H (T - a) was transplanted into mice and treated against the tumor cells with carboxyether germanium sesquioxide (t), which is said to have antitumor properties. G4CH2CJL
A small amount of C0OH)tOs showed an excellent inhibition rate.
次に本発明の実施例について述べる。Next, examples of the present invention will be described.
エステル体２の合成
Ｌ−フェニルアラニン１５０．０ｇ （０，３０５モル
）全１沼の９９５％エタノールに加えてがくはんし。Synthesis of Ester Form 2 150.0 g (0,305 mol) of L-phenylalanine was added to one volume of 995% ethanol.
こねに塩酸カスを１時間吹き込み、その後２時間還流す
る反応中、溶液は透明でおる。冷却後溶媒全留去し、結
晶を乾燥後秤量すると、エステル体２の塩酸成金６５．
４６ｇ（α２８５モル）得る。During the reaction, the dough was bubbled with hydrochloric acid residue for 1 hour and then refluxed for 2 hours, during which time the solution remained clear. After cooling, all of the solvent was distilled off, and the crystals were dried and weighed.
46 g (α285 mol) are obtained.
収率９４係。Yield: 94.
この塩酸塩を２６７５ｇ（０１１６モル）秤ｆ゛シて。Weigh out 2,675 g (0,116 mol) of this hydrochloride.
７１（３００ｍｌに溶かし、炭酸カリウム１６．０５
ｇ （０，２５２モル）ケ徐々に加えていく。全量を加
え終ったら酢酸エステルの１ｏ ｏｍ１３で４回抽出し
、芒硝で乾燥後、酢酸ニスデルを留去しで、残渣全再度
酢酸エステルに溶かして濾過する。酢酸エステル全留去
後秤量するとエステル体２ｉ１５．２＋ｇ（０，０７８
８モル）得る。収率６８％。71 (dissolved in 300 ml, potassium carbonate 16.05
g (0,252 mol) is gradually added. When the entire amount has been added, the mixture is extracted four times with 10 ml of acetic acid ester, dried over Glauber's salt, Nisder acetate is distilled off, and the entire residue is redissolved in acetic ester and filtered. When the acetate ester was completely distilled off and weighed, the ester form 2i15.2+g (0,078
8 mol) is obtained. Yield 68%.
エステル体２
無色油状物質
ＩＲ（ＮＥＡＴｃｒｎ−”） ３０［］０，１７３５
，１６０［］、１５［’ＩＯ，１４５５゜１１９０．１
０３０．７０Ｏ
ＮＭＲ（Ｃ■右ｐｐｍ） １．２３ （３Ｈｔ −０−
ＣＩＬＣ）ｊ４ ）２．９５（２■Ｉｏｃｔ Ｃｈ
Ｃ６Ｈａ ）５．６６（１ＨＱ Ｃ−Ｉｎ ４．１３
（２Ｈｑ−〇−（’Ｈ，ＣＨ◇
トリクロル体４の合成
エステル体２１５．２３ ｇ （０，０７８８モル）全
エーテル１００蛎に溶解し、これにトリクロルゲルミル
プロピオニルクロライド３１０．６６ ｇ （０，［］
３９４−Ｃ−ル）ノーエーテル１００ｍ、、ｅに溶解し
た溶液’１−１０分で滴下する。４時間反応後、生成Ｌ
７（塩酸塩不・沖過して除き、溶媒を留去する。残渣
にｎ−ヘキサノ１ｓｏｍ−１３に加えると結晶が析出し
始める。Ester body 2 Colorless oily substance IR (NEATcrn-”) 30[]0,1735
,160[],15['IO,1455°1190.1
030.70O NMR (C ■ right ppm) 1.23 (3Ht -0-
CILC)j4)2.95(2■Ioct Ch
C6Ha ) 5.66 (1HQ C-In 4.13
(2Hq-〇-('H,CH◇ 215.23 g (0,0788 mol) of the synthetic ester of trichloride 4 was dissolved in 100 mol of total ether, and 310.66 g of trichlorgermylpropionyl chloride (0, []
394-C-le) solution dissolved in 100 m, e of no ether, added dropwise over 1-10 minutes. After 4 hours of reaction, the product L
7 (filter off the hydrochloride salt and distill off the solvent. When the residue is added to n-hexano 1som-13, crystals begin to precipitate.
析出し終ったらこ′ｒＩをＰ取して乾゛片し、クロロホ
ルノ・−ヘキサノ混液から再結晶すると、トリクｇ Ａ
、体４ ？ １１．１２ｇ （ｎ、ＣＪ２６ｎ−Ｅｌｋ
）４Ｒた。When the precipitation is complete, P is removed from this rI, dried, and recrystallized from a chloroform-hexano mixture.
, body 4? 11.12g (n, CJ26n-Elk
) 4R.
トリクロル体４
融 点 ６９℃〜７０℃ＩＲ（ＫＢｒ
ｃｎ＋−’） ５Ｓ２０．３（ＪｎＪｉ７２０，
１６２０，１５６０゜１５００〜１２００，１１００，
１ｎ２０，８１゜７６０．７００，６０５．５０［）、
１５ＮＭＲ（ＣｌｍＫ−Ｑ、 ｐｐｍ） １．２８
（３Ｈｔ、 −ｏ−ＣＬＣＨ３） ２．１９（
２Ｈｔ Ｇｅ ＣＨｙ ） ２．６８ （２Ｈｔ−
以ＴｙＣＯＮ） ３１２ （２Ｈｑ −Ｃｑ町−Ｃａ
ｂｓ ’） ４．１８ （２Ｈｑ ＯＣＨｙＣＩｉ
ｌ）４．８８ （１Ｈ５ｅＸｔｃｔ Ｃ−Ｈ）６．５９
（１Ｈｄ Ｎ−Ｈ） ７．１７ （５Ｈｍ ＣｅＨ
ｓ）
本発明化合物（Ｔ−ａ）の合成
トリクロル体４ ｓ、ｏｏ ｇ （０，０１１７モル）
ゲとり。Trichloride 4 Melting point 69℃~70℃IR (KBr
cn+-') 5S20.3 (JnJi720,
1620,1560°1500~1200,1100,
1n20,81°760.700,605.50[),
15NMR (ClmK-Q, ppm) 1.28
(3Ht, -o-CLCH3) 2.19(
2Ht Ge CHy ) 2.68 (2Ht-
(TyCON) 312 (2Hq -Cq Town-Ca
bs') 4.18 (2Hq OCHyCIi
l) 4.88 (1H5eXtct C-H) 6.59
(1Hd N-H) 7.17 (5Hm CeH
s) Synthetic trichloride of the compound (T-a) of the present invention 4 s,oo g (0,0117 mol)
Gatori.
水５０ｃｃ？加え一晩かくはんする。かくはん終了後結
晶をＰ ＩＩＶ Ｉ、 、乾燥すると本発明化合物（７
−ａ）全３．３６ｇ得る。収率８３劣。50cc of water? Add and stir overnight. After stirring, the crystals are dried to give the compound of the present invention (7
-a) Obtain a total of 3.36 g. Yield: 83 poor.
本発明化合物（（−ａ）
融 点 明確に示さず（示差熱分析によれば
発熱ピーク３４２℃）
ＩＲｆＴ（Ｂｒ ｔｙｎ−’）３３（］ｎ、１７４０，
１６５０，１５４０゜１２１０．１０３０，９００，８
（Ｔｏ、７（１（ＩＮＭＲ（ＣＤＣＥｎ ｐｐｍ）
ｉ１８ （３Ｈｔ −０−ＣＦＬ（４％、）１６５ （
２Ｈｔ Ｇｅ ＣＨｓ’ｌ ２．５０（２Ｈｔ Ｇｅ
ＣＨｙＣ％’） ５．ｏｙ （２Ｈｄ ＣＨｙ Ｃ
’６Ｈ＋）４．０９ （２ＨｑＯＣ）ｉｃＨｓ） ４
．８［］ （１１（ｔＣＫ） ７２０ （５Ｈｍ Ｃ
Ｈｐ−ＣａＨ））元素分析ｒ鳶を襲） 炭素 水素
窒素計Ｘｉ値 ４ａ７５ ５．２７ ４．０６分
析値 ａ７０７ ５．０５ ３．９５５本発明化
物（Ｔ−ａ）の条稗試験
実験動物として９週令のＣＤＦｌ 系マウス？用い、
こｎ−に腫瘍細胞でらるＩｈ１Ｃｃａｒｃｉｎｏｒｎａ
？ｌＸ１（＋’個皮下に移殖し１本発明化合物（Ｔ−
ａ）を１５日間経口にて連続投与し、抑制率音調べたと
ころ、下表に示すように抗腫瘍剤として効果の堅められ
ているカルボギシエチルゲルマニウムセスキオキサイド
（表中ＣＥＧと略（巳しｆｃ）エリ少い投与量で優ｔま
た抑制率金示した。Compound of the present invention ((-a) Melting point not clearly indicated (exothermic peak 342°C according to differential thermal analysis) IRfT(Br tyn-') 33(]n, 1740,
1650,1540°1210.1030,900,8
(To, 7(1(INMR(CDCEn ppm)
i18 (3Ht -0-CFL (4%,)165 (
2Ht Ge CHs'l 2.50 (2Ht Ge
CHyC%') 5. oy (2Hd CHy C
'6H+)4.09 (2HqOC)icHs) 4
．． 8[] (11(tCK) 720 (5Hm C
Hp-CaH)) Elemental analysis r) Carbon Hydrogen
Nitrogen meter Xi value 4a75 5.27 4.06 Analysis value a707 5.05 3.955 9-week-old CDFl mouse as experimental animal use,
Ih1Ccarcinorna, which appears in tumor cells
? l
A) was orally administered continuously for 15 days, and the inhibition rate was examined. As shown in the table below, carboxyethyl germanium sesquioxide (abbreviated as CEG in the table), which has been shown to be highly effective as an antitumor agent. fc) Eri showed excellent inhibition rate at a small dose.
Claims (1)
素原子、低級アルキル基又はベンジル基、Ｒ８゜Ｆ？４
に水素原子又は低級アルキル基金そ庇ぞれ示すで表わさ
ｎ、ること′ｆＩ−特徴とする有機ゲルマニウム化合物[Claims] In the formula, R1 is a hydroxyl group or a 〇-lower alkyl group, R is a hydrogen atom, a lower alkyl group or a benzyl group, and R8°F? 4
An organogermanium compound characterized by a hydrogen atom or a lower alkyl group, respectively represented by n, and fI.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57143198A JPS601316B2 (en) | 1982-08-20 | 1982-08-20 | organic germanium compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57143198A JPS601316B2 (en) | 1982-08-20 | 1982-08-20 | organic germanium compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5933292A true JPS5933292A (en) | 1984-02-23 |
| JPS601316B2 JPS601316B2 (en) | 1985-01-14 |
Family
ID=15333149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57143198A Expired JPS601316B2 (en) | 1982-08-20 | 1982-08-20 | organic germanium compounds |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS601316B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63247100A (en) * | 1987-04-03 | 1988-10-13 | サカエ理研工業株式会社 | Light-transmitting decorating having irregular cut surface in rear and manufacture thereof |
| US5008416A (en) * | 1989-06-20 | 1991-04-16 | Sanwa Kagaku Kenkyusho Co., Ltd. | Organogermanium compound, process for the preparation of same as well as use thereof |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6266507U (en) * | 1985-10-17 | 1987-04-24 | ||
| JPS6266508U (en) * | 1985-10-17 | 1987-04-24 | ||
| JPS6266509U (en) * | 1985-10-17 | 1987-04-24 |
-
1982
- 1982-08-20 JP JP57143198A patent/JPS601316B2/en not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63247100A (en) * | 1987-04-03 | 1988-10-13 | サカエ理研工業株式会社 | Light-transmitting decorating having irregular cut surface in rear and manufacture thereof |
| US5008416A (en) * | 1989-06-20 | 1991-04-16 | Sanwa Kagaku Kenkyusho Co., Ltd. | Organogermanium compound, process for the preparation of same as well as use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS601316B2 (en) | 1985-01-14 |
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