JPS6222995B2 - - Google Patents
Info
- Publication number
- JPS6222995B2 JPS6222995B2 JP52076425A JP7642577A JPS6222995B2 JP S6222995 B2 JPS6222995 B2 JP S6222995B2 JP 52076425 A JP52076425 A JP 52076425A JP 7642577 A JP7642577 A JP 7642577A JP S6222995 B2 JPS6222995 B2 JP S6222995B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- alkaloid
- compounds
- thiotepa
- solvent
- 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
- 150000001875 compounds Chemical class 0.000 claims description 11
- GHKISGDRQRSCII-ZOCIIQOWSA-N chelidonine Chemical compound C1=C2[C@H]3N(C)CC4=C(OCO5)C5=CC=C4[C@H]3[C@@H](O)CC2=CC2=C1OCO2 GHKISGDRQRSCII-ZOCIIQOWSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 7
- 150000003797 alkaloid derivatives Chemical group 0.000 claims description 6
- WEEFNMFMNMASJY-UHFFFAOYSA-M 1,2-dimethoxy-12-methyl-[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium;chloride Chemical compound [Cl-].C1=C2OCOC2=CC2=CC=C3C4=CC=C(OC)C(OC)=C4C=[N+](C)C3=C21 WEEFNMFMNMASJY-UHFFFAOYSA-M 0.000 claims description 5
- LLEJIEBFSOEYIV-UHFFFAOYSA-N Chelerythrine Natural products C1=C2OCOC2=CC2=CC=C3C4=CC=C(OC)C(OC)=C4C=[N+](C)C3=C21 LLEJIEBFSOEYIV-UHFFFAOYSA-N 0.000 claims description 5
- RATMHCJTVBHJSU-UHFFFAOYSA-N Dihydrochelerythrine Natural products C1=C2OCOC2=CC2=C(N(C)C(O)C=3C4=CC=C(C=3OC)OC)C4=CC=C21 RATMHCJTVBHJSU-UHFFFAOYSA-N 0.000 claims description 5
- GHKISGDRQRSCII-UHFFFAOYSA-N chelidonine Natural products C1=C2C3N(C)CC4=C(OCO5)C5=CC=C4C3C(O)CC2=CC2=C1OCO2 GHKISGDRQRSCII-UHFFFAOYSA-N 0.000 claims description 5
- 229930013930 alkaloid Natural products 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229960001196 thiotepa Drugs 0.000 description 6
- 230000008018 melting Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- -1 alkaloid thiophosphate salts Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical compound OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 230000001085 cytostatic effect Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 241001233914 Chelidonium majus Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003578 thiophosphoric acid amides Chemical class 0.000 description 1
- 150000003580 thiophosphoric acid esters Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/36—Amides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/44—Amides thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
【発明の詳細な説明】
本発明は、改善された制癌効果をもつ新規化合
物に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel compounds with improved anticancer effects.
この新規化合物は、変異原性物質及び有害生物
防除剤としても使用できる。 This new compound can also be used as a mutagen and pest control agent.
遊離塩基の形の特定のアルカロイドのチオ燐酸
エステルは、既に公知である。この種の公知誘導
体の例は、チオ燐酸−ジ−（エチレンイミド）−Ｎ
−ベルベリノール−エチルアミド、チオ燐酸−ト
リ−（Ｎ−サンギナリノール）−エチルアミド及び
クサノオウの糖合インキノリン系の全アルカロイ
ドのチオ燐酸アミド誘導体である。 Thiophosphate esters of certain alkaloids in free base form are already known. Examples of known derivatives of this type are thiophosphoric acid-di-(ethyleneimide)-N
-Berberinol-ethylamide, thiophosphoric acid-tri-(N-sanguinalinol)-ethylamide and celandine saccharide ink Thiophosphoric acid amide derivatives of all alkaloids of the quinoline series.
これらの化合物はすべて、制細胞作用を有す
る。しかしこれらは水に極めて難溶性であり、薬
学的に応用するため有機溶剤に溶解しなければな
らないという欠点を有する。これらを溶解するに
は、水1.5部、分子量400ポリエテレングリコール
1.5部及びジメチルスルホキシド２部の溶剤混合
〓〓〓〓〓
物が特に適当であることが実証された。 All these compounds have cytostatic effects. However, these have the disadvantage that they are extremely poorly soluble in water and must be dissolved in organic solvents for pharmaceutical applications. To dissolve these, 1.5 parts water, 400 molecular weight polyethylene glycol
Solvent mixture of 1.5 parts and 2 parts of dimethyl sulfoxide
have proven to be particularly suitable.
特に注射用溶液を調整するため、溶剤として水
を使用することは、常に同じ目的で有機溶剤を使
用するより好ましいことは別としても、特にジメ
チルスルホキシドは毒性示すので、製薬の目的に
使用するには適当でない。 Apart from the fact that the use of water as a solvent, especially for preparing solutions for injection, is always preferable to the use of organic solvents for the same purpose, it should not be used for pharmaceutical purposes, especially since dimethyl sulfoxide is toxic. is not appropriate.
ところで意外にも、前記有効成分を生理学的に
許容しうる酸で塩に変えると該有効成分をその製
細胞作用を失わず、また好ましくない副作用を起
こさずに、水に易溶性の形に変えうることが判つ
た。 Surprisingly, however, converting the active ingredient into a salt with a physiologically acceptable acid converts the active ingredient into a water-soluble form without losing its cell-forming activity or causing any undesirable side effects. I found out that it works.
更に、ほとんどすべてのアルカロイドは、常用
の制癌剤、例えばアルキル化剤、代謝拮抗剤等と
共に、出発物質より高い治療効果及びそれより著
しく少ない中毒作用を有する、特定の化合物を生
じうることが判つた。 Furthermore, it has been found that almost all alkaloids, together with commonly used anticancer drugs, such as alkylating agents, antimetabolites, etc., can give rise to certain compounds that have a higher therapeutic effect and a significantly lower toxic effect than the starting materials.
従つて、本発明の対象は新規化合物であつて、
アルカロイドを制癌剤アルキル化剤であるチオテ
パと反応させて得られた生成物であり、また、そ
れらのものの薬学的に無害な酸との塩である。 Therefore, the subject of the present invention is a novel compound, which
It is a product obtained by reacting an alkaloid with thiotepa, an anticancer alkylating agent, and is also a salt of these compounds with a pharmaceutically harmless acid.
アルカロイド成分としては、コプテシン、ケリ
ドニン、ケレリスリンが適当であることが判明し
た。 Coptesine, chelidonine, and chelerythrine were found to be suitable as alkaloid components.
本発明の反応に使用する制癌剤としては、下記
のトリエチレンチオホスホン酸アミド（チオテ
パ）が使用される。 As the anticancer agent used in the reaction of the present invention, the following triethylenethiophosphonic acid amide (thiotepa) is used.
即ち、本発明の対象は、一般式
の化合物（式中、Ａは、それぞれ、ケリドニン、
ケレリトリン、または、コプチジンからなるアル
カロイド残基である
であり、ｎは１から３の整数である）ならびにそ
れらの薬学的に使用可能な塩である。 That is, the object of the present invention is the general formula compounds (wherein A is chelidonine,
An alkaloid residue consisting of chelerythrine or coptidine and n is an integer from 1 to 3) and pharmaceutically acceptable salts thereof.
本発明により得られる新規アルカロイド−チオ
燐酸−塩は、制細胞作用及び従つて薬理作用の点
で対応する塩基とは異なる。しかし、本発明によ
る化合物は、その著しく良好な水溶性のため容易
にかつ性格に計量でき、従来必ず使用された有機
溶剤に基づく有害な副作用を生じない。 The novel alkaloid thiophosphate salts obtained according to the invention differ from the corresponding bases in their cytostatic and therefore pharmacological action. However, the compounds according to the invention, due to their extremely good water solubility, can be easily and neatly metered out and do not produce any harmful side effects due to the organic solvents that have hitherto always been used.
本発明の化合物は、アルカロイド塩を制細胞剤
と、好ましくは溶剤又は溶剤混合物中で高めた温
度で反応させることによつて製造される。しか
し、まずアルカロイド塩基をチオ燐酸アミドと反
応させ、その後、反応生成物を塩に変えることも
できる。制細胞剤とアルカロイドとの化合物を有
機溶剤中で、その都度所望の酸と反応させるのが
有利であり、その際造塩後、その都度の塩が生ず
るか、又は水或は酸水溶液と振盪することによつ
て水溶液中に抽出することが出来る。 The compounds of the invention are prepared by reacting an alkaloid salt with a cytostatic agent, preferably in a solvent or solvent mixture at elevated temperature. However, it is also possible to first react the alkaloid base with the thiophosphoamide and then convert the reaction product into the salt. It is advantageous to react the compound of anticytostatic agent and alkaloid with the respective desired acid in an organic solvent, the respective salt being formed after salt formation, or by shaking with water or an aqueous acid solution. It can be extracted into an aqueous solution by doing this.
次に実施例に基づいて本発明を詳述するが、本
発明はこれに限定されるものではない。 Next, the present invention will be described in detail based on Examples, but the present invention is not limited thereto.
実施例 １
生成物の構造式
〓〓〓〓〓
160mg（0.453ｍモル）のケリドニン（２−メチ
ル−3′−ヒドロキシ−７・８・6′・7′−ビス−メ
チレンジオキシ−１・２・３・４・3′・4′−ヘキ
サヒドロ−（ナフト−1′・2′；３・４−イソキノ
リン））（融点135℃）と120mg（0.634ｍモル）の
トリエチレンチオホスホル酸アミド（チオテパ）
とを16mlのベンゾールに溶かし、この溶液を還流
冷却器を付したコルベン中で２時間煮沸する。え
られた混合物を活性炭で脱色し溶剤を除去する。
乾燥残渣を注意深くエーテルで洗い、未反応の原
料を除去する。黄色結晶物として500mgのチオホ
スホル酸トリ−（Ｎ−ケリドニノール）−エチルア
ミドがえられる。収率17.86重量％（対理論値）
融点は120〜123℃。Example 1 Structural formula of product
160 mg (0.453 mmol) of chelidonine (2-methyl-3'-hydroxy-7,8,6',7'-bis-methylenedioxy-1,2,3,4,3',4'-hexahydro- (naphtho-1', 2'; 3,4-isoquinoline)) (melting point 135°C) and 120 mg (0.634 mmol) of triethylenethiophosphoric acid amide (thiotepa)
was dissolved in 16 ml of benzene and the solution was boiled for 2 hours in a Kolben equipped with a reflux condenser. The resulting mixture is decolorized with activated carbon and the solvent is removed.
The dried residue is carefully washed with ether to remove unreacted materials. 500 mg of thiophosphoric acid tri-(N-chelidoninol)-ethylamide are obtained as a yellow crystalline product. Yield 17.86% by weight (based on theoretical value)
Melting point is 120-123℃.
（３モルのケリドニン＋１モルトリエチレンチ
オホスホル酸アシド）
分析値 C66H75N6O18PSとして
計算値 S2.45、P2.37、N6.44 H5.79
C60.82％
実験値 C61.14、61.32；H5.76、5.77
N5.94、5.83；S20.9、1.89；
P2.40、2.29％
実施例 ２
生成物の構造式
950mg（2.6ｍモル）のケレリトリンと120mg
（0.634ｍモル）のトリエチレンチオホスホル酸ア
ミド（チオテパ）とを50mlのクロロホルムに溶か
し、この混合物を還流冷却器を付したコルベン中
で２時間煮沸する。えられた混合物を活性炭で脱
色し溶液をとばす、乾燥残渣を注意深くエーテル
で洗い、未反応の原料を除去する。300mgのチオ
ホスホル酸トリ−（Ｎ−ケレリルトリノール）−エ
ルアミドが褐色の固形としてえられる。収率理論
値に対し28.04重量％、融点65〜75℃。 (3 moles of chelidonine + 1 mole of triethylenethiophosphoric acid) Analytical value Calculated value as C66H75N6O18PS S2.45, P2.37, N6.44 H5.79 C60.82% Experimental value C61.14, 61.32; H5.76, 5.77 N5.94, 5.83; S20.9, 1.89; P2.40, 2.29% Example 2 Structural formula of product 950mg (2.6mmol) of chelerythrine and 120mg
(0.634 mmol) of triethylenethiophosphoric acid amide (thiotepa) is dissolved in 50 ml of chloroform and the mixture is boiled for 2 hours in a Kolben equipped with a reflux condenser. The resulting mixture is decolorized with activated carbon and the solution is evaporated, and the dried residue is carefully washed with ether to remove unreacted raw materials. 300 mg of thiophosphoric acid tri-(N-chelerythrinol)-elamide are obtained as a brown solid. Yield: 28.04% by weight based on theoretical value, melting point: 65-75°C.
（３モルのケレリトリン＋１モルトリエチレン
トリホスホル酸アシド）
分析値 C66H69N6O15PSとして
計算値 C63.45、H5.56、N6.72、P2.47
実験値 C62.69；H5.39；N6.73；P2.35
実施例 ３
生成物の構造式
〓〓〓〓〓
14mg（0.041Mmol）コプチジン（融点300℃）
及び45mg（0.237Mmol）とチオテパとを５mlベン
ゾール中で２時間煮沸する。えられた混合物を活
性炭で脱色し溶剤をとばす。残渣をエーテルで洗
うと、12mgのチオホスホル酸−ジ−（エチレンイ
ミド）−Ｎ−コプチジンエチレンイミドが淡灰色
生成物としてえられる。融点44〜45℃
コプチジン：チオテパ＝１：１
分析 C25H27N4PO5Sとして
計算値 C57.02、H5.16、N10.64、P5.88、S6.08
実験値 C55.94、H5.12、N11.10、P5.89、S6.10
〓〓〓〓〓
(3 moles of chelerythrine + 1 mole of triethylene triphosphoric acid) Analytical value As C66H69N6O15PS Calculated value C63.45, H5.56, N6.72, P2.47 Experimental value C62.69; H5.39; N6.73; P2. 35 Example 3 Structural formula of the product 〓〓〓〓〓
14mg (0.041Mmol) coptidine (melting point 300℃)
and 45 mg (0.237 Mmol) of thiotepa are boiled in 5 ml benzene for 2 hours. The resulting mixture is decolorized with activated carbon and the solvent is evaporated. Washing the residue with ether gives 12 mg of thiophosphoric acid-di-(ethyleneimide)-N-coptidine ethyleneimide as a light gray product. Melting point 44-45℃ Coptidine: Thiotepa = 1:1 Analysis As C25H27N4PO5S Calculated value C57.02, H5.16, N10.64, P5.88, S6.08 Experimental value C55.94, H5.12, N11.10, P5.89, S6.10 〓〓〓〓〓
Claims (1)
ケレリトリン、または、コプチジンからなるアル
カロイド残基である であり、ｎは１から３の整数である）ならびにそ
れらの薬学的に使用可能な塩。[Claims] 1. General formula compounds (wherein A is chelidonine,
An alkaloid residue consisting of chelerythrine or coptidine and n is an integer from 1 to 3) and pharmaceutically usable salts thereof.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT472876A AT377988B (en) | 1976-06-28 | 1976-06-28 | METHOD FOR PRODUCING NEW PHOSPHORUS DERIVATIVES FROM ALKALOIDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5341415A JPS5341415A (en) | 1978-04-14 |
| JPS6222995B2 true JPS6222995B2 (en) | 1987-05-20 |
Family
ID=3567633
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7642577A Granted JPS5341415A (en) | 1976-06-28 | 1977-06-27 | Preparation of novel antitumor agent |
| JP61252786A Granted JPS63183540A (en) | 1976-06-28 | 1986-10-23 | Manufacture of novel anticancer |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61252786A Granted JPS63183540A (en) | 1976-06-28 | 1986-10-23 | Manufacture of novel anticancer |
Country Status (4)
| Country | Link |
|---|---|
| JP (2) | JPS5341415A (en) |
| AT (1) | AT377988B (en) |
| DK (1) | DK283377A (en) |
| FR (1) | FR2366020A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3128018A1 (en) * | 1981-07-13 | 1983-04-07 | Wassyl 1060 Wien Nowicky | "METHOD FOR DIAGNOSTICING AND FOR THE THERAPEUTIC TREATMENT OF TUMORS AND / OR INFECTIOUS DISEASES OF DIFFERENT TYPES WITH PREPARATIVE USE OF ALKALOID COMPOUNDS OR THEIR SALTS" |
| FR2623504B1 (en) * | 1987-11-25 | 1990-03-09 | Adir | NOVEL N- (VINBLASTINOYL-23) DERIVATIVES OF 1-AMINO METHYLPHOSPHONIC ACID, PROCESSES FOR THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| AT407608B (en) * | 1994-03-18 | 2001-05-25 | Nowicky Wassili | AGENT FOR TREATING OSTEOPOROSIS |
| AT407833B (en) * | 1995-06-01 | 2001-06-25 | Nowicky Wassyl Dr | AGENTS FOR THE TREATMENT OF RADIATION DAMAGES |
| AU8414098A (en) | 1997-08-19 | 1999-03-08 | Emory University | Noscapine derivatives, useful as anticancer agents |
| CH695417A5 (en) * | 2001-11-15 | 2006-05-15 | Ddr Wassyl Nowicky Dipl Ing | Process for reacting alkaloids. |
| EP1459753A1 (en) | 2003-03-18 | 2004-09-22 | Nowicky, Wassyl, Dipl.-Ing. DDr. | Quaternary chelidonine and alkaloid derivatives, process for their preparation and their use in the manufacture of medicaments |
| US7823627B2 (en) * | 2006-05-19 | 2010-11-02 | Exxonmobil Research & Engineering Company | Device for generating acoustic and/or vibration energy for heat exchanger tubes |
| CA2990665A1 (en) * | 2015-06-24 | 2016-12-29 | Threshold Pharmaceuticals, Inc. | Aziridine containing dna alkylating agents |
-
1976
- 1976-06-28 AT AT472876A patent/AT377988B/en not_active IP Right Cessation
-
1977
- 1977-06-27 DK DK283377A patent/DK283377A/en unknown
- 1977-06-27 JP JP7642577A patent/JPS5341415A/en active Granted
- 1977-06-28 FR FR7719877A patent/FR2366020A1/en not_active Withdrawn
-
1986
- 1986-10-23 JP JP61252786A patent/JPS63183540A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| DK283377A (en) | 1977-12-29 |
| AT377988B (en) | 1985-05-28 |
| JPS63183540A (en) | 1988-07-28 |
| ATA472876A (en) | 1984-10-15 |
| FR2366020A1 (en) | 1978-04-28 |
| JPH0342279B2 (en) | 1991-06-26 |
| JPS5341415A (en) | 1978-04-14 |
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