CH376123A - Process for the preparation of new thiocolchicine derivatives - Google Patents
Process for the preparation of new thiocolchicine derivativesInfo
- Publication number
- CH376123A CH376123A CH7650359A CH7650359A CH376123A CH 376123 A CH376123 A CH 376123A CH 7650359 A CH7650359 A CH 7650359A CH 7650359 A CH7650359 A CH 7650359A CH 376123 A CH376123 A CH 376123A
- Authority
- CH
- Switzerland
- Prior art keywords
- carboxylic acid
- derivatives
- preparation
- new
- derivative
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- CMEGANPVAXDBPL-INIZCTEOSA-N n-[(7s)-1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5h-benzo[a]heptalen-7-yl]acetamide Chemical class C1([C@@H](NC(C)=O)CC2)=CC(=O)C(SC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC CMEGANPVAXDBPL-INIZCTEOSA-N 0.000 title description 3
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical class OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- HFPMXDMZJUJZBX-AWEZNQCLSA-N Deacetylcolchicine Chemical class C1([C@@H](N)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC HFPMXDMZJUJZBX-AWEZNQCLSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical class C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 5
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- OMIHGPLIXGGMJB-UHFFFAOYSA-N 7-oxabicyclo[4.1.0]hepta-1,3,5-triene Chemical compound C1=CC=C2OC2=C1 OMIHGPLIXGGMJB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- SJSOFNCYXJUNBT-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1OC SJSOFNCYXJUNBT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 229960001338 colchicine Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000031864 metaphase Effects 0.000 description 2
- -1 nausea Chemical compound 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NUNCOHUMTCDISK-AWEZNQCLSA-N (7s)-7-amino-1,2,3-trimethoxy-10-methylsulfanyl-6,7-dihydro-5h-benzo[a]heptalen-9-one Chemical compound C1([C@@H](N)CC2)=CC(=O)C(SC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC NUNCOHUMTCDISK-AWEZNQCLSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000003468 Ehrlich Tumor Carcinoma Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940045695 antineooplastic colchicine derivative Drugs 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- IPIVAXLHTVNRBS-UHFFFAOYSA-N decanoyl chloride Chemical compound CCCCCCCCCC(Cl)=O IPIVAXLHTVNRBS-UHFFFAOYSA-N 0.000 description 1
- 125000003074 decanoyl 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(*)=O 0.000 description 1
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- NTQYXUJLILNTFH-UHFFFAOYSA-N nonanoyl chloride Chemical compound CCCCCCCCC(Cl)=O NTQYXUJLILNTFH-UHFFFAOYSA-N 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- JUKPJGZUFHCZQI-UHFFFAOYSA-N undecanoyl chloride Chemical compound CCCCCCCCCCC(Cl)=O JUKPJGZUFHCZQI-UHFFFAOYSA-N 0.000 description 1
- 125000000297 undecanoyl group Chemical group O=C([*])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
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von neuen Thiocolchicin-Derivaten
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von neuen Thiocolcbicm-Derivaten der aNgemeinen Formel I,
EMI1.1
in welcher R, fülr eine niedere Alkylmercaptogruppe steht und R2 den Rest einer aliphatischen Carbon- säure mit 6 oder mehr Kohlenstoffatomen oder den Rest einer gegebenenfalls substituierten aromatischen Carbonsäure bedeutet.
Gemäss dem Verfahren der vorliegenden Erfindung werden die neuen Derivate der Formel I hergestellt, indem man ein Desacetyl-colchicin-Derivat der allgemeinen Formel II,
EMI1.2
mit einem reaktionsfähigen funktionellen Derivat einer aliphatischen Carbonsäure mit 6 oder mehr Kohlenstoffatomen oder einer gegebenenfalls substituierten aromatischen Carbonsäure umsetzt und das Umsetzungsprodukt durch Chromatographie oder Kristallisation reinigt oder, falls es nicht kristallisiert, es einer Gefriertrocknung unterwirft.
Das erfindungsgemϯe Verfahren wird vorzugsweise folgendermassen ausgeführt :
Ein Amin der Formel II wird z. B. in Pyridin gelöst, mit 1, 2-1, 5 Äquivalentes Säurechlorid versetzt und während 24-48 Std. im Dunkel'n bei einer Temperatu r von 20¯ stehengelassen. Die Reaktionslösung wird mit Methylenchlorid verdünnt, mit verd. Salz säure und verd. Natronlauge gründlich gewaschen und dann eingedampft. Das verbleibende Rohprodukt wird durch Kristallisation aus einem geeigneten Losungsmittel oder Lösungsmittelgemiscb, wie z. B.
Benzol-Äther, oder durch Chromatographie an Alu minmmoxyd gereinigt. Die nicht kristallisierenden Derivate werden z. B. in Benzol gelöst und die Ben zollösung einer Gefriertrocknung unterworfen, wobei die Verbindungen in festem, amorphem Zustand er- halten werden.
Die neuen Derivate obiger Formel 1 sind bei Raumtemperatur feste, kristallisierte oder amorphe Substanzen. Sie losen sich in den meisten organischen Lösungsmitteln leicht auf, so z. B. in Chloroform, Methylenchlorid und niederen Alkanolen, sind aber in Ather und PetrolÏther schwer l¯slich und unl¯slich in Wasser. Im Infrarot-Spektrum zeigen sie die für Säureamide typischen Absorptionsbanden bei etwa 1670-1675 cm-1 (in Methylenchlorid). Sie können papierchromatographisch auf Reinheit geprüft werden.
Die neuen Thiocolchicin-Derivate zeichnen sich durch eine starke und selektive Hemmwirkung auf die Teilungsvorgänge im Zellkern bzw. durch spe zifische mitosehemmende Eigenschaften aus. Bei der Pr fung in vitro an der Fibroblastenkultur hemmen sie die Zellteilung in der frühen Metaphase gleich stark, teilweise sogar stÏrker als bekannte Colchicin- derivate. Die Prüfung in vivo erfolgte an dem experi mentellen Ehrlichschen Ascitestumor der Maus : Bei intraperitonealer Verabreichung der Substanz wird die Zellteilung in der frühen Metaphase während 10 bis 40 Std. gÏnzlich gehemmt.
Bei dieser langen Wirkungsdauer erweisen sich die neuen Verbindun- gen jedoch als nicht cytotoxisch und kaum allgemein toxisch. Infolge dieser geringen Toxizität und des Fehlens der bekannten Nebenwirkungen des Colchicins, wie Nausea, Erbrechen und Durchfall, sind sie in den verschiedenen klassischen Anwendungs- bereichen des Colchicins vorteilhaft verwendbar. Sie sollen in die Therapie eingeführt werden, stellen aber auch Zwischenprodukte zur Herstellung von Arzneimittein dar.
In den nachfolgenden Beispielen erfolgen alle Temperaturangaben in Celsiusgraden. Die Schmelz- punkte sind im evakuiertenRöhrchenbestimmt und unkorrigiert.
Beispiel 1 N- (Capronyl)-desacetyl-thiocolch. icin [Formel I : Ri = SCH3, R2 = CO-(CH2)4-CH3]
250 mg Desacetyl-thiocolchicin werden in 3 cm3 abs. Pyridin gelöst, mit 130 mg frisch destil'tiertem Capronsäurechlorid versetzt und 48 Std. im Dunkeln bei einer Temperatur von 20 stehengelassen. Dann wird mit 10 cm3 Methylenchlorid verdünnt und die organische Phase der Reihe nach mehrmals mit 2n SalzsÏure, 2n Natriumcarbonatlösung und Wasser gewaschen, dann ber Natriumsulfat getrocknet und im Vakuum zur Trockne gebracht. Der Rückstand gibt aus Benzol-Ather orangegelbe Prismen vom Smp.
206-207¯. Umkristalilisation aus Benzol-Ather gibt einen Smp. von 209-209, 5 ; [a] 2D =-196, 5 (c= 1, 237 in Chloroform), IR : u. a. 1680 cm-1 (in Me thylenchlorid).
Beispiel 2 N-(Trimethyl-galloyl)-desacetyl-thiocolchicin
EMI2.1
Analog wie in Beispiel 1 wird mit Trimethyl gallussäurechlurid das im Titel genannte Derivat hergestellt. Smp. 162-183 /285 (Zers), [a] 23D = +38¯ (c = 1, 006 in Chloroform). IR : u. a. 1660 cm-l (in Methylenchlodd und Nujol).
Beispiel 3 N-(Pelargonyl)-desacetyl-thiocolchicin [Formel I : Ri = SCH3, R2 = Co- (CH2) -CH.]
Analog wie in Beispiel 1 wird mit Pelargonsäure- chlorid das im Titel genannte Derivat dargestellt. Da das Produkt nicht kristallisiert, wird dessen Chloroformlösung durch Aluminiumoxyd filtriert, im Va kuum zur Trockne gebracht, die Verbindung in Benzol gelöst und aus dieser Lösung der Gefrier trockn, unterworfen. [α]20D = -188¯ (c = 1, 20 in Chloroform). IR : u. a. 1675 cm-1 (in Methylenchlorid).
Beispiel 4 N- (Caprinyl)-desacetyl-thiocolchicin [Formel I : Ri = SCH3, R2 = CO-(CH2)8-CH3]
Analog wie in Beispiel 1 wird mit CaprinsÏurechlorid das im Titel genannte Derivat dargestellt. Die Reinigung des amorphen Produktes erfolgt wie in Beispiel 3 beschrieben. [a] 22D =- 172¯ (c = 1, 50 in Chloroform). IR : u. a. 1675 cm-t (in Methylenchlorid).
Beispiel 5 N-(Undecanoyl)-desacetyl-thiocolchicin [Formel I : Ri = SCH3, R2 = CO-(CH2)9-CH3]
Analog wie in Beispiel 1 wird mit Undecansäurechlorid das im Titel genannte Derivat dargestellt. Die Reinigung des amorphen Produktes erfolgt wie in Beispiel 3 beschrieben. [α]21D = - 184,5¯ (c = 1, 05 in Chloroform). IR : u. a. 1670 cm-1 (in Methylenchlorid).
Beispiel 6 N- (Laurinyl)-desacetyl-thiocolchicin [Formel I : R1 = SCH3, R2 = CO-(CH2)10-CH3]
Analog wie in Beispiel 1 wird mit Laurinsäure- chlorid das im Titel genannte Derivat dargestellt. Die Reinigung des amorphen Produktes erfolgt wie in Beispiel 3 beschrieben. [a] 21D = - 190¯ (c= 0, 94 in Chloroform). IR : u. a. 1670 cm-1 (in Methylenchlorid).
Process for the preparation of new thiocolchicine derivatives
The present invention relates to a process for the preparation of new Thiocolcbicm derivatives of the general formula I,
EMI1.1
in which R 1 stands for a lower alkyl mercapto group and R 2 denotes the radical of an aliphatic carboxylic acid having 6 or more carbon atoms or the radical of an optionally substituted aromatic carboxylic acid.
According to the process of the present invention, the new derivatives of the formula I are prepared by adding a deacetylcolchicine derivative of the general formula II,
EMI1.2
with a reactive functional derivative of an aliphatic carboxylic acid having 6 or more carbon atoms or an optionally substituted aromatic carboxylic acid and the reaction product is purified by chromatography or crystallization or, if it does not crystallize, subjecting it to freeze-drying.
The method according to the invention is preferably carried out as follows:
An amine of formula II is z. B. dissolved in pyridine, treated with 1, 2-1, 5 equivalents of acid chloride and left to stand for 24-48 hours in the dark at a temperature of 20¯. The reaction solution is diluted with methylene chloride, washed thoroughly with dilute hydrochloric acid and dilute sodium hydroxide solution and then evaporated. The remaining crude product is crystallized from a suitable solvent or solvent mixture, such as. B.
Benzene ether, or purified by chromatography on aluminum oxide. The non-crystallizing derivatives are z. B. dissolved in benzene and the Ben Zollösung subjected to freeze-drying, the compounds being obtained in a solid, amorphous state.
The new derivatives of formula 1 above are solid, crystallized or amorphous substances at room temperature. They dissolve easily in most organic solvents, e.g. B. in chloroform, methylene chloride and lower alkanols, but are sparingly soluble in ether and petroleum ether and insoluble in water. In the infrared spectrum they show the typical absorption bands for acid amides at around 1670-1675 cm-1 (in methylene chloride). They can be checked for purity by paper chromatography.
The new thiocolchicine derivatives are characterized by a strong and selective inhibitory effect on the division processes in the cell nucleus or by specific mitosis-inhibiting properties. When tested in vitro on fibroblast culture, they inhibit cell division in the early metaphase to the same extent, sometimes even more so than known colchicine derivatives. The in vivo test was carried out on the experimental Ehrlich ascites tumor in mice: when the substance is administered intraperitoneally, cell division is completely inhibited in the early metaphase for 10 to 40 hours.
With this long duration of action, however, the new compounds prove to be non-cytotoxic and hardly generally toxic. As a result of this low toxicity and the lack of the known side effects of colchicine, such as nausea, vomiting and diarrhea, they can advantageously be used in the various classic areas of application of colchicine. They are intended to be introduced into therapy, but are also intermediate products in the manufacture of pharmaceuticals.
In the following examples, all temperatures are given in degrees Celsius. The melting points are determined and uncorrected in the evacuated tube.
Example 1 N- (Capronyl) -desacetyl-thiocolch. icin [Formula I: Ri = SCH3, R2 = CO- (CH2) 4-CH3]
250 mg desacetyl-thiocolchicine are in 3 cm3 abs. Dissolved pyridine, mixed with 130 mg of freshly distilled caproic acid chloride and left to stand in the dark at a temperature of 20 hours. It is then diluted with 10 cm3 of methylene chloride and the organic phase is washed several times in sequence with 2N hydrochloric acid, 2N sodium carbonate solution and water, then dried over sodium sulfate and brought to dryness in vacuo. The residue is from benzene ether orange-yellow prisms of mp.
206-207¯. Recrystallization from benzene ether gives a melting point of 209-209.5; [a] 2D = -196.5 (c = 1.237 in chloroform), IR: u. a. 1680 cm-1 (in methylene chloride).
Example 2 N- (Trimethyl-galloyl) -desacetyl-thiocolchicine
EMI2.1
Analogously to Example 1, the derivative mentioned in the title is prepared with trimethyl gallic acid chloride. M.p. 162-183 / 285 (dec), [a] 23D = + 38¯ (c = 1.006 in chloroform). IR: u. a. 1660 cm-l (in methylene clod and nujol).
Example 3 N- (Pelargonyl) -desacetyl-thiocolchicine [Formula I: Ri = SCH3, R2 = Co- (CH2) -CH.]
Analogously to example 1, the derivative mentioned in the title is prepared with pelargonic acid chloride. Since the product does not crystallize, its chloroform solution is filtered through aluminum oxide, brought to dryness in a vacuum, the compound is dissolved in benzene and freeze-dry from this solution. [α] 20D = -188¯ (c = 1.20 in chloroform). IR: u. a. 1675 cm-1 (in methylene chloride).
Example 4 N- (Caprinyl) -desacetyl-thiocolchicine [Formula I: Ri = SCH3, R2 = CO- (CH2) 8-CH3]
Analogously as in Example 1, the derivative mentioned in the title is prepared using capric acid chloride. The amorphous product is purified as described in Example 3. [a] 22D = - 172¯ (c = 1.50 in chloroform). IR: u. a. 1675 cm-t (in methylene chloride).
Example 5 N- (Undecanoyl) -desacetyl-thiocolchicine [Formula I: Ri = SCH3, R2 = CO- (CH2) 9-CH3]
Analogously to Example 1, the derivative mentioned in the title is prepared using undecanoic acid chloride. The amorphous product is purified as described in Example 3. [α] 21D = -184.5¯ (c = 1.05 in chloroform). IR: u. a. 1670 cm-1 (in methylene chloride).
Example 6 N- (Laurinyl) -desacetyl-thiocolchicine [Formula I: R1 = SCH3, R2 = CO- (CH2) 10-CH3]
The derivative mentioned in the title is prepared analogously to Example 1 with lauric acid chloride. The amorphous product is purified as described in Example 3. [a] 21D = - 190¯ (c = 0.94 in chloroform). IR: u. a. 1670 cm-1 (in methylene chloride).
Claims (1)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH7650359A CH376123A (en) | 1959-08-03 | 1959-08-03 | Process for the preparation of new thiocolchicine derivatives |
| GB2579860A GB934193A (en) | 1959-08-03 | 1960-07-25 | Improvements in or relating to thiocolchicine compounds |
| LU39030D LU39030A1 (en) | 1959-08-03 | 1960-08-01 | |
| ES0260062A ES260062A1 (en) | 1959-08-03 | 1960-08-01 | PROCEDURE FOR OBTAINING TIOCOLCHICINA DERIVATIVES |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH7650359A CH376123A (en) | 1959-08-03 | 1959-08-03 | Process for the preparation of new thiocolchicine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH376123A true CH376123A (en) | 1964-03-31 |
Family
ID=4534978
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH7650359A CH376123A (en) | 1959-08-03 | 1959-08-03 | Process for the preparation of new thiocolchicine derivatives |
Country Status (4)
| Country | Link |
|---|---|
| CH (1) | CH376123A (en) |
| ES (1) | ES260062A1 (en) |
| GB (1) | GB934193A (en) |
| LU (1) | LU39030A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6825236B2 (en) * | 2003-04-14 | 2004-11-30 | California Pacific Medical Center | Colchicine derivatives |
-
1959
- 1959-08-03 CH CH7650359A patent/CH376123A/en unknown
-
1960
- 1960-07-25 GB GB2579860A patent/GB934193A/en not_active Expired
- 1960-08-01 ES ES0260062A patent/ES260062A1/en not_active Expired
- 1960-08-01 LU LU39030D patent/LU39030A1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB934193A (en) | 1963-08-14 |
| LU39030A1 (en) | 1961-02-01 |
| ES260062A1 (en) | 1961-03-16 |
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