DE10047529A1 - New triazolyl-thiazolyl-epothilone derivatives, useful as fungicides or in the treatment of tumors and cell growth disorders, e.g. cancers - Google Patents

New triazolyl-thiazolyl-epothilone derivatives, useful as fungicides or in the treatment of tumors and cell growth disorders, e.g. cancers

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Publication number
DE10047529A1
DE10047529A1 DE2000147529 DE10047529A DE10047529A1 DE 10047529 A1 DE10047529 A1 DE 10047529A1 DE 2000147529 DE2000147529 DE 2000147529 DE 10047529 A DE10047529 A DE 10047529A DE 10047529 A1 DE10047529 A1 DE 10047529A1
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Prior art keywords
epothilone
triazolo
alkyl
thiazole
heteroaryl
Prior art date
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DE2000147529
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German (de)
Inventor
Gerhard Hoefle
Nicole Glaser
Florenz Sasse
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Helmholtz Zentrum fuer Infektionsforschung HZI GmbH
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Helmholtz Zentrum fuer Infektionsforschung HZI GmbH
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Priority to DE2000147529 priority Critical patent/DE10047529A1/en
Priority to HU0302905A priority patent/HUP0302905A3/en
Priority to AU2001291876A priority patent/AU2001291876C1/en
Priority to PCT/EP2001/010991 priority patent/WO2002024712A1/en
Priority to IL15498601A priority patent/IL154986A0/en
Priority to MXPA03002521A priority patent/MXPA03002521A/en
Priority to KR10-2003-7004136A priority patent/KR20030069993A/en
Priority to BR0114065-5A priority patent/BR0114065A/en
Priority to NZ524861A priority patent/NZ524861A/en
Priority to RU2003111475/04A priority patent/RU2003111475A/en
Priority to AU9187601A priority patent/AU9187601A/en
Priority to US10/381,176 priority patent/US6900160B2/en
Priority to JP2002529120A priority patent/JP2004509899A/en
Priority to PL36222501A priority patent/PL362225A1/en
Priority to CA002422500A priority patent/CA2422500A1/en
Priority to EP01972077A priority patent/EP1319011B1/en
Priority to ZA200302241A priority patent/ZA200302241B/en
Priority to CZ2003845A priority patent/CZ2003845A3/en
Priority to ES01972077T priority patent/ES2395895T3/en
Priority to CNB018161138A priority patent/CN1190440C/en
Publication of DE10047529A1 publication Critical patent/DE10047529A1/en
Priority to NO20031318A priority patent/NO20031318L/en
Priority to HK04104391A priority patent/HK1061560A1/en
Priority to US11/055,124 priority patent/US7419993B2/en
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Triazolyl-thiazolyl-epothilone derivatives are new. Triazolyl-thiazolyl-epothilone derivatives compounds of formula (I) are new: R = H or CH3; and Z' = H, alkyl, aryl or heteroaryl. Independent claims are also included for: (1) Preparation of compound (I); (2) Conversion of (I) into C-21 esters (II) by reaction with a carboxylic acid R'-COOH (III); (3) Photolysis of (I) in the presence of a nucleophile to compounds of formula (IV); and (4) Reaction of (I) in a 1,3-dipolar cycloaddition with an ethylenic or acetylenic system to give heterocyclic cycloaddition products (V). R' = H; alkyl; alkenyl; alkynyl; aryl; or heteroaryl; Nu = nucleophile; and R = defined as above.

Description

Die Erfindung betrifft Triazolo-thiazol-Analoge von Epothilon A und Epothilon B.The invention relates to triazolo-thiazole analogs of epothilone A and Epothilon B.

Epothilone sind macrocyclische Lactone mit fungizider und cytotoxischer Wirkung. Es besteht ein kontinuierlicher Bedarf für Analoge oder Derivate mit vergleichbarer oder besserer Wirksamkeit, die als Fungizide oder Cytostatika verwendet werden können.Epothilones are macrocyclic lactones with fungicidal and cytotoxic effect. There is an ongoing need for analogs or derivatives with comparable or better Efficacy used as fungicides or cytostatics can be.

Eine Übersicht über die Chemie der Epothilone wird beispiels­ weise von Nicolaou et al. in Angew. Chem. Int. Ed. 1998, Bd. 37, 2014-2045 gegeben.An overview of the chemistry of epothilones is given, for example by Nicolaou et al. in Angew. Chem. Int. Ed. 1998, vol. 37, 2014-2045.

Aufgabe der Erfindung ist die Bereitstellung derartiger Epothilon-Analogen bzw. -Derivate.The object of the invention is to provide such Epothilone analogs or derivatives.

Die Erfindung betrifft somit Triazolo-thiazol-Analoge von Epothilon A und Epothilon B mit der Formel 4a oder 4b:
The invention thus relates to triazolo-thiazole analogs of epothilone A and epothilone B with the formula 4a or 4b:

in denen bedeuten:
R: H, CH3
Z: H, Alkyl, Aryl, Heteroaryl.in which mean:
R: H, CH 3
Z: H, alkyl, aryl, heteroaryl.

Die erfindungsgemäßen Triazolo-thiazol-Epothilone sind sehr wirksame Fungizide und hochpotente Cytostatika mit günstigen pharmakologischen Eigenschaften.The triazolothiazole epothilones according to the invention are very effective fungicides and highly potent cytostatics with cheap pharmacological properties.

Alkyl bedeutet geradkettiges oder verzweigtes C1-C6-Alkyl, das beliebig substituiert (einfach oder mehrfach) sein kann, beispielsweise Methyl, Ethyl, Propyl, iso-Propyl, Butyl, iso- Butyl, tert.-Butyl, Pentyl, Hexyl. Beispiele für Substituen­ ten sind C1-C6-Alkoxy, C1-C6-Acyl, Hydroxyl, Halogen wie Brom, Chlor, Fluor und Jod.Alkyl means straight-chain or branched C 1 -C 6 -alkyl which can be substituted as desired (single or multiple), for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl. Examples of substituents are C 1 -C 6 alkoxy, C 1 -C 6 acyl, hydroxyl, halogen such as bromine, chlorine, fluorine and iodine.

Aryl bedeutet einkernige oder mehrkernige aromatische Syste­ me, die beliebig substituiert (einfach oder mehrfach) sein können, beispielsweise Phenyl, o-, m-, p-Tolyl, o-, m-, p- Xylyl, Benzyl, Phenethyl, Naphthyl. Beispiele für Substituen­ ten sind C1-C6-Alkyl, C1-C6-Alkoxy, C1-C6-Acyl, Hydroxyl, Halo­ gen wie Brom, Chlor, Fluor und Jod. Aryl means mononuclear or polynuclear aromatic systems which can be substituted as desired (single or multiple), for example phenyl, o-, m-, p-tolyl, o-, m-, p-xylyl, benzyl, phenethyl, naphthyl. Examples of substituents are C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 acyl, hydroxyl, halogen such as bromine, chlorine, fluorine and iodine.

Heteroaryl bedeutet einkernige oder mehrkernige heteroaroma­ tische Systeme, die beliebig substituiert (einfach oder mehr­ fach) sein können, wobei der aromatische Kern ein oder mehre­ re unter N, O, S ausgewählte Heteroatome aufweisen kann. Bei­ spiel für Heteroaryl sind Furanyl, Pyranyl, Pyrrolyl, Imida­ zolyl, Pyrazolyl, Pyridinyl, Indolyl. Beispiele für Substitu­ enten sind C1-C6-Alkyl, C1-C6-Alkoxy, C1-C6-Acyl, Hydroxyl, Ha­ logen wie Brom, Chlor, Fluor und Jod.Heteroaryl means mononuclear or multinuclear heteroaromatic systems which can be substituted as desired (simple or multiple), the aromatic nucleus having one or more heteroatoms selected from N, O, S. Examples of heteroaryl are furanyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, indolyl. Examples of substituents are C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 acyl, hydroxyl, halogen such as bromine, chlorine, fluorine and iodine.

Die Erfindung betrifft ferner ein Verfahren zur Herstellung der erfindungsgemäßen Triazolo-thiazol-Analogen von Epothilon A und Epothilon B sowie fungizide und pharmazeutische Zusam­ mensetzungen, die ein oder mehrere derartige Analoge enthal­ ten, und die Verwendung der Analogen und der diese enthalten­ den fungiziden oder pharmazeutischen Zusammensetzungen zur Bekämfung von Pilzen oder zur Behandlung von Erkrankungen, die sich mit Cytostatika behandeln lassen, beispielsweise Tu­ morerkrankungen wie Krebs oder Zellwachstumsstörungen.The invention further relates to a method of manufacture the triazolo-thiazole analogs of epothilone according to the invention A and Epothilon B as well as fungicidal and pharmaceutical co resolutions containing one or more such analogs ten, and the use of the analogues and these included the fungicidal or pharmaceutical compositions for Combating fungi or for treating diseases, that can be treated with cytostatics, for example Tu diseases like cancer or cell growth disorders.

Die fungiziden und pharmazeutischen Zusammensetzungen können neben dem eigentlichen Wirkstoff übliche Träger, Verdünnungs­ mittel oder Hilfsstoffe enthalten, beispielsweise Stabilisa­ toren wie UV-Absorber, Antioxidationsmittel, Konservierungs­ mittel.The fungicidal and pharmaceutical compositions can in addition to the actual active ingredient, usual carriers, diluents contain agents or auxiliaries, for example Stabilisa gates such as UV absorbers, antioxidants, preservatives medium.

Fig. 1 zeigt einen Syntheseweg zur Herstellung der erfin­ dungsgemäßen Triazolo-thiazol-Analogen von Epothilon A und Epothilon B. Fig. 1 shows a synthetic route for the preparation of the inventive triazolo-thiazole analogs of epothilone A and epothilone B.

Im folgenden wird ohne Beschränkung unter Bezugnahme auf Fig. 1 die Herstellung der erfindungsgemäßen Triazolo-thiazol- Analogen von Epothilon A und Epothilon B beschrieben. Die Ab­ kürzung Met bedeutet Metall.The production of the triazolo-thiazole analogs of epothilone A and epothilone B according to the invention is described below without limitation with reference to FIG. 1. The abbreviation Met means metal.

Die Herstellung von C21-modifizierten Epothilonen, d. h. der Aldehyde, Ketone und Hydrazone mit den Formeln 1, 2 bzw. 3, ist in der offengelegten deutschen Patentanmeldung DE 199 07 588 und in der offengelegten internationalen Patentanmeldung WO 2000/050423 der Anmelderin beschrieben. Bei dem erfin­ dungsgemäßen Verfahren wird an den Hydrazon-Derivaten der Formeln 3a und 3b der oxidative Ringschluß mit Hilfe von Me­ talloxiden, vorzugsweise mit NiO2, K3[Fe(CN)6], Bleitetraace­ tat oder Natriumhypochlorid (vgl. Houben-Weyl, Bd. E 14b, 4. Auflage, 1999) vorgenommen.The preparation of C21-modified epothilones, ie the aldehydes, ketones and hydrazones with the formulas 1, 2 and 3, is described in the published German patent application DE 199 07 588 and in the international patent application WO 2000/050423 by the applicant. In the process according to the invention, the oxidative ring closure is carried out on the hydrazone derivatives of the formulas 3a and 3b with the aid of metal oxides, preferably with NiO 2 , K 3 [Fe (CN) 6 ], lead tetraacetate or sodium hypochlorite (cf. Houben-Weyl , Vol. E 14b, 4th edition, 1999).

Synthese eines Triazolo-thiazol-Analogen von Epothilon A (Formel 4a, Z = H)Synthesis of a triazolo-thiazole analogue of epothilone A (Formula 4a, Z = H)

24.6 mg (47.2 µmol) Epothilon-A-21-aldehydhydrazon (Formel 3a) werden in 1.5 ml abs. Dichlormethan gelöst. Im Abstand von 15 min werden dreimal je 42.8 mg (472.2 µmol) Nickelper­ oxid hinzugegeben, wobei bei Raumtemperatur gerührt wird. An­ schließend wird über Celite filtriert und mit Dichlormethan nachgewaschen. Die vereinigten organischen Phasen werden ein­ geengt und im Hochvakuum getrocknet. Die Reinigung des Roh­ produktes erfolgt mittels präparativer HPLC (Laufmittel: Ace­ tonitril/Wasser 38 : 62; Säule: Nucleosil 100 C18 7 µm, 21 × 250 mm). Es wurden 12.0 mg (49%) Produkt erhalten.24.6 mg (47.2 µmol) epothilone A-21 aldehyde hydrazone (formula 3a) in 1.5 ml abs. Dichloromethane dissolved. At a distance From 15 min, 42.8 mg (472.2 µmol) of nickel per three times added oxide, stirring at room temperature. to finally it is filtered through Celite and with dichloromethane rewashed. The combined organic phases become one concentrated and dried in a high vacuum. Cleaning the raw product is carried out using preparative HPLC (eluent: Ace tonitrile / water 38: 62; Column: Nucleosil 100 C18 7 µm, 21 × 250 mm). 12.0 mg (49%) of product were obtained.

Die spektroskopischen Daten sind identisch mit Epothilon A (vgl. DE 41 38 042 C2) mit Ausnahme von:
1H-NMR (400 MHz, CDCl3): d = 2.25 (dt, 2a-H), 2.57 (dd, 2b- H), 4.63 (m, 3-H), 5.02 (dd, 3-OH), 1.68 (m, 14a-H), 2.31 (dt, 14b-H), 5.53 (d, 15-H), 6.92 (bs, 17-H), 7.06 (s, 19-H), 7.84 (s, 21-H), 1.08 (s, 22-H), 1.55 (s, 23-H); 13C-NMR (100 MHz, CDCl3): d = 73.0 (3-C), 54.7 (4-C), 41.4 (6-C), 71.4 (7- C), 32.0 (14-C), 74.9 (15-C), 145.1 (16-C), 109.2 (17-C), 129.2 (18-C), 115.5 (19-C), 136.4 (20-C), 124.8 (21-C), 15.9 (C-22), 23.3 (23-C), 12.7 (24-.C), 18.1 (27-C); HRMS (DCI): C26H37N3O6S: [M + NH4+] ber. 537.2747, gef. 537.2721.The spectroscopic data are identical to epothilone A (cf. DE 41 38 042 C2) with the exception of:
1 H-NMR (400 MHz, CDCl 3 ): d = 2.25 (dt, 2a-H), 2.57 (dd, 2b-H), 4.63 (m, 3-H), 5.02 (dd, 3-OH), 1.68 (m, 14a-H), 2.31 (dt, 14b-H), 5.53 (d, 15-H), 6.92 (bs, 17-H), 7.06 (s, 19-H), 7.84 (s, 21 -H), 1.08 (s, 22-H), 1.55 (s, 23-H); 13 C-NMR (100 MHz, CDCl 3 ): d = 73.0 (3-C), 54.7 (4-C), 41.4 (6-C), 71.4 (7- C), 32.0 (14-C), 74.9 (15-C), 145.1 (16-C), 109.2 (17-C), 129.2 (18-C), 115.5 (19-C), 136.4 (20-C), 124.8 (21-C), 15.9 ( C-22), 23.3 (23-C), 12.7 (24-.C), 18.1 (27-C); HRMS (DCI): C 26 H 37 N 3 O 6 S: [M + NH 4 +] calc. 537.2747, found. 537.2721.

Synthese eines Triazolothiazol-Analogen von Epothilon 8 (For­ mel 4b, Z = H)Synthesis of a triazolothiazole analogue of epothilone 8 (For mel 4b, Z = H)

8.1 mg (15.1 µmol) Epothilon-B-21-aldehydhydrazon (Formel 3b) werden in 1 ml abs. Dichlormethan gelöst. Zur Lösung werden 13.7 mg (151.4 µmol) Nickelperoxid gegeben, worauf 15 min bei Raumtemperatur gerührt wird. Das Nickelperoxid wird über Ce­ lite abfiltriert und mit Dichlormethan gewaschen. Die verei­ nigten organischen Phasen werden eingeengt und im Hochvakuum getrocknet. Die Reinigung des Rohproduktes erfolgt mittels präparativer HPLC (Laufmittel: Acetonitril/Wasser 40 : 60; Säule: Nucleosil 100 C18 7 µm, 21 × 250 mm) und ergab 4.7 mg (58%) Produkt.8.1 mg (15.1 µmol) epothilone B-21 aldehyde hydrazone (Formula 3b) are abs in 1 ml. Dichloromethane dissolved. Be the solution 13.7 mg (151.4 µmol) of nickel peroxide were added, followed by 15 min Room temperature is stirred. The nickel peroxide is over Ce filtered off and washed with dichloromethane. The verei nigen organic phases are concentrated and in a high vacuum dried. The raw product is cleaned by means of preparative HPLC (mobile phase: acetonitrile / water 40:60; Column: Nucleosil 100 C18 7 µm, 21 × 250 mm) and gave 4.7 mg (58%) product.

Die spektroskopischen Daten sind identisch mit Epothilon 8 (vgl. DE 41 38 042 C2) mit Ausnahme von:
1H-NMR (400 MHz, CDCl3): d = 2.25 (dt, 2a-H), 2.59 (dd, 2b- H), 4.69 (m, 3-H), 5.02 (dd, 3-OH), 1.76 (m, 14a-H), 2.31 (dt, 14b-H), 5.53 (d, 15-H), 6.91 (bs, 17-H), 7.06 (s, 19-H), 7.85 (s, 21-H), 1.08 (s, 22-H), 1.56 (s, 23-H); 13C-NMR (100 MHz, CDCl3): d = 71.3 (3-C), 54.9 (4-C), 41.0 (6-C), 72.4 (7- C), 33.1 (14-C), 75.2 (15-C), 145.3 (16-C), 108.9 (17-C), 129.2 (18-C), 115.5 (19-C), 136.5 (20-C), 124.9 (21-C), 15.7 (22-C), 23.2 (23-C), 12.0 (24-C), 18.1 (27-C); MS (ESI): [M + H+] = 534.The spectroscopic data are identical to epothilone 8 (cf. DE 41 38 042 C2) with the exception of:
1 H-NMR (400 MHz, CDCl 3 ): d = 2.25 (dt, 2a-H), 2.59 (dd, 2b-H), 4.69 (m, 3-H), 5.02 (dd, 3-OH), 1.76 (m, 14a-H), 2.31 (dt, 14b-H), 5.53 (d, 15-H), 6.91 (bs, 17-H), 7.06 (s, 19-H), 7.85 (s, 21 -H), 1.08 (s, 22-H), 1.56 (s, 23-H); 13 C-NMR (100 MHz, CDCl 3 ): d = 71.3 (3-C), 54.9 (4-C), 41.0 (6-C), 72.4 (7- C), 33.1 (14-C), 75.2 (15-C), 145.3 (16-C), 108.9 (17-C), 129.2 (18-C), 115.5 (19-C), 136.5 (20-C), 124.9 (21-C), 15.7 ( 22-C), 23.2 (23-C), 12.0 (24-C), 18.1 (27-C); MS (ESI): [M + H + ] = 534.

Die pharmakologisch Wirksamkeit ist in der folgenden Tabelle dargestellt:The pharmacological effectiveness is in the table below shown:

Wachstumstests mit Säugerzellkulturen Growth tests with mammalian cell cultures

Claims (9)

1. Triazolo-thiazol-Analoge von Epothilon A und Epothilon B mit der Formel 4a oder 4b:
in denen bedeuten:
R: H, CH3
Z: H, Alkyl, Aryl, Heteroaryl.1. Triazolo-thiazole analogs of epothilone A and epothilone B with the formula 4a or 4b:
in which mean:
R: H, CH 3
Z: H, alkyl, aryl, heteroaryl. 2. Triazolo-thiazol-Analoge von Epothilon A und Epothilon B nach Anspruch 1, wobei bedeutet:
Alkyl: geradkettiges oder verzweigtes C1-C6-Alkyl, das belie­ big substituiert (einfach oder mehrfach) sein kann,
Aryl: einkernige oder mehrkernige aromatische Systeme, die beliebig substituiert (einfach oder mehrfach) sein können,
Heteroaryl: einkernige oder mehrkernige heteroaromatische Sy­ steme, die beliebig substituiert (einfach oder mehrfach) sein können. 2. Triazolo-thiazole analogs of epothilone A and epothilone B according to claim 1, wherein:
Alkyl: straight-chain or branched C 1 -C 6 -alkyl, which can be arbitrarily substituted (single or multiple),
Aryl: mononuclear or multinuclear aromatic systems which can be substituted as desired (single or multiple),
Heteroaryl: mononuclear or multinuclear heteroaromatic systems which can be substituted as desired (single or multiple). 3. Triazolo-thiazol-Analoge von Epothilon A und Epothilon B nach Anspruch 2, wobei bedeutet:
Alkyl: Methyl, Ethyl, Propyl, iso-Propyl, Butyl, iso-Butyl, tert.-Butyl, Pentyl, Hexyl, gegebenenfalls substituiert mit C1-C6-Alkoxy, C1-C6-Acyl, Hydroxyl, Halogen, insbesondere Br, Cl, F, J,
Aryl: Phenyl, o-, m-, p-Tolyl, o-, m-, p-Xylyl, Benzyl, Phe­ nethyl, Naphthyl, gegebenenfalls substituiert mit C1-C6- Alkyl, C1-C6-Alkoxy, C1-C6-Acyl, Hydroxyl, Halogen, insbeson­ dere Br, Cl, F, J,
Heteroaryl: Furanyl, Pyranyl, Pyrrolyl, Imidazolyl, Pyrazo­ lyl, Pyridinyl, Indolyl, gegebenenfalls substituiert mit C1- C6-Alkyl, C1-C6-Alkoxy, C1-C6-Acyl, Hydroxyl, Halogen, insbe­ sondere Br, Cl, F, J.3. Triazolo-thiazole analogs of epothilone A and epothilone B according to claim 2, wherein:
Alkyl: methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, optionally substituted with C 1 -C 6 alkoxy, C 1 -C 6 acyl, hydroxyl, halogen, especially Br, Cl, F, J,
Aryl: phenyl, o-, m-, p-tolyl, o-, m-, p-xylyl, benzyl, phenyl, naphthyl, optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 acyl, hydroxyl, halogen, in particular Br, Cl, F, J,
Heteroaryl: furanyl, pyranyl, pyrrolyl, imidazolyl, pyrazo lyl, pyridinyl, indolyl, optionally substituted with C 1 - C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 acyl, hydroxyl, halogen, in particular special Br, Cl, F, J. 4. Verfahren zur Herstellung der Triazolo-thiazol-Analogen von Epothilon A oder Epothilon B nach einem der vorstehenden Ansprüche, bei dem an einem Hydrazon-Derivat von Epothilon A oder Epothilon B mit der Formel 3a oder 3b:
wobei R und Z die oben definierten Bedeutungen haben, mit Hilfe von Metalloxiden, K3[Fe(CN)6], Bleitetraacetat oder Na­ triumhypochlorid ein oxidativer Ringschluß vorgenommen wird.4. A process for the preparation of the triazolo-thiazole analogs of epothilone A or epothilone B according to one of the preceding claims, in which on a hydrazone derivative of epothilone A or epothilon B with the formula 3a or 3b:
where R and Z have the meanings defined above, with the aid of metal oxides, K 3 [Fe (CN) 6 ], lead tetraacetate or sodium hypochlorite, an oxidative ring closure is carried out. 5. Verfahren nach Anspruch 4, wobei das Metalloxid NiO2 ist.5. The method of claim 4, wherein the metal oxide is NiO 2 . 6. Pharmazeutische Zusammensetzung, enthaltend oder beste­ hend aus einem oder mehreren Triazolo-thiazol-Analogen von Epothilon A oder Epothilon B nach einem der Ansprüche 1 bis 3 neben einem pharmazeutisch akzeptablen Träger, Verdünnungs­ mittel oder Hilfsstoff.6. Pharmaceutical composition containing or best consisting of one or more triazolo-thiazole analogues of Epothilon A or Epothilon B according to one of claims 1 to 3 in addition to a pharmaceutically acceptable carrier, dilution medium or auxiliary. 7. Verwendung eines Triazolo-thiazol-Analogen von Epothilon A oder Epothilon B nach einem der Ansprüche 1 bis 3 oder ei­ ner pharmazeutischen Zusammensetzung nach Anspruch 6 zur Be­ handlung von Tumorerkrankungen und Zellwachstumsstörungen.7. Use of a triazolo-thiazole analog of epothilone A or epothilone B according to any one of claims 1 to 3 or egg ner pharmaceutical composition according to claim 6 for loading act of tumor diseases and cell growth disorders. 8. Verwendung nach Anspruch 7, wobei es sich bei der Tumo­ rerkrankung um Krebs handelt.8. Use according to claim 7, wherein it is the tumo disease is cancer. 9. Fungizide Zusammensetzung, enthaltend oder bestehend aus einem oder mehreren Triazolo-thiazol-Analogen von Epothilon A oder Epothilon B nach einem der Ansprüche 1 bis 3 neben einem für Fungizide akzeptablen Träger, Verdünnungsmittel oder Hilfsstoff.9. Fungicidal composition containing or consisting of one or more triazolo-thiazole analogs of epothilone A or epothilone B according to one of claims 1 to 3 in addition to one for fungicides acceptable carriers, diluents or Excipient.
DE2000147529 2000-09-22 2000-09-22 New triazolyl-thiazolyl-epothilone derivatives, useful as fungicides or in the treatment of tumors and cell growth disorders, e.g. cancers Withdrawn DE10047529A1 (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
DE2000147529 DE10047529A1 (en) 2000-09-22 2000-09-22 New triazolyl-thiazolyl-epothilone derivatives, useful as fungicides or in the treatment of tumors and cell growth disorders, e.g. cancers
US10/381,176 US6900160B2 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
CZ2003845A CZ2003845A3 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
PCT/EP2001/010991 WO2002024712A1 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
IL15498601A IL154986A0 (en) 2000-09-22 2001-09-21 Triazolo-epothilone derivatives, pharmaceutical compositions containing the same and methods for the preparation thereof
MXPA03002521A MXPA03002521A (en) 2000-09-22 2001-09-21 Triazolo-epothilones.
KR10-2003-7004136A KR20030069993A (en) 2000-09-22 2001-09-21 Triazolo-epothilones
BR0114065-5A BR0114065A (en) 2000-09-22 2001-09-21 Triazole-epothilones
NZ524861A NZ524861A (en) 2000-09-22 2001-09-21 Epothilone A and epothilone B derivaitves and their use as fungicides and as a cytotoxic substances in the treatment of cancer
RU2003111475/04A RU2003111475A (en) 2000-09-22 2001-09-21 TRIAZOLEPOTHYLONES
AU9187601A AU9187601A (en) 2000-09-22 2001-09-21 Triazolo-epothilones
HU0302905A HUP0302905A3 (en) 2000-09-22 2001-09-21 Triazolo-epothilone-analogs, process for their preparation and pharmaceutical compositions containing them
JP2002529120A JP2004509899A (en) 2000-09-22 2001-09-21 Triazolo-epothilone
EP01972077A EP1319011B1 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
CA002422500A CA2422500A1 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
PL36222501A PL362225A1 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
ZA200302241A ZA200302241B (en) 2000-09-22 2001-09-21 Triazolo-epothilones.
AU2001291876A AU2001291876C1 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
ES01972077T ES2395895T3 (en) 2000-09-22 2001-09-21 Triazolo-epothilones
CNB018161138A CN1190440C (en) 2000-09-22 2001-09-21 Triazolo-epothilones
NO20031318A NO20031318L (en) 2000-09-22 2003-03-21 Triazole-epothilones
HK04104391A HK1061560A1 (en) 2000-09-22 2004-06-16 Triazolo-epothilones.
US11/055,124 US7419993B2 (en) 2000-09-22 2005-02-09 Triazolo-epothilones

Applications Claiming Priority (1)

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DE2000147529 DE10047529A1 (en) 2000-09-22 2000-09-22 New triazolyl-thiazolyl-epothilone derivatives, useful as fungicides or in the treatment of tumors and cell growth disorders, e.g. cancers

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110577551A (en) * 2018-06-08 2019-12-17 遵义医学院 Camptothecin-glycine-5, 6-dibromo norcantharidin conjugate and application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110577551A (en) * 2018-06-08 2019-12-17 遵义医学院 Camptothecin-glycine-5, 6-dibromo norcantharidin conjugate and application thereof

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