WO1997046562A1 - Novel water-soluble c-ring analogues of 20(s)-camptothecin - Google Patents
Novel water-soluble c-ring analogues of 20(s)-camptothecin Download PDFInfo
- Publication number
- WO1997046562A1 WO1997046562A1 PCT/US1997/006960 US9706960W WO9746562A1 WO 1997046562 A1 WO1997046562 A1 WO 1997046562A1 US 9706960 W US9706960 W US 9706960W WO 9746562 A1 WO9746562 A1 WO 9746562A1
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- WO
- WIPO (PCT)
- Prior art keywords
- formula
- substituted
- lower alkyl
- compounds
- compound
- Prior art date
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- XDTMQSROBMDMFD-UHFFFAOYSA-N C1CCCCC1 Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Definitions
- R 5 represents hydrogen, lower alkyl, substituted lower alkyl, lower aralkyl, hydroxymethyl, carboxy ethyl, aminomethyl, substituted aminomethyl where the amino group is mono or disubstituted in which both substituents are independent or combined together to form 5 or 6 embered cyclic ring system containing carbon and optionally containing one or two heteroatoms selected from, oxygen, nitrogen and sulfur, the number of atoms in the cyclic ring system is 5 or 6.
- R represents hydrogen, lower alkyl, lower alkenyl, lower alkanoyl, substituted lower alkyl, substituted lower alkanoyl, substituted lower alkenyl, lower alkoxycarbonyl, phenyl, benzyl or benzoyl in which the phenyl group may be unsubstituted or substituted; and R represents hydrogen, hydroxy, lower alkoxy or COOR' where R' represents hydrogen, lower alkyl or lower aralkyl; R 6 may also represent amide or amino group in which the amide or the amino group can be unsubstituted, or mono or disubstituted in which both substituents are independent or combined together to form a cyclic ring system of 3 to 8 atoms containing carbon and optionally contains one or two heteroatoms selected from, nitrogen, oxygen and sulfur, the number of atoms in the cyclic ring system is 3 to 8 atoms; phenoxy, phenyl, benzoyl or benzyl where the pheny
- camptothecin It was first isolated from the plant Camptotheca acuminata by Wall and co-workers in 1966. However, its development as a potential drug for cancer treatment has been abandoned due to unacceptable side effects on humans and due to its low water solubility as well as high toxicity problems. Since the discovery of its mechanism of action as an inhibitor of topoisomerise I by Liu and co-workers in 1985 [L.F.Liu, et al. , JB ⁇ ol . Chem. 260, 14873 (1985)], the research interest on camptothecin has once again taken momentum.
- camptothecin analogues involving the modification of rings A-E or the introduction of a variety of substituents on all the five rings of camptothecin of the formula 2 [M.E.Wall et al. , J. Med. Chem . , 3_6/ 2689 (1993); R.P. Hertzberg et al., J. Med. Chem . , 715 (1989); S.W.Sawada et al. , Chem. Pharm. Bull, 41(2), 310 (1993)].
- camptothecin analogues prepared to date only two of them namely, CPT-11 having the formula 3 [Chem. Pharm. Bull . , 3_9, 1446 (1991)],
- camptothecin like inhibition of topoisomerase I activity. Both these reports are contrary to the assumption that 20 (S) -oc-hydroxy functionality in camptothecin is an essential feature for its biological activity.
- camptothecin analogues prepared in the literature Based on the structure-activity results obtained for the camptothecin analogues prepared in the literature, it was established that the modification of substituents at C-9 and C-7 position of camptothecin of the formula 2 plays an important role in the enhancement of anticancer activity by imparting stability to the E-ring lactone [T.G.Burke etal., J.Afed.Chem 37., 40(1994)] . It has also been recognized that the open form of the lactone moiety, namely, ' the Carboxylate form' is less effective therapeutically than the closed 'Lactone form ' [Hertzberg et al. ,
- R represents hydroxy, lower alkyl, lower alkoxy or acyloxy
- R represents hydrogen, ethoxy at 9th position
- R represents hydrogen, lower alkyl, lower aralkyl, CH 2 0H, COOH, COOMe, CH 2 OR' where R' represents lower alkyl or acyl group.
- R 1 to R 5 have the meaning described above, in the presence of an acid and an oxidizing agent which is a ferric salt, with a compound having the formula R -OH where R represents lower alkyl, lower alkenyl, (C 3 - C 7 ) cycloalkyl, haloalkyl or hydroxyalkyl, to obtain compounds of the formula 12 and compounds of the formula 17,
- R , R , R and R 5 have the meaning described above and R i ⁇ as defined above.
- the present invention provides a novel process for the preparation of various C-5-N- substituted 20 (S) -camptothecin derivatives of the formula 1 where R has the meaning described above, starting from the compounds of the formula 12,
- R, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 have the meaning described above. Throughout the present invention, the terms representing R through R in these compounds have the following definitions.
- lower alkyl denotes a univalent, branched or straight hydrocarbon chain containing 1 to
- alkyl groups are methyl, ethyl, propyl, i ⁇ opropyl, butyl, sec.butyl tert.butyl pentyl, iso pentyl, tert. pentyl, hexyl, isohexyl and octyl.
- alkenyl groups are vinyl, propenyl, butenyl pentenyl, isopropenyl, isobutenyl, proparginyl, hexenyl and octenyl.
- the term 'halogen' or 'halo' represents chlorine, bromine or fluorine.
- the term 'haloalkyl' denotes alkyl groups substituted with halogens, preferably fluorine, bromine or chlorine. Representative examples of the haloalkyl groups are chloroethyl, bromopropyl, fluoroethyl, trifluoroethyl, trichloroethyl and trifluorobutyl.
- the term 'lower alkoxy' denotes lower alkyl groups as defined above attached via oxygen linkage to the rest of the molecule. Representative examples of these groups are methoxy, ethoxy, isopropoxy, tert.butoxy, hexoxy, heptoxy and octoxy.
- lower alkanoyl denotes lower alkyl or lower alkenyl groups as defined above attached via a carbonyl group to the rest of the molecule. Representative examples of these groups are acetyl, propionyl, propenoyl, crotanoyl, butanoyl, pentanoyl and isopentanoyl.
- aminoalkyl ' represents the lower alkyl groups as defined above substituted with amino groups.
- Representative examples of the aminoalkyl groups are 2-aminopropyl, 4-aminobutyl and 5- aminopentyl.
- the amino groups may also be mono or disubstituted and representative examples of these substituted amino groups are dimethylamino, diethylamino, dibenzylamino, ethylisopropylamino, pyrrolidino, piperidino, morphilino and piperizino.
- heteroatom' refers to oxygen, nitrogen or sulfur.
- 'aryl or heteroaryl' represents groups of aromatic nature having 5 or 6 membered rings which may be selected from phenyl, biphenyl, naphthyl, pyridyl, quinoline, iso uinoline, indole, pyrol, furan, benzofuran, thiophene, pyramidine, piperizine, thiozolidine and imidazole.
- phenyl' group used in the present invention refers to those substituents which can be selected from groups such as hydroxyl, lower alkyl, haloalkyl, phenyl, benzyl, halogen, lower alkoxy, thioalkoxy, benzyloxy, carboxyl, cyano, nitro, amido, amino, and alkylamino.
- groups such as 4-hydroxyphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, N,N-dimethylaminophenyl, and 4-carbomethoxyphenyl.
- substituted alkyl' group used in the present invention refers to those substituents which can be selected from groups such as hydroxyl, alkyl, haloalkyl, phenyl, benzyl, halogen, alkoxy, thioalkoxy,. benzyloxy, carboxyl, carbonyloxy, cyano, nitro, amido, amino and alkylamino.
- Examples of such groups are fluoroethyl, chloropropyl, hydroxyethyl, methoxypropyl, N,N-diethylaminoethyl, N-benzoyl- aminopropyl, trifluoroethoxyethyl, phenoxyethy1, carbomethoxyethyl, (p-fluorobenzoyloxy) ethyl, aminopropyl, and 2-thioethyl.
- substituted amino' group used in the present invention refers to those substituents which can be selected from groups such as hydroxyl, alkyl, haloalkyl, benzyl, benzoyl, alkoxy, carboxyl, amido, amino, and alkylamino.
- substituents which can be selected from groups such as hydroxyl, alkyl, haloalkyl, benzyl, benzoyl, alkoxy, carboxyl, amido, amino, and alkylamino.
- substituents such as hydroxyl, alkyl, haloalkyl, benzyl, benzoyl, alkoxy, carboxyl, amido, amino, and alkylamino.
- substituents such as hydroxyl, alkyl, haloalkyl, benzyl, benzoyl, alkoxy, carboxyl, amido, amino, and alkylamino.
- Examples of such groups are N,N-diethylamino, N-benzo
- both the substituents on the amino group can be combined together to form 5 or 6-membered cyclic ring system which may be represented by pyrrolidino, piperidino, piperizino, morphilino, imidazolino, or thiazolidino.
- Examples of 3 to 8 membered cyclic ring systems containing carbon and optionally containing one or two heteroatoms selected from oxygen, sulfur and nitrogen are piperidine and pyrrolidine.
- the present invention provides a process for the preparation of the compounds of the formula 1,
- R represents lower alkyl, phenyl, benzyl or benzoyl in which the phenyl group may be unsubstituted or substituted; lower alkoxycarbonyl, lower alkenyl, substituted lower alkenyl, substituted lower alkyl, lower alkanoyl, or substituted lower alkanoyl and R" through R have the meaning described above.
- the compounds of the formula 12 were reacted with compounds of the general formula R 6 -NH 2 , where R 6 has the meaning mentioned above, in the presence of a base to afford compounds of the formula 13.
- the bases employed in this reaction sequence can be selected from inorganic or organic bases such as sodium bicarbonate, potassium carbonate, sodium hydride, potassium hydride, pyridine, piperdine, triethylamine, diisopropylamine, pyrrolidine, or dimethylaminopyridine.
- the solvents used in the reaction can be selected from methanol, ethanol, benzene, toluene, N,N-dimethylformamide, chloroform, or dichloroethane.
- the reaction can be effected at a temperature in the range of 40-140°C.
- compounds of the formula 13 were reacted with reagents having the formula R-G where G denotes halogen and R represents lower alkyl, phenyl, benzyl or benzoyl in which the phenyl group may be unsubstituted or substituted; lower alkoxycarbonyl, lower alkanoyl, substituted lower alkanoyl; lower alkenyl; substituted lower alkyl; or substituted lower alkenyl in the presence of a base.
- the base used in the reaction can be selected from sodium carbonate, sodium bicarbonate, potassium carbonate, barium carbonate, lithium carbonate, pyridine, piperidine, triethylamine, diisopropylamine or 4-N,N-dimethyl-aminopyridine.
- the solvent used in the reaction can be chosen from dichloromethane, chloroform, benzene, toluene, tetrahydrofuran, ethyl acetate or a combination of these solvents.
- the reaction temperature can be in the range of 0°C. to 100°C., preferably in the range of 0°C. to 60°JC.
- the present invention is of particular significance in developing 5-N-substituted 20 (S) - camptothecin derivatives as a new class of C-ring modified camptothecin analogues which are useful as anti-tumor and/or anti-viral agents.
- the present invention is also of particular significance as the process developed and described here is highly versatile and amenable for large scale preparation of these camptothecin derivatives having the general formula 1.
- R is nitro, amino, aminoalkyl, hydroxy, or methoxy
- R* is hydroxy, carbonyloxy or halo
- R , R combined together represent methylenedioxy or ethylenedioxy
- R is ethyl, aminomethyl or substituted aminomethyl
- R 6 is hydroxy, methyl, 2' -hydroxyethyl, 4- hydroxybutyl, alkoxyethyl or aminoethyl where amino group may be dimethylamino, diethylamino, pyrrolidino, piperidino, morphilino, piperizino, or imidazolino
- R group may be methyl, allyl, benzyl, tert.butoxy- carbonyl (Boc) , benzoy
- Most of the compounds prepared by the present invention have water solubility ranging from 1 mg to 15 mg per ml at 37°C.
- Compounds prepared in the present invention exhibited good in vitro anti-cancer activity towards various human tumor cell lines, according to the results obtained from 60 human tumor cell line assay performed at National Cancer Institute (NCI) , Bethesda, Maryland, U.S.A.
- Tables 1 and 2 were obtained from conducting experiments according to U. S. National Cancer Institute (NCI) protocols as given below: Each test compound was screened against a battery of 60 human cell lines obtained from eight organs. In a typical procedure, the cell suspensions that were diluted according to the particular cell type and the expected target cell density (5000-40,000 cells per well based on cell growth characteristics) were added into 96-well microtiter plates. Inoculates were allowed a preincubation period of 24h at 37°C. for stabilization. Dilutions at twice the intended test concentrations were added at time zero in 100- ⁇ l aliquots to microtiter plate wells. Usually test compounds were evaluated at five 10-fold dilutions.
- the highest well concentration used in the test is 10 "4 M.
- the cells are then incubated in the presence of drug (the test compound) for a further 48h in 5% C0 2 atmosphere and 100% humidity.
- the adherent cells are fixed to the plate by means of trichloroacetic acid, and after a number of washes, the cell layer is treated with the protein stain Sulforhodamine B.
- the optical density which is proportional to protein mass, is then read by automated spectrophotometric plate readers at a wavelength of 515 nm. Readings are transferred to a microcomputer and final reports are generated using especially developed software.
- IC50 the mean value of the minimum drug concentration ( ⁇ m) of the agent required to produce 50% cell growth inhibition (GI50) against NCI's 60 human tumor cell line assay.
- GI 50 Growth Inhibition
- All of the compounds of the general formula 1 of the present invention are useful as anti-cancer and anti-viral agents.
- Administration of the novel active compounds of the formula 1, in pure form or in an appropriate pharmaceutical composition can be carried out via any of the accepted modes of administration for serving similar utilities.
- administration can be, for example, orally, nasally, parenterally or topically, in the form of solid, semi- solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, capsules, powders, solutions, suspensions, emulsions, creams, lotions, aerosols, ointments, injections or the like, preferably, in unit dosage forms suitable, for simple administration of precise dosages.
- the compositions will include a conventional pharmaceutical carrier, diluent or excipient and an active compound of general formula 1 and, in addition, may include either medicinal agents, pharmaceutical agents, diluents carriers, adjuvants, etc.
- Step 2 To a solution of lOOmg of 5- (N- methylamino) camptothecin of the formula 13 where
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97922465A EP0906317A1 (en) | 1996-06-05 | 1997-04-22 | Novel water-soluble c-ring analogues of 20(s)-camptothecin |
JP10500567A JP2000511556A (en) | 1996-06-05 | 1997-04-22 | Novel water-soluble C-ring analog of 20 (S) -camptothecin |
AU28124/97A AU2812497A (en) | 1996-06-05 | 1997-04-22 | Novel water-soluble c-ring analogues of 20(s)-camptothecin |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65525996A | 1996-06-05 | 1996-06-05 | |
US08/655,259 | 1996-06-05 | ||
US08/771,390 US5972955A (en) | 1995-06-06 | 1996-12-19 | Water soluble C-ring analogues of 20(S)-camptothecin |
US08/771,390 | 1996-12-19 |
Publications (1)
Publication Number | Publication Date |
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WO1997046562A1 true WO1997046562A1 (en) | 1997-12-11 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1997/006960 WO1997046562A1 (en) | 1996-06-05 | 1997-04-22 | Novel water-soluble c-ring analogues of 20(s)-camptothecin |
Country Status (8)
Country | Link |
---|---|
US (1) | US5972955A (en) |
EP (1) | EP0906317A1 (en) |
JP (1) | JP2000511556A (en) |
CN (1) | CN1221421A (en) |
AR (1) | AR006991A1 (en) |
AU (1) | AU2812497A (en) |
TW (1) | TW472058B (en) |
WO (1) | WO1997046562A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5972955A (en) * | 1995-06-06 | 1999-10-26 | Dr. Reddy's Research Foundation | Water soluble C-ring analogues of 20(S)-camptothecin |
US7709640B2 (en) | 2000-11-01 | 2010-05-04 | Millennium Pharmaceuticals, Inc. | Nitrogenous heterocyclic compounds and process for making nitrogenous heterocyclic compounds and intermediates thereof |
LU102067B1 (en) * | 2020-09-17 | 2022-03-18 | Narodowy Inst Lekow | 7-Ethyl-10-hydroxycamptothecin derivatives for use in the treatment of cancer |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT1044977E (en) * | 1999-03-09 | 2002-09-30 | Sigma Tau Ind Farmaceuti | CAMPTOTECIN DERIVATIVES WITH ANTITUMORAL ACTIVITY |
US7105492B2 (en) * | 1999-03-09 | 2006-09-12 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Camptothecin derivatives having antitumor activity |
EP2266607A3 (en) | 1999-10-01 | 2011-04-20 | Immunogen, Inc. | Immunoconjugates for treating cancer |
PL363618A1 (en) | 2000-11-09 | 2004-11-29 | Neopharm, Inc. | Sn-38 lipid complexes and methods of use |
WO2003030864A1 (en) | 2001-05-29 | 2003-04-17 | Neopharm, Inc. | Liposomal formulation of irinotecan |
US7908924B2 (en) * | 2003-06-18 | 2011-03-22 | Schnitta Bonnie S | Sound focusing mechanism and method of estimating acoustic leakage of an object and method of estimating transmission loss of an object |
US20070269790A1 (en) * | 2003-12-01 | 2007-11-22 | Technion Research & Development | Methods of Generating Stem Cells and Embryonic Bodies Carrying Disease-Causing Mutations and Methods of Using same for Studying Genetic Disorders |
JP4433918B2 (en) * | 2004-07-15 | 2010-03-17 | コニカミノルタエムジー株式会社 | Image forming method |
KR100651728B1 (en) * | 2004-11-10 | 2006-12-06 | 한국전자통신연구원 | Compounds having anchoring group and electronic device including the same and methods for producing the same |
ITMI20061474A1 (en) * | 2006-07-26 | 2008-01-27 | Indena Spa | DERIVATIVES OF CAMPTOTECIN WITH ANTITUMORAL ACTIVITY |
ITMI20061473A1 (en) * | 2006-07-26 | 2008-01-27 | Indena Spa | DERIVATIVES OF CAMPTOTECIN WITH ANTITUMORAL ACTIVITY |
ITMI20061475A1 (en) | 2006-07-26 | 2008-01-27 | Indena Spa | DERIVATIVES OF CAMPTOTECIN WITH ANTITUMORAL ACTIVITY |
Citations (2)
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GB2056973A (en) * | 1979-07-10 | 1981-03-25 | Yakult Honsha Kk | Camptothecin derivatives useful as antitumour agents |
EP0074256A1 (en) * | 1981-09-04 | 1983-03-16 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives, processes for preparing same, formulations containing such derivatives and their use |
Family Cites Families (12)
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JPS5839685A (en) * | 1981-09-04 | 1983-03-08 | Yakult Honsha Co Ltd | Novel camptothecin derivative and its preparation |
JPS58154584A (en) * | 1982-03-10 | 1983-09-14 | Yakult Honsha Co Ltd | Preparation of camptothecin derivative substituted with hydroxyl in 5-position |
JPS6019790A (en) * | 1983-07-14 | 1985-01-31 | Yakult Honsha Co Ltd | Novel camptothecin derivative |
US5053512A (en) * | 1987-04-14 | 1991-10-01 | Research Triangle Institute | Total synthesis of 20(S) and 20(R)-camptothecin and compthothecin derivatives |
US4981968A (en) * | 1987-03-31 | 1991-01-01 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
US5122526A (en) * | 1987-03-31 | 1992-06-16 | Research Triangle Institute | Camptothecin and analogs thereof and pharmaceutical compositions and method using them |
US5446047A (en) * | 1992-07-23 | 1995-08-29 | Sloan-Kettering Institute For Cancer Research | Camptothecin analogues |
US5391745A (en) * | 1992-07-23 | 1995-02-21 | Sloan-Kettering Institute For Cancer Research | Methods of preparation of camptothecin analogs |
US5468754A (en) * | 1994-04-19 | 1995-11-21 | Bionumerik Pharmaceuticals, Inc. | 11,7 substituted camptothecin derivatives and formulations of 11,7 substituted camptothecin derivatives and methods for uses thereof |
US5972955A (en) * | 1995-06-06 | 1999-10-26 | Dr. Reddy's Research Foundation | Water soluble C-ring analogues of 20(S)-camptothecin |
US6214836B1 (en) * | 1995-06-06 | 2001-04-10 | Dr. Reddy's Research Foundation | Water soluble analogues of 20(S)-camptothecin |
HU225989B1 (en) * | 1996-06-05 | 2008-02-28 | Reddys Lab Ltd Dr | 20-(s)-camptothecin derivatives substituted at position 5, process for their preparation, their use and pharmaceutical compositions containing the same compounds |
-
1996
- 1996-12-19 US US08/771,390 patent/US5972955A/en not_active Expired - Fee Related
-
1997
- 1997-04-22 AU AU28124/97A patent/AU2812497A/en not_active Abandoned
- 1997-04-22 WO PCT/US1997/006960 patent/WO1997046562A1/en not_active Application Discontinuation
- 1997-04-22 CN CN97195256A patent/CN1221421A/en active Pending
- 1997-04-22 EP EP97922465A patent/EP0906317A1/en not_active Withdrawn
- 1997-04-22 JP JP10500567A patent/JP2000511556A/en active Pending
- 1997-04-24 TW TW086105386A patent/TW472058B/en not_active IP Right Cessation
- 1997-04-30 AR ARP970101799A patent/AR006991A1/en unknown
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GB2056973A (en) * | 1979-07-10 | 1981-03-25 | Yakult Honsha Kk | Camptothecin derivatives useful as antitumour agents |
EP0074256A1 (en) * | 1981-09-04 | 1983-03-16 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives, processes for preparing same, formulations containing such derivatives and their use |
Non-Patent Citations (1)
Title |
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SEIGO SAWADA ET AL: "Chemical modification of an antitumor alkaloid Camptothecin:Synthesis and antitumor activity of 7-C-substituted Camptothecin", CHEMICAL AND PHARMACEUTICAL BULLETIN, vol. 39, no. 10, October 1991 (1991-10-01), TOKYO JP, pages 2574 - 2580, XP002034620 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5972955A (en) * | 1995-06-06 | 1999-10-26 | Dr. Reddy's Research Foundation | Water soluble C-ring analogues of 20(S)-camptothecin |
US7709640B2 (en) | 2000-11-01 | 2010-05-04 | Millennium Pharmaceuticals, Inc. | Nitrogenous heterocyclic compounds and process for making nitrogenous heterocyclic compounds and intermediates thereof |
USRE43098E1 (en) | 2000-11-01 | 2012-01-10 | Millennium Pharmaceuticals, Inc. | Nitrogenous heterocyclic compounds and process for making nitrogenous heterocyclic compounds and intermediates thereof |
US8536184B2 (en) | 2000-11-01 | 2013-09-17 | Millennium Pharmaceuticals, Inc. | Nitrogenous heterocyclic compounds and process for making nitrogenous heterocyclic compounds and intermediates thereof |
LU102067B1 (en) * | 2020-09-17 | 2022-03-18 | Narodowy Inst Lekow | 7-Ethyl-10-hydroxycamptothecin derivatives for use in the treatment of cancer |
EP3971189A1 (en) * | 2020-09-17 | 2022-03-23 | Narodowy Instytut Leków | 7-ethyl-10-hydroxycamptothecin derivatives for use in the treatment of cancer |
Also Published As
Publication number | Publication date |
---|---|
US5972955A (en) | 1999-10-26 |
JP2000511556A (en) | 2000-09-05 |
AR006991A1 (en) | 1999-10-13 |
EP0906317A1 (en) | 1999-04-07 |
CN1221421A (en) | 1999-06-30 |
TW472058B (en) | 2002-01-11 |
AU2812497A (en) | 1998-01-05 |
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