CA2526663A1 - Indole derivatives with apoptosis-inducing effect - Google Patents
Indole derivatives with apoptosis-inducing effect Download PDFInfo
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- CA2526663A1 CA2526663A1 CA002526663A CA2526663A CA2526663A1 CA 2526663 A1 CA2526663 A1 CA 2526663A1 CA 002526663 A CA002526663 A CA 002526663A CA 2526663 A CA2526663 A CA 2526663A CA 2526663 A1 CA2526663 A1 CA 2526663A1
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- Prior art keywords
- substituted
- unsubstituted
- alkyl
- chlorobenzyl
- indol
- Prior art date
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- 150000002475 indoles Chemical class 0.000 title claims abstract 13
- 229940054051 antipsychotic indole derivative Drugs 0.000 title claims abstract 4
- 230000006907 apoptotic process Effects 0.000 title 1
- 230000001939 inductive effect Effects 0.000 title 1
- 239000003814 drug Substances 0.000 claims abstract 6
- 201000009030 Carcinoma Diseases 0.000 claims abstract 2
- -1 7-quinolyl Chemical group 0.000 claims 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 11
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 150000001875 compounds Chemical class 0.000 claims 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 239000001301 oxygen Substances 0.000 claims 3
- 239000011593 sulfur Substances 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 2
- WPPLMWPBWRANIX-UHFFFAOYSA-N 2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxo-n-pyrido[2,3-b]pyrazin-7-ylacetamide Chemical compound C1=CC(Cl)=CC=C1CN1C2=CC=CC=C2C(C(=O)C(=O)NC=2C=C3N=CC=NC3=NC=2)=C1 WPPLMWPBWRANIX-UHFFFAOYSA-N 0.000 claims 2
- WZSTWPSBLYYIPI-UHFFFAOYSA-N 2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-n-quinolin-6-yl-2-sulfanylideneacetamide Chemical compound C1=CC(Cl)=CC=C1CN1C2=CC=CC=C2C(C(=S)C(=O)NC=2C=C3C=CC=NC3=CC=2)=C1 WZSTWPSBLYYIPI-UHFFFAOYSA-N 0.000 claims 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 2
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- PPDRWYAWYHRPRD-UHFFFAOYSA-N ethyl n-[2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxoacetyl]-n-pyridin-4-ylcarbamate Chemical compound C=1C=NC=CC=1N(C(=O)OCC)C(=O)C(=O)C(C1=CC=CC=C11)=CN1CC1=CC=C(Cl)C=C1 PPDRWYAWYHRPRD-UHFFFAOYSA-N 0.000 claims 2
- FPIPHMPAEQBYLF-UHFFFAOYSA-N ethyl n-[2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxoacetyl]-n-quinolin-6-ylcarbamate Chemical compound C=1C=C2N=CC=CC2=CC=1N(C(=O)OCC)C(=O)C(=O)C(C1=CC=CC=C11)=CN1CC1=CC=C(Cl)C=C1 FPIPHMPAEQBYLF-UHFFFAOYSA-N 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- QHVFXXIITFTTDE-UHFFFAOYSA-N methyl n-[2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxoacetyl]-n-quinolin-6-ylcarbamate Chemical compound C=1C=C2N=CC=CC2=CC=1N(C(=O)OC)C(=O)C(=O)C(C1=CC=CC=C11)=CN1CC1=CC=C(Cl)C=C1 QHVFXXIITFTTDE-UHFFFAOYSA-N 0.000 claims 2
- YIWBTTUMNYYKOL-UHFFFAOYSA-N n-[2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxoacetyl]-n-quinolin-6-ylpropanamide Chemical compound C=1C=C2N=CC=CC2=CC=1N(C(=O)CC)C(=O)C(=O)C(C1=CC=CC=C11)=CN1CC1=CC=C(Cl)C=C1 YIWBTTUMNYYKOL-UHFFFAOYSA-N 0.000 claims 2
- ATFHZEWOVRKGDZ-UHFFFAOYSA-N n-acetyl-2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxo-n-quinolin-6-ylacetamide Chemical compound C=1C=C2N=CC=CC2=CC=1N(C(=O)C)C(=O)C(=O)C(C1=CC=CC=C11)=CN1CC1=CC=C(Cl)C=C1 ATFHZEWOVRKGDZ-UHFFFAOYSA-N 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- YPQRPJKUVTWPHT-UHFFFAOYSA-N propyl n-[2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-2-oxoacetyl]-n-quinolin-6-ylcarbamate Chemical compound C=1C=C2N=CC=CC2=CC=1N(C(=O)OCCC)C(=O)C(=O)C(C1=CC=CC=C11)=CN1CC1=CC=C(Cl)C=C1 YPQRPJKUVTWPHT-UHFFFAOYSA-N 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- WBSRJJCANNZEFG-UHFFFAOYSA-N 2-[1-[(4-chlorophenyl)methyl]indol-3-yl]-n-(1h-indazol-5-yl)-2-oxoacetamide Chemical compound C1=CC(Cl)=CC=C1CN1C2=CC=CC=C2C(C(=O)C(=O)NC=2C=C3C=NNC3=CC=2)=C1 WBSRJJCANNZEFG-UHFFFAOYSA-N 0.000 claims 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims 1
- 206010059866 Drug resistance Diseases 0.000 claims 1
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000008298 dragée Substances 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 238000001802 infusion Methods 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000002674 ointment Substances 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 239000007940 sugar coated tablet Substances 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 239000000829 suppository Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000001173 tumoral effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention relates to indole derivatives used as medicaments for the treatment of tumoral diseases, particularly in case of resistance of medicaments against other active ingredients and metastasing carcinoma.
Claims (13)
1. An indole derivative of the general formula I
wherein R: is a saturated, unsaturated or aromatic, substituted or unsubstituted (C2-C14) -heterocycle which contains one or more heteroatoms selected from the group N, O
and S and is linked directly to the amide nitrogen, R1: is unsubstituted or substituted alkyl-aryl, R2: is (i) hydrogen, (ii) unsubstituted or substituted (C1-C6)-alkyl, R3-R6: are (i) hydrogen (ii) unsubstituted or substituted (C1-C6)-alkyl, (iii) unsubstituted or substituted (C3-C7)-cycloalkyl, (iv) amino, mono-(C1-C4)-alkylamino, di (C1-C4)-alkylamino, (v) halogen, (vi) (C1-C4)-alkyl which is substituted by one or more fluorine atoms, preferably trifluoromethyl group, (vii) cyano, straight-chain or branched cyano-(C1-C6)-alkyl, (viii) (C1-C6)-alkylcarbonyl, (ix) carboxyl, (C1-C4)-alkoxycarbonyl, carboxy-(C1-C6)-alkyl or (C1-C6)-alkoxycarbonyl-(C1-C6)-alkyl, (x) hydroxyl, (xi) -(C1-C6)-alkoxy, (xii) aryl-(C1-C4)-alkoxy, preferably benzyloxy, (xiii) (C1-C6)-alkoxycarbonylamino, (C1-C6)-alkoxycarbonylamino-(C1-C6)-alkyl, R7: is (C1-C6)-alkylcarbonyl or (C1-C6)-alkoxy-carbonyl and X, Y: are oxygen or sulfur, with the proviso that, when R is an unsubstituted or substituted 2-, 3-, 4-, 5- or 6-pyridyl group and R1-R6 have the abovementioned meaning, R7 is not an acetyl radical or a tert-butyloxycarbonyl group;
the tautomers, stereoisomers, including the diastereomers and enantiomers, thereof, and also the physiologically tolerated salts thereof.
wherein R: is a saturated, unsaturated or aromatic, substituted or unsubstituted (C2-C14) -heterocycle which contains one or more heteroatoms selected from the group N, O
and S and is linked directly to the amide nitrogen, R1: is unsubstituted or substituted alkyl-aryl, R2: is (i) hydrogen, (ii) unsubstituted or substituted (C1-C6)-alkyl, R3-R6: are (i) hydrogen (ii) unsubstituted or substituted (C1-C6)-alkyl, (iii) unsubstituted or substituted (C3-C7)-cycloalkyl, (iv) amino, mono-(C1-C4)-alkylamino, di (C1-C4)-alkylamino, (v) halogen, (vi) (C1-C4)-alkyl which is substituted by one or more fluorine atoms, preferably trifluoromethyl group, (vii) cyano, straight-chain or branched cyano-(C1-C6)-alkyl, (viii) (C1-C6)-alkylcarbonyl, (ix) carboxyl, (C1-C4)-alkoxycarbonyl, carboxy-(C1-C6)-alkyl or (C1-C6)-alkoxycarbonyl-(C1-C6)-alkyl, (x) hydroxyl, (xi) -(C1-C6)-alkoxy, (xii) aryl-(C1-C4)-alkoxy, preferably benzyloxy, (xiii) (C1-C6)-alkoxycarbonylamino, (C1-C6)-alkoxycarbonylamino-(C1-C6)-alkyl, R7: is (C1-C6)-alkylcarbonyl or (C1-C6)-alkoxy-carbonyl and X, Y: are oxygen or sulfur, with the proviso that, when R is an unsubstituted or substituted 2-, 3-, 4-, 5- or 6-pyridyl group and R1-R6 have the abovementioned meaning, R7 is not an acetyl radical or a tert-butyloxycarbonyl group;
the tautomers, stereoisomers, including the diastereomers and enantiomers, thereof, and also the physiologically tolerated salts thereof.
2. An indole derivative as claimed in claim 1, wherein R is (i) unsubstituted or substituted 5-, 6-, 7-quinolyl, (ii) unsubstituted or substituted 2-, 3-, 6-, 7-and 8-pyridopyrazinyl, (iii) unsubstituted or substituted 3-, 4-, 5-, 6-and 7-indazolyl, (iv) unsubstituted or substituted 2-, 3-, 4-, 5-and 6-pyridyl, (v) unsubstituted or substituted 3- , 4- and 5-isoxazolyl, (vi) unsubstituted or substituted 3-, 4- and 5-isothiazolyl.
3. An indole derivative as claimed in claim 1 or 2, characterized in that R7 is methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, acetyl or propionyl.
4. An indole derivative as claimed in one or more of claims 1 to 3, characterized in that the compounds of the general formula I is selected from the following group of compounds:
N-{2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}-N-quinolin-6-ylacetamide (2) methyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}quinolin-6-ylcarbamate (3) ethyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}quinolin-6-ylcarbamate (5) propyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}quinolin-6-ylcarbamate (6) N-{2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}-N-quinolin-6-ylpropionamide (7) ethyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}pyridin-4-ylcarbamate (8)
N-{2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}-N-quinolin-6-ylacetamide (2) methyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}quinolin-6-ylcarbamate (3) ethyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}quinolin-6-ylcarbamate (5) propyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}quinolin-6-ylcarbamate (6) N-{2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}-N-quinolin-6-ylpropionamide (7) ethyl {2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxoacetyl}pyridin-4-ylcarbamate (8)
5. An indole derivative of the general formula I, characterized in that R: is, directly linked to the amide nitrogen, (i) substituted 6-quinolyl, unsubstituted or substituted 7-quinolyl, where 2-methyl-6-quinolyl is excluded and where, when X is a sulfur atom, R can also be unsubstituted 6-quinolyl.
(ii) unsubstituted or substituted 2-, 3-,
(ii) unsubstituted or substituted 2-, 3-,
6-, 7- and 8-pyridopyrazinyl, (iii) unsubstituted or substituted 3-, 4-, 5-, 6- and 7-indazolyl, R1: is unsubstituted or substituted alkyl-aryl, R2: is hydrogen, R3-R6: are (i) hydrogen (ii) unsubstituted or substituted (C1-C6)-alkyl, (iii) unsubstituted or substituted (C3-C7)-cycloalkyl, (iv) amino, mono-(C1-C4)-alkylamino, di-(C1-C4) -alkylamino, (v) halogen, (vi) (C1-C4)-alkyl which is substituted by one or more fluorine atoms, preferably trifluoromethyl group, (vii) cyano, straight-chain or branched cyano-(C1-C6)-alkyl, (viii) (C1-C6)-alkylcarbonyl, (ix) carboxyl, (C1-C4)-alkoxycarbonyl, carboxy-(C1-C6)-alkyl or (C1-C6)-alkoxycarbonyl-(C1-C6)-alkyl, (x) -(C1-C6)-alkoxy, (xi) aryl-(C1-C4)-alkoxy, preferably benzyloxy, (xii) (C1-C6)-alkoxycarbonylamino, (C1-C6)-alkoxycarbonylamino-(C1-C6)-alkyl, and R7: hydrogen and X, Y: are oxygen or sulfur, the tautomers and stereoisomers, including the diastereomers and enantiomers, thereof, and also the physiologically tolerated salts thereof.
6. An indole derivative as claimed in claim 5, characterized in that the compound of the general formula I is selected from the following group of compounds:
2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-N-quinolin-6-yl-2-thioxoacetamide (11) 2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxo-N-pyrido[2,3-b]pyrazin-7-ylacetamide (1) 2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-N-(1H-indazol-5-yl)-2-oxoacetamide (4).
6. An indole derivative as claimed in claim 5, characterized in that the compound of the general formula I is selected from the following group of compounds:
2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-N-quinolin-6-yl-2-thioxoacetamide (11) 2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxo-N-pyrido[2,3-b]pyrazin-7-ylacetamide (1) 2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-N-(1H-indazol-5-yl)-2-oxoacetamide (4).
7. An indole derivative as claimed in one or more of claims 1 to 6, characterized in that R1 is 4-chlorobenzyl, R2-R6 are hydrogen and X, Y are oxygen or sulfur.
8. A drug which comprises at least one of the indole derivatives as claimed in claims 1 to 7.
9. A drug as claimed in claim 8 which comprises the indole derivative in a microparticulate or nanoparticulate composition.
10. A drug as claimed in claim 8 or 9 which comprises the indole derivative and a pharmaceutically utilizable carrier and/or diluent and auxiliary substance in the form of tablets, sugar-coated tablets, capsules, solutions for infusion or ampoules, suppositories, plasters, powder preparations which can be used inhalatively, suspensions, creams and ointments.
11. The use of the indole derivatives as claimed in claims 1 to 6 for producing a drug for treating tumor diseases.
12. The use as claimed in claim 11 for treatment in the case of tumor diseases involving drug resistance against other active compounds.
13. The use as claimed in claim 11 for treatment in the case of tumor diseases involving a metastasizing carcinoma.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47627703P | 2003-06-05 | 2003-06-05 | |
| US60/476,277 | 2003-06-05 | ||
| EP03012868.0 | 2003-06-06 | ||
| EP03012868A EP1484329A1 (en) | 2003-06-06 | 2003-06-06 | Indole derivatives with apoptosis inducing activity |
| EP04011598A EP1595878A1 (en) | 2004-05-15 | 2004-05-15 | Indole derivatives with apoptosis inducing activity |
| EP04011598.2 | 2004-05-15 | ||
| PCT/EP2004/005593 WO2004108702A1 (en) | 2003-06-05 | 2004-05-25 | Indole derivatives with apoptosis-inducing effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2526663A1 true CA2526663A1 (en) | 2004-12-16 |
| CA2526663C CA2526663C (en) | 2011-07-19 |
Family
ID=43661564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2526663A Expired - Fee Related CA2526663C (en) | 2003-06-05 | 2004-05-25 | Indole derivatives with apoptosis-inducing effect |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1641777A1 (en) |
| JP (1) | JP4878285B2 (en) |
| KR (1) | KR101132599B1 (en) |
| CN (1) | CN1816543B (en) |
| AU (1) | AU2004245198B2 (en) |
| BR (1) | BRPI0410998A (en) |
| CA (1) | CA2526663C (en) |
| MX (1) | MXPA05013121A (en) |
| NZ (1) | NZ543853A (en) |
| RS (1) | RS20050901A (en) |
| RU (1) | RU2327696C2 (en) |
| WO (1) | WO2004108702A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007054556A1 (en) * | 2005-11-11 | 2007-05-18 | Æterna Zentaris Gmbh | Novel pyridopyrazines and their use as modulators of kinases |
| EP1790342A1 (en) | 2005-11-11 | 2007-05-30 | Zentaris GmbH | Pyridopyrazine derivatives and their use as signal transduction modulators |
| US8217042B2 (en) | 2005-11-11 | 2012-07-10 | Zentaris Gmbh | Pyridopyrazines and their use as modulators of kinases |
| WO2007062399A2 (en) | 2005-11-23 | 2007-05-31 | The Board Of Regents Of The University Of Texas System | Oncogenic ras-specific cytotoxic compound and methods of use thereof |
| CA2660704A1 (en) * | 2006-08-07 | 2008-02-14 | Ironwood Pharmaceuticals, Inc. | Indole compounds |
| EP2091532A1 (en) * | 2006-11-28 | 2009-08-26 | Ziopharm Oncology, Inc. | Use of indolyl-3-glyoxylic acid derivatives including indibulin, alone or in combination with further agents for treating cancer |
| UA106214C2 (en) * | 2008-10-16 | 2014-08-11 | Эррей Биофарма Инк. | Inhibitors of mitosis for increasing apoptosis in therapy |
| WO2012017325A2 (en) * | 2010-07-19 | 2012-02-09 | Procaps Sa | Apparatus and process for encapsulating microparticles with liquid in soft gel capsules |
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| DE19814838C2 (en) * | 1998-04-02 | 2001-01-18 | Asta Medica Ag | Indolyl-3-glyoxylic acid derivatives with anti-tumor effects |
| TWI269654B (en) * | 1999-09-28 | 2007-01-01 | Baxter Healthcare Sa | N-substituted indole-3-glyoxylamide compounds having anti-tumor action |
| DE19962300A1 (en) * | 1999-12-23 | 2001-06-28 | Asta Medica Ag | New N-benzylindolyl glyoxylic acid derivatives are useful as antitumor agents |
| IT1318641B1 (en) * | 2000-07-25 | 2003-08-27 | Novuspharma Spa | AMID ACIDS 2- (1H-INDOL-3-IL) -2-OXO-ACETICS WITH ANTI-TUMOR ACTIVITY. |
| DE10037310A1 (en) * | 2000-07-28 | 2002-02-07 | Asta Medica Ag | New indole derivatives and their use as medicines |
| WO2003022280A2 (en) * | 2001-09-13 | 2003-03-20 | Synta Pharmaceuticals Corp. | 3-glyoxlylamideindoles for treating cancer |
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- 2004-05-25 CN CN2004800192716A patent/CN1816543B/en not_active Expired - Fee Related
- 2004-05-25 RU RU2006100022/04A patent/RU2327696C2/en not_active IP Right Cessation
- 2004-05-25 MX MXPA05013121A patent/MXPA05013121A/en active IP Right Grant
- 2004-05-25 AU AU2004245198A patent/AU2004245198B2/en not_active Ceased
- 2004-05-25 RS YUP-2005/0901A patent/RS20050901A/en unknown
- 2004-05-25 BR BRPI0410998-8A patent/BRPI0410998A/en not_active IP Right Cessation
- 2004-05-25 WO PCT/EP2004/005593 patent/WO2004108702A1/en active Application Filing
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- 2004-05-25 JP JP2006508197A patent/JP4878285B2/en not_active Expired - Fee Related
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- 2004-05-25 NZ NZ543853A patent/NZ543853A/en not_active IP Right Cessation
- 2004-05-25 CA CA2526663A patent/CA2526663C/en not_active Expired - Fee Related
Also Published As
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|---|---|
| CN1816543B (en) | 2011-01-19 |
| RU2006100022A (en) | 2006-05-27 |
| MXPA05013121A (en) | 2006-03-17 |
| WO2004108702A1 (en) | 2004-12-16 |
| EP1641777A1 (en) | 2006-04-05 |
| JP2007523850A (en) | 2007-08-23 |
| KR101132599B1 (en) | 2012-06-21 |
| RS20050901A (en) | 2007-12-31 |
| NZ543853A (en) | 2009-09-25 |
| KR20060034230A (en) | 2006-04-21 |
| CN1816543A (en) | 2006-08-09 |
| JP4878285B2 (en) | 2012-02-15 |
| AU2004245198A1 (en) | 2004-12-16 |
| CA2526663C (en) | 2011-07-19 |
| AU2004245198B2 (en) | 2009-04-23 |
| BRPI0410998A (en) | 2006-07-04 |
| RU2327696C2 (en) | 2008-06-27 |
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