ES2287256T3 - Indolinas y tetrahidroquinolina como profarmacos para el tratamiento de tumores. - Google Patents
Indolinas y tetrahidroquinolina como profarmacos para el tratamiento de tumores. Download PDFInfo
- Publication number
- ES2287256T3 ES2287256T3 ES02712112T ES02712112T ES2287256T3 ES 2287256 T3 ES2287256 T3 ES 2287256T3 ES 02712112 T ES02712112 T ES 02712112T ES 02712112 T ES02712112 T ES 02712112T ES 2287256 T3 ES2287256 T3 ES 2287256T3
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- Spain
- Prior art keywords
- alkyl
- optionally substituted
- group
- use according
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 206010028980 Neoplasm Diseases 0.000 title claims description 22
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 title description 4
- 150000002476 indolines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 23
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 23
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 16
- -1 -OH Chemical group 0.000 claims abstract description 13
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 8
- 241001465754 Metazoa Species 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 229910004013 NO 2 Inorganic materials 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 3
- HEQLRKRQBGXRAJ-UHFFFAOYSA-N [8-(chloromethyl)-6-(5-methoxy-1h-indole-2-carbonyl)-7,8-dihydropyrrolo[3,2-e]indol-3-yl]-phenylmethanone Chemical compound C=1C2=CC(OC)=CC=C2NC=1C(=O)N1CC(CCl)C(C=2C=C3)=C1C=CC=2N3C(=O)C1=CC=CC=C1 HEQLRKRQBGXRAJ-UHFFFAOYSA-N 0.000 claims description 2
- FNMIWLJPAHYRGW-UHFFFAOYSA-N (4-chloro-3,4-dihydro-2h-quinolin-1-yl)-(5-methoxy-1h-indol-2-yl)methanone Chemical compound C1CC(Cl)C2=CC=CC=C2N1C(=O)C1=CC2=CC(OC)=CC=C2N1 FNMIWLJPAHYRGW-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 4
- 101000585507 Solanum tuberosum Cytochrome b-c1 complex subunit 7 Proteins 0.000 abstract 1
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- 235000012239 silicon dioxide Nutrition 0.000 description 8
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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- 238000003818 flash chromatography Methods 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical group C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 4
- 101000725164 Homo sapiens Cytochrome P450 1B1 Proteins 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 230000002152 alkylating effect Effects 0.000 description 4
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- 229910000104 sodium hydride Inorganic materials 0.000 description 4
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 3
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- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
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- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
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- CBAITGIVJZCMKA-UHFFFAOYSA-N tert-butyl 3-amino-2-iodobenzoate Chemical compound C(C)(C)(C)OC(=O)C1=C(C(=CC=C1)N)I CBAITGIVJZCMKA-UHFFFAOYSA-N 0.000 description 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01301609 | 2001-02-22 | ||
| EP01301609 | 2001-02-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2287256T3 true ES2287256T3 (es) | 2007-12-16 |
Family
ID=8181734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02712112T Expired - Lifetime ES2287256T3 (es) | 2001-02-22 | 2002-02-22 | Indolinas y tetrahidroquinolina como profarmacos para el tratamiento de tumores. |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7179921B2 (enExample) |
| EP (1) | EP1408970B1 (enExample) |
| JP (1) | JP2004522781A (enExample) |
| AT (1) | ATE361750T1 (enExample) |
| DE (1) | DE60220057T2 (enExample) |
| ES (1) | ES2287256T3 (enExample) |
| WO (1) | WO2002067937A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4862120B2 (ja) * | 2001-02-22 | 2012-01-25 | ユニヴァーシティ オブ ブラッドフォード | 腫瘍治療のためのプロドラッグとしてのベンズ−インドールおよびベンゾ−キノリン誘導体 |
| FR2825705B1 (fr) * | 2001-06-08 | 2005-05-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens |
| FR2835186B1 (fr) | 2002-01-28 | 2006-10-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, actifs comme inhibiteurs de beta-lactamases |
| FR2844273B1 (fr) | 2002-09-05 | 2008-04-04 | Aventis Pharma Sa | Nouveaux composes heterocycliques, procede et intermediaires de preparation et utilisation comme medicament, notamment comme inhibiteurs de beta-lactamases et anti-bacteriens. |
| GB0302094D0 (en) | 2003-01-29 | 2003-02-26 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| GB0324269D0 (en) | 2003-10-16 | 2003-11-19 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| GB0505644D0 (en) | 2005-03-18 | 2005-04-27 | Univ London Pharmacy | Analogues of the azinomycins as anti-tumour agents and as prodrugs |
| KR20080114709A (ko) * | 2006-02-02 | 2008-12-31 | 신타가 비.브이. | 수용성 ｃｃ-1065 유사체 및 그들의 결합체 |
| US9901567B2 (en) | 2007-08-01 | 2018-02-27 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| JP5677970B2 (ja) | 2008-11-03 | 2015-02-25 | シンタルガ・ビーブイ | 新規ｃｃ−１０６５類似体およびその複合体 |
| NO3056203T3 (enExample) | 2010-04-21 | 2018-05-12 | ||
| MX373458B (es) | 2014-01-10 | 2020-05-11 | Byondis Bv | Metodo para purificar conjugados de anticuerpo-farmaco enlazados a cisteina. |
| WO2016001485A1 (en) | 2014-06-30 | 2016-01-07 | Glykos Finland Oy | Saccharide derivative of a toxic payload and antibody conjugates thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5214065A (en) * | 1990-06-11 | 1993-05-25 | Kyowa Hakko Kogyo Co., Ltd. | Dc-89 derivatives |
| EP0702004A2 (de) | 1994-09-15 | 1996-03-20 | Ciba-Geigy Ag | 2,9-Diamino- und 2-amino-8-carbamoyl-4-hydroxy-alkansäureamid-derivative |
| JPH08143565A (ja) * | 1994-11-16 | 1996-06-04 | Fujisawa Pharmaceut Co Ltd | ベンズアミド化合物 |
-
2002
- 2002-02-22 AT AT02712112T patent/ATE361750T1/de not_active IP Right Cessation
- 2002-02-22 EP EP02712112A patent/EP1408970B1/en not_active Expired - Lifetime
- 2002-02-22 JP JP2002567304A patent/JP2004522781A/ja active Pending
- 2002-02-22 WO PCT/GB2002/000785 patent/WO2002067937A1/en not_active Ceased
- 2002-02-22 DE DE60220057T patent/DE60220057T2/de not_active Expired - Lifetime
- 2002-02-22 US US10/468,743 patent/US7179921B2/en not_active Expired - Fee Related
- 2002-02-22 ES ES02712112T patent/ES2287256T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE60220057T2 (de) | 2008-01-10 |
| WO2002067937A1 (en) | 2002-09-06 |
| US20040157880A1 (en) | 2004-08-12 |
| ATE361750T1 (de) | 2007-06-15 |
| EP1408970A1 (en) | 2004-04-21 |
| EP1408970B1 (en) | 2007-05-09 |
| DE60220057D1 (de) | 2007-06-21 |
| JP2004522781A (ja) | 2004-07-29 |
| US7179921B2 (en) | 2007-02-20 |
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