PT1107964E - Derivados de isoquinolina com actividade inibidora da angiogénese - Google Patents
Derivados de isoquinolina com actividade inibidora da angiogénese Download PDFInfo
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- PT1107964E PT1107964E PT99942827T PT99942827T PT1107964E PT 1107964 E PT1107964 E PT 1107964E PT 99942827 T PT99942827 T PT 99942827T PT 99942827 T PT99942827 T PT 99942827T PT 1107964 E PT1107964 E PT 1107964E
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- phenyl
- substituted
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- 230000033115 angiogenesis Effects 0.000 title claims abstract description 15
- 230000002401 inhibitory effect Effects 0.000 title description 2
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title 1
- -1 di-substituted amino Chemical group 0.000 claims abstract description 228
- 150000001875 compounds Chemical class 0.000 claims abstract description 179
- 150000003839 salts Chemical class 0.000 claims abstract description 78
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 66
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 45
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 42
- 125000001424 substituent group Chemical group 0.000 claims abstract description 36
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 35
- 150000002367 halogens Chemical class 0.000 claims abstract description 35
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 24
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 21
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 21
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 17
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 16
- 241000534944 Thia Species 0.000 claims abstract description 13
- 125000003118 aryl group Chemical group 0.000 claims abstract description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 10
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims abstract description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 10
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 83
- 229910052757 nitrogen Inorganic materials 0.000 claims description 53
- 201000010099 disease Diseases 0.000 claims description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 41
- 230000008569 process Effects 0.000 claims description 40
- 125000003282 alkyl amino group Chemical group 0.000 claims description 33
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 30
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 30
- 150000003254 radicals Chemical class 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 239000007858 starting material Substances 0.000 claims description 26
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 25
- 230000005764 inhibitory process Effects 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 18
- 241001465754 Metazoa Species 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 11
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 11
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 10
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 5
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 230000014399 negative regulation of angiogenesis Effects 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 108091008598 receptor tyrosine kinases Proteins 0.000 claims description 5
- 102000027426 receptor tyrosine kinases Human genes 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims 1
- UIOAQJNADLELPQ-UHFFFAOYSA-N C[C]1OCCO1 Chemical group C[C]1OCCO1 UIOAQJNADLELPQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- NZONQNNHGYRXNN-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical compound CC1=CC(C)=CC(NC=2C3=CC=CC=C3C(CC=3C=CN=CC=3)=CN=2)=C1 NZONQNNHGYRXNN-UHFFFAOYSA-N 0.000 claims 1
- 125000004660 phenylalkylthio group Chemical group 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract description 2
- 235000002639 sodium chloride Nutrition 0.000 description 63
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- 206010028980 Neoplasm Diseases 0.000 description 40
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- 239000002904 solvent Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
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- 239000004480 active ingredient Substances 0.000 description 20
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- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
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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
- C07D401/06—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
- 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
- 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
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH165498 | 1998-08-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1107964E true PT1107964E (pt) | 2010-06-11 |
Family
ID=4215521
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT99942827T PT1107964E (pt) | 1998-08-11 | 1999-08-09 | Derivados de isoquinolina com actividade inibidora da angiogénese |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6608071B2 (https=) |
| EP (1) | EP1107964B8 (https=) |
| JP (1) | JP4516690B2 (https=) |
| CN (1) | CN1152031C (https=) |
| AT (1) | ATE459616T1 (https=) |
| AU (1) | AU5620299A (https=) |
| BR (1) | BR9912938B1 (https=) |
| CA (1) | CA2339961C (https=) |
| DE (1) | DE69942097D1 (https=) |
| ES (1) | ES2342240T3 (https=) |
| PT (1) | PT1107964E (https=) |
| WO (1) | WO2000009495A1 (https=) |
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| ES2289791T3 (es) | 1997-08-22 | 2008-02-01 | Astrazeneca Ab | Derivados de oxindolilquinazolina como inhibidores de la angiogenesis. |
| US6265403B1 (en) | 1999-01-20 | 2001-07-24 | Merck & Co., Inc. | Angiogenesis inhibitors |
| US6245759B1 (en) | 1999-03-11 | 2001-06-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| AU779908B2 (en) | 1999-09-10 | 2005-02-17 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6689883B1 (en) | 1999-09-28 | 2004-02-10 | Bayer Pharmaceuticals Corporation | Substituted pyridines and pyridazines with angiogenesis inhibiting activity |
| DOP2000000070A (es) * | 1999-09-28 | 2002-02-28 | Bayer Healthcare Llc | Piridinas y piridacinas sustituidas con actividad de inhibición de angiogénesis |
| CA2387351C (en) | 1999-10-19 | 2009-09-08 | Merck & Co., Inc. | Indole derivatives as tyrosine kinase inhibitors |
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| JPH0215067A (ja) * | 1988-07-04 | 1990-01-18 | Hokuriku Seiyaku Co Ltd | イソキノリンスルホンアミド誘導体 |
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| AU2103097A (en) * | 1996-03-15 | 1997-10-10 | Zeneca Limited | Cinnoline derivatives and use as medicine |
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| EP1107964A1 (en) | 2001-06-20 |
| DE69942097D1 (de) | 2010-04-15 |
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| CA2339961A1 (en) | 2000-02-24 |
| EP1107964B8 (en) | 2010-04-07 |
| ATE459616T1 (de) | 2010-03-15 |
| BR9912938A (pt) | 2001-05-08 |
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