MXPA06013876A - Derivados de tetrahidro-2h-isoquinolin-1-ona sustituida, metodo para su produccion, y uso de los mismos como medicamentos. - Google Patents
Derivados de tetrahidro-2h-isoquinolin-1-ona sustituida, metodo para su produccion, y uso de los mismos como medicamentos.Info
- Publication number
- MXPA06013876A MXPA06013876A MXPA06013876A MXPA06013876A MXPA06013876A MX PA06013876 A MXPA06013876 A MX PA06013876A MX PA06013876 A MXPA06013876 A MX PA06013876A MX PA06013876 A MXPA06013876 A MX PA06013876A MX PA06013876 A MXPA06013876 A MX PA06013876A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- heteroaryl
- phenyl
- fluorine
- hydroxy
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 26
- NTNKZGHUNBWBBV-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-isoquinolin-1-one Chemical class C1C=CC=C2C(=O)NCCC21 NTNKZGHUNBWBBV-UHFFFAOYSA-N 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 214
- -1 hydroxy, chloro, methoxy Chemical group 0.000 claims description 172
- 125000001424 substituent group Chemical group 0.000 claims description 140
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 134
- 125000001072 heteroaryl group Chemical group 0.000 claims description 115
- 125000000623 heterocyclic group Chemical group 0.000 claims description 110
- 125000003118 aryl group Chemical group 0.000 claims description 99
- 239000011737 fluorine Chemical group 0.000 claims description 94
- 229910052731 fluorine Inorganic materials 0.000 claims description 94
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 75
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 68
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 68
- 239000000460 chlorine Chemical group 0.000 claims description 68
- 229910052801 chlorine Inorganic materials 0.000 claims description 68
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 56
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 54
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 48
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 48
- 229910052794 bromium Inorganic materials 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 44
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 44
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 40
- 125000001153 fluoro group Chemical group F* 0.000 claims description 39
- 125000004076 pyridyl group Chemical group 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 37
- 201000006417 multiple sclerosis Diseases 0.000 claims description 32
- 150000003254 radicals Chemical class 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000002541 furyl group Chemical group 0.000 claims description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 24
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 23
- 239000012634 fragment Substances 0.000 claims description 22
- 125000004043 oxo group Chemical group O=* 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000001544 thienyl group Chemical group 0.000 claims description 20
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 239000012661 PARP inhibitor Substances 0.000 claims description 16
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 13
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000003826 tablet Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 8
- 125000001041 indolyl group Chemical group 0.000 claims description 8
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
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- 238000006268 reductive amination reaction Methods 0.000 claims description 7
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 5
- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
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- 206010008118 cerebral infarction Diseases 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 125000005048 dihydroisoxazolyl group Chemical group O1N(CC=C1)* 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 239000007937 lozenge Substances 0.000 claims description 5
- 208000031225 myocardial ischemia Diseases 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000005695 Ammonium acetate Substances 0.000 claims description 4
- 206010063837 Reperfusion injury Diseases 0.000 claims description 4
- 229940043376 ammonium acetate Drugs 0.000 claims description 4
- 235000019257 ammonium acetate Nutrition 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 238000007675 cardiac surgery Methods 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 229940127557 pharmaceutical product Drugs 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 210000001519 tissue Anatomy 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 3
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 238000001802 infusion Methods 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 239000006210 lotion Substances 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 239000002674 ointment Substances 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- YMMHAIJRFWRDMG-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-1h-quinolin-2-one Chemical group C1C=CC=C2NC(=O)CCC21 YMMHAIJRFWRDMG-UHFFFAOYSA-N 0.000 claims description 2
- AMTRUQYJMJGKBL-UHFFFAOYSA-N 3-methyl-4-(3-methylsulfonylanilino)-5,6,7,8-tetrahydro-2h-isoquinolin-1-one Chemical compound CC=1NC(=O)C=2CCCCC=2C=1NC1=CC=CC(S(C)(=O)=O)=C1 AMTRUQYJMJGKBL-UHFFFAOYSA-N 0.000 claims description 2
- ZORYARKCMSNXMI-UHFFFAOYSA-N 4-[5-(hydroxymethyl)furan-2-yl]-3-methyl-5,6,7,8-tetrahydro-2h-isoquinolin-1-one Chemical compound CC=1NC(=O)C=2CCCCC=2C=1C1=CC=C(CO)O1 ZORYARKCMSNXMI-UHFFFAOYSA-N 0.000 claims description 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 206010028851 Necrosis Diseases 0.000 claims description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 2
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 230000006907 apoptotic process Effects 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 230000005779 cell damage Effects 0.000 claims description 2
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- 229940097496 nasal spray Drugs 0.000 claims description 2
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- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 229940098465 tincture Drugs 0.000 claims description 2
- 230000000451 tissue damage Effects 0.000 claims description 2
- 231100000827 tissue damage Toxicity 0.000 claims description 2
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- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
- SCRJIIOWXOEMEL-UHFFFAOYSA-N 4-[5-(butylaminomethyl)furan-2-yl]-3-methyl-5,6,7,8-tetrahydro-2h-isoquinolin-1-one Chemical compound O1C(CNCCCC)=CC=C1C1=C(C)NC(=O)C2=C1CCCC2 SCRJIIOWXOEMEL-UHFFFAOYSA-N 0.000 claims 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 229910052770 Uranium Inorganic materials 0.000 claims 1
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- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 abstract description 24
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 abstract description 24
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 abstract description 23
- 239000003112 inhibitor Substances 0.000 abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 10
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- 229910052786 argon Inorganic materials 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 125000002950 monocyclic group Chemical group 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
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- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 5
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
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- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
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- 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
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- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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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
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- C—CHEMISTRY; METALLURGY
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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
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- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
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- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004028973A DE102004028973A1 (de) | 2004-06-16 | 2004-06-16 | Substituierte Tetrahydro-2H-isochinolin-1-on-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Medikament |
| PCT/EP2005/005871 WO2005123687A1 (de) | 2004-06-16 | 2005-06-01 | Substituierte tetrahydro-2h-isochinolin-1-on-derivate, verfahren zu ihrer herstellung und ihre verwendung als medikament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06013876A true MXPA06013876A (es) | 2007-03-07 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06013876A MXPA06013876A (es) | 2004-06-16 | 2005-06-01 | Derivados de tetrahidro-2h-isoquinolin-1-ona sustituida, metodo para su produccion, y uso de los mismos como medicamentos. |
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| Country | Link |
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| US (2) | US7795278B2 (enExample) |
| EP (1) | EP1758864B1 (enExample) |
| JP (1) | JP4928446B2 (enExample) |
| KR (1) | KR101169919B1 (enExample) |
| CN (1) | CN1968929B (enExample) |
| AU (1) | AU2005254632B2 (enExample) |
| BR (1) | BRPI0512139A (enExample) |
| CA (1) | CA2570942C (enExample) |
| DE (1) | DE102004028973A1 (enExample) |
| IL (1) | IL179758A (enExample) |
| MX (1) | MXPA06013876A (enExample) |
| WO (1) | WO2005123687A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007113202A1 (en) | 2006-03-31 | 2007-10-11 | Glaxo Group Limited | Piperazine derivatives as growth hormone secretagogue (ghs) receptor agonists |
| US8304413B2 (en) | 2008-06-03 | 2012-11-06 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US8735391B2 (en) | 2008-09-26 | 2014-05-27 | University Of Kansas | Synthesis of functionalized octahydro-isoquinolin-1-one-8-carboxamides, octahydro-isoquinolin-1-one-8-carboxylic esters and analogs, and therapeutic methods |
| US8815891B2 (en) | 2008-11-11 | 2014-08-26 | Je Il Pharmaceutical Co., Ltd. | Tricyclic derivative or pharmaceutically acceptable salts thereof, preparation method thereof, and pharmaceutical composition containing the same |
| WO2010081778A1 (en) | 2009-01-17 | 2010-07-22 | Universität Zürich | Blockers of parp for the prevention and treatment of helicobacter pylori induced gastric cancer |
| TWI499418B (zh) * | 2009-05-21 | 2015-09-11 | Nerviano Medical Sciences Srl | 異喹啉－１（２ｈ）－酮衍生物 |
| CN101602725B (zh) * | 2009-07-21 | 2012-07-11 | 浙江大学 | 六氢异喹啉酮类化合物的合成方法 |
| WO2011058367A2 (en) | 2009-11-13 | 2011-05-19 | Astrazeneca Ab | Diagnostic test for predicting responsiveness to treatment with poly(adp-ribose) polymerase (parp) inhibitor |
| EP2593434A1 (en) | 2010-07-16 | 2013-05-22 | Purdue Pharma LP | Pyridine compounds as sodium channel blockers |
| AU2013203824A1 (en) | 2012-03-16 | 2013-10-03 | Purdue Pharma L.P. | Substituted pyridines and pryimidines as sodium channel blockers |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| US9714252B2 (en) | 2012-12-20 | 2017-07-25 | Purdue Pharma L.P. | Cyclic sulfonamides as sodium channel blockers |
| KR102373700B1 (ko) | 2014-04-02 | 2022-03-11 | 인터뮨, 인크. | 항섬유성 피리디논 |
| US10730866B2 (en) | 2014-04-07 | 2020-08-04 | Purdue Pharma L.P. | Indole derivatives and use thereof |
| CN105272936B (zh) * | 2014-05-27 | 2019-05-17 | 中国科学院上海药物研究所 | 一类氮芳基苯并噻唑类parp抑制剂及其制备方法和用途 |
| CN104163796A (zh) * | 2014-08-04 | 2014-11-26 | 上海师范大学 | 一类取代的1,2,3,4-四氢喹啉-4-酮盐酸盐的制备方法 |
| MX375707B (es) | 2015-06-09 | 2025-03-06 | Onconic Therapeutics Inc | Compuesto derivativo triciclico, metodo para prepararlo y composicion farmaceutica que comprende el mismo. |
| JP6457696B2 (ja) | 2015-07-23 | 2019-01-23 | アンスティテュ・キュリＩｎｓｔｉｔｕｔ Ｃｕｒｉｅ | 癌を処置するためのＤｂａｉｔ分子とＰＡＲＰインヒビターとの組合せの使用 |
| GB201519573D0 (en) | 2015-11-05 | 2015-12-23 | King S College London | Combination |
| WO2018162439A1 (en) | 2017-03-08 | 2018-09-13 | Onxeo | New predictive biomarker for the sensitivity to a treatment of cancer with a dbait molecule |
| AU2018260094A1 (en) | 2017-04-28 | 2019-11-07 | Akribes Biomedical Gmbh | A PARP inhibitor in combination with a glucocorticoid and/or ascorbic acid and/or a protein growth factor for the treatment of impaired wound healing |
| WO2019175132A1 (en) | 2018-03-13 | 2019-09-19 | Onxeo | A dbait molecule against acquired resistance in the treatment of cancer |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| CN114437072B (zh) * | 2020-10-30 | 2023-03-31 | 中国科学院大连化学物理研究所 | 一种6-甲基异吲哚并[2,1-a]喹喔啉类化合物的合成方法 |
| GB202217888D0 (en) * | 2022-11-29 | 2023-01-11 | Duke Street Bio Ltd | Pharmaceutical compound |
| WO2024261243A1 (en) | 2023-06-21 | 2024-12-26 | Hemispherian As | Combination comprising a deoxycytidine derivative and a parp inhibitor for use in a method of treating hr proficient cancer |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3594380A (en) * | 1969-02-18 | 1971-07-20 | American Home Prod | Isoquinolin-1(2h)-ones |
| CA1334969C (en) * | 1988-08-19 | 1995-03-28 | Mark James Suto | Substituted dihydroisoquinoline and phthalazine derivatives as potentiators of the lethal effects of radiation and certain chemotherapeutic agents, selected compounds, analogs andprocess |
| US20020022636A1 (en) * | 1997-09-03 | 2002-02-21 | Jia-He Li | Oxo-substituted compounds, process of making, and compositions and methods for inhibiting parp activity |
| US6444676B1 (en) * | 1999-12-20 | 2002-09-03 | Iok-Hou Pang | Use of PARP inhibitors in the treatment of glaucoma |
| US6664269B2 (en) * | 2001-05-08 | 2003-12-16 | Maybridge Plc | Isoquinolinone derivatives |
| JP2004043458A (ja) * | 2002-05-22 | 2004-02-12 | Kyorin Pharmaceut Co Ltd | ４−アリール−５−ヒドロキシイソキノリン誘導体およびその製造法 |
| DE10233388A1 (de) * | 2002-07-23 | 2004-02-12 | Basf Ag | Verfahren zur kontinuierlich betriebenen Reindestillation des bei der koppel-produktfreien Propylenoxidsynthese verwendeten Lösungsmittels Methanol unter gleichzeitiger Abtrennung der Methoxypropanole und der Schwersieder |
| AU2003264386A1 (en) * | 2002-09-10 | 2004-04-30 | Kyorin Pharmaceutical Co., Ltd. | 4-(substituted aryl)-5-hydroxyisoquinolinone derivative |
| PE20060285A1 (es) * | 2004-03-30 | 2006-05-08 | Aventis Pharma Inc | Piridonas sustituidas como inhibidores de pol(adp-ribosa)-polimerasa (parp) |
-
2004
- 2004-06-16 DE DE102004028973A patent/DE102004028973A1/de not_active Withdrawn
-
2005
- 2005-06-01 JP JP2007515811A patent/JP4928446B2/ja not_active Expired - Fee Related
- 2005-06-01 KR KR1020067026566A patent/KR101169919B1/ko not_active Expired - Fee Related
- 2005-06-01 BR BRPI0512139-6A patent/BRPI0512139A/pt not_active IP Right Cessation
- 2005-06-01 WO PCT/EP2005/005871 patent/WO2005123687A1/de not_active Ceased
- 2005-06-01 MX MXPA06013876A patent/MXPA06013876A/es active IP Right Grant
- 2005-06-01 AU AU2005254632A patent/AU2005254632B2/en not_active Ceased
- 2005-06-01 CN CN2005800201245A patent/CN1968929B/zh not_active Expired - Fee Related
- 2005-06-01 CA CA2570942A patent/CA2570942C/en not_active Expired - Fee Related
- 2005-06-01 EP EP05754335.7A patent/EP1758864B1/de not_active Expired - Lifetime
-
2006
- 2006-11-30 IL IL179758A patent/IL179758A/en not_active IP Right Cessation
- 2006-12-06 US US11/567,352 patent/US7795278B2/en not_active Expired - Fee Related
-
2010
- 2010-08-04 US US12/850,328 patent/US20110021462A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP4928446B2 (ja) | 2012-05-09 |
| HK1100409A1 (zh) | 2007-09-21 |
| EP1758864A1 (de) | 2007-03-07 |
| KR20070024612A (ko) | 2007-03-02 |
| AU2005254632B2 (en) | 2011-09-15 |
| KR101169919B1 (ko) | 2012-08-06 |
| US7795278B2 (en) | 2010-09-14 |
| DE102004028973A1 (de) | 2006-01-05 |
| IL179758A0 (en) | 2007-05-15 |
| JP2008502614A (ja) | 2008-01-31 |
| WO2005123687A1 (de) | 2005-12-29 |
| BRPI0512139A (pt) | 2008-02-12 |
| CN1968929B (zh) | 2010-09-08 |
| CN1968929A (zh) | 2007-05-23 |
| US20070142430A1 (en) | 2007-06-21 |
| AU2005254632A1 (en) | 2005-12-29 |
| US20110021462A1 (en) | 2011-01-27 |
| CA2570942A1 (en) | 2005-12-29 |
| EP1758864B1 (de) | 2013-04-10 |
| CA2570942C (en) | 2012-12-11 |
| IL179758A (en) | 2010-12-30 |
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