HRP20120346T1 - Derivati kinolinona kao parp i tank inhibitori - Google Patents
Derivati kinolinona kao parp i tank inhibitori Download PDFInfo
- Publication number
- HRP20120346T1 HRP20120346T1 HRP20120346AT HRP20120346T HRP20120346T1 HR P20120346 T1 HRP20120346 T1 HR P20120346T1 HR P20120346A T HRP20120346A T HR P20120346AT HR P20120346 T HRP20120346 T HR P20120346T HR P20120346 T1 HRP20120346 T1 HR P20120346T1
- Authority
- HR
- Croatia
- Prior art keywords
- 6alkyl
- formula
- hydrogen
- methyl
- 6alkynyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 20
- -1 azaindolizinyl Chemical group 0.000 claims 40
- 229910052739 hydrogen Inorganic materials 0.000 claims 26
- 239000001257 hydrogen Substances 0.000 claims 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 26
- 150000002431 hydrogen Chemical class 0.000 claims 19
- 125000005843 halogen group Chemical group 0.000 claims 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 17
- 125000003118 aryl group Chemical group 0.000 claims 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 11
- 239000000543 intermediate Substances 0.000 claims 11
- 125000004076 pyridyl group Chemical group 0.000 claims 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 10
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 8
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 7
- 125000004193 piperazinyl group Chemical group 0.000 claims 6
- 125000003386 piperidinyl group Chemical group 0.000 claims 6
- 150000003254 radicals Chemical class 0.000 claims 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 6
- 125000001544 thienyl group Chemical group 0.000 claims 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 5
- 125000004432 carbon atom Chemical group C* 0.000 claims 5
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims 5
- 125000002883 imidazolyl group Chemical group 0.000 claims 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 4
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims 4
- 125000002541 furyl group Chemical group 0.000 claims 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 4
- 239000002904 solvent Substances 0.000 claims 4
- 125000000335 thiazolyl group Chemical group 0.000 claims 4
- 125000001425 triazolyl group Chemical group 0.000 claims 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 3
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 125000001246 bromo group Chemical group Br* 0.000 claims 3
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000005059 halophenyl group Chemical group 0.000 claims 3
- 125000006389 halopyrimidinyl group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 3
- 125000001041 indolyl group Chemical group 0.000 claims 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 3
- 125000002757 morpholinyl group Chemical group 0.000 claims 3
- 125000002971 oxazolyl group Chemical group 0.000 claims 3
- 150000002923 oximes Chemical class 0.000 claims 3
- HCMJWOGOISXSDL-UHFFFAOYSA-N (2-isothiocyanato-1-phenylethyl)benzene Chemical compound C=1C=CC=CC=1C(CN=C=S)C1=CC=CC=C1 HCMJWOGOISXSDL-UHFFFAOYSA-N 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 125000000815 N-oxide group Chemical group 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000002193 Pain Diseases 0.000 claims 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 230000003034 chemosensitisation Effects 0.000 claims 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims 2
- 229910021419 crystalline silicon Inorganic materials 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 2
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 125000001422 pyrrolinyl group Chemical group 0.000 claims 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 230000000451 tissue damage Effects 0.000 claims 2
- 231100000827 tissue damage Toxicity 0.000 claims 2
- 125000004306 triazinyl group Chemical group 0.000 claims 2
- 208000030507 AIDS Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010006895 Cachexia Diseases 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 201000005569 Gout Diseases 0.000 claims 1
- 206010019196 Head injury Diseases 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 206010028851 Necrosis Diseases 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 208000001647 Renal Insufficiency Diseases 0.000 claims 1
- 206010063837 Reperfusion injury Diseases 0.000 claims 1
- 206010040070 Septic Shock Diseases 0.000 claims 1
- 229910007161 Si(CH3)3 Inorganic materials 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 230000032683 aging Effects 0.000 claims 1
- 230000006907 apoptotic process Effects 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 230000005779 cell damage Effects 0.000 claims 1
- 230000030833 cell death Effects 0.000 claims 1
- 208000037887 cell injury Diseases 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 230000007850 degeneration Effects 0.000 claims 1
- 230000003412 degenerative effect Effects 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 230000014509 gene expression Effects 0.000 claims 1
- 208000026278 immune system disease Diseases 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- 230000007574 infarction Effects 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- 125000000468 ketone group Chemical group 0.000 claims 1
- 201000006370 kidney failure Diseases 0.000 claims 1
- 230000003387 muscular Effects 0.000 claims 1
- 201000006938 muscular dystrophy Diseases 0.000 claims 1
- 230000017074 necrotic cell death Effects 0.000 claims 1
- 210000000944 nerve tissue Anatomy 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 201000008482 osteoarthritis Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- 230000000637 radiosensitizating effect Effects 0.000 claims 1
- 230000003362 replicative effect Effects 0.000 claims 1
- 208000032253 retinal ischemia Diseases 0.000 claims 1
- 230000036303 septic shock Effects 0.000 claims 1
- 208000013363 skeletal muscle disease Diseases 0.000 claims 1
- 230000009759 skin aging Effects 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 239000012661 PARP inhibitor Substances 0.000 abstract 1
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- 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
- 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
- C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Spoj formule (I), njegovi N-oksidni oblici, farmaceutski prihvatljive adicijske soli i stereokemijski izomerni oblici, naznačen time dam je 0, 1 ili 2 i kada m je 0 tada je namjeravana direktna veza; n je 0, 1, 2, 3 ili 4 i kada n je 0 tada je namjeravana direktna veza; X je direktna veza, CR10R11, (C=O)NR8, NR8, O ili C?C; R1 je aril ili Het; pri čemu aril je fenil ili naftalenil; pri čemu Het je tienil, pirolil, pirolinil, oksazolil, tiazolil, imidazolil, pirazolil, izoksazolil, izotiazolil, oksadiazolil, triazolil, tetrazolil, tiadiazolil, furanil, piperidinil, piridinil, piridazinil, pirimidinil, piperazinil, pirazinil, triazinil, indolizinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kromanil, purinil, kinolinil, cinolinil, ftalazinil, kinazolinil, kinoksazolinil, naftiridinil ili pteridinil; dva atoma ugljika na arilu ili Het mogu biti premoštena (tj. formiraju bi- ili triciklički dio) sa dvovalentnim radikalom odabranim od????????-O-CH2-CH2-O- (a-1), ????????-CH2-O-CH2-O- (a-2), ????????-O-CH2-CH2- CH2- (a-3), ????????-O-CH2-CH2-NR8- (a-4), ????????-O-CR82-O- (a-5), ????????-O-CH2-CH2- (a-6), ????????-CH2-N-CH2-CH2- (a-7), ????????-(CH2)3- (a-8), ili????????-(CH2)4- (a-9); svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, C3-6cikloalkila, aminoC3-6cikloalkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkenilkarbonila, oksima, C1-6alkiloksima, amidoksima, -C?C-CH2O-CH3, -C?C-CH2N(CH3)2, -C?C-Si(CH3)3, hidroksiC1-6alkila, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, aminokarbonilC1-6alkila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, C1-6alkilsulfonilC1-6alkinila, -PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, tienila, pirazolila, pirolila, pirolidinila, piridinila, pirimidinila, oksadiazolila, imidazolila, imidazolilC2-6alkinila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC1-6alkila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila; R2 je vodik, metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil, cijanofenil ili trifluorometil; R3 je metil, etil, propil, hidroksimetil, halo, trifluorometil, metiloksi ili C1-6alkilkarbonil; R4 je vodik, halo, metil, aminokarbonil, hidroksiaminokarbonil, NR8R9C1-6alkil-, cijanometil, hidroksimetil ili Het; svaki R5, R6 i R7 je neovisno oda
Claims (15)
1. Spoj formule (I),
[image]
njegovi N-oksidni oblici, farmaceutski prihvatljive adicijske soli i stereokemijski izomerni oblici, naznačen time da
m je 0, 1 ili 2 i kada m je 0 tada je namjeravana direktna veza;
n je 0, 1, 2, 3 ili 4 i kada n je 0 tada je namjeravana direktna veza;
X je direktna veza, CR10R11, (C=O)NR8, NR8, O ili C≡C;
R1 je aril ili Het;
pri čemu aril je fenil ili naftalenil;
pri čemu Het je tienil, pirolil, pirolinil, oksazolil, tiazolil, imidazolil, pirazolil, izoksazolil, izotiazolil, oksadiazolil, triazolil, tetrazolil, tiadiazolil, furanil, piperidinil, piridinil, piridazinil, pirimidinil, piperazinil, pirazinil, triazinil, indolizinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kromanil, purinil, kinolinil, cinolinil, ftalazinil, kinazolinil, kinoksazolinil, naftiridinil ili pteridinil;
dva atoma ugljika na arilu ili Het mogu biti premoštena (tj. formiraju bi- ili triciklički dio) sa dvovalentnim radikalom odabranim od
-O-CH2-CH2-O- (a-1),
-CH2-O-CH2-O- (a-2),
-O-CH2-CH2- CH2- (a-3),
-O-CH2-CH2-NR8- (a-4),
-O-CR82-O- (a-5),
-O-CH2-CH2- (a-6),
-CH2-N-CH2-CH2- (a-7),
-(CH2)3- (a-8),
ili
-(CH2)4- (a-9);
svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, C3-6cikloalkila, aminoC3-6cikloalkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkenilkarbonila, oksima, C1-6alkiloksima, amidoksima, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC1-6alkila, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, aminokarbonilC1-6alkila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, C1-6alkilsulfonilC1-6alkinila, -PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, tienila, pirazolila, pirolila, pirolidinila, piridinila, pirimidinila, oksadiazolila, imidazolila, imidazolilC2-6alkinila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC1-6alkila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila;
R2 je vodik, metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil, cijanofenil ili trifluorometil;
R3 je metil, etil, propil, hidroksimetil, halo, trifluorometil, metiloksi ili C1-6alkilkarbonil;
R4 je vodik, halo, metil, aminokarbonil, hidroksiaminokarbonil, NR8R9C1-6alkil-, cijanometil, hidroksimetil ili Het;
svaki R5, R6 i R7 je neovisno odabran od vodika, halo, C1-6alkiloksi, cijano, C1-6alkila, -OCH2CH2NR8R9, -CH2OCH2CH2NR8R9, -OCH2CH2CH2NR8R9 ili C1-6alkiloksiC1-6alkiloksi;
svaki R8 i R9 je neovisno odabran od vodika, halo, C1-6alkila, C2-6alkenila, C2-6alkinila, karbonila, C1-6alkilsulfonilC1-6alkila, C1-6alkiloksiC1-6alkil, hidroksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, (diC1-6alkil)aminoC1-6alkila, C1-6alkilsulfonila, morfolinilC1-6alkila, morfolinilkarbonila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, piperidinilC1-6alkila, tiomorfolinilC1-6alkila, C3-6cikloalkilmetila, piridinila, pirimidinila, fenila, halofenila, oksanilC1-6alkila, C1-6alkilsulfonilC1-6alkila ili C1-6alkilkarbonilaminoC1-6alkila;
svaki R10 i R11 je neovisno odabran od vodika, metila, hidroksila, ili uzeti zajedno sa atomom ugljika na koji su spojeni mogu formirati ciklopropilni prsten ili radikal formule C(=O).
2. Spoj formule (I) prema zahtjevu 1 naznačen time da
m je 0;
X je CR10R11 i tada n je 0; ili X je O i tada n je 2;
Het je tienil, oksazolil, tiazolil, oksadiazolil, triazolil, tiadiazolil, furanil, piridinil, pirimidinil, azaindolizinil, indazolil, benzoksazolil, benzofuranil, benzotiazolil, benzotriazolil, kinolinil ili kinoksazolinil;
dva atoma ugljika na arilu ili Het mogu biti premoštena sa dvovalentnim radikalom odabranim od (a-1), (a-2), (a-4) ili (a-5);
svaki aril ili Het ili premošteni aril može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, amino, hidroksikarbonila, C1-6alkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkinila, -CH=CH-CN, hidroksiC1-6alkila, cijanoC1-6alkila, -PO(OC1-6alkil)2, -S-CH3, C1-6alkilsulfonila, -NR8R9, -CH2NR8R9, -OR8, -CH2OR8, -CONR8R9, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, C1-6alkiloksifenila, pirazolila, metilpirazolila ili oksadiazolila;
R2 je metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fenil ili cijanofenil;
R3 je metil, etil ili hidroksimetil;
R4 je vodik;
svaki R5, R6 i R7 je vodik; ili
svaki R8 i R9 je neovisno odabran od vodika, C1-6alkila, C1-6alkiloksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, C1-6alkilsulfonila, morfolinilC1-6alkila, morfolinilkarbonila, piperazinilC1-6alkila ili C1-6alkilpiperazinilC1-6alkila.
3. Spoj formule (I) prema zahtjevu 1 naznačen time da Het je tienil, tiazolil, imidazolil, oksadiazolil, triazolil, tiadiazolil, furanil, piperidinil, piridinil, pirimidinil, piperazinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kinolinil, cinolinil ili kinoksazolinil; svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, aminoC3-6cikloalkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, oksima, C1-6alkiloksima, amidoksima, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, -PO(OC1-6alkil)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, C1-6alkilpiperazinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, pirolila, pirolidinila, piridinila, oksadiazolila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila;
R2 je metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil ili cijanofenil;
R3 je metil, etil, propil, hidroksimetil, metiloksi ili C1-6alkilkarbonil; R4 je vodik, halo ili metil; svaki R5, R6 i R7 je neovisno odabran od vodika, halo, C1-6alkiloksi, C1-6alkila ili C1-6alkiloksiC1-6alkiloksi;
svaki R8 i R9 je neovisno odabran od vodika, C1-6alkila, C2-6alkinila, C1-6alkiloksiC1-6alkila, hidroksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, C1-6alkilsulfonila,
morfolinilC1-6alkil, morfolinilkarbonila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, C3-6cikloalkilmetila, piridinila, pirimidinila, fenila, halofenila, oksanilC1-6alkila ili C1-6alkilsulfonilC1-6alkila; ili
svaki R10 i R11 je neovisno odabran od vodika ili metila.
4. Spoj formule (I) prema bilo kojem od zahtjeva 1 do 3 naznačen time da
m je 0 ili I; n je 0 ili 1; X je direktna veza, CR10R11 ili NR8; R1 je fenil, tiadiazolil, piridinil ili pirimidinil; R1 je fenil i je premošten sa dvovalentnim radikalom odabranim od (a-3) ili (a-8); svaki fenil, premošteni fenil, tiadiazolil, piridinil ili pirimidinil može biti supstituiran sa jednim ili dva supstituenta koji su svaki neovisno odabrani od vodika, halo, cijano, C1-6alkila, C2-6alkinila, hidroksiC2-6alkenila ili -OR8; R2 je metil; R3 je metil ili etil; R4 je vodik; svaki R5, R6 i R7 je vodik; svaki R8 je neovisno odabran od vodika ili C1-6alkila i svaki R10 i R11 je vodik.
5. Spoj formule (I) prema bilo kojem od zahtjeva 1, 3 i 4 naznačen time da spoj je
Spoj br. 34, Spoj br. 36, Spoj br. 42, Spoj br. 43, Spoj br. 3, Spoj br. 51, Spoj br. 53, Spoj br. 46, Spoj br. 381, Spoj br. 242, Spoj br. 246, Spoj br. 183, Spoj br. 253, Spoj br. 207, Spoj br. 232, Spoj br. 204, Spoj br. 174 ili Spoj br. 252.
[image]
6. Spoj formule (I) prema bilo kojem od zahtjeva 1 do 5 naznačen time da je za uporabu kao lijek.
7. Farmaceutski pripravak naznačen time da sadrži farmaceutski prihvatljive nosače i kao aktivni sastojak terapeutski učinkovitu količinu spoja formule (I) prema bilo kojem od zahtjeva 1 do 5.
8. Uporaba spoja prema bilo kojem od zahtjeva 1 do 5 naznačena time da je za proizvodnju lijeka za liječenje oštećenja tkiva koje proizlazi iz oštećenja stanice ili smrti zbog nekroze ili apoptoze, za liječenje oštećenja živčanog tkiva nastalih zbog ishemije i reperfuzijske ozljede, neuroloških poremećaja i neurodegenerativnih bolesti, za liječenje krvožilnog infarkta; za liječenje kardiovaskularnih bolesti, za liječenje mišićne degeneracije povezane sa starenjem, AIDS-a, imunoloških bolesti povezanih sa starenjem, upale, gihta, artritisa, ateroskleroza, kaheksije, raka, degenerativnih bolesti skeletnih mišića koje uključuju replikativno starenje, dijabetes, traumu glave, poremećaje ulceroznog kolitisa, mišićnu distrofiju, osteoartritis, osteoporozu, kroničnu i/ili akutnu bol, zatajenje bubrega, ishemiju mrežnice, septički šok, te starenje kože; za produljivanje trajanja života i proliferativnog kapaciteta stanica; za promjenu ekspresije gena starih stanica; za kemosenzitiziranje i/ili radiosenzitiziranje tumorskih stanica.
9. Uporaba spoja prema bilo kojem od zahtjeva 1 do 5 naznačena time da je za proizvodnju lijeka za liječenje raka.
10. Uporaba prema zahtjevu 8 i zahtjevu 9 naznačena time da liječenje uključuje kemosenzitiziranje.
11. Uporaba prema zahtjevima 8 i 9 naznačena time da liječenje uključuje radiosenzitiziranje.
12. Kombinirani spoj prema bilo kojem od zahtjeva 1 do 5 naznačen time da je kombinirana sa kemoterapeutskim sredstvom ili antitumorskim sredstvom.
13. Postupak za dobivanje spoja formule (I) prema zahtjevu 1, naznačen time da sadrži
a) reakciju intermedijera formule (II) sa odgovarajućim reagensom u reakcijski-inertnom otapalu uz dobivanje spoja formule (I)
[image]
b) reakciju intermedijera formule (V-a) uz dodavanje suviška baze, u prisutnosti intermedijera formule (VI), pri čemu Halo je kloro ili bromo, u pogodnom otapalu.
[image]
14. Spoj formule (II)
[image]
njegovi N-oksidni oblici, farmaceutski prihvatljive adicijske soli i stereokemijski izomerni oblici, naznačen time da
m je 0, 1 ili 2 i kada n je 0 tada je namjeravana direktna veza;
n je 0, 1, 2, 3 ili 4 i kada n je 0 tada je namjeravana direktna veza;
X je direktna veza, CR10R11, (C=O)NR8, NR8, O ili C≡C;
R1 je aril ili Het;
pri čemu aril je fenil ili naftalenil;
pri čemu Het je tienil, pirolil, pirolinil, oksazolil, tiazolil, imidazolil, pirazolil, izoksazolil, izotiazolil, oksadiazolil, triazolil, tetrazolil, tiadiazolil, furanil, piperidinil, piridinil, piridazinil, pirimidinil, piperazinil, pirazinil, triazinil, indolizinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kromanil, purinil, kinolinil, cinolinil, ftalazinil, kinazolinil, kinoksazolinil, naftiridinil ili pteridinil;
dva atoma ugljika na arilu ili Het mogu biti premoštena (tj. formiraju bi- ili triciklički dio) sa dvovalentnim radikalom odabranim od
-O-CH2-CH2-O- (a-1),
-CH2-O-CH2-O- (a-2),
-O-CH2-CH2- CH2- (a-3),
-O-CH2-CH2-NR8- (a-4),
-O-CR82-O- (a-5),
-O-CH2-CH2- (a-6),
-CH2-N-CH2-CH2- (a-7),
-(CH2)3- (a-8),
ili
-(CH2)4- (a-9);
svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, C3-6cikloalkila, aminoC3-6cikloalkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkenilkarbonila, oksima, C1-6alkiloksima, amidoksima, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC1-6alkila, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, aminokarbonilC1-6alkila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, C1-6alkilsulfonilC1-6alkinila,-PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, tienila, pirazolila, pirolila, pirolidinila, piridinila, pirimidinila, oksadiazolila, imidazolila, imidazolilC2-6alkinila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC1-6alkila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila;
R2 je vodik, metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil, cijanofenil ili trifluorometil;
R3 je metil, etil, propil, hidroksimetil, halo, trifluorometil, metiloksi ili C1-6alkilkarbonil;
R4 je vodik, halo, metil, aminokarbonil, hidroksiaminokarbonil, NR8R9C1-6alkil-, cijanometil, hidroksimetil ili Het;
svaki R5, R6 i R7 je neovisno odabran od vodika, halo, C1-6alkiloksi, cijano, C1-6alkila, -OCH2CH2NR8R9, -CH2OCH2CH2NR8R9, -OCH2CH2CH2NR8R9 ili C1-6alkiloksiC1-6alkiloksi;
svaki R8 i R9 je neovisno odabran od vodika, halo, C1-6alkila, C2-6alkenila, C2-6alkinila, karbonila, C1-6alkilsulfonilC1-6alkila, C1-6alkiloksiC1-6alkila, hidroksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, (diC1-6alkil)aminoC1-6alkila, C1-6alkilsulfonila, morfolinilC1-6alkila, morfolinilkarbonila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, piperidinilC1-6alkila, tiomorfolinilC1-6alkila, C3-6cikloalkilmetila, piridinila, pirimidinila, fenila, halofenila, oksanilC1-6alkila, C1-6alkilsulfonilC1-6alkila ili C1-6alkilkarbonilaminoC1-6alkila;
svaki R10 i R11 je neovisno odabran od vodika, metila, hidroksila, ili uzeti zajedno sa atomom ugljika na koji su spojeni mogu formirati ciklopropilni prsten ili radikal formule C(=O).
15. Postupak za dobivanje spoja formule (11) prema zahtjevu 14, naznačen time da sadrži
a) konverziju ketonske skupine intermedijera formule (III) u hidroksi skupinu, sa odgovarajućim redukcijskim sredstvom, u pogodnom otapalu, uz formiranje spojeva formule (II), pri čemu R3 je hidroksimetil, koji se ovdje nazivaju intermedijeri formule (II-a),
[image]
b) dodavanje kalijeve soli 2-metil-2-propanola, u intermedijere formule (V-b) u prisutnosti intermedijera formule (VI), pri čemu Halo je kloro ili bromo, u pogodnom otapalu, uz formiranje spojeva formule (II), pri čemu R3 je metil, etil ili propil i R2 je metil, etil, C3-6cikloalkil ili fenil, koji se ovdje nazivaju intermedijeri formule (II-b),
[image]
c) dodavanje kalijeve soli 2-metil-2-propanola, u intermedijere formule (VII) u prisutnosti intermedijera formule (VIII), pri čemu Halo je kloro ili bromo, u pogodnom otapalu, uz formiranje spojeva formule (II), pri čemu R3 je metil, etil ili propil i R2 je propil ili C3-6cikloalkilmetil, koji se ovdje nazivaju intermedijeri formule (II-c).
[image]
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US89368007P | 2007-03-08 | 2007-03-08 | |
EP07103788 | 2007-03-08 | ||
PCT/EP2008/052764 WO2008107478A1 (en) | 2007-03-08 | 2008-03-07 | Quinolinone derivatives as parp and tank inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20120346T1 true HRP20120346T1 (hr) | 2012-05-31 |
Family
ID=38421149
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20120346AT HRP20120346T1 (hr) | 2007-03-08 | 2012-04-18 | Derivati kinolinona kao parp i tank inhibitori |
Country Status (11)
Country | Link |
---|---|
US (2) | US8299256B2 (hr) |
EP (1) | EP2134691B1 (hr) |
JP (1) | JP5545955B2 (hr) |
AT (1) | ATE542799T1 (hr) |
AU (1) | AU2008223793B2 (hr) |
CA (1) | CA2678248C (hr) |
DK (1) | DK2134691T3 (hr) |
ES (1) | ES2381446T3 (hr) |
HR (1) | HRP20120346T1 (hr) |
SI (1) | SI2134691T1 (hr) |
WO (1) | WO2008107478A1 (hr) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101118582B1 (ko) | 2003-11-20 | 2012-02-27 | 얀센 파마슈티카 엔.브이. | 폴리(adp-리보스)폴리머라제 저해제로서의 6-알케닐 및6-페닐알킬 치환된 2-퀴놀리논 및 2-퀴녹살리논 |
NZ546990A (en) | 2003-11-20 | 2010-03-26 | Janssen Pharmaceutica Nv | 7-Phenylalkyl substituted 2-quinolinones and 2 quinoxalinones as poly(adp-ribose) polymerase inhibitors |
MXPA06014541A (es) | 2004-06-30 | 2007-03-23 | Janssen Pharmaceutica Nv | Derivados de quinazolindiona como inhibidores de la poli(adp-ribosa) polimerasa. |
NZ551680A (en) | 2004-06-30 | 2010-02-26 | Janssen Pharmaceutica Nv | Quinazolinone derivatives as PARP inhibitors |
MXPA06014542A (es) | 2004-06-30 | 2007-03-23 | Janssen Pharmaceutica Nv | Derivados de ftalazina como inhibidores de poli(adp-ribosa) polimerasa-i. |
CN101242822B (zh) | 2005-07-18 | 2011-08-24 | 彼帕科学公司 | 治疗卵巢癌的药物 |
JP2010502730A (ja) | 2006-09-05 | 2010-01-28 | バイパー サイエンシズ,インコーポレイティド | 癌の治療法 |
CN101534836B (zh) | 2006-09-05 | 2011-09-28 | 彼帕科学公司 | Parp抑制剂在制备治疗肥胖症的药物中的用途 |
WO2008107478A1 (en) | 2007-03-08 | 2008-09-12 | Janssen Pharmaceutica Nv | Quinolinone derivatives as parp and tank inhibitors |
US8404713B2 (en) | 2007-10-26 | 2013-03-26 | Janssen Pharmaceutica Nv | Quinolinone derivatives as PARP inhibitors |
WO2009064738A2 (en) | 2007-11-12 | 2009-05-22 | Bipar Sciences, Inc. | Treatment of breast cancer with a parp inhibitor alone or in combination with anti-tumor agents |
RU2490260C2 (ru) * | 2008-03-27 | 2013-08-20 | Янссен Фармацевтика Нв | Тетрагидрофенантридиноны и тетрагидроциклопентахинолиноны в качестве ингибиторов parp и ингибиторов полимеризации тубулина |
ATE513818T1 (de) * | 2008-03-27 | 2011-07-15 | Janssen Pharmaceutica Nv | Chinazolinonderivate als tubulinpolymerisationshemmer |
JP5439745B2 (ja) * | 2008-05-27 | 2014-03-12 | 宇部興産株式会社 | ハロゲノメチルペンタフルオロスルファニルベンゼン化合物及びその製造方法 |
EP2313093A4 (en) | 2008-07-10 | 2012-03-28 | Angion Biomedica Corp | METHOD AND COMPOSITIONS FOR LOW-MOLECULAR MODULATORS OF THE HEPATOCYTE GROWTH FACTOR (SCATTER FACTOR) ACTIVITY |
US20110098304A1 (en) * | 2008-10-22 | 2011-04-28 | Bijoy Panicker | Small molecule inhibitors of PARP activity |
NZ608069A (en) | 2010-10-06 | 2014-06-27 | Glaxosmithkline Llc | Benzimidazole derivatives as pi3 kinase inhibitors |
CN110711188A (zh) | 2012-01-20 | 2020-01-21 | 德玛公司 | 经取代的己糖醇类用于治疗恶性肿瘤的用途 |
NZ630170A (en) | 2012-02-09 | 2016-03-31 | Merck Patent Gmbh | Tetrahydro-quinazolinone derivatives as tank and parp inhibitors |
CN104169284B (zh) | 2012-03-28 | 2017-03-29 | 默克专利股份公司 | 双环吡嗪酮衍生物 |
JP6097820B2 (ja) * | 2012-05-04 | 2017-03-15 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | ピロロトリアジノン誘導体 |
CA2881330C (en) | 2012-08-08 | 2020-07-21 | Merck Patent Gmbh | (aza-)isoquinolinone derivatives |
US9505749B2 (en) | 2012-08-29 | 2016-11-29 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
EP2900643B1 (en) | 2012-09-26 | 2017-09-27 | Merck Patent GmbH | Quinazolinone derivatives as parp inhibitors |
WO2014085486A2 (en) | 2012-11-30 | 2014-06-05 | Waters Technologies Corporation | Methods and apparatus for the analysis of vitamin d metabolites |
AU2014251038A1 (en) | 2013-04-08 | 2015-11-26 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
WO2015013581A1 (en) | 2013-07-26 | 2015-01-29 | Update Pharma Inc. | Combinatorial methods to improve the therapeutic benefit of bisantrene |
KR102359214B1 (ko) | 2014-04-04 | 2022-02-07 | 델 마 파마슈티컬스 | 폐의 비소세포 암종 및 난소암을 치료하기 위한 디안하이드로갈락티톨 및 이의 유사체 또는 유도체 |
BR112016025396A2 (pt) | 2014-05-07 | 2017-08-15 | Merck Patent Gmbh | derivados de heterociclil-butanamida |
CA2977685C (en) | 2015-03-02 | 2024-02-20 | Sinai Health System | Homologous recombination factors |
DK3356345T3 (da) | 2015-09-30 | 2024-02-12 | Max Planck Gesellschaft | Heteroaryl-derivater som sepiapterin-reduktase-inhibitorer |
IL274936B2 (en) | 2017-12-13 | 2023-09-01 | Lupin Ltd | Transmuted heterocyclic bicyclic compounds as prmt5 inhibitors |
AU2019392502A1 (en) | 2018-12-03 | 2021-07-22 | Merck Patent Gmbh | 4-heteroarylcarbonyl-N-(phenyl or heteroaryl) piperidine-1-carboxamides as inhibitors of tankyrases |
CN114026085A (zh) | 2019-04-11 | 2022-02-08 | 安吉昂生物医药公司 | (e)-3-[2-(2-噻吩基)乙烯基]-1h-吡唑的固体形式 |
CA3145644A1 (en) | 2019-07-19 | 2021-01-28 | Astrazeneca Ab | Parp1 inhibitors |
WO2022247816A1 (zh) | 2021-05-24 | 2022-12-01 | 江苏恒瑞医药股份有限公司 | 含氮杂环类化合物、其制备方法及其在医药上的应用 |
AU2023235233A1 (en) | 2022-03-14 | 2024-09-12 | Slap Pharmaceuticals Llc | Multicyclic compounds |
Family Cites Families (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1006423B (de) | 1952-01-18 | 1957-04-18 | Ciba Geigy | Verfahren zur Herstellung von Hydrazinophthalazinen |
GB732581A (en) | 1952-01-18 | 1955-06-29 | Ciba Ltd | Manufacture of hydrazine compounds |
US3274194A (en) * | 1963-03-29 | 1966-09-20 | Miles Lab | Quinazolinedione derivatives |
GB1062357A (en) | 1965-03-23 | 1967-03-22 | Pfizer & Co C | Quinazolone derivatives |
GB1293565A (en) * | 1969-05-03 | 1972-10-18 | Aspro Nicholas Ltd | Aminophthalazines and pharmaceutical compositions thereof |
US3919425A (en) * | 1971-04-09 | 1975-11-11 | Miles Lab | Method of producing vasodilation using certain 3-substituted-quinazoline derivatives |
BE792206A (hr) | 1971-12-02 | 1973-06-01 | Byk Gulden Lomberg Chem Fab | |
US3879393A (en) | 1973-06-18 | 1975-04-22 | Miles Lab | Derivatives of 1,3-disubstituted 2,4(1h,3h)-quinazolinediones |
FR2436781A1 (fr) | 1978-09-19 | 1980-04-18 | Berri Balzac | Derives d'amino-3 (1h,3h) quinazolinedione-2,4, leur procede de preparation et leurs applications en therapeutique |
US4335127A (en) * | 1979-01-08 | 1982-06-15 | Janssen Pharmaceutica, N.V. | Piperidinylalkyl quinazoline compounds, composition and method of use |
JPS5976082A (ja) | 1982-10-23 | 1984-04-28 | Kyowa Hakko Kogyo Co Ltd | 新規なピペリジン誘導体 |
JPS60120872A (ja) | 1983-12-01 | 1985-06-28 | Kyowa Hakko Kogyo Co Ltd | 新規なヘテロ環状化合物及び強心剤 |
ZM1785A1 (en) | 1984-03-26 | 1986-03-27 | Janssen Pharmaceutica Nv | Anti-virally active phyridazinamines |
US5001125A (en) | 1984-03-26 | 1991-03-19 | Janssen Pharmaceutica N.V. | Anti-virally active pyridazinamines |
DK623586A (da) * | 1985-12-27 | 1987-06-28 | Eisai Co Ltd | Piperidinderivater eller salte deraf og farmaceutiske kompositioner indeholdende forbindelserne |
US5231184A (en) * | 1987-11-23 | 1993-07-27 | Janssen Pharmaceutica N.V. | Pridazinamine derivatives |
US5177075A (en) * | 1988-08-19 | 1993-01-05 | Warner-Lambert Company | Substituted dihydroisoquinolinones and related compounds as potentiators of the lethal effects of radiation and certain chemotherapeutic agents; selected compounds, analogs and process |
CA2002864C (en) | 1988-11-29 | 1999-11-16 | Eddy J. E. Freyne | (1h-azol-1-ylmethyl) substituted quinoline, quinazoline or quinoxaline derivatives |
GB8827822D0 (en) * | 1988-11-29 | 1988-12-29 | Janssen Pharmaceutica Nv | (1h-azol-1-ylmethyl)substituted quinoline derivatives |
US5374637A (en) * | 1989-03-22 | 1994-12-20 | Janssen Pharmaceutica N.V. | N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or dihydrobenzodioxin)carboxamide derivatives |
EP0391462A1 (en) | 1989-04-05 | 1990-10-10 | Janssen Pharmaceutica N.V. | Synergistic compositions containing ketanserin |
US5160727A (en) | 1990-02-13 | 1992-11-03 | Warner-Lambert Company | Tumor cell sensitization method using quinazolinedione derivatives |
IE913473A1 (en) * | 1990-10-15 | 1992-04-22 | Fujisawa Pharmaceutical Co | Quinazoline derivatives and their preparation |
ATE201677T1 (de) | 1992-04-23 | 2001-06-15 | Merrell Pharma Inc | 4-imidomethyl-1-(2'-phenyl-2-oxoethyl)-piperidi e als serotonin-5ht2-antagonisten, ihre herstellung und therapeutische anwendung |
TW294595B (hr) | 1992-11-20 | 1997-01-01 | Janssen Pharmaceutica Nv | |
EP0638567A4 (en) | 1993-02-18 | 1995-05-10 | Kyowa Hakko Kogyo Kk | ADENOSINE INHIBITORS. |
GB9404485D0 (en) | 1994-03-09 | 1994-04-20 | Cancer Res Campaign Tech | Benzamide analogues |
TW445263B (en) | 1996-02-29 | 2001-07-11 | Janssen Pharmaceutica Nv | Novel esters of 1,4-disubstituted piperidine derivatives |
JPH107572A (ja) | 1996-06-17 | 1998-01-13 | Sumitomo Pharmaceut Co Ltd | 腫瘍壊死因子産生阻害剤 |
EP0927192B1 (de) | 1996-09-10 | 2004-05-12 | Boehringer Ingelheim Pharma GmbH & Co.KG | Abgewandelte aminosäuren, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
CA2291630A1 (en) * | 1997-05-30 | 1998-12-03 | Tetsutaro Niizato | Nitrogen-containing heterocyclic compounds and therapeutic agents for hyperlipidemia comprising the same |
JPH10330377A (ja) | 1997-06-02 | 1998-12-15 | Kyowa Hakko Kogyo Co Ltd | ピペリジン誘導体 |
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 |
US6635642B1 (en) | 1997-09-03 | 2003-10-21 | Guilford Pharmaceuticals Inc. | PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same |
US6407116B1 (en) | 1997-09-16 | 2002-06-18 | Takeda Chemical Industries, Inc. | Nitrogenous fused-ring compounds, process for the preparation of the same, and drugs |
US6133277A (en) | 1997-12-05 | 2000-10-17 | Janssen Pharmaceutica N.V. | (Benzodioxan, benzofuran or benzopyran) derivatives having fundic relaxation properties |
JP2000191659A (ja) | 1999-01-04 | 2000-07-11 | Sumitomo Pharmaceut Co Ltd | 腫瘍壊死因子産生阻害剤 |
AU773795B2 (en) | 1999-01-29 | 2004-06-03 | Abbott Laboratories | Diazabicyclic derivatives as nicotinic acetylcholine receptor ligands |
US7265115B2 (en) * | 1999-01-29 | 2007-09-04 | Abbott Laboratories | Diazabicyclic CNS active agents |
US6566372B1 (en) * | 1999-08-27 | 2003-05-20 | Ligand Pharmaceuticals Incorporated | Bicyclic androgen and progesterone receptor modulator compounds and methods |
ES2309095T3 (es) | 2000-10-02 | 2008-12-16 | Janssen Pharmaceutica Nv | Antagonistas de los receptores metabotropicos de glutamato. |
ITMI20002358A1 (it) | 2000-10-31 | 2002-05-01 | Flavio Moroni | Derivati di tieno ,2, 3-c|isochinolin-3-one come inibitori della poli(a dp-ribosio)polimerasi |
AUPR201600A0 (en) | 2000-12-11 | 2001-01-11 | Fujisawa Pharmaceutical Co., Ltd. | Quinazolinone derivative |
JP2002284699A (ja) | 2001-03-28 | 2002-10-03 | Sumitomo Pharmaceut Co Ltd | 視細胞変性疾患治療剤 |
EP1396488A1 (en) * | 2001-05-23 | 2004-03-10 | Mitsubishi Pharma Corporation | Fused heterocyclic compound and medicinal use thereof |
EP1423120A4 (en) | 2001-08-15 | 2005-12-28 | Icos Corp | 2H-PHTALAZINE-1-ONES AND METHODS OF USE THEREOF |
AU2002363429B2 (en) | 2001-11-07 | 2008-05-08 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
AUPR975601A0 (en) | 2001-12-24 | 2002-01-31 | Fujisawa Pharmaceutical Co., Ltd. | Quinazolinone derivatives |
US6822097B1 (en) | 2002-02-07 | 2004-11-23 | Amgen, Inc. | Compounds and methods of uses |
AUPS137402A0 (en) | 2002-03-26 | 2002-05-09 | Fujisawa Pharmaceutical Co., Ltd. | Novel tricyclic compounds |
CA2479109C (en) | 2002-03-29 | 2011-08-02 | Janssen Pharmaceutica N.V. | Radiolabelled quinoline and quinolinone derivatives and their use as metabotropic glutamate receptor ligands |
US7119111B2 (en) | 2002-05-29 | 2006-10-10 | Amgen, Inc. | 2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use |
AR043059A1 (es) | 2002-11-12 | 2005-07-13 | Bayer Pharmaceuticals Corp | Derivados de indolil pirazinona utiles para el tratamiento de trastornos hiper-proliferativos |
ATE540928T1 (de) | 2002-11-22 | 2012-01-15 | Mitsubishi Tanabe Pharma Corp | Isochinolinverbindungen und ihre medizinische verwendung |
US20050075364A1 (en) | 2003-07-01 | 2005-04-07 | Kap-Sun Yeung | Indole, azaindole and related heterocyclic N-substituted piperazine derivatives |
NZ546990A (en) * | 2003-11-20 | 2010-03-26 | Janssen Pharmaceutica Nv | 7-Phenylalkyl substituted 2-quinolinones and 2 quinoxalinones as poly(adp-ribose) polymerase inhibitors |
KR101118582B1 (ko) * | 2003-11-20 | 2012-02-27 | 얀센 파마슈티카 엔.브이. | 폴리(adp-리보스)폴리머라제 저해제로서의 6-알케닐 및6-페닐알킬 치환된 2-퀴놀리논 및 2-퀴녹살리논 |
CN102127056B (zh) | 2003-12-03 | 2013-08-21 | Ym生物科学澳大利亚私人有限公司 | 微管蛋白抑制剂 |
US7879857B2 (en) * | 2003-12-05 | 2011-02-01 | Janssen Pharmaceutica Nv | 6-substituted 2-quinolinones and 2-quinoxalinones as poly (adp-ribose) polymerase inhibitors |
UA91007C2 (ru) * | 2003-12-10 | 2010-06-25 | Янссен Фармацевтика Н.В. | Замещенные 6-циклогексилалкилом замещенные 2-хинолиноны и 2-хиноксалиноны как ингибиторы поли-(адф-рибоза)полимеразы |
PE20060285A1 (es) | 2004-03-30 | 2006-05-08 | Aventis Pharma Inc | Piridonas sustituidas como inhibidores de pol(adp-ribosa)-polimerasa (parp) |
DE102004023332A1 (de) | 2004-05-12 | 2006-01-19 | Bayer Cropscience Gmbh | Chinoxalin-2-on-derivate, diese enthaltende nutzpflanzenschützende Mittel und Verfahren zu ihrer Herstellung und deren Verwendung |
CN1988907B (zh) | 2004-06-01 | 2010-12-22 | 弗吉尼亚大学专利基金会 | 癌瘤及血管生成的双重小分子抑制剂 |
MXPA06014542A (es) | 2004-06-30 | 2007-03-23 | Janssen Pharmaceutica Nv | Derivados de ftalazina como inhibidores de poli(adp-ribosa) polimerasa-i. |
MXPA06014541A (es) | 2004-06-30 | 2007-03-23 | Janssen Pharmaceutica Nv | Derivados de quinazolindiona como inhibidores de la poli(adp-ribosa) polimerasa. |
NZ551680A (en) * | 2004-06-30 | 2010-02-26 | Janssen Pharmaceutica Nv | Quinazolinone derivatives as PARP inhibitors |
AU2006214164B2 (en) | 2005-02-17 | 2010-12-09 | Synta Pharmaceuticals Corp. | Isoxazole combretastin derivatives for the treatment of disorders |
WO2006118231A1 (ja) * | 2005-04-28 | 2006-11-09 | Mitsubishi Tanabe Pharma Corporation | シアノピリジン誘導体及びその医薬としての用途 |
BRPI0615096A2 (pt) | 2005-08-24 | 2009-07-14 | Inotek Pharmaceuticals Corp | análogos de indenoisoquinolinona e métodos de uso dos mesmos |
DK1984333T3 (da) | 2006-02-03 | 2012-07-23 | Bionomics Ltd | Substituerede benzofuraner, benzothiophener, benzoselenophener og indoler og deres anvendelse som inhibitorer af tubulinpolymerisering |
EP1989204B1 (en) | 2006-02-15 | 2014-05-21 | AbbVie Inc. | Pyrazoloquinolones are potent parp inhibitors |
US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
US8466150B2 (en) * | 2006-12-28 | 2013-06-18 | Abbott Laboratories | Inhibitors of poly(ADP-ribose)polymerase |
WO2008107478A1 (en) | 2007-03-08 | 2008-09-12 | Janssen Pharmaceutica Nv | Quinolinone derivatives as parp and tank inhibitors |
EP2170866B1 (en) * | 2007-06-25 | 2014-08-13 | Amgen Inc. | Phthalazine compounds, compositions and methods of use |
-
2008
- 2008-03-07 WO PCT/EP2008/052764 patent/WO2008107478A1/en active Application Filing
- 2008-03-07 CA CA2678248A patent/CA2678248C/en active Active
- 2008-03-07 EP EP08717511A patent/EP2134691B1/en active Active
- 2008-03-07 AU AU2008223793A patent/AU2008223793B2/en not_active Ceased
- 2008-03-07 JP JP2009552213A patent/JP5545955B2/ja active Active
- 2008-03-07 ES ES08717511T patent/ES2381446T3/es active Active
- 2008-03-07 DK DK08717511.3T patent/DK2134691T3/da active
- 2008-03-07 AT AT08717511T patent/ATE542799T1/de active
- 2008-03-07 US US12/529,142 patent/US8299256B2/en active Active
- 2008-03-07 SI SI200830607T patent/SI2134691T1/sl unknown
-
2012
- 2012-04-18 HR HRP20120346AT patent/HRP20120346T1/hr unknown
- 2012-09-14 US US13/617,686 patent/US8778966B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
DK2134691T3 (da) | 2012-05-07 |
WO2008107478A1 (en) | 2008-09-12 |
US20100168065A1 (en) | 2010-07-01 |
WO2008107478A8 (en) | 2008-10-23 |
CA2678248A1 (en) | 2008-09-12 |
JP5545955B2 (ja) | 2014-07-09 |
US8299256B2 (en) | 2012-10-30 |
ES2381446T3 (es) | 2012-05-28 |
AU2008223793A1 (en) | 2008-09-12 |
JP2010520262A (ja) | 2010-06-10 |
AU2008223793B2 (en) | 2012-08-23 |
US8778966B2 (en) | 2014-07-15 |
SI2134691T1 (sl) | 2012-06-29 |
CA2678248C (en) | 2016-06-28 |
EP2134691B1 (en) | 2012-01-25 |
EP2134691A1 (en) | 2009-12-23 |
US20130018017A1 (en) | 2013-01-17 |
ATE542799T1 (de) | 2012-02-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20120346T1 (hr) | Derivati kinolinona kao parp i tank inhibitori | |
ES2949404T3 (es) | Compuestos y composiciones para el tratamiento de afecciones asociadas a la actividad de NLRP | |
ES2902806T3 (es) | Composiciones que contienen compuestos de [1,2,4]triazolo[1,5-a]pirimidin-7-ilo sustituidos como inhibidores de PDE2 | |
JP6524081B2 (ja) | ジヒドロピリミジン化合物及び医薬におけるその適用 | |
ES2795366T3 (es) | Compuestos de indol carboxamida útiles como inhibidores de cinasas | |
ES2901197T3 (es) | Moduladores alostéricos de los receptores nicotínicos de la acetilcolina | |
RU2655914C2 (ru) | Соединения дигидропиримидина и их применение в фармацевтических препаратах | |
JP6162144B2 (ja) | 4,4−二置換−1,4−ジヒドロピリミジン、及びb型肝炎の処置のための医薬としてのその使用 | |
CA2829117C (en) | Novel 6-arylamino pyridone carboxamide as mek inhibitors | |
AU2006297124B2 (en) | 2-amino-7,8-dihydro-6H-pyrido(4,3-d) pyrimidin-5-ones | |
HRP20150139T1 (hr) | Tetrahidrofenanthridinoni i tetrahidrociklopentakinolinoni kao inhibitori parp i polimerizacije tubulina | |
ES2627788T3 (es) | Compuestos heteroarilo y procedimientos de uso de los mismos | |
CN108699077A (zh) | 作为rsv抑制剂的杂环化合物 | |
AU2016322848B2 (en) | 1-phenylpyrrolidin-2-one derivatives as perk inhibitors | |
ES2702477T3 (es) | Compuestos (hetero) aromáticos bicíclicos fusionados útiles para el tratamiento de cánceres | |
JP2015533782A (ja) | スルファモイル−アリールアミド及びb型肝炎の治療のための薬剤としてのその使用 | |
WO2012151567A1 (en) | Pyrimidinone compounds and methods for preventing and treating influenza | |
HRP20170695T1 (hr) | Fenil-3-aza-biciklo[3.1.0]heks-3-il-metanoni i njihova uporaba u obliku lijeka | |
WO2008150899A1 (en) | Combination therapies for treatment of cancer and inflammatory diseases | |
KR20050013562A (ko) | Jak 및 cdk2 프로테인 키나아제의 억제제 | |
CA2647036A1 (en) | Tetrahydropyridothienopyrimidine compounds and methods of use thereof | |
AU2014234908B2 (en) | N-(2-cyano heterocyclyl)pyrazolo pyridones as Janus kinase inhibitors | |
WO2014204263A1 (en) | Substituted pyridinone compounds as mek inhibitors | |
CN103476776A (zh) | 作为FAK/Pyk2抑制剂的2,4-二氨基-6,7-二氢-5H-吡咯并[2,3]嘧啶衍生物 | |
AU2020295399A1 (en) | Small molecule target bromo/acetyl proteins and uses thereof |