HRP20150139T1 - Tetrahidrofenanthridinoni i tetrahidrociklopentakinolinoni kao inhibitori parp i polimerizacije tubulina - Google Patents
Tetrahidrofenanthridinoni i tetrahidrociklopentakinolinoni kao inhibitori parp i polimerizacije tubulina Download PDFInfo
- Publication number
- HRP20150139T1 HRP20150139T1 HRP20150139TT HRP20150139T HRP20150139T1 HR P20150139 T1 HRP20150139 T1 HR P20150139T1 HR P20150139T T HRP20150139T T HR P20150139TT HR P20150139 T HRP20150139 T HR P20150139T HR P20150139 T1 HRP20150139 T1 HR P20150139T1
- Authority
- HR
- Croatia
- Prior art keywords
- 6alkyl
- formula
- phenyl
- hydrogen
- independently selected
- Prior art date
Links
- FFFLACVXJQXTQE-UHFFFAOYSA-N 1,3,4,4a-tetrahydrocyclopenta[h]quinolin-2-one Chemical class N1C(CCC2C=CC=3C(=C12)C=CC=3)=O FFFLACVXJQXTQE-UHFFFAOYSA-N 0.000 title 1
- NXHQOGQCVYTDHU-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-phenanthridin-1-one Chemical class C1=CC=CC2=C3C(=O)CCCC3NC=C21 NXHQOGQCVYTDHU-UHFFFAOYSA-N 0.000 title 1
- 239000012661 PARP inhibitor Substances 0.000 title 1
- 239000003744 tubulin modulator Substances 0.000 title 1
- -1 azaindolizinyl Chemical group 0.000 claims 23
- 150000001875 compounds Chemical class 0.000 claims 20
- 229910052739 hydrogen Inorganic materials 0.000 claims 15
- 239000001257 hydrogen Substances 0.000 claims 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 15
- 125000003118 aryl group Chemical group 0.000 claims 12
- 125000005843 halogen group Chemical group 0.000 claims 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 12
- 125000004076 pyridyl group Chemical group 0.000 claims 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims 10
- 150000002431 hydrogen Chemical class 0.000 claims 9
- 125000000217 alkyl group Chemical group 0.000 claims 8
- 150000003254 radicals Chemical class 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 5
- 239000002253 acid Substances 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 4
- 239000002585 base Substances 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000004193 piperazinyl group Chemical group 0.000 claims 4
- 125000003386 piperidinyl group Chemical group 0.000 claims 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims 4
- 125000001544 thienyl group Chemical group 0.000 claims 4
- 125000000815 N-oxide group Chemical group 0.000 claims 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims 3
- 239000012453 solvate Substances 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
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 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 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
- 239000003937 drug carrier Substances 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 125000005059 halophenyl group Chemical group 0.000 claims 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 2
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims 2
- 125000001041 indolyl group Chemical group 0.000 claims 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 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
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 150000002923 oximes Chemical class 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 125000001422 pyrrolinyl group Chemical group 0.000 claims 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- 125000004306 triazinyl group Chemical group 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 125000006389 halopyrimidinyl group Chemical group 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (15)
1. Spoj formule (I),
[image]
uključujući njegov stereokemijski izomerni oblik;
naznačen time da Y je CH2 ili CH2-CH2;
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. tvore bi- ili triciklički dio) s 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 mogu biti supstituirani s jednim, dva, tri, četiri ili pet supstituenata koji su svaki neovisno odabrani od halo, cijano, nitro, hidroksikarbonil, C1-6alkil, C2-6alkenil, C2-6alkinil, C3-6cikloalkil, C3-6cikloalkilamino, metiletilamino, aminoC3-6cikloalkil, haloC1-6alkil, trihaloC1-6alkil, C1-6alkilkarbonil, C1-6alkiloksikarbonil, C2-6alkenilkarbonil, oksim, C1-6alkiloksim, amidoksim, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC1-6alkil, hidroksiC2-6alkenil, hidroksiC2-6alkinil, cijanoC1-6alkil, cijanoC2-6alkenil, aminokarbonilC1-6alkil, C1-6alkilsulfonilC1-6alkil, C1-6alkilsulfonilC2-6alkenil, C1-6alkilsulfonilC2-6alkinil,-PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonil, -NR8R9, -C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkil, piperazinilC1-6alkil, C1-6alkilpiperazinilC1-6alkil, morfolinilC1-6alkil, piperidinil, piperazinil, C1-6alkilpiperazinil, morfolinil, fenil, tienil, pirazolil, pirolil, pirolidinil, piridinil, pirimidinil, oksadiazolil, imidazolil, imidazolilC2-6alkinil, C1-6alkilimidazolilC2-6alkinil, cijanopiridinil, fenilC1-6alkil, fenilC2-6alkenil, morfolinilC1-6alkil, C1-6alkiloksifenil, trihaloC1-6alkilfenil, metilpirazolil, halopirimidinil ili dimetilaminopirolidinil; ili
R1 je radikal s formulom
[image]
pri čemu X1 je CH2, NH ili N-CH3;
pri čemu X2 je CH2, C=O, O, NH ili N-CH3;
pri čemu R10 je fenil, piridinil, piridazinil ili pirimidinil, pri čemu svaki fenil, piridinil, piridazinil ili pirimidinil mogu biti supstituirani s jednim ili dva supstituenta svakim neovisno odabranim od halo, hidroksi, cijano, C1-6alkil, amino, polihaloC1-6alkil ili C1-6alkiloksi; ili
R1 je radikal s formulom
[image]
pri čemu X3 je CH ili N;
R2 je metil, etil, propil ili C3-6cikloalkil;
svaki R3 i R4 je neovisno odabran od vodika, metila, etila, propila, hidroksi, trifluorometila, metiloksi; ili R3 i R4 su uzeti zajedno s atomom ugljika na koji su vezani, tako da tvore ciklopropilni prsten ili radikal s formulom C(=O);
svaki R5 i R6 je neovisno odabran od vodika, halo, C1-6alkiloksi, cijano, C1-6alkila, -OCH2CH2NR8R9, -CH2OCH2CH2NR8R9, -OCH2CH2CH2NR8R9;
R7 je vodik, metil ili fluor;
svaki R8 i R9 je neovisno odabran od vodika, halo, C1-6alkil, C2-6alkenil, C2-6alkinil, karbonil, C1-6alkilsulfonilC1-6alkil, C1-6alkiloksiC1-6alkil, hidroksiC1-6alkil, dihidroksiC1-6alkil, cijanoC1-6alkil, trihaloC1-6alkil, fenilC1-6alkil, (diC1-6alkil)aminoC1-6alkil, C1-6alkilsulfonil, morfolinilC1-6alkil, morfolinilkarbonil, piperazinilC1-6alkil, C1-6alkilpiperazinilC1-6alkil, piperidinilC1-6alkil, tiomorfolinilC1-6alkil, C3-6cikloalkilmetil, piridinil, pirimidinil, fenil, halofenil, oksanilC1-6alkil, C1-6alkilsulfonilC1-6alkil ili C1-6alkilkarbonilaminoC1-6alkil;
njegov N-oksidni oblik, njegova farmaceutski prihvatljiva adicijska sol ili njegov solvat.
2. Spoj prema zahtjevu 1 naznačen time da
Y je CH2-CH2; aril je fenil; Het je piridinil, pirimidinil, benzimidazolil ili indazolil; svaki aril ili Het može biti supstituiran s jednim ili dva supstituenta svakim neovisno odabranim od halo, cijano, C1-6alkil, C1-6alkiloksikarbonil, -C1-6alkilNR8R9 ili -OR8; X1 je CH2 ili N-CH3; X2 je CH2, C=O ili O; R10 je fenil koji može biti supstituiran s cijano; R2 je metil; R3 i R4 su vodik; R5 i R6 su vodik; R7 je vodik; i svaki R8 i R9 je neovisno odabran od vodika, halo, C1-6alkila ili trihaloC1-6alkila.
3. Spoj prema bilo kojem zahtjevu 1 ili 2 naznačen time da
Y je CH2-CH2; R1 je fenil, piridinil ili pirimidinil; svaki fenil, piridinil ili pirimidinil može biti supstituiran s jednim ili dva supstituenta svakim neovisno odabranim od halo, cijano ili C1-6alkiloksi; X1 je CH2; X2 je O; R10 je fenil supstituiran s cijano; R2 je metil; R3 i R4 su vodik; R5 i R6 su vodik; i R7 je vodik.
4. Spoj prema bilo kojem zahtjevu 1 do 3 naznačen time da je spoj odabran između slijedećih spojeva :
[image]
njegova farmaceutski prihvatljiva adicijska sol ili njegov solvat.
5. Spoj prema bilo kojem zahtjevu 1 do 4 naznačen time da je za uporabu kao lijek.
6. Farmaceutski pripravak naznačen time da sadrži farmaceutski prihvatljiv nosač i kao aktivni sastojak terapeutski učinkovitu količinu spoja prema bilo kojem zahtjevu 1 do 4.
7. Postupak za pripravu farmaceutskog pripravka prema zahtjevu 6 naznačen time da su farmaceutski prihvatljiv nosač i spoj prema bilo kojem zahtjevu 1 do 4 blisko pomiješani.
8. Uporaba spoja prema bilo kojem zahtjevu 1 do 4 naznačena time da je za proizvodnju lijeka za liječenje poremećaja posredovanog s PARP ili polimerizacijom tubulina.
9. Kombinacija spoja prema bilo kojem zahtjevu 1 do 4 naznačena time da sadrži drugo antitumorsko sredstvo.
10. Postupak za pripravu spoja prema zahtjevu 1, naznačen time da sadrži
a) reakciju intermedijera s formulom (II) s odgovarajućim reagensom u reakcijski-inertnom otapalu uz tvorbu spoja formule (I)
[image]
s varijablama kako je definirano u zahtjevu 1;
b) dodavanje suviška baze u intermedijer s formulom (III) u prisutnosti intermedijera s formulom (IV), pri čemu Halo je kloro ili bromo, u pogodnom otapalu
[image]
sa varijablama kako je definirano u zahtjevu 1;
ili, ako se želi, pretvaranje spojeva formule (I) u drugi slijedeći u struci poznate transformacije, te nadalje, ako se želi, pretvaranje spojeva formule (I), u farmaceutski prihvatljivu kiselu adicijsku sol obradom s kiselinom, ili u farmaceutski prihvatljivu baznu adicijsku sol obradom s bazom, ili obrnuto, pretvaranje oblika kisele adicijske soli u slobodnu bazu obradom s lužinom, ili pretvaranje bazne adicijske soli u slobodnu kiselinu obradom s kiselinom; te ako se želi, pripremu stereokemijskih izomernih oblika ili njihovih oblika N-oksida.
11. Spoj formule (II)
[image]
uključujući njegov stereokemijski izomerni oblik;
naznačen time da
Y je CH2 ili CH2-CH2;
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. tvore bi- ili triciklički dio) s 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 mogu biti supstituirani s jednim, dva, tri, četiri ili pet supstituenata koji su svaki neovisno odabrani od halo, cijano, nitro, hidroksikarbonil, C1-6alkil, C2-6alkenil, C2-6alkinil, C3-6cikloalkil, C3-6cikloalkilamino, metiletilamino, aminoC3-6cikloalkil, haloC1-6alkil, trihaloC1-6alkil, C1-6alkilkarbonil, C1-6alkiloksikarbonil, C2-6alkenilkarbonil, oksim, C1-6alkiloksim, amidoksim, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC1-6alkil, hidroksiC2-6alkenil, hidroksiC2-6alkinil, cijanoC1-6alkil, cijanoC2-6alkenil, aminokarbonilC1-6alkil, C1-6alkilsulfonil-C1-6alkil, C1-6alkilsulfonilC2-6alkenil, C1-6alkilsulfonilC2-6alkinil, -PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonil, -NR8R9, -C1-6alkil-NR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkil, piperazinilC1-6alkil, C1-6alkilpiperazinilC1-6alkil, morfolinilC1-6alkil, piperidinil, piperazinil, C1-6alkilpiperazinil, morfolinil, fenil, tienil, pirazolil, pirolil, pirolidinil, piridinil, pirimidinil, oksadiazolil, imidazolil, imidazolilC2-6alkinil, C1-6alkil-imidazolilC2-6alkinil, cijanopiridinil, fenilC1-6alkil, fenilC2-6alkenil, morfolinilC1-6alkil, C1-6alkiloksifenil, trihaloC1-6alkilfenil, metilpirazolil, halopirimidinil ili dimetilaminopirolidinil; ili
R1 je radikal s formulom
[image]
pri čemu X1 je CH2, NH ili N-CH3;
pri čemu X2 je CH2, C=O, O, NH ili N-CH3;
pri čemu R10 je fenil, piridinil, piridazinil ili pirimidinil, pri čemu svaki fenil, piridinil, piridazinil ili pirimidinil mogu biti supstituirani s jednim ili dva supstituenta svakim neovisno odabranim od halo, hidroksi, cijano, C1-6alkil, amino, polihaloC1-6alkil ili C1-6alkiloksi; ili
R1 je radikal s formulom
[image]
pri čemu X3 je CH ili N;
R2 je metil, etil, propil ili C3-6cikloalkil ;
svaki R3 i R4 je neovisno odabran od vodika, metila, etila, propila, hidroksi, trifluorometila, metiloksi; ili R3 i R4 su uzeti zajedno s atomom ugljika na koji su vezani, tako da tvore ciklopropilni prsten ili radikal s formulom C(=O);
svaki R5 i R6 je neovisno odabran od vodika, halo, C1-6alkiloksi, cijano, C1-6alkila, -OCH2CH2NR8R9 , -CH2OCH2CH2NR8R9, -OCH2CH2CH2NR8R9;
R7 je vodik, metil ili fluor;
svaki R8 i R9 je neovisno odabran od vodika, halo, C1-6alkil, C2-6alkenil, C2-6alkinil, karbonil, C1-6alkilsulfonilC1-6alkil, C1-6akiloksiC1-6alkil, hidroksiC1-6alkil, dihidroksiC1-6alkil, cijanoC1-6alkil, trihaloC1-6alkil, fenilC1-6alkil, (diC1-6alkil)aminoC1-6alkil, C1-6alkilsulfonil, morfolinilC1-6alkil, morfolinilkarbonil, piperazinilC1-6alkil, C1-6alkilpiperazinilC1-6alkil, piperidinilC1-6alkil, tiomorfolinilC1-6alkil, C3-6cikloalkilmetil, piridinil, pirimidinil, fenil, halofenil, oksanilC1-6alkil, C1-6alkilsulfonilC1-6alkil ili C1-6alkilkarbonilaminoC1-6alkil;
njegov N-oksidni oblik, njegova farmaceutski prihvatljiva adicijska sol ili njegov solvat.
12. Postupak za pripravu spoja prema zahtjevu 11, naznačen time da sadrži dodavanje kalijeve soli 2-metil-2-propanola, u intermedijar formule (V) u prisutnosti intermedijara formule (VI), pri čemu W je izlazna skupina, u pogodnom otapalu,
[image]
s varijablama kako je definirano u zahtjevu 1.
13. Spoj prema bilo kojem zahtjevu 1 do 4 naznačen time da je za uporabu kao lijek za liječenje raka.
14. Spoj prema zahtjevu 13 naznačen time da je za uporabu kao lijek za liječenje raka pluća.
15. Spoj prema zahtjevu 13 naznačen time da je za uporabu kao lijek za liječenje raka dojke.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08153432 | 2008-03-27 | ||
| EP09725177.1A EP2271626B1 (en) | 2008-03-27 | 2009-03-26 | Tetrahydrophenanthridinones and tetrahydrocyclopentaquinolinones as parp and tubulin polymerization inhibitors |
| PCT/EP2009/053598 WO2009118382A1 (en) | 2008-03-27 | 2009-03-26 | Tetrahydrophenanthridinones and tetrahydrocyclopentaquinolinones as parp and tubulin polymerization inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20150139T1 true HRP20150139T1 (hr) | 2015-05-22 |
Family
ID=39665796
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20150139TT HRP20150139T1 (hr) | 2008-03-27 | 2015-02-04 | Tetrahidrofenanthridinoni i tetrahidrociklopentakinolinoni kao inhibitori parp i polimerizacije tubulina |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US8889866B2 (hr) |
| EP (1) | EP2271626B1 (hr) |
| JP (1) | JP5492183B2 (hr) |
| CN (1) | CN101981013B (hr) |
| AU (1) | AU2009228943B2 (hr) |
| BR (1) | BRPI0909017A2 (hr) |
| CA (1) | CA2716726C (hr) |
| DK (1) | DK2271626T3 (hr) |
| ES (1) | ES2529545T3 (hr) |
| HK (1) | HK1151796A1 (hr) |
| HR (1) | HRP20150139T1 (hr) |
| MX (1) | MX2010010406A (hr) |
| RU (1) | RU2490260C2 (hr) |
| SI (1) | SI2271626T1 (hr) |
| WO (1) | WO2009118382A1 (hr) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0909017A2 (pt) * | 2008-03-27 | 2020-11-10 | Janssen Pharmaceutica N.V. | tetra-hidrofenantridinonas e tetraidrociclopentaquinolinonas como inibidores de polimerização de tibilina e parp, seus usos, processos de preparação, combinação e composição farmacêutica que as compreende, bem como processo de preparação de uma composição farmacêutica |
| DK2624696T3 (en) | 2010-10-06 | 2017-03-13 | Glaxosmithkline Llc Corp Service Company | BENZIMIDAZOLD DERIVATIVES AS PI3-KINASE INHIBITORS |
| KR20140051944A (ko) | 2011-07-13 | 2014-05-02 | 노파르티스 아게 | 탄키라제 억제제로서 사용하기 위한 4-피페리디닐 화합물 |
| WO2013010092A1 (en) * | 2011-07-13 | 2013-01-17 | Novartis Ag | 4-oxo-3,5,7,8-tetrahydro-4h-pyrano {4,3-d} pyrminidinyl compounds for use as tankyrase inhibitors |
| CN103781776A (zh) | 2011-07-13 | 2014-05-07 | 诺华股份有限公司 | 用作端锚聚合酶抑制剂的新的2-哌啶-1-基-乙酰胺化合物 |
| US9719970B2 (en) | 2012-11-30 | 2017-08-01 | Waters Technologies Corporation | Methods and apparatus for the analysis of vitamin D metabolites |
| CN103304494B (zh) * | 2013-06-20 | 2015-05-27 | 河北大学 | 茚(1,2-b)喹喔啉-11-酮肟衍生物及其制备方法和用途 |
| ES2901152T3 (es) * | 2015-09-30 | 2022-03-21 | Hubei Bio Pharmaceutical Industrial Tech Institute Inc | Tipo de sal y tipo de cristal de un compuesto de 4H-pirazol[1,5-alfa]bencimidazol y método de preparación e intermedio del mismo |
| WO2017223516A1 (en) * | 2016-06-24 | 2017-12-28 | The Regents Of The University Of California | Phthalazine derivatives as inhibitors of parp1, parp2 and/or tubulin useful for the treatment of cancer |
| CN109761902B (zh) * | 2017-11-09 | 2022-06-10 | 四川大学 | 6-菲啶酮衍生物及其制备方法和用途 |
| JP7372253B2 (ja) * | 2018-04-05 | 2023-10-31 | ノビガ・リサーチ・エービー | 癌の治療における使用のためのチューブリン重合阻害剤とポリ（ａｄｐ－リボース）ポリメラーゼ（ｐａｒｐ）阻害剤との新規組合せ |
| RS64283B1 (sr) | 2018-04-30 | 2023-07-31 | Ribon Therapeutics Inc | Piridazinoni kao inhibitori parp7 |
| CN108707147A (zh) * | 2018-06-20 | 2018-10-26 | 桑文军 | 一种新型微管蛋白抑制剂及其在抗肿瘤药物中的应用 |
| WO2021087025A1 (en) | 2019-10-30 | 2021-05-06 | Ribon Therapeutics, Inc. | Pyridazinones as parp7 inhibitors |
| WO2023224998A1 (en) * | 2022-05-17 | 2023-11-23 | 858 Therapeutics, Inc. | Inhibitors of parg |
| US11939335B2 (en) | 2022-05-17 | 2024-03-26 | 858 Therapeutics, Inc. | Substituted imidazo[1,2-a]quinazolines and imidazo [1,2-a]pyrido[4,3-e]pyrimidines as inhibitors of PARG |
Family Cites Families (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB732581A (en) | 1952-01-18 | 1955-06-29 | Ciba Ltd | Manufacture of hydrazine compounds |
| DE1006423B (de) | 1952-01-18 | 1957-04-18 | Ciba Geigy | Verfahren zur Herstellung von Hydrazinophthalazinen |
| 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 |
| US5001125A (en) | 1984-03-26 | 1991-03-19 | Janssen Pharmaceutica N.V. | Anti-virally active pyridazinamines |
| PL147465B1 (en) | 1984-03-26 | 1989-06-30 | Janssen Pharmaceutica Nv | Method of obtaining novel pyridazionoamine compounds |
| 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 |
| GB8827822D0 (en) | 1988-11-29 | 1988-12-29 | Janssen Pharmaceutica Nv | (1h-azol-1-ylmethyl)substituted quinoline derivatives |
| CA2002864C (en) | 1988-11-29 | 1999-11-16 | Eddy J. E. Freyne | (1h-azol-1-ylmethyl) substituted quinoline, quinazoline or quinoxaline 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 |
| DK0637306T3 (da) | 1992-04-23 | 2001-07-30 | Merrell Pharma Inc | 4-Imidomethyl-1-[2'-phenyl-2'-oxoethyl]-piperidiner som serotonin-5HT2-antagonister, deres fremstilling og anvendelse til terapi |
| 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. |
| US6270867B1 (en) * | 1993-06-24 | 2001-08-07 | Pechiney Plastic Packaging, Inc. | Structures of polymers made from single site catalysts |
| 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 |
| ATE266673T1 (de) | 1996-09-10 | 2004-05-15 | Boehringer Ingelheim Pharma | Abgewandelte aminosäuren, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| TW460464B (en) * | 1996-11-25 | 2001-10-21 | Nippon Kayaku Kk | Novel phenanthridinium derivative having an anti-tumor activity and pharmaceutical composition containing the same |
| US6417362B1 (en) | 1997-05-30 | 2002-07-09 | Meiji Seika Kaisha, Ltd. | Nitrogenous heterocyclic compounds and hyperlipemia remedy containing the same |
| JPH10330377A (ja) | 1997-06-02 | 1998-12-15 | Kyowa Hakko Kogyo Co Ltd | ピペリジン誘導体 |
| US6635642B1 (en) | 1997-09-03 | 2003-10-21 | Guilford Pharmaceuticals Inc. | PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same |
| US20030069231A1 (en) | 1999-10-12 | 2003-04-10 | Klaus Rudolf | Modified aminoacids, pharmaceuticals containing these compounds and method for their production |
| EP1026160A4 (en) | 1997-09-16 | 2003-01-22 | Takeda Chemical Industries Ltd | CONNECTIONS WITH NITROGEN-CONDENSED RINGS, METHOD FOR THEIR PRODUCTION AND MEDICINES |
| 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 |
| ATE253067T1 (de) | 1999-01-29 | 2003-11-15 | Abbott Lab | Diazabicyloderivate als nikotin-acetylcholin- rezeptorliganden |
| 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 |
| WO2002094790A1 (fr) | 2001-05-23 | 2002-11-28 | Mitsubishi Pharma Corporation | Compose heterocyclique condense et son utilisation medicale |
| JP2005501848A (ja) | 2001-08-15 | 2005-01-20 | アイコス コーポレイション | ２ｈ−フタラジン−１−オンおよびその使用方法 |
| CA2465491A1 (en) | 2001-11-07 | 2003-05-15 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
| AUPR975601A0 (en) | 2001-12-24 | 2002-01-31 | Fujisawa Pharmaceutical Co., Ltd. | Quinazolinone derivatives |
| AUPS137402A0 (en) | 2002-03-26 | 2002-05-09 | Fujisawa Pharmaceutical Co., Ltd. | Novel tricyclic compounds |
| BR0308945A (pt) | 2002-03-29 | 2005-01-04 | Janssen Pharmaceutica Nv | Derivados radiomarcados de quinolina e quinolinona e uso dos mesmos como ligantes para receptores de glutamato metabotrópicos |
| 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 |
| US20050075364A1 (en) | 2003-07-01 | 2005-04-07 | Kap-Sun Yeung | Indole, azaindole and related heterocyclic N-substituted piperazine derivatives |
| MY154363A (en) * | 2003-11-20 | 2015-06-15 | Janssen Pharmaceutica Nv | 6-alkenyl and 6-phenylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly (adp-ribose) polymerase inhibitors |
| JP4864717B2 (ja) | 2003-11-20 | 2012-02-01 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ポリ（ａｄｐ−リボース）ポリメラーゼインヒビターとしての７−フェニルアルキル置換２−キノリノンおよび２−キノキサリノン |
| SG150533A1 (en) | 2003-11-20 | 2009-03-30 | Janssen Pharmaceutica Nv | 6-alkenyl and 6-phenylalkyl substituted 2-quinolinones and 2- quinoxalinones as poly(adp-ribose) polymerase inhibitors |
| CN1890218B (zh) | 2003-12-03 | 2011-08-03 | Ym生物科学澳大利亚私人有限公司 | 微管蛋白抑制剂 |
| EA010488B1 (ru) | 2003-12-05 | 2008-10-30 | Янссен Фармацевтика Н.В. | 6-замещённые 2-хинолиноны и 2-хиноксалиноны как ингибиторы поли (адф-рибоза) полимеразы |
| WO2005058843A1 (en) | 2003-12-10 | 2005-06-30 | Janssen Pharmaceutica N.V. | Substituted 6-cyclohexylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors |
| 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 |
| KR101258298B1 (ko) | 2004-06-01 | 2013-04-25 | 유니버시티 오브 버지니아 페이턴트 파운데이션 | 암 및 혈관형성의 이중 소분자 억제제 |
| BRPI0512938A (pt) * | 2004-06-30 | 2008-04-15 | Janssen Pharmaceutica Nv | derivados da quinazolinediona como inibidores parp |
| WO2006003146A1 (en) | 2004-06-30 | 2006-01-12 | Janssen Pharmaceutica N.V. | Quinazolinone derivatives as parp inhibitors |
| CA2569824C (en) | 2004-06-30 | 2013-03-19 | Janssen Pharmaceutica N.V. | Phthalazine derivatives as parp inhibitors |
| JP2008518964A (ja) * | 2004-11-01 | 2008-06-05 | ユニバーシティ オブ サザン カリフォルニア | 癌と、血管新生機能に関連する疾患との治療用新規化合物 |
| BRPI0607688A2 (pt) | 2005-02-17 | 2009-09-22 | Synta Pharmaceuticals Corp | método para inibir a polimerização de tubulina em uma célula; método para tratar ou prevenir um distúrbio proliferativo em um indivìduo; método para bloquear, ocluir ou de outro modo romper o fluxo sangüìneo na neovasculatura; composto; composição farmacêutica e uso do referido método e composto |
| US7928126B2 (en) | 2005-04-28 | 2011-04-19 | Mitsubishi Tanabe Pharma Corporation | Cyanopyridine derivative and use thereof as medicine |
| WO2007025009A2 (en) | 2005-08-24 | 2007-03-01 | Inotek Pharmaceuticals Corporation | Indenoisoquinolinone analogs and methods of use thereof |
| JP2009510071A (ja) * | 2005-09-30 | 2009-03-12 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 異常脂血症、高コレステロール血症及び糖尿病の処置のためのｒｘｒアゴニストとしての１，２，３，５−テトラヒドロ−シクロペンタ［ｃ］キノリン−４−オン誘導体 |
| AU2007211840B2 (en) | 2006-02-03 | 2012-03-01 | Bionomics Limited | Substituted benzofurans, benzothiophenes, benzoselenophenes and indoles and their use as tubulin polymerisation inhibitors |
| TW200811173A (en) * | 2006-02-15 | 2008-03-01 | Abbott Lab | Pyrazoloquinolones are potent PART 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 |
| AU2008223793B2 (en) * | 2007-03-08 | 2012-08-23 | Janssen Pharmaceutica Nv | Quinolinone derivatives as PARP and TANK inhibitors |
| US8153633B2 (en) | 2007-06-25 | 2012-04-10 | Amgen Inc. | Phthalazine compounds, compositions and methods of use |
| BRPI0909017A2 (pt) * | 2008-03-27 | 2020-11-10 | Janssen Pharmaceutica N.V. | tetra-hidrofenantridinonas e tetraidrociclopentaquinolinonas como inibidores de polimerização de tibilina e parp, seus usos, processos de preparação, combinação e composição farmacêutica que as compreende, bem como processo de preparação de uma composição farmacêutica |
-
2009
- 2009-03-26 BR BRPI0909017-7A patent/BRPI0909017A2/pt not_active Application Discontinuation
- 2009-03-26 CN CN2009801123862A patent/CN101981013B/zh active Active
- 2009-03-26 CA CA2716726A patent/CA2716726C/en active Active
- 2009-03-26 WO PCT/EP2009/053598 patent/WO2009118382A1/en active Application Filing
- 2009-03-26 EP EP09725177.1A patent/EP2271626B1/en active Active
- 2009-03-26 AU AU2009228943A patent/AU2009228943B2/en not_active Ceased
- 2009-03-26 JP JP2011501234A patent/JP5492183B2/ja active Active
- 2009-03-26 MX MX2010010406A patent/MX2010010406A/es active IP Right Grant
- 2009-03-26 SI SI200931124T patent/SI2271626T1/sl unknown
- 2009-03-26 RU RU2010143857/04A patent/RU2490260C2/ru active
- 2009-03-26 ES ES09725177.1T patent/ES2529545T3/es active Active
- 2009-03-26 DK DK09725177.1T patent/DK2271626T3/en active
- 2009-03-26 US US12/934,753 patent/US8889866B2/en active Active
-
2011
- 2011-06-10 HK HK11105902.3A patent/HK1151796A1/xx not_active IP Right Cessation
-
2014
- 2014-10-14 US US14/513,814 patent/US9150540B2/en active Active
-
2015
- 2015-02-04 HR HRP20150139TT patent/HRP20150139T1/hr unknown
- 2015-08-18 US US14/829,493 patent/US9598396B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CA2716726C (en) | 2017-01-24 |
| EP2271626B1 (en) | 2014-11-26 |
| US20150353526A1 (en) | 2015-12-10 |
| JP5492183B2 (ja) | 2014-05-14 |
| CA2716726A1 (en) | 2009-10-01 |
| DK2271626T3 (en) | 2015-02-23 |
| RU2490260C2 (ru) | 2013-08-20 |
| US20150038521A1 (en) | 2015-02-05 |
| MX2010010406A (es) | 2010-10-25 |
| SI2271626T1 (sl) | 2015-03-31 |
| BRPI0909017A2 (pt) | 2020-11-10 |
| HK1151796A1 (en) | 2012-02-10 |
| JP2011515450A (ja) | 2011-05-19 |
| US8889866B2 (en) | 2014-11-18 |
| US9598396B2 (en) | 2017-03-21 |
| US9150540B2 (en) | 2015-10-06 |
| CN101981013A (zh) | 2011-02-23 |
| AU2009228943B2 (en) | 2013-04-04 |
| EP2271626A1 (en) | 2011-01-12 |
| CN101981013B (zh) | 2013-05-29 |
| US20110263622A1 (en) | 2011-10-27 |
| RU2010143857A (ru) | 2012-05-10 |
| AU2009228943A1 (en) | 2009-10-01 |
| ES2529545T3 (es) | 2015-02-23 |
| WO2009118382A1 (en) | 2009-10-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20150139T1 (hr) | Tetrahidrofenanthridinoni i tetrahidrociklopentakinolinoni kao inhibitori parp i polimerizacije tubulina | |
| HRP20120346T1 (hr) | Derivati kinolinona kao parp i tank inhibitori | |
| CN102869661A (zh) | 抗感染化合物 | |
| HRP20170317T1 (hr) | Spojevi pirimidin-2-amina i njihova uporaba kao inhibitora jak kinaza | |
| KR101464060B1 (ko) | 피라졸-4-일-헤테로사이클릴-카복사마이드 화합물 및 사용 방법 | |
| HRP20170695T1 (hr) | Fenil-3-aza-biciklo[3.1.0]heks-3-il-metanoni i njihova uporaba u obliku lijeka | |
| HRP20151250T1 (hr) | Derivati izoksazolo-piridina | |
| RU2012126083A (ru) | Производные аминооксазина | |
| HRP20160852T1 (hr) | Biciklični heterociklični spojevi kao inhibitori protein tirozin kinaze | |
| AU2017237930A1 (en) | Allosteric modulators of nicotinic acetylcholine receptors | |
| HRP20141108T1 (hr) | Antagonisti piperidinon karboksamid azaindan cgrp receptora | |
| HRP20161032T1 (hr) | Ciklički amidi kao inhibitori metap-2 | |
| WO2013006408A1 (en) | Compounds and methods | |
| JP2009532452A5 (hr) | ||
| NO324155B1 (no) | Kinolinderivater, farmasoytisk sammensetning omfattende samme og anvendelse av samme for fremstilling av medikament | |
| JP2019532067A5 (hr) | ||
| BRPI0720452A2 (pt) | Compostos orgânicos | |
| BRPI0616701A2 (pt) | 2-amino-7,8-diidro-6h-pirido [4,3-d] pirimidin-5-onas | |
| JP2006524222A5 (hr) | ||
| JP2007527901A5 (hr) | ||
| HRP20110394T1 (hr) | Inhibitori interakcije između mdm2 i p53 | |
| JP2013529684A (ja) | フラビウイルス感染の処置または予防のための化合物および方法 | |
| JP2016513648A5 (hr) | ||
| HRP20120510T1 (hr) | Derivati beta amino kiseline za liječenje dijabetesa | |
| RU2019142111A (ru) | Усилитель противоопухолевого эффекта с применением нового соединения бифенила |