DK2271626T3 - Tetrahydrophenanthridinoner og tetrahydrocyclopentaquinolinoner som inhibitorer af polymerisering af parp og tubulin - Google Patents

Tetrahydrophenanthridinoner og tetrahydrocyclopentaquinolinoner som inhibitorer af polymerisering af parp og tubulin Download PDF

Info

Publication number
DK2271626T3
DK2271626T3 DK09725177.1T DK09725177T DK2271626T3 DK 2271626 T3 DK2271626 T3 DK 2271626T3 DK 09725177 T DK09725177 T DK 09725177T DK 2271626 T3 DK2271626 T3 DK 2271626T3
Authority
DK
Denmark
Prior art keywords
alkyl
6alkyl
formula
compounds
hydrogen
Prior art date
Application number
DK09725177.1T
Other languages
English (en)
Inventor
Patrick René Angibaud
Laurence Anne Mevellec
Bruno Roux
Pierre-Henri Storck
Christophe Meyer
Jorge Eduardo Vialard
Original Assignee
Janssen Pharmaceutica Nv
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv
Application granted granted Critical
Publication of DK2271626T3 publication Critical patent/DK2271626T3/da

Links

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)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Claims (15)

1. Forbindelse med formel (I),
CO herunder en stereokemisk isomer form deraf; hvor Y er CH2 eller CH2-CH2; R1 er aryl eller Het; hvor aryl er phenyl eller naphthalenyl; hvor Het er thienyl, pyrrolyl, pyrrolinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, furanyl, piperidinyl, pyridinyl, pyridazinyl, pyrimidinyl, piperazinyl, pyrazinyl, triazinyl, indolizinyl, azaindolizinyl, indolyl, indolinyl, benzothienyl, indazolyl, benzoxazolyl, benzimidazolyl, benzofuranyl, benzothiazolyl, benzotriazolyl, chromanyl, purinyl, quinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxazolinyl, naphthyridinyl eller pteridinyl; to carbonatomer på aryl eller Het kan være broforbundet (det vil sige danner en bi- eller tricyklisk del) med et bivalent radikal, der er udvalgt blandt: -0-CH2-CH2-0- (a-1) , -CH2-O-CH2-O- (a-2), -0-CH2-CH2-CH2- (a-3) , -O-CH2-CH2-NR8- (a-4) , -0-CR82-0- (a-5), -0-CH2-CH2- (a-6) , -CH2-N-CH2-CH2- (a-7), - (CH2) 3- (a-8) eller - (CH2) 4- (a-9); hver aryl, Het, broforbundet aryl eller broforbundet Het kan være substitueret med én, to, tre, fire eller fem substituenter, der hver for sig er udvalgt blandt halo, cyano, nitro, hydroxycarbonyl, Ci_6alkyl, C2_6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3_6cycloalkylamino, methylethylamino, aminoC3_ ecycloalkyl, haloCi_6alkyl, trihaloCi_6alkyl, Ci-6alkylcarbonyl, Ci_6alkyloxycarbonyl, C2-6alkenylcarbonyl, oxim, Ci_6alkyloxim, amidoxim, -C^C-CH20-CH3, -C^C-CH2N (CH3) 2, -C^C-Si (CH3) 3, hydroxyCi_6alkyl, hydroxyC2_6alkenyl, hydroxyC2-6alkynyl, cyanoCi-6alkyl, cyanoC2_6alkenyl, aminocarbonylCi-6alkyl, Ci_ 6alkylsulfonylCi-6alkyl, Ci-6alkylsulfonylC2-6alkenyl, Ci- 6alkylsulfonylC2-6alkynyl,-P0 (OCi-6alkyl) 2, -B(OH)2, -S-CH3, SF5, Ci-6alkylsulf onyl, -NR8R9, -Ci_6alkylNR8R9, -OR8, -Ci-6alkylOR8, CONR8R9, piperidinylCi-6alkyl, piperazinylCi-6alkyl, Ci_ 6alkylpiperazinylCi-6alkyl, morpholinylCi-6alkyl, piperidinyl, piperazinyl, Ci_6alkylpiperazinyl, morpholinyl, phenyl, thienyl, pyrazolyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, oxadiazolyl, imidazolyl, imidazolylC2-6alkynyl, Ci-6alkylimidazolylC2-6alkynyl, cyanopyridinyl, phenylCi-ealkyl, phenylC2-6alkenyl, morpholinylCi_6alkyl, Ci-6alkyloxyphenyl,
trihaloCi_6alkylphenyl, methylpyrazolyl, halopyrimidinyl eller dimethylaminopyrrolidinyl; el 1 »r R1 er et radikal med formlen Ο5"1)* hvor Xi er CH2, NH eller N-CH3; hvor X2 er CH2, C=0, 0, NH eller N-CH3;
hvor R10 er phenyl, pyridinyl, pyridazinyl eller pyrimidinyl, hvor hver phenyl, pyridinyl, pyridazinyl eller pyrimidinyl kan være substitueret med én eller to substituenter, der hver for sig er udvalgt blandt halo, hydroxy, cyano, Ci-6alkyl, amino, polyhaloCi_6alkyl eller Ci-6alkvi nxv: pi ier R1 er et radikal med formlen 05-¾ hvor X3 er CH eller N; R2 er methyl, ethyl, propyl eller C3_6cycloalkyl; hver R3 og R4 er udvalgt uafhængigt blandt hydrogen, methyl, ethyl, propyl, hydroxy, trifluormethyl, methyloxy; eller R3 og R4 sammen med carbonatomet, hvortil de er bundet, danner en cyclopropylring eller et radikal med formlen C(=0); hver R5 og R6 er udvalgt uafhængigt blandt hydrogen, halo, Ci_ 6alkyloxy, cyano, Ci_6alkyl, -OCH2CH2NR8R9, -CH2OCH2CH2NR8R9, - OCH2CH2CH2NR8R9; R7 er hydrogen, methyl eller fluor; hver R8 og R9 er udvalgt uafhængigt blandt hydrogen, halo, Ci_ 6alkyl, C2_6alkenyl, C2-6alkynyl, carbonyl, Ci-6alkylsulf onylCi-6alkyl, Ci-6alkyloxyCi_6alkyl, hydroxyCi_6alkyl, dihydroxyCi-6alkyl, cyanoCi_6alkyl, trihaloCi_6alkyl, phenylCi_6alkyl, (diCi-6alkyl) aminoCi_6alkyl, Ci_6alkylsulfonyl, morpholinylCi_6alkyl, morpholinylcarbonyl, piperazinylCi_6alkyl, Ci- 6alkylpiperazinylCi-6alkyl, piper idinylCi_6al kyl, thiomorpholinylCi-6alkyl, C3-6Cycloalkylmethyl, pyridinyl, pyrimidinyl, phenyl, halophenyl, oxanylCi_6alkyl, Ci-6alkylsulfonylCi-6alkyl eller Ci-6alkylcarbonylaminoCi_6alkyl; en A/-oxidform deraf, et farmaceutisk acceptabelt additionssalt deraf eller et solvat deraf.
2. Forbindelse ifølge krav 1, hvor Y er CH2-CH2; aryl er phenyl; Het er pyridinyl, pyrimidinyl, benzimidazolyl eller indazolyl; hver aryl eller Het kan være substitueret med én eller to substituenter, der hver for sig er udvalgt blandt halo, cyano, Ci_6alkyl, Ci-6alkyloxycarbonyl, -Ci-6alkylNR8R9 eller -OR8; Xi er CH2 eller N-CH3; X2 er CH2, C=0 eller 0; R10 er phenyl, der kan være substitueret med cyano; R2 er methyl; R3 og R4 er hydrogen; R5 og R6 er hydrogen; R7 er hydrogen; og hver R8 og R9 er udvalgt uafhængigt blandt hydrogen, halo, Ci_6alkyl eller trihaloCi_6alkyl.
3. Forbindelse ifølge et hvilket som helst af kravene 1 eller 2, hvor Y er CH2-CH2; R1 er phenyl, pyridinyl eller pyrimidinyl; hver phenyl, pyridinyl eller pyrimidinyl kan være substitueret med én eller to substituenter, der hver for sig er udvalgt blandt halo, cyano eller Ci_6alkyloxy; Xi er CH2; X2 er 0; R10 er phenyl, der er substitueret med cyano; R2 er methyl; R3 og R4 er hydrogen; R5 og R6 er hydrogen; og R7 er hydrogen.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor forbindelsen er udvalgt blandt følgende forbindelser:
et farmaceutisk acceptabelt additionssalt deraf eller et solvat deraf.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse som en medicin.
6. Farmaceutisk præparat, der omfatter et farmaceutisk acceptabelt bæremateriale og som aktiv bestanddel en terapeutisk effektiv mængde af en forbindelse ifølge et hvilket som helst af kravene 1 til 4.
7. Fremgangsmåde til fremstilling af et farmaceutisk præparat ifølge krav 6, hvor det farmaceutisk acceptable bæremateriale og forbindelsen ifølge et hvilket som helst af kravene 1 til 4 blandes grundigt.
8. Anvendelse af en forbindelse ifølge et hvilket som helst af kravene 1 til 4 til fremstilling af et medikament til behandling af en PARP- eller en tubulin- polymeriseringsmedieret forstyrrelse.
9. Kombination af en forbindelse ifølge et hvilket som helst af kravene 1 til 4 med et andet anticancermiddel.
10. Fremgangsmåde til fremstilling af en forbindelse ifølge krav 1, der er kendetegnet ved: a) reaktion af et mellemprodukt med formel (II) med et passende reagens i et reaktions-inert opløsningsmiddel til f romhri nrrol qo p-F on fnrhi nHol οο ττίωΗ '^^'ΠΤΙθΙ (I)
CD) (D med variabierne ifølge krav 1; b) tilsætning af et overskud af en base til et mellemprodukt med formel (III) i nærvær af et mellemprodukt med formel (IV), hunr Hal η οη γΊί Ί nr οΊΊοη Frnm ϊ o +- ωγττι o +- ηηΊ /9(αηΐ rirrcjjji Ciciø 1
med variabierne ifølge krav 1; eller om ønsket omdannelse af forbindelser med formel (I) til hinanden ifølge velkendte transformationer og yderligere om ønsket omdannelse af forbindelserne med formel (I) til et farmaceutisk acceptabelt syreadditionssalt ved hjælp af behandling med en syre eller til et farmaceutisk acceptabelt baseadditionssalt ved hjælp af behandling med en base eller omvendt omdannelse af syreadditionssaltformen til den fri base ved hjælp af behandling med alkali eller omdannelse af baseadditionssaltet til den fri syre ved hjælp af behandling med syre; og om ønsket fremstilling af stereokemisk isomere former eller N-oxidformer deraf.
11. Forbindelse med formel (II)
(H) herunder en stereokemisk isomer form deraf; hvor Y er CH2 eller CH2-CH2; R1 er aryl eller Het; hvor aryl er phenyl eller naphthalenyl; hvor Het er thienyl, pyrrolyl, pyrrolinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, furanyl, piperidinyl, pyridinyl, pyridazinyl, pyrimidinyl, piperazinyl, pyrazinyl, triazinyl, indolizinyl, azaindolizinyl, indolyl, indolinyl, benzothienyl, indazolyl, benzoxazolyl, benzimidazolyl, benzofuranyl, benzothiazolyl, benzotriazolyl, chromanyl, purinyl, quinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxazolinyl, naphthyridinyl eller pteridinyl; to carbonatomer på aryl eller Het kan være broforbundet (det vil sige danner en bi- eller tricyklisk del) med et bivalent radikal, der er udvalgt blandt: -0-CH2-CH2-0- (a-1), -CH2-0-CH2-0- (a-2), -0-CH2-CH2-CH2- (a-3), -0-CH2-CH2-NR8- (a-4), -0-CR82-0- (a-5) , -0-CH2-CH2- (a-6), -CH2-N-CH2-CH2- (a-7) , - (CH2) 3- (a-8) eller - (CH2) 4- (a-9) ; hver aryl, Het, broforbundet aryl eller broforbundet Het kan være substitueret med én, to, tre, fire eller fem substituenter, der hver for sig er udvalgt blandt halo, cyano, nitro, hydroxycarbonyl, Ci_6alkyl, C2_6alkenyl, C2_6alkynyl, C3-6cycloalkyl, C3_6cycloalkylamino, methylethylamino, aminoC3_ 6cycloalkyl, haloCi_6alkyl, trihaloCi_6alkyl, Ci_6alkylcarbonyl, Ci_6alkyloxycarbonyl, C2_6alkenylcarbonyl, oxim, Ci_6alkyloxim, amidoxim, -C=C-CH20-CH3, -C=c-CH2N (CH3) 2, -C=C-Si (CH3) 3, hydroxyCi_6alkyl, hydroxyC2_6alkenyl, hydroxyC2_6alkynyl, cyanoCi-6alkyl, cyanoC2_6alkenyl, aminocarbonylCi_6alkyl, Ci_ 6alkylsulfonyl-Ci-6alkyl, Ci_6alkylsulf onylC2_6alkenyl, Ci_ 6alkylsulfonylC2-6alkynyl, -P0 (0Ci-6alkyl) 2, -B(OH)2, -S-CH3, SF5, Ci_6alkylsulf onyl, -NR8R9, -Ci_6alkyl-NR8R9, -OR8, -Ci_6alkylOR8, - CONR8R9, piperidinylCi_6alkyl, piperazinylCi_6alkyl, Ci_
6alkylpiperazinylCi_6alkyl, morpholinylCi_6alkyl, piperidinyl, piperazinyl, Ci_6alkylpiperazinyl, morpholinyl, phenyl, thienyl, pyrazolyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, oxadiazolyl, imidazolyl, imidazolylC2-6alkynyl, Ci-6alkyl-imidazolylC2-6alkynyl, cyanopyridinyl, phenylCi-6alkyl, phenylC2-6alkenyl, morpholinylCi-6alkyl, Ci-6alkyloxyphenyl, trihaloCi_6alkylphenyl, methylpyrazolyl, halopyrimidinyl eller dimethylaminopyrrolidinyl; 1θ1" R1 er et radikal med formler hvor X2 er CH2, NH eller N-CH3; hvor X2 er CH2, C=0, 0, NH eller N-CH3; hvor R10 er phenyl, pyridinyl, pyridazinyl eller pyrimidinyl, hvor hver phenyl, pyridinyl, pyridazinyl eller pyrimidinyl kan være substitueret med én eller to substituenter, der hver for sig er udvalgt blandt halo, hydroxy, cyano, Ci_6alkyl, amino, polyhaloCi_6alkyl eller Ci_6alkyloxy; eller R1 er et radikal med formlen
(b-2), hvor X3 er CH eller N; R2 er methyl, ethyl, propyl eller C3_6Cycloalkyl; hver R3 og R4 er udvalgt uafhængigt blandt hydrogen, methyl, ethyl, propyl, hydroxy, trifluormethyl, methyloxy; eller R og R4 sammen med carbonatomet, hvortil de er bundet, danner en cyclopropylring eller et radikal med formlen C(=0); hver R5 og R6 er udvalgt uafhængigt blandt hydrogen, halo, Ci- ealkyloxy, cyano, Ci-6alkyl, -OCH2CH2NR8R9 , -CH2OCH2CH2NR8R9, - OCH2CH2CH2NR8R9 ; R7 er hydrogen, methyl eller fluor; hver R8 og R9 er udvalgt uafhængigt blandt hydrogen, halo, Ci-6alkyl, C2-galkenyl, C2_6alkynyl, carbonyl, Ci-6alkylsulf onylCi-ealkyl, Ci-6akyloxyCi-6alkyl, hydroxyCi-6alkyl, dihydroxyCi-6alkyl, cyanoCi-6alkyl, trihaloCi-6alkyl, phenylCi_6alkyl, (diCi- 6alkyl) aminoCi-6alkyl, Ci-6alkylsulfonyl, morpholinylCi-6alkyl, morpholinylcarbonyl, piperazinylCi-6alkyl, Ci- 6alkylpiperazinylCi_6alkyl, piper idinylCi_6al kyl, thiomorpholinylCi-6alkyl, C3-6Cycloalkylmethyl, pyridinyl, pyrimidinyl, phenyl, halophenyl, oxanylCi_6alkyl, Ci_ 6alkylsulfonylCi-6alkyl eller Ci-6alkylcarbonylaminoCi-6alkyl; en N-oxidform deraf, et farmaceutisk acceptabelt additionssalt deraf eller et solvat deraf.
12. Fremgangsmåde til fremstilling af en forbindelse ifølge krav 11, der er kendetegnet ved tilsætning af 2-methyl-2-propanol, kaliumsalt til et mellemprodukt med formel (V) i nærvær af et mellemprodukt med formel (VI), hvor W er en fraspaltelig enhed, i et egnet opløsningsmiddel,
(II) med variabierne ifølge krav 1.
13. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse som en medicin til behandling af cancer.
14. Forbindelse ifølge krav 13 til anvendelse som en medicin til behandling af lungecancer.
15. Forbindelse ifølge krav 13 til anvendelse som en medicin til behandling af brystcancer.
DK09725177.1T 2008-03-27 2009-03-26 Tetrahydrophenanthridinoner og tetrahydrocyclopentaquinolinoner som inhibitorer af polymerisering af parp og tubulin DK2271626T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08153432 2008-03-27
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
DK2271626T3 true DK2271626T3 (da) 2015-02-23

Family

ID=39665796

Family Applications (1)

Application Number Title Priority Date Filing Date
DK09725177.1T DK2271626T3 (da) 2008-03-27 2009-03-26 Tetrahydrophenanthridinoner og tetrahydrocyclopentaquinolinoner som inhibitorer af polymerisering af parp og tubulin

Country Status (15)

Country Link
US (3) US8889866B2 (da)
EP (1) EP2271626B1 (da)
JP (1) JP5492183B2 (da)
CN (1) CN101981013B (da)
AU (1) AU2009228943B2 (da)
BR (1) BRPI0909017A2 (da)
CA (1) CA2716726C (da)
DK (1) DK2271626T3 (da)
ES (1) ES2529545T3 (da)
HK (1) HK1151796A1 (da)
HR (1) HRP20150139T1 (da)
MX (1) MX2010010406A (da)
RU (1) RU2490260C2 (da)
SI (1) SI2271626T1 (da)
WO (1) WO2009118382A1 (da)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101981013B (zh) * 2008-03-27 2013-05-29 詹森药业有限公司 作为parp和微管蛋白聚合抑制剂的四氢菲啶酮和四氢环戊二烯并喹啉酮
ME02663B (me) 2010-10-06 2017-06-20 Glaxosmithkline Llc Derivati benzimidazola kao inhibitori pi3 kinaze
CN103814032A (zh) * 2011-07-13 2014-05-21 诺华股份有限公司 用作端锚聚合酶抑制剂的4-氧代-3,5,7,8-四氢-4H-吡喃并[4,3-d]嘧啶基化合物
JP2014520858A (ja) 2011-07-13 2014-08-25 ノバルティス アーゲー タンキラーゼ阻害剤として用いるための新規な２−ピペリジン−１−イル−アセトアミド化合物
WO2013008217A1 (en) 2011-07-13 2013-01-17 Novartis Ag 4 - piperidinyl compounds for use as tankyrase inhibitors
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
KR102664193B1 (ko) 2015-09-30 2024-05-10 후베이 바이오-파마슈티컬 인더스트리얼 테크놀로지컬 인스티튜트 인크. 4H-피라졸로[1,5-α]벤즈이미다졸계 화합물의 염형, 결정형 및 이의 제조방법과 중간체
AU2017280334C1 (en) * 2016-06-24 2022-10-20 AtlasMedx, Inc 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
US11590130B2 (en) * 2018-04-05 2023-02-28 Noviga Research Ab Combinations of a tubulin polymerization inhibitor and a poly (ADP-ribose) polymerase (PARP) inhibitor for use in the treatment of cancer
CA3098585A1 (en) 2018-04-30 2019-11-07 Ribon Therapeutics Inc. Pyridazinones as parp7 inhibitors
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
AU2020375821A1 (en) 2019-10-30 2022-06-02 Ribon Therapeutics, Inc. Pyridazinones as PARP7 inhibitors
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
AR129339A1 (es) * 2022-05-17 2024-08-14 858 Therapeutics Inc Inhibidores de parg

Family Cites Families (79)

* Cited by examiner, † Cited by third party
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 (da) 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
JPS60226862A (ja) 1984-03-26 1985-11-12 ジヤンセン・フア−マシユ−チカ・ナ−ムロ−ゼ・フエンノ−トシヤツプ 抗ウイルス活性ピリダジンアミン類
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
KR100259107B1 (ko) 1992-04-23 2000-07-01 슈테펜 엘. 네스비트 세로토닌 5ht₂길항제로서의 4-이미도메틸-1-[2'-페닐-2'-옥소에틸]피페리딘, 이의 제조방법 및 이를 포함하는 약제학적 조성물
TW294595B (da) 1992-11-20 1997-01-01 Janssen Pharmaceutica Nv
US5624926A (en) 1993-02-18 1997-04-29 Kyowa Hakko Kogyo Co., Ltd. Piperidinyl-dioxoquinazolines as adenosine reuptake 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
ES2314305T3 (es) 1996-09-10 2009-03-16 BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG Aminoacidos modificados, medicamentos que contienen estos compuestos y procedimiento para su obtencion.
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
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
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
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
US7265115B2 (en) 1999-01-29 2007-09-04 Abbott Laboratories Diazabicyclic CNS active agents
EP1147112B1 (en) 1999-01-29 2003-10-29 Abbott Laboratories Diazabicyclic derivatives as nicotinic acetylcholine receptor ligands
US6566372B1 (en) 1999-08-27 2003-05-20 Ligand Pharmaceuticals Incorporated Bicyclic androgen and progesterone receptor modulator compounds and methods
AU2001293847B2 (en) 2000-10-02 2007-05-24 Janssen Pharmaceutica N.V. Metabotropic glutamate receptor antagonists
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
US6924284B2 (en) 2001-08-15 2005-08-02 Icos Corporation PARP inhibitors
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
KR101061561B1 (ko) 2002-03-29 2011-09-02 얀센 파마슈티카 엔.브이. 대사자극성 글루타메이트 수용체 리간드로서 방사능표지된 퀴놀린 및 퀴놀리논 유도체 및 그의 용도
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
MXPA06005686A (es) 2003-11-20 2006-08-17 Janssen Pharmaceutica Nv 2-quinolinonas y 2-quinoxalinonas 7-fenilaquilo sustituidas como inhibidores de la poli(adp-ribosa)polimerasa.
ES2670349T3 (es) * 2003-11-20 2018-05-30 Janssen Pharmaceutica Nv 2-Quinolinonas y 2-quinoxalinonas sustituidas con 6-alquenilo y 6-fenilalquilo como inhibidores de poli(ADP-ribosa) polimerasa
EP1687277B1 (en) 2003-11-20 2018-04-04 Janssen Pharmaceutica NV 6-alkenyl and 6-phenylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors
ES2528302T3 (es) 2003-12-03 2015-02-06 Ym Biosciences Australia Pty Ltd Heterociclos con 6 anillos de nitrógeno fenilsustituidos como inhibidores de la polimerización de microtúbulos
NZ547193A (en) 2003-12-05 2010-03-26 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
AU2005249527B2 (en) 2004-06-01 2011-08-04 University Of Virginia Patent Foundation Dual small molecule inhibitors of cancer and angiogenesis
UA86237C2 (uk) 2004-06-30 2009-04-10 Янссен Фармацевтика Н.В. Похідні заміщеного 2-алкілхіназолінону як інгібітори parp
US7803795B2 (en) 2004-06-30 2010-09-28 Janssen Pharmaceutica N.V. Phthalazine derivatives as parp inhibitors
CN1980913B (zh) 2004-06-30 2011-12-14 詹森药业有限公司 作为parp抑制剂的喹唑啉二酮衍生物
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
SG164378A1 (en) 2005-02-17 2010-09-29 Synta Pharmaceuticals Corp Compounds for the treatment of proliferative disorders
EP1876178B1 (en) 2005-04-28 2015-05-27 Mitsubishi Tanabe Pharma Corporation Cyanopyridine derivative and use thereof as medicine
CN101316592A (zh) 2005-08-24 2008-12-03 伊诺泰克制药公司 茚并异喹啉酮类似物及其用法
CN101316822A (zh) * 2005-09-30 2008-12-03 詹森药业有限公司 作为RXR激动剂用于治疗异常脂肪血症、高胆固醇血症和糖尿病的1,2,3,5-四氢-环戊烯并[c]喹啉-4-酮衍生物
EP1984333B1 (en) 2006-02-03 2012-04-25 Bionomics Limited Substituted benzofurans, benzothiophenes, benzoselenophenes and indoles and their use as tubulin polymerisation inhibitors
AU2007214411B2 (en) 2006-02-15 2010-07-01 Abbott Laboratories 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
EP2134691B1 (en) 2007-03-08 2012-01-25 Janssen Pharmaceutica, N.V. Quinolinone derivatives as parp and tank inhibitors
US8153633B2 (en) 2007-06-25 2012-04-10 Amgen Inc. Phthalazine compounds, compositions and methods of use
CN101981013B (zh) * 2008-03-27 2013-05-29 詹森药业有限公司 作为parp和微管蛋白聚合抑制剂的四氢菲啶酮和四氢环戊二烯并喹啉酮

Also Published As

Publication number Publication date
BRPI0909017A2 (pt) 2020-11-10
AU2009228943B2 (en) 2013-04-04
HRP20150139T1 (hr) 2015-05-22
JP2011515450A (ja) 2011-05-19
SI2271626T1 (sl) 2015-03-31
US9150540B2 (en) 2015-10-06
CA2716726A1 (en) 2009-10-01
AU2009228943A1 (en) 2009-10-01
US8889866B2 (en) 2014-11-18
ES2529545T3 (es) 2015-02-23
CA2716726C (en) 2017-01-24
EP2271626A1 (en) 2011-01-12
HK1151796A1 (en) 2012-02-10
JP5492183B2 (ja) 2014-05-14
US20150353526A1 (en) 2015-12-10
WO2009118382A1 (en) 2009-10-01
US20150038521A1 (en) 2015-02-05
RU2010143857A (ru) 2012-05-10
EP2271626B1 (en) 2014-11-26
RU2490260C2 (ru) 2013-08-20
CN101981013A (zh) 2011-02-23
MX2010010406A (es) 2010-10-25
CN101981013B (zh) 2013-05-29
US9598396B2 (en) 2017-03-21
US20110263622A1 (en) 2011-10-27

Similar Documents

Publication Publication Date Title
DK2271626T3 (da) Tetrahydrophenanthridinoner og tetrahydrocyclopentaquinolinoner som inhibitorer af polymerisering af parp og tubulin
EP2215075B1 (en) Quinolinone derivatives as parp inhibitors
US8299256B2 (en) Quinolinone derivatives as PARP and TANK inhibitors
MXPA06014541A (es) Derivados de quinazolindiona como inhibidores de la poli(adp-ribosa) polimerasa.
CA2716088C (en) Quinazolinone derivatives as tubulin polymerization inhibitors