NZ572815A - Pyridinone and pyridazinone derivatives as inhibitors of poly(adp-ribose)polymerase (parp) - Google Patents
Pyridinone and pyridazinone derivatives as inhibitors of poly(adp-ribose)polymerase (parp)Info
- Publication number
- NZ572815A NZ572815A NZ572815A NZ57281507A NZ572815A NZ 572815 A NZ572815 A NZ 572815A NZ 572815 A NZ572815 A NZ 572815A NZ 57281507 A NZ57281507 A NZ 57281507A NZ 572815 A NZ572815 A NZ 572815A
- Authority
- NZ
- New Zealand
- Prior art keywords
- methyl
- oxo
- dihydropyridazin
- trifluoroacetate
- fluorobenzoyl
- Prior art date
Links
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 title claims abstract description 46
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 title claims abstract description 46
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 title claims abstract description 43
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title claims description 12
- 239000003112 inhibitor Substances 0.000 title abstract description 70
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title abstract description 4
- -1 pyridazinone derivative compounds Chemical class 0.000 claims abstract description 341
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 74
- 238000011282 treatment Methods 0.000 claims abstract description 69
- 201000011510 cancer Diseases 0.000 claims abstract description 63
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 11
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 11
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
- 206010063837 Reperfusion injury Diseases 0.000 claims abstract description 10
- 230000000302 ischemic effect Effects 0.000 claims abstract description 10
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 9
- 208000006011 Stroke Diseases 0.000 claims abstract description 8
- 206010038997 Retroviral infections Diseases 0.000 claims abstract description 7
- 208000019553 vascular disease Diseases 0.000 claims abstract description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 6
- 206010057430 Retinal injury Diseases 0.000 claims abstract description 5
- 230000009758 senescence Effects 0.000 claims abstract description 5
- 230000037380 skin damage Effects 0.000 claims abstract description 5
- 208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 3
- 201000006370 kidney failure Diseases 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 234
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 227
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 212
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 87
- 125000000623 heterocyclic group Chemical group 0.000 claims description 46
- 239000003814 drug Substances 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 38
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 31
- 229920006395 saturated elastomer Polymers 0.000 claims description 31
- 230000002265 prevention Effects 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 12
- 239000002246 antineoplastic agent Substances 0.000 claims description 11
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
- CKNYWTABPYGPEX-UHFFFAOYSA-N pyrrolidin-1-ium;2,2,2-trifluoroacetate Chemical compound C1CC[NH2+]C1.[O-]C(=O)C(F)(F)F CKNYWTABPYGPEX-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 229910003827 NRaRb Inorganic materials 0.000 claims description 6
- 230000001668 ameliorated effect Effects 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- FTMVNUGLWHCBJK-UHFFFAOYSA-N piperidin-1-ium;2,2,2-trifluoroacetate Chemical compound C1CCNCC1.OC(=O)C(F)(F)F FTMVNUGLWHCBJK-UHFFFAOYSA-N 0.000 claims description 5
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 4
- JLUQWVZMDRUTGQ-UHFFFAOYSA-N 3-[[3-(1,8-diazaspiro[4.5]decane-8-carbonyl)-4-fluorophenyl]methyl]-5-ethyl-1h-pyridazin-2-ium-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1C(=O)C(CC)=CC(CC=2C=C(C(F)=CC=2)C(=O)N2CCC3(NCCC3)CC2)=[NH+]1 JLUQWVZMDRUTGQ-UHFFFAOYSA-N 0.000 claims description 3
- VLZAESAXVDBRFX-UHFFFAOYSA-N 3-[[4-fluoro-3-(4-propanoylpiperazine-1-carbonyl)phenyl]methyl]-4,5-dimethyl-1h-pyridazin-6-one Chemical compound C1CN(C(=O)CC)CCN1C(=O)C1=CC(CC=2C(=C(C)C(=O)NN=2)C)=CC=C1F VLZAESAXVDBRFX-UHFFFAOYSA-N 0.000 claims description 3
- SOOQWALEZNJUSY-UHFFFAOYSA-N 3-[[4-fluoro-3-(4-quinazolin-3-ium-4-ylpiperazine-1-carbonyl)phenyl]methyl]-4,5-dimethyl-1h-pyridazin-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1C(=O)C(C)=C(C)C(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C=2C3=CC=CC=C3[NH+]=CN=2)=N1 SOOQWALEZNJUSY-UHFFFAOYSA-N 0.000 claims description 3
- DCAPOCOHTPCWPV-UHFFFAOYSA-N 3-[[4-fluoro-3-[4-(2,2,2-trifluoroacetyl)piperazine-1-carbonyl]phenyl]methyl]-4,5-dimethyl-1h-pyridazin-2-ium-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1C(=O)C(C)=C(C)C(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C(=O)C(F)(F)F)=[NH+]1 DCAPOCOHTPCWPV-UHFFFAOYSA-N 0.000 claims description 3
- DATYPDUHBWBLNF-UHFFFAOYSA-N 3-[[4-fluoro-3-[4-(2,2,3,3,3-pentafluoropropanoyl)piperazine-1-carbonyl]phenyl]methyl]-4,5-dimethyl-1h-pyridazin-2-ium-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1C(=O)C(C)=C(C)C(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C(=O)C(F)(F)C(F)(F)F)=[NH+]1 DATYPDUHBWBLNF-UHFFFAOYSA-N 0.000 claims description 3
- OAPNPJLTWTUAJF-UHFFFAOYSA-N 3-[[4-fluoro-3-[4-(2-methylpyrrolidin-1-ium-2-carbonyl)piperazine-1-carbonyl]phenyl]methyl]-4,5-dimethyl-1h-pyridazin-6-one;chloride Chemical compound [Cl-].CC1=C(O)N=NC(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C(=O)C2(C)[NH2+]CCC2)=C1C OAPNPJLTWTUAJF-UHFFFAOYSA-N 0.000 claims description 3
- PRWUSOQACLUHCV-UHFFFAOYSA-N 3-[[4-fluoro-3-[4-(3,3,3-trifluoropropanoyl)piperazine-1-carbonyl]phenyl]methyl]-4,5-dimethyl-1h-pyridazin-6-one Chemical compound N1C(=O)C(C)=C(C)C(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C(=O)CC(F)(F)F)=N1 PRWUSOQACLUHCV-UHFFFAOYSA-N 0.000 claims description 3
- JHSBRKCIIORYOE-UHFFFAOYSA-N 3-[[4-fluoro-3-[4-(oxolane-2-carbonyl)piperazine-1-carbonyl]phenyl]methyl]-4,5-dimethyl-1h-pyridazin-6-one Chemical compound N1C(=O)C(C)=C(C)C(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C(=O)C2OCCC2)=N1 JHSBRKCIIORYOE-UHFFFAOYSA-N 0.000 claims description 3
- QQESHTSOZPDHMR-UHFFFAOYSA-N 3-[[4-fluoro-3-[4-(pyrrolidine-1-carbonyl)piperazine-1-carbonyl]phenyl]methyl]-4,5-dimethyl-1h-pyridazin-2-ium-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1C(=O)C(C)=C(C)C(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C(=O)N2CCCC2)=[NH+]1 QQESHTSOZPDHMR-UHFFFAOYSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- MBCLRULCFCYDDQ-UHFFFAOYSA-N 3-[5-[(4,5-dimethyl-6-oxo-1h-pyridazin-2-ium-3-yl)methyl]-2-fluorophenyl]-5-methylimidazolidine-2,4-dione;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O=C1C(C)NC(=O)N1C1=CC(CC=2C(=C(C)C(=O)N[NH+]=2)C)=CC=C1F MBCLRULCFCYDDQ-UHFFFAOYSA-N 0.000 claims description 2
- CKJFBEAKZIDFKT-UHFFFAOYSA-N 3-[[3-(1,4-diazepan-4-ium-1-carbonyl)-4-fluorophenyl]methyl]-4,5-diethyl-1h-pyridazin-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1C(=O)C(CC)=C(CC)C(CC=2C=C(C(F)=CC=2)C(=O)N2CC[NH2+]CCC2)=N1 CKJFBEAKZIDFKT-UHFFFAOYSA-N 0.000 claims description 2
- WFWMSFWIVZDZPJ-UHFFFAOYSA-N 3-[[3-[4-(2,2-difluoroacetyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-4,5-dimethyl-1h-pyridazin-6-one Chemical compound N1C(=O)C(C)=C(C)C(CC=2C=C(C(F)=CC=2)C(=O)N2CCN(CC2)C(=O)C(F)F)=N1 WFWMSFWIVZDZPJ-UHFFFAOYSA-N 0.000 claims description 2
- NMDUOVAGQCOSCY-UHFFFAOYSA-N 3-[[4-fluoro-3-[4-(2-methylpropanoyl)piperazine-1-carbonyl]phenyl]methyl]-4,5-dimethyl-1h-pyridazin-2-ium-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1CN(C(=O)C(C)C)CCN1C(=O)C1=CC(CC=2C(=C(C)C(=O)N[NH+]=2)C)=CC=C1F NMDUOVAGQCOSCY-UHFFFAOYSA-N 0.000 claims description 2
- UVIKJZNEJZFQND-UHFFFAOYSA-N 5-ethyl-3-[[4-fluoro-3-[4-[(3-methoxyphenyl)methyl]piperazin-4-ium-1-carbonyl]phenyl]methyl]-1h-pyridazin-6-one;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1C(=O)C(CC)=CC(CC=2C=C(C(F)=CC=2)C(=O)N2CC[NH+](CC=3C=C(OC)C=CC=3)CC2)=N1 UVIKJZNEJZFQND-UHFFFAOYSA-N 0.000 claims description 2
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
- 239000002534 radiation-sensitizing agent Substances 0.000 claims description 2
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PT1919878E (pt) * | 2005-07-21 | 2010-11-02 | Hoffmann La Roche | Derivados de piridazinona como agonistas do receptor da hormona da tiróide |
ES2317584T3 (es) * | 2005-09-30 | 2009-04-16 | F. Hoffmann-La Roche Ag | Inhibidores de nnrt. |
JP4611441B2 (ja) * | 2006-04-03 | 2011-01-12 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | ポリ(adp−リボース)ポリメラーゼ(parp)阻害剤としてのアミド置換インダゾール及びベンゾトリアゾール誘導体 |
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US20090023727A1 (en) | 2007-07-05 | 2009-01-22 | Muhammad Hashim Javaid | Phthalazinone derivatives |
WO2011055270A1 (en) * | 2009-11-04 | 2011-05-12 | Wyeth Llc | Indole based receptor crth2 antagonists |
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JP2009538896A (ja) | 2009-11-12 |
NO343950B1 (no) | 2019-07-22 |
US20090176765A1 (en) | 2009-07-09 |
AU2007266836B2 (en) | 2013-09-26 |
JP5351755B2 (ja) | 2013-11-27 |
IL195113A0 (en) | 2009-09-22 |
ZA200809238B (en) | 2009-12-30 |
IL195113A (en) | 2014-05-28 |
BRPI0711741A2 (pt) | 2011-12-06 |
EP2029551B1 (en) | 2018-10-31 |
BRPI0711741B1 (pt) | 2020-12-29 |
MX2008015014A (es) | 2009-04-17 |
KR20090015092A (ko) | 2009-02-11 |
WO2007138351A2 (en) | 2007-12-06 |
RU2008152824A (ru) | 2010-07-10 |
EP2029551A2 (en) | 2009-03-04 |
AU2007266836A1 (en) | 2007-12-06 |
NO20085397L (no) | 2009-02-25 |
KR101529891B1 (ko) | 2015-06-18 |
CN101501006A (zh) | 2009-08-05 |
ES2702781T3 (es) | 2019-03-05 |
US8188084B2 (en) | 2012-05-29 |
WO2007138351A3 (en) | 2008-08-07 |
CA2653529A1 (en) | 2007-12-06 |
CN103420988A (zh) | 2013-12-04 |
BRPI0711741B8 (pt) | 2021-05-25 |
GB0610680D0 (en) | 2006-07-12 |
CA2653529C (en) | 2016-02-09 |
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