JP2014516989A5 - - Google Patents
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- Publication number
- JP2014516989A5 JP2014516989A5 JP2014513717A JP2014513717A JP2014516989A5 JP 2014516989 A5 JP2014516989 A5 JP 2014516989A5 JP 2014513717 A JP2014513717 A JP 2014513717A JP 2014513717 A JP2014513717 A JP 2014513717A JP 2014516989 A5 JP2014516989 A5 JP 2014516989A5
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- azaphosphinan
- oxide
- fluoro
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 166
- 150000003839 salts Chemical class 0.000 claims description 151
- 239000012453 solvate Substances 0.000 claims description 151
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 claims description 92
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 62
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 60
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 52
- 150000002431 hydrogen Chemical class 0.000 claims description 45
- -1 1-azetidinyl Chemical group 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 claims description 11
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 6
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 230000005764 inhibitory process Effects 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 4
- 230000001668 ameliorated effect Effects 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 238000004806 packaging method and process Methods 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 3
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 claims description 3
- 229910052805 deuterium Inorganic materials 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- OTUFIKSADHPTNT-UHFFFAOYSA-N 4-[2-fluoro-5-[(4-oxo-3h-phthalazin-1-yl)methyl]phenyl]-n,n-dimethyl-4-oxo-1,4$l^{5}-azaphosphinane-1-carboxamide Chemical compound C1CN(C(=O)N(C)C)CCP1(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F OTUFIKSADHPTNT-UHFFFAOYSA-N 0.000 claims description 2
- FEMVTGCOAIXYPF-UHFFFAOYSA-N 4-[[3-(4-ethoxy-4-oxo-1,4$l^{5}-azaphosphinane-1-carbonyl)-4-fluorophenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CP(OCC)(=O)CCN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F FEMVTGCOAIXYPF-UHFFFAOYSA-N 0.000 claims description 2
- ZGNPQBZYKKGONQ-UHFFFAOYSA-N 4-[[3-(4-ethyl-4-oxo-1,4$l^{5}-azaphosphinane-1-carbonyl)-4-fluorophenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CP(CC)(=O)CCN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F ZGNPQBZYKKGONQ-UHFFFAOYSA-N 0.000 claims description 2
- ZFXYFCAQJYKEKE-UHFFFAOYSA-N 4-[[4-fluoro-3-(4-methyl-4-oxo-1,4$l^{5}-azaphosphinane-1-carbonyl)phenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CP(C)(=O)CCN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F ZFXYFCAQJYKEKE-UHFFFAOYSA-N 0.000 claims description 2
- GYYUJGPNSBAXSG-UHFFFAOYSA-N 4-[[4-fluoro-3-(4-oxo-4-propan-2-yl-1,4$l^{5}-azaphosphinane-1-carbonyl)phenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CP(C(C)C)(=O)CCN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F GYYUJGPNSBAXSG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 2
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims description 2
- 108091026813 Poly(ADPribose) Proteins 0.000 claims description 2
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 230000002950 deficient Effects 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 230000003834 intracellular effect Effects 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 238000000034 method Methods 0.000 description 7
- 230000002265 prevention Effects 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 0 *c(ccc(CC(c1ccccc11)=NNC1=O)c1)c1P1(CCN(*)CC1)=O Chemical compound *c(ccc(CC(c1ccccc11)=NNC1=O)c1)c1P1(CCN(*)CC1)=O 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161491851P | 2011-05-31 | 2011-05-31 | |
| US61/491,851 | 2011-05-31 | ||
| PCT/US2012/040304 WO2012166983A1 (en) | 2011-05-31 | 2012-05-31 | Tricyclic inhibitors of poly(adp-ribose)polymerase |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014516989A JP2014516989A (ja) | 2014-07-17 |
| JP2014516989A5 true JP2014516989A5 (enExample) | 2015-07-16 |
| JP5960253B2 JP5960253B2 (ja) | 2016-08-02 |
Family
ID=47259874
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014513717A Active JP5960253B2 (ja) | 2011-05-31 | 2012-05-31 | ポリ（ａｄｐ−リボース）ポリメラーゼの三環系阻害剤 |
Country Status (8)
| Country | Link |
|---|---|
| US (5) | US20140221314A1 (enExample) |
| EP (2) | EP3925962A1 (enExample) |
| JP (1) | JP5960253B2 (enExample) |
| CN (1) | CN103717609B (enExample) |
| CA (1) | CA2875025C (enExample) |
| ES (1) | ES2871052T3 (enExample) |
| TW (1) | TWI577693B (enExample) |
| WO (1) | WO2012166983A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3925962A1 (en) | 2011-05-31 | 2021-12-22 | Rakovina Therapeutics Inc. | Tricyclic inhibitors of poly(adp-ribose) polymerase |
| DK2938598T3 (en) | 2012-12-31 | 2017-02-13 | Cadila Healthcare Ltd | Substituted phthalazine-1 (2H) -one derivatives as selective inhibitors of poly (adp-ribose) polymerase-1 |
| US10562886B2 (en) | 2015-05-21 | 2020-02-18 | The Regents Of The University Of California | Anti-cancer compounds |
| 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 |
| CN111936143A (zh) * | 2018-04-05 | 2020-11-13 | 诺维嘉研究公司 | 用于治疗癌症的微管蛋白聚合抑制剂和聚(adp-核糖)聚合酶(parp)抑制剂的新型联用药品 |
| CN119390683A (zh) | 2019-08-15 | 2025-02-07 | 黑钻治疗公司 | 炔基喹唑啉化合物 |
| CN112574122B (zh) * | 2019-09-27 | 2024-05-31 | 上海天慈国际药业有限公司 | 一种奥拉帕尼关键中间体的制备方法 |
| CN114276301B (zh) * | 2020-09-27 | 2025-04-01 | 江西科睿药业有限公司 | Parp抑制剂的中间体化合物及其制备方法和应用 |
| CN112624981B (zh) * | 2021-03-09 | 2021-05-25 | 南京桦冠生物技术有限公司 | 一种2-氟-5-[(4-氧代-3h-2,3-二氮杂萘基)甲基]苯甲酸的制备方法 |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE218556T1 (de) | 1995-11-17 | 2002-06-15 | Biotechnolog Forschung Gmbh | Epothilon-derivate und deren herstellung |
| US6242469B1 (en) | 1996-12-03 | 2001-06-05 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| JP2002536968A (ja) | 1999-01-29 | 2002-11-05 | イムクローン システムズ インコーポレイティド | Ｋｄｒに特異的な抗体およびその使用 |
| GB9904387D0 (en) | 1999-02-25 | 1999-04-21 | Pharmacia & Upjohn Spa | Antitumour synergistic composition |
| AU4972900A (en) | 1999-04-08 | 2000-11-14 | Arch Development Corporation | Use of anti-vegf antibody to enhance radiation in cancer therapy |
| AU9578901A (en) | 2000-10-30 | 2002-05-15 | Kudos Pharm Ltd | Phthalazinone derivatives |
| US7151102B2 (en) * | 2000-10-30 | 2006-12-19 | Kudos Pharmaceuticals Limited | Phthalazinone derivatives |
| US7402580B2 (en) | 2002-02-19 | 2008-07-22 | Ono Pharmaceutical Co., Ltd. | Fused pyridazine derivative compounds and drugs containing these compounds as the active ingredient |
| US7196085B2 (en) | 2002-04-30 | 2007-03-27 | Kudos Pharmaceuticals Limited | Phthalazinone derivatives |
| US7223749B2 (en) | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| AU2004220321B2 (en) * | 2003-03-12 | 2010-02-25 | Kudos Pharmaceuticals Ltd | Phthalazinone derivatives |
| EP1791827A1 (en) | 2004-08-26 | 2007-06-06 | Kudos Pharmaceuticals Limited | 4-heteroarylmethyl substituted phthalazinone derivatives |
| GB0419072D0 (en) * | 2004-08-26 | 2004-09-29 | Kudos Pharm Ltd | Phthalazinone derivatives |
| GB0521373D0 (en) | 2005-10-20 | 2005-11-30 | Kudos Pharm Ltd | Pthalazinone derivatives |
| GB0610680D0 (en) | 2006-05-31 | 2006-07-12 | Istituto Di Ricerche D Biolog | Therapeutic compounds |
| JP2009544611A (ja) * | 2006-07-20 | 2009-12-17 | メルク エンド カムパニー インコーポレーテッド | ヒストン脱アセチル化酵素阻害剤としてのリン誘導体 |
| US8466150B2 (en) | 2006-12-28 | 2013-06-18 | Abbott Laboratories | Inhibitors of poly(ADP-ribose)polymerase |
| PT2698062E (pt) | 2006-12-28 | 2015-10-19 | Abbvie Inc | Inibidores da poli (adp-ribose) polimerase |
| US20080280910A1 (en) | 2007-03-22 | 2008-11-13 | Keith Allan Menear | Phthalazinone derivatives |
| TW200900396A (en) | 2007-04-10 | 2009-01-01 | Kudos Pharm Ltd | Phthalazinone derivatives |
| US20090023727A1 (en) | 2007-07-05 | 2009-01-22 | Muhammad Hashim Javaid | Phthalazinone derivatives |
| AU2008299721A1 (en) | 2007-09-14 | 2009-03-19 | Astrazeneca Ab | Phthalazinone derivatives |
| AU2008313467B2 (en) * | 2007-10-17 | 2013-08-29 | Kudos Pharmaceuticals Limited | 4- [3- (4-cyclopropanecarbonyl-piperazine-1-carbonyl) -4 -fluoro-benzyl] -2H-phthalazin-1-one |
| WO2009063244A1 (en) | 2007-11-15 | 2009-05-22 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Pyridazinone derivatives as parp inhibitors |
| AR070221A1 (es) | 2008-01-23 | 2010-03-25 | Astrazeneca Ab | Derivados de ftalazinona inhibidores de polimerasas, composiciones farmaceuticas que los contienen y usos de los mismos para prevenir y/o tratar tumores cancerigenos,lesiones isquemicas y otras enfermedades asociadas. |
| EP2300013B2 (en) * | 2008-05-21 | 2024-11-13 | Takeda Pharmaceutical Company Limited | Phosphorous derivatives as kinase inhibitors |
| NZ597140A (en) * | 2009-06-05 | 2014-01-31 | Cephalon Inc | Preparation and uses of 1,2,4-triazolo [1,5a] pyridine derivatives |
| JP5721709B2 (ja) | 2009-07-02 | 2015-05-20 | ニューゲン セラピューティクス， インコーポレイテッド | リンを含むキナゾリン化合物および使用方法 |
| EP3925962A1 (en) | 2011-05-31 | 2021-12-22 | Rakovina Therapeutics Inc. | Tricyclic inhibitors of poly(adp-ribose) polymerase |
-
2012
- 2012-05-31 EP EP21161257.7A patent/EP3925962A1/en not_active Withdrawn
- 2012-05-31 ES ES12792550T patent/ES2871052T3/es active Active
- 2012-05-31 WO PCT/US2012/040304 patent/WO2012166983A1/en not_active Ceased
- 2012-05-31 EP EP12792550.1A patent/EP2714703B1/en active Active
- 2012-05-31 US US14/122,983 patent/US20140221314A1/en not_active Abandoned
- 2012-05-31 JP JP2014513717A patent/JP5960253B2/ja active Active
- 2012-05-31 CA CA2875025A patent/CA2875025C/en active Active
- 2012-05-31 CN CN201280024255.0A patent/CN103717609B/zh active Active
- 2012-05-31 TW TW101119653A patent/TWI577693B/zh active
-
2016
- 2016-04-01 US US15/089,131 patent/US20170057984A1/en not_active Abandoned
-
2017
- 2017-06-15 US US15/624,201 patent/US20180094010A1/en not_active Abandoned
-
2019
- 2019-10-28 US US16/666,307 patent/US11248013B2/en active Active
-
2022
- 2022-02-14 US US17/671,436 patent/US12612425B2/en active Active
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