JP2014516992A5 - - Google Patents
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- JP2014516992A5 JP2014516992A5 JP2014513788A JP2014513788A JP2014516992A5 JP 2014516992 A5 JP2014516992 A5 JP 2014516992A5 JP 2014513788 A JP2014513788 A JP 2014513788A JP 2014513788 A JP2014513788 A JP 2014513788A JP 2014516992 A5 JP2014516992 A5 JP 2014516992A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- group
- cycloalkyl
- itself
- optionally
- 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
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- 125000000217 alkyl group Chemical group 0.000 claims description 398
- 125000001424 substituent group Chemical group 0.000 claims description 280
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 256
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 194
- 125000005843 halogen group Chemical group 0.000 claims description 187
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 180
- -1 hydroxy, carbonyloxy Chemical group 0.000 claims description 161
- 125000005842 heteroatom Chemical group 0.000 claims description 146
- 125000003118 aryl group Chemical group 0.000 claims description 140
- 229910052739 hydrogen Inorganic materials 0.000 claims description 133
- 239000001257 hydrogen Substances 0.000 claims description 133
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 132
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 99
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 98
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 71
- 125000004104 aryloxy group Chemical group 0.000 claims description 63
- 125000003282 alkyl amino group Chemical group 0.000 claims description 60
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 55
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 54
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 53
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 41
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 33
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims description 32
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 31
- 229940124647 MEK inhibitor Drugs 0.000 claims description 30
- 102000004000 Aurora Kinase A Human genes 0.000 claims description 27
- 108090000461 Aurora Kinase A Proteins 0.000 claims description 27
- 229940124639 Selective inhibitor Drugs 0.000 claims description 27
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 17
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 17
- 229940124530 sulfonamide Drugs 0.000 claims description 14
- 150000003456 sulfonamides Chemical class 0.000 claims description 14
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 6
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 230000002062 proliferating effect Effects 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 3
- ZLHFILGSQDJULK-UHFFFAOYSA-N 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3C4=CC=C(Cl)C=C4C(=NCC3=CN=2)C=2C(=CC=CC=2F)OC)=C1 ZLHFILGSQDJULK-UHFFFAOYSA-N 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 12
- 125000004429 atom Chemical group 0.000 claims 11
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 8
- 239000002552 dosage form Substances 0.000 claims 4
- 150000001408 amides Chemical class 0.000 claims 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 2
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims 1
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 claims 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 description 16
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 5
- 125000001475 halogen functional group Chemical group 0.000 description 5
- 125000003107 substituted aryl group Chemical group 0.000 description 5
- 125000002723 alicyclic group Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- RCLQNICOARASSR-SECBINFHSA-N 3-[(2r)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione Chemical compound FC=1C(=O)N(C)C=2N=CN(C[C@@H](O)CO)C(=O)C=2C=1NC1=CC=C(I)C=C1F RCLQNICOARASSR-SECBINFHSA-N 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161493217P | 2011-06-03 | 2011-06-03 | |
| US61/493,217 | 2011-06-03 | ||
| US201261613207P | 2012-03-20 | 2012-03-20 | |
| US61/613,207 | 2012-03-20 | ||
| PCT/US2012/040733 WO2012167247A1 (en) | 2011-06-03 | 2012-06-04 | Combination of mek inhibitors and selective inhibitors of aurora a kinase |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017130266A Division JP2017178969A (ja) | 2011-06-03 | 2017-07-03 | Ｍｅｋ阻害剤およびオーロラａキナーゼの選択的阻害剤の組み合わせ |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014516992A JP2014516992A (ja) | 2014-07-17 |
| JP2014516992A5 true JP2014516992A5 (enExample) | 2015-07-23 |
| JP6263468B2 JP6263468B2 (ja) | 2018-01-17 |
Family
ID=47259953
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014513788A Active JP6263468B2 (ja) | 2011-06-03 | 2012-06-04 | Ｍｅｋ阻害剤およびオーロラａキナーゼの選択的阻害剤の組み合わせ |
| JP2017130266A Pending JP2017178969A (ja) | 2011-06-03 | 2017-07-03 | Ｍｅｋ阻害剤およびオーロラａキナーゼの選択的阻害剤の組み合わせ |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017130266A Pending JP2017178969A (ja) | 2011-06-03 | 2017-07-03 | Ｍｅｋ阻害剤およびオーロラａキナーゼの選択的阻害剤の組み合わせ |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9629850B2 (enExample) |
| EP (1) | EP2713727B1 (enExample) |
| JP (2) | JP6263468B2 (enExample) |
| CN (1) | CN103957709A (enExample) |
| AR (1) | AR086656A1 (enExample) |
| CA (1) | CA2837724C (enExample) |
| TW (1) | TW201316991A (enExample) |
| UY (1) | UY34114A (enExample) |
| WO (1) | WO2012167247A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| PE20190736A1 (es) | 2012-06-13 | 2019-05-23 | Incyte Holdings Corp | Compuestos triciclicos sustituidos como inhibidores del receptor del factor de crecimiento de fibroblastos (fgfr) |
| WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| KR102269032B1 (ko) | 2013-04-19 | 2021-06-24 | 인사이트 홀딩스 코포레이션 | Fgfr 저해제로서 이환식 헤테로사이클 |
| CN103408552B (zh) * | 2013-07-25 | 2015-07-01 | 苏州明锐医药科技有限公司 | 阿立塞替的制备方法 |
| CN103408551B (zh) * | 2013-07-25 | 2015-08-05 | 苏州明锐医药科技有限公司 | 阿立塞替的制备方法 |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| ES2895769T3 (es) | 2015-02-20 | 2022-02-22 | Incyte Corp | Heterociclos bicíclicos como inhibidores de FGFR |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| JP2018524292A (ja) * | 2015-07-21 | 2018-08-30 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | オーロラキナーゼインヒビターと化学療法剤の投与 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| SG11202010882XA (en) | 2018-05-04 | 2020-11-27 | Incyte Corp | Salts of an fgfr inhibitor |
| SI3788047T1 (sl) | 2018-05-04 | 2024-11-29 | Incyte Corporation | Trdne oblike inhibitorja fgfr in postopki priprave le-teh |
| JP7253181B2 (ja) * | 2018-12-21 | 2023-04-06 | 株式会社Ｎｔｔドコモ | 情報処理装置、情報処理方法及びプログラム |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| US11607416B2 (en) | 2019-10-14 | 2023-03-21 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2021113462A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Derivatives of an fgfr inhibitor |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| KR20220032607A (ko) * | 2020-02-27 | 2022-03-15 | 국립대학법인 홋가이도 다이가쿠 | 항암제를 스크리닝하는 방법 및 췌장암 치료를 위한 키나아제 억제제의 조합 의약 |
| WO2022221170A1 (en) | 2021-04-12 | 2022-10-20 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
| WO2022261160A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2299080T3 (es) | 2004-05-14 | 2008-05-16 | Millennium Pharmaceuticals, Inc. | Compuestos y metodos para inhibir la progresion mitotica mediante la inhibicion de quinasas aurora. |
| CN101014603B (zh) * | 2004-05-14 | 2014-08-20 | 千禧药品公司 | 通过抑制极光激酶抑制有丝分裂的化合物和方法 |
| US8624027B2 (en) * | 2005-05-12 | 2014-01-07 | Abbvie Inc. | Combination therapy for treating cancer and diagnostic assays for use therein |
| EP2054413A2 (en) | 2006-08-09 | 2009-05-06 | Millennium Pharmaceuticals, Inc. | Pyridobenzazepine compounds and methods for inhibiting mitotic progression |
| CL2007003244A1 (es) | 2006-11-16 | 2008-04-04 | Millennium Pharm Inc | Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer. |
| JO2985B1 (ar) | 2006-12-20 | 2016-09-05 | Takeda Pharmaceuticals Co | مثبطات كينازmapk/erk |
| US20100004247A1 (en) | 2007-12-12 | 2010-01-07 | Astrazeneca Ab | Combination comprising a mek inhibitor and an aurora kinase inhibitor 188 |
| WO2009114703A2 (en) * | 2008-03-12 | 2009-09-17 | Fox Chase Cancer Center | Combination therapy for the treatment of cancer |
| CN102216274A (zh) | 2008-11-18 | 2011-10-12 | 武田药品工业株式会社 | (R)-3-(2,3-二羟基丙基)-6-氟-5-(2-氟-4-碘苯基氨基)-8-甲基吡啶并[2,3-d]嘧啶-4,7(3H,8H)-二酮及其中间体的制备方法 |
| JO3635B1 (ar) | 2009-05-18 | 2020-08-27 | Millennium Pharm Inc | مركبات صيدلانية صلبة وطرق لانتاجها |
| JO3434B1 (ar) | 2009-07-31 | 2019-10-20 | Millennium Pharm Inc | مركبات صيدلانية لمعالجة السرطان وامراض واضطرابات اخري |
| US8653064B2 (en) | 2010-02-19 | 2014-02-18 | Millennium Pharmaceuticals, Inc. | Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-D][2]benzazepin-2-yl]amino}-2-methoxybenzoate |
-
2012
- 2012-06-01 UY UY0001034114A patent/UY34114A/es not_active Application Discontinuation
- 2012-06-01 AR ARP120101958A patent/AR086656A1/es not_active Application Discontinuation
- 2012-06-01 TW TW101119852A patent/TW201316991A/zh unknown
- 2012-06-04 WO PCT/US2012/040733 patent/WO2012167247A1/en not_active Ceased
- 2012-06-04 JP JP2014513788A patent/JP6263468B2/ja active Active
- 2012-06-04 CA CA2837724A patent/CA2837724C/en active Active
- 2012-06-04 CN CN201280036936.9A patent/CN103957709A/zh active Pending
- 2012-06-04 EP EP12793812.4A patent/EP2713727B1/en active Active
- 2012-06-04 US US14/122,779 patent/US9629850B2/en active Active
-
2017
- 2017-07-03 JP JP2017130266A patent/JP2017178969A/ja active Pending
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