PE20131164A1 - IMIDAZOPIRIDAZINAS SUSTITUIDAS COMO INHIBIDORES DE LA QUINASA Mps-1 - Google Patents
IMIDAZOPIRIDAZINAS SUSTITUIDAS COMO INHIBIDORES DE LA QUINASA Mps-1Info
- Publication number
- PE20131164A1 PE20131164A1 PE2013000392A PE2013000392A PE20131164A1 PE 20131164 A1 PE20131164 A1 PE 20131164A1 PE 2013000392 A PE2013000392 A PE 2013000392A PE 2013000392 A PE2013000392 A PE 2013000392A PE 20131164 A1 PE20131164 A1 PE 20131164A1
- Authority
- PE
- Peru
- Prior art keywords
- alkyl
- integer
- response
- cellular
- methylbenzamide
- Prior art date
Links
- 108091000080 Phosphotransferase Proteins 0.000 title abstract 2
- 150000005233 imidazopyridazines Chemical group 0.000 title abstract 2
- 102000020233 phosphotransferase Human genes 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 title 1
- -1 2-HYDROXY-2-METHYLPROPYL Chemical class 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 230000024932 T cell mediated immunity Effects 0.000 abstract 1
- 230000004663 cell proliferation Effects 0.000 abstract 1
- 230000001413 cellular effect Effects 0.000 abstract 1
- 230000036755 cellular response Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 230000004044 response Effects 0.000 abstract 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material 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)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
- Paper (AREA)
Abstract
REFERIDA A DERIVADOS IMIDAZOPIRIDAZINAS DE FORMULA (I), DONDE A ES UN GRUPO (a), (b), (c) O (d); Z ES C(=O)N(H)R2, C(=S)N(H)R2, ENTRE OTROS; R2 ES H, ALQUILO C1-C6, HALO-ALQUILO C1-C6, ENTRE OTROS; R3 ES ARIL-X O HETEROARIL-X; X ES O, NR6, S(=O)p, ENTRE OTROS; p ES UN ENTERO DE 0 A 2; n ES UN ENTERO DE 0 A 5; m ES UN ENTERO DE 0 A 6; R4a Y R4d SON H; R4b Y R4c SON H, HALO, CN, OH, ENTRE OTROS; R5 ES H, ALQUILO C1-C6, (CH2)n-ALQUENILO C2-C6, ENTRE OTROS; R6, R6 ES H, ALQUILO C1-C6, CICLOALQUILO C3-C6, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: N-CICLOPROPIL-4-{6-[(2-METOXIFENIL)SULFANIL)]-8-[(3,3,3-TRIFLUOROPROPIL)AMINO]IMIDAZO[1,2-b]PIRIDAZIN-3-IL}-2-METILBENZAMIDA, N-CICLOPROPIL-4-{8-[(2-HIDROXI-2-METILPROPIL)AMINO]-6-[(4-HIDROXIFENIL)SULFANIL]-IMIDAZO[1,2-b]PIRIDAZIN-3-IL}-2-METILBENZAMIDA, ENTRE OTROS. TAMBIEN ESTA REFERIDA A UNA COMPOSICION FARMACEUTICA Y A UN METODO DE PREPARACION. DICHOS COMPUESTOS INHIBEN LA QUINASA Mps-1 (DEL HUSO MONOPOLAR 1) Y SON UTILES EN EL TRATAMIENTO DE ENFERMEDADES RELACIONADAS CON LA PROLIFERACION CELULAR DESCONTROLADA, CON UNA RESPUESTA INMUNE CELULAR INAPROPIADA, RESPUESTA INFLAMATORIA CELULAR INAPROPIADA, ENTRE OTRAS
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10176134 | 2010-09-10 | ||
| EP11075022 | 2011-02-04 | ||
| EP11170771 | 2011-06-21 | ||
| EP11170775 | 2011-06-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20131164A1 true PE20131164A1 (es) | 2013-10-30 |
Family
ID=44545741
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2013000392A PE20131164A1 (es) | 2010-09-10 | 2011-09-06 | IMIDAZOPIRIDAZINAS SUSTITUIDAS COMO INHIBIDORES DE LA QUINASA Mps-1 |
Country Status (38)
| Country | Link |
|---|---|
| US (1) | US9255100B2 (es) |
| EP (1) | EP2614063B1 (es) |
| JP (1) | JP5824050B2 (es) |
| KR (1) | KR20140032337A (es) |
| CN (1) | CN103370318B (es) |
| AP (1) | AP3607A (es) |
| AR (1) | AR082946A1 (es) |
| AU (1) | AU2011298844B2 (es) |
| BR (1) | BR112013005679A2 (es) |
| CA (1) | CA2810755A1 (es) |
| CO (1) | CO6720961A2 (es) |
| CR (1) | CR20130102A (es) |
| CU (1) | CU24187B1 (es) |
| CY (1) | CY1117352T1 (es) |
| DK (1) | DK2614063T3 (es) |
| DO (1) | DOP2013000054A (es) |
| EA (1) | EA023420B1 (es) |
| EC (1) | ECSP13012752A (es) |
| ES (1) | ES2568220T3 (es) |
| HR (1) | HRP20160360T1 (es) |
| HU (1) | HUE028771T2 (es) |
| IL (1) | IL225058A (es) |
| MA (1) | MA34516B1 (es) |
| ME (1) | ME02389B (es) |
| MX (1) | MX2013002713A (es) |
| MY (1) | MY185139A (es) |
| NZ (1) | NZ607904A (es) |
| PE (1) | PE20131164A1 (es) |
| PH (1) | PH12013500454A1 (es) |
| PL (1) | PL2614063T3 (es) |
| RS (1) | RS54661B1 (es) |
| SA (1) | SA111320735B1 (es) |
| SG (1) | SG188417A1 (es) |
| SI (1) | SI2614063T1 (es) |
| TW (1) | TWI541243B (es) |
| UY (1) | UY33598A (es) |
| WO (1) | WO2012032031A1 (es) |
| ZA (1) | ZA201301756B (es) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI541243B (zh) | 2010-09-10 | 2016-07-11 | 拜耳知識產權公司 | 經取代咪唑并嗒 |
| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| PT3409278T (pt) | 2011-07-21 | 2020-12-18 | Sumitomo Dainippon Pharma Oncology Inc | Inibidores de proteína cinase heterocíclicos |
| ES2605946T3 (es) * | 2012-03-14 | 2017-03-17 | Bayer Intellectual Property Gmbh | Imidazopiridazinas sustituidas |
| CN107652289B (zh) | 2012-06-13 | 2020-07-21 | 因塞特控股公司 | 作为fgfr抑制剂的取代的三环化合物 |
| WO2014020041A1 (en) | 2012-08-02 | 2014-02-06 | Bayer Pharma Aktiengesellschaft | Combinations for the treatment of cancer |
| WO2014020043A1 (en) | 2012-08-02 | 2014-02-06 | Bayer Pharma Aktiengesellschaft | Combinations for the treatment of cancer |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| JP6377068B2 (ja) | 2012-11-16 | 2018-08-22 | ユニバーシティ・ヘルス・ネットワーク | ピラゾロピリミジン化合物 |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| TW201437211A (zh) * | 2013-03-01 | 2014-10-01 | Bayer Pharma AG | 經取代咪唑并嗒□ |
| JP6449244B2 (ja) | 2013-04-19 | 2019-01-09 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｆｇｆｒ抑制剤としての二環式複素環 |
| JP2016526534A (ja) | 2013-06-11 | 2016-09-05 | バイエル・ファルマ・アクティエンゲゼルシャフト | 置換トリアゾロピリジンのプロドラッグ誘導体 |
| JP2016521740A (ja) * | 2013-06-13 | 2016-07-25 | バイエル・ファルマ・アクティエンゲゼルシャフト | 癌を治療するためのイミダゾピリダジン誘導体と有糸分裂阻害剤の組合せ |
| CN103360399B (zh) * | 2013-08-02 | 2016-03-02 | 北京大学 | 6-芳基取代-咪唑-[1,2-b]哒嗪类衍生物，其制备方法及用途 |
| GB201321734D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| SG11201606869TA (en) * | 2014-02-21 | 2016-09-29 | Frost Biolog Inc | Antimitotic amides for the treatment of cancer and proliferative disorders |
| WO2015157955A1 (en) | 2014-04-17 | 2015-10-22 | Abbvie Inc. | Heterocyclic btk inhibit ors |
| TW201613927A (en) * | 2014-09-01 | 2016-04-16 | Bayer Pharma AG | Method for preparation of substituted imidazopyridazines |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| ES2751669T3 (es) | 2015-02-20 | 2020-04-01 | Incyte Corp | Heterociclos bicíclicos como inhibidores FGFR |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | 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 |
| EP3283642B1 (en) | 2015-04-17 | 2023-10-11 | Netherlands Translational Research Center Holding B.V. | Prognostic biomarkers for ttk inhibitor chemotherapy |
| WO2016187028A1 (en) * | 2015-05-15 | 2016-11-24 | Celgene Avilomics Research, Inc. | Heteroaryl compounds, synthesis thereof, and intermediates thereto |
| KR102685635B1 (ko) * | 2015-12-04 | 2024-07-15 | 엑손모빌 테크놀로지 앤드 엔지니어링 컴퍼니 | 신규한 합성 결정질 물질인 emm-28, 이의 제조 및 용도 |
| US11352328B2 (en) | 2016-07-12 | 2022-06-07 | Arisan Therapeutics Inc. | Heterocyclic compounds for the treatment of arenavirus |
| SI3484888T1 (sl) * | 2016-07-18 | 2023-07-31 | University Health Network | Trdne oblike inhibitorja ttk |
| ES2901421T3 (es) * | 2017-04-11 | 2022-03-22 | Straumann Holding Ag | Implante dental |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| CN119241541A (zh) | 2018-05-04 | 2025-01-03 | 因赛特公司 | Fgfr抑制剂的固体形式和其制备方法 |
| PE20210919A1 (es) | 2018-05-04 | 2021-05-19 | Incyte Corp | Sales de un inhibidor de fgfr |
| ES2992256T3 (es) | 2018-05-08 | 2024-12-11 | Nippon Shinyaku Co Ltd | Compuestos de azabencimidazol y producto farmacéutico |
| US12419865B2 (en) | 2018-12-06 | 2025-09-23 | Arisan Therapeutics Inc. | Compounds for the treatment of arenavirus infection |
| CA3127502A1 (en) | 2019-02-12 | 2020-08-20 | Sumitomo Dainippon Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| CN111978325B (zh) * | 2019-05-22 | 2023-11-17 | 中国药科大学 | 咪唑并哒嗪类mnk1/mnk2激酶抑制剂及其制备方法和应用 |
| 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 |
| GEP20247679B (en) | 2019-10-14 | 2024-10-10 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| CN114929697A (zh) | 2019-11-13 | 2022-08-19 | 日本新药株式会社 | 氮杂苯并咪唑化合物和药物 |
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| JP2024513575A (ja) | 2021-04-12 | 2024-03-26 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤及びネクチン－４標的化剤を含む併用療法 |
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| AR126101A1 (es) | 2021-06-09 | 2023-09-13 | Incyte Corp | Heterociclos tricíclicos como inhibidores de fgfr |
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| WO2024155834A1 (en) * | 2023-01-19 | 2024-07-25 | Skyhawk Therapeutics, Inc. | Compositions useful for modulating splicing |
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| EP2343297A1 (en) | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Triazolopyridines |
| EP2343294A1 (en) | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Substituted triazolopyridines |
| JP5841078B2 (ja) | 2010-03-18 | 2016-01-06 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | イミダゾピラジン |
| EP2576560B1 (en) | 2010-06-01 | 2015-09-30 | Bayer Intellectual Property GmbH | Substituted imidazopyrazines |
| TWI541243B (zh) | 2010-09-10 | 2016-07-11 | 拜耳知識產權公司 | 經取代咪唑并嗒 |
| EP2651945A1 (en) | 2010-12-17 | 2013-10-23 | Bayer Intellectual Property GmbH | 6-substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| EP2651947B1 (en) | 2010-12-17 | 2014-12-10 | Bayer Intellectual Property GmbH | 6-thio-substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| CN103370322B (zh) | 2010-12-17 | 2016-02-10 | 拜耳知识产权有限责任公司 | 在过度增殖性病症的治疗中用作mps-1和tkk抑制剂的2-取代的咪唑并吡嗪 |
| US20130303532A1 (en) | 2010-12-17 | 2013-11-14 | Bayer Intellectual Property Gmbh | Imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment hyperproliferative disorders |
| WO2012080230A1 (en) | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | 6 substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| CA2821817A1 (en) | 2010-12-17 | 2012-06-21 | Bayer Intellectual Property Gmbh | Substituted 6-imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
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