ES2746839T3 - Derivados de pirimidina y triazina y su uso como inhibidores de AXL - Google Patents
Derivados de pirimidina y triazina y su uso como inhibidores de AXL Download PDFInfo
- Publication number
- ES2746839T3 ES2746839T3 ES15812888T ES15812888T ES2746839T3 ES 2746839 T3 ES2746839 T3 ES 2746839T3 ES 15812888 T ES15812888 T ES 15812888T ES 15812888 T ES15812888 T ES 15812888T ES 2746839 T3 ES2746839 T3 ES 2746839T3
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- alkyl
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- independently selected
- cycloalkyl
- halogen
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- 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
- C07D401/14—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 three or more hetero 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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- 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
-
- 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
Abstract
Un compuesto de Fórmula (I):**Fórmula** en la que: cada uno de X es N o CR6, en el que al menos uno de X es N, en el que cada R6 se selecciona independientemente entre el grupo que consiste en hidrógeno, halógeno, alquilo (C1-C8), alquenilo (C2-C3), alquinilo (C1-C8), haloalquilo (C1-C8), -alquilen (C1-C4)-R7, -OR7, -CN, -NO2 y -NR7R7, en el que cada R7 se selecciona independientemente entre el grupo que consiste en hidrógeno y alquilo (C1-C8) y en el que cada uno de dicho alquilo (C1-C8) en R6 está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente entre el grupo que consiste en halógeno, hidroxilo y alcoxi (C1-C8); Y es Y1-Y2 o Y2-Y1, en el que Y1 está ausente o es alquileno (C1-C8), y en el que Y2 está ausente o es oxígeno; Z es Z1-Z2, en el que cada uno de Z1 y Z2 está independientemente ausente o se selecciona entre el grupo que consiste en alquileno (C1-C8), alquenileno (C2-C8), cicloalquilo (C3-C10), heterociclilo de 3-12 miembros y heteroalquileno (C1-C8), en el que Z está de manera opcional independientemente sustituido con uno o más R10, en el que cada R10 se selecciona independientemente entre el grupo que consiste en halógeno, alquilo (C1-C8), - CN, =O, -OR11 y -NO2, y en el que cada R11 se selecciona independientemente entre el grupo que consiste en hidrógeno, alquilo (C1-C8), cicloalquilo (C3-C10), heterociclilo de 3-12 miembros, arilo (C6-C12) y heteroarilo de 5-12 miembros; cada R1 se selecciona independientemente entre el grupo que consiste en hidrógeno, halógeno, alquilo (C1-C8), haloalquilo (C1-C8), -(alquil C1-C4)R7, -OR7, -CN, -C(O)R7, -CO2R7, -C(O)NR7R7, -SR7, -SOR7, -SO2R7, -SO2NR7R7, -NO2, -NR7R7, -NR7C(O)R7, -NR7C(O)NR7R7, -NR7C(O)OR7, -NR7SO2R7, -NR7SO2NR7R7, -OC(O)R7 y - OC(O)NR7R7; en el que cualquier conjunto de dos R1 en los mismos o diferentes carbonos de piperidina se unen opcionalmente para formar un sistema de anillo espirocíclicos, condensados o puenteados que comprende de 1-4 miembros no de piperidina y de 1-2 heteroátomos seleccionados entre N, O y S, y en el que cualquier conjunto de dos R1 en los carbonos de piperidina adyacentes se unen opcionalmente para formar un enlace carbono-carbono; R2 y R3 cada uno de se selecciona independientemente entre el grupo que consiste en hidrógeno, alquilo (C1-C8), haloalquilo (C1-C8), cicloalquilo (C3-C10), heterociclilo de 3-12 miembros, -OR13 y -SO2R14, en el que cada R13 se selecciona independientemente entre el grupo que consiste en hidrógeno, alquilo (C1-C4) y haloalquilo (C1-C4), en el que cada R14 se selecciona independientemente entre el grupo que consiste en hidrógeno y alquilo (C1-C8) y en el que R2, R3 o ambos R2 y R3 está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente entre halógeno, alquilo (C1-C8), hidroxilo, alcoxi (C1-C4), -CN, NH2, NH(alquilo C1-C4) y N(alquilo C1-C4)2; piperazinilo, piperadinonilo, piperazinonilo y morfolinilo, opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente entre el grupo que consiste en R15 y alquilen (C1-C4)-R15, en el que R15 se selecciona independientemente entre el grupo que consiste en halógeno, alquilo (C1-C4), haloalquilo (C1-C4), hidroxilo, alcoxi (C1-C4), CN, NH2, NH(alquilo C1-C4), N(alquilo C1-C4)2 y cicloalquilo (C3-C10); R4 se selecciona entre el grupo que consiste en alquilo (C1-C8), haloalquilo (C1-C8), cicloalquilo (C3-C10), heterociclilo de 3-12 miembros y -C(O)NR14R14, en el que R4 está opcionalmente sustituido con uno o más R12 independientemente seleccionados entre halógeno, hidroxilo, alcoxi (C1-C4), -CN, NH2, NH(alquilo C1-C4), N(alquilo C1-C4)2, cicloalquilo (C3-C10), heterociclilo de 3-12 miembros, arilo (C6-C12) y heteroarilo de 5-12 miembros, y en el que, cuando R12 es alcoxi (C1-C4), NH(alquilo C1-C4), N(alquilo C1-C4)2, cicloalquilo (C3-C10), heterociclilo de 3-12 miembros, arilo (C6-C12) o heteroarilo de 5-12 miembros, está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente entre halógeno, hidroxilo, alcoxi (C1-C4), -CN, NH2, NH(alquilo C1-C4), N(alquilo C1-C4)2, cicloalquilo (C3-C10), heterociclilo de 3-12 miembros, arilo (C6-C12) y heteroarilo de 5-12 miembros; R5 es heteroarilo mono o bicíclico, opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente entre el grupo que consiste en alquilo (C1-C8), -OR13, -NR14R14,-C(O)NR14R14 y heteroarilo monocíclico, dicho uno o más sustituyentes opcionales están adicionalmente opcionalmente sustituidos con uno o más sustituyentes seleccionados del grupo que consiste en alquilo (C1-C8), alquilen (C1-C8)-OH, haloalquilo (C1- C8), cicloalquilo (C3-C10), heterociclilo de 3-12 miembros, -OR13, -NR14R14, -C(O)NR14R14, -SO2NR14R14, -SO2R14, -NR14SO2R14 y CN; y m es 1-9, o una sal farmacéuticamente aceptable del mismo.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462093844P | 2014-12-18 | 2014-12-18 | |
PCT/IB2015/059360 WO2016097918A1 (en) | 2014-12-18 | 2015-12-04 | Pyrimidine and triazine derivatives and their use as axl inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2746839T3 true ES2746839T3 (es) | 2020-03-09 |
Family
ID=54851370
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES15812888T Active ES2746839T3 (es) | 2014-12-18 | 2015-12-04 | Derivados de pirimidina y triazina y su uso como inhibidores de AXL |
Country Status (6)
Country | Link |
---|---|
US (1) | US9593097B2 (es) |
EP (1) | EP3233829B1 (es) |
JP (1) | JP6621477B2 (es) |
CA (1) | CA2915356A1 (es) |
ES (1) | ES2746839T3 (es) |
WO (1) | WO2016097918A1 (es) |
Families Citing this family (21)
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WO2016183071A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Hetero-tricyclic compounds and their use for the treatment of cancer |
WO2017027717A1 (en) | 2015-08-12 | 2017-02-16 | Incyte Corporation | Bicyclic fused pyrimidine compounds as tam inhibitors |
US10053465B2 (en) | 2015-08-26 | 2018-08-21 | Incyte Corporation | Pyrrolopyrimidine derivatives as TAM inhibitors |
JP6885390B2 (ja) | 2016-02-26 | 2021-06-16 | 小野薬品工業株式会社 | Axl阻害剤と免疫チェックポイント阻害剤とを組み合わせて投与することを特徴とする癌治療のための医薬 |
UA123785C2 (uk) | 2016-03-28 | 2021-06-02 | Інсайт Корпорейшн | Сполуки піролотриазину як інгібітори tam |
RS62913B1 (sr) * | 2016-09-09 | 2022-03-31 | Novartis Ag | Jedinjenja i sastavi kao inhibitori endozomskih toličnih receptora |
US20200197385A1 (en) | 2017-08-23 | 2020-06-25 | Ono Pharmaceutical Co., Ltd. | Therapeutic agent for cancer containing axl inhibitor as active ingredient |
JP2020535168A (ja) | 2017-09-27 | 2020-12-03 | インサイト・コーポレイションIncyte Corporation | Tam阻害剤として有用なピロロトリアジン誘導体の塩 |
JP7223998B2 (ja) | 2017-10-13 | 2023-02-17 | 小野薬品工業株式会社 | Axl阻害剤を有効成分として含む固形がん治療剤 |
GB201801355D0 (en) | 2018-01-26 | 2018-03-14 | Enterprise Therapeutics Ltd | Compounds |
MA54133B1 (fr) | 2018-03-08 | 2022-01-31 | Incyte Corp | Composés d'aminopyrazine diol utilisés comme inhibiteurs de pi3k-y |
EP3813800A1 (en) | 2018-06-29 | 2021-05-05 | Incyte Corporation | Formulations of an axl/mer inhibitor |
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JP7458406B2 (ja) | 2018-12-21 | 2024-03-29 | セルジーン コーポレーション | Ripk2のチエノピリジン阻害剤 |
WO2020188015A1 (en) | 2019-03-21 | 2020-09-24 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
KR102286372B1 (ko) * | 2019-05-27 | 2021-08-05 | 주식회사한국파마 | Jak 저해제 화합물, 및 이를 포함하는 의약 조성물 |
WO2021089791A1 (en) | 2019-11-08 | 2021-05-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
WO2022220227A1 (ja) * | 2021-04-14 | 2022-10-20 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | テトラヒドロピリドピリミジン化合物 |
CN113354638A (zh) * | 2021-07-12 | 2021-09-07 | 天津敬康生物科技有限公司 | 一种5-氟-3-碘-1H-吡唑并[3,4-b]吡啶的制备方法 |
CN114853768A (zh) * | 2022-07-08 | 2022-08-05 | 南昌大学 | 一种合成手性3-氟-1-氮杂二环[2,2,1]庚烷的方法 |
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-
2015
- 2015-12-04 ES ES15812888T patent/ES2746839T3/es active Active
- 2015-12-04 JP JP2017531839A patent/JP6621477B2/ja active Active
- 2015-12-04 EP EP15812888.4A patent/EP3233829B1/en active Active
- 2015-12-04 WO PCT/IB2015/059360 patent/WO2016097918A1/en active Application Filing
- 2015-12-14 US US14/968,405 patent/US9593097B2/en active Active
- 2015-12-15 CA CA2915356A patent/CA2915356A1/en active Pending
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EP3233829B1 (en) | 2019-08-14 |
US20160176850A1 (en) | 2016-06-23 |
CA2915356A1 (en) | 2016-06-18 |
US9593097B2 (en) | 2017-03-14 |
EP3233829A1 (en) | 2017-10-25 |
JP2017537951A (ja) | 2017-12-21 |
WO2016097918A1 (en) | 2016-06-23 |
JP6621477B2 (ja) | 2019-12-18 |
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