DK2966079T1 - Pyridopyrimidin eller pyrimidopyrimidinforbindelse, fremstillingsmetode, pharmaceutisk præparat og anvendelse heraf - Google Patents
Pyridopyrimidin eller pyrimidopyrimidinforbindelse, fremstillingsmetode, pharmaceutisk præparat og anvendelse heraf Download PDFInfo
- Publication number
- DK2966079T1 DK2966079T1 DK14760712.1T DK14760712T DK2966079T1 DK 2966079 T1 DK2966079 T1 DK 2966079T1 DK 14760712 T DK14760712 T DK 14760712T DK 2966079 T1 DK2966079 T1 DK 2966079T1
- Authority
- DK
- Denmark
- Prior art keywords
- pharmaceutically acceptable
- octanyl
- azabicyclo
- oxa
- solvate
- Prior art date
Links
- -1 PYRIMIDOPYRIMIDINE COMPOUND Chemical class 0.000 title claims 22
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 title claims 10
- 238000000034 method Methods 0.000 title 1
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 150000002148 esters Chemical class 0.000 claims 11
- 239000000651 prodrug Substances 0.000 claims 11
- 229940002612 prodrug Drugs 0.000 claims 11
- 150000003839 salts Chemical class 0.000 claims 11
- 239000012453 solvate Substances 0.000 claims 11
- 150000001875 compounds Chemical class 0.000 claims 7
- 229910052736 halogen Chemical group 0.000 claims 7
- 150000002367 halogens Chemical group 0.000 claims 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 229910003827 NRaRb Inorganic materials 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 230000004064 dysfunction Effects 0.000 claims 2
- 229940124302 mTOR inhibitor Drugs 0.000 claims 2
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 125000006413 ring segment Chemical group 0.000 claims 2
- 230000019491 signal transduction Effects 0.000 claims 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical group C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims 1
- ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical group C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 claims 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 1
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 108091007960 PI3Ks Proteins 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- 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
- A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (14)
- ÆNDREDE PATENTKRAV1. Pyridopyrimidin- eller pyrimidopyrimidinforbindelse angivet med formlen (la) eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf:hvor R-ι og R2 hver især uafhængigt af hinanden er 3-oxa-8-azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl eller NRaRb, og mindst ét af Ri og R2 er 3-oxa-8-azabicyclo[3.2.1]octanyl eller 8-oxa-3-azabicyclo[3.2.1]octanyl; hvor Ra og RB hver især uafhængigt af hinanden er H, C1-C6-alkyl, der er usubstitueret eller substitueret med C1-C6-alkoxy eller halogen, eller C1-C6-alkoxy, der er usubstitueret eller substitueret med halogen, eller RA og RB sammen med N, til hvilket de er bundet, danner en nitrogenholdig mættet heterocyklisk gruppe med 4 til 8 ringatomer, der er usubstitueret eller substitueret med C1-C6-alkyl, C1-C6-alkoxy eller halogen, den nitrogenholdige mættede heterocykliske gruppe er en piperidinring, morpholinring, piperazinring, N-methylpiperazinring, homomorpholinring, homopiperazinring; og,hvor Rc er H eller C1-C3-alkyl.
- 2. Pyridopyrimidin- eller pyrimidopyrimidinforbindelsen ifølge krav 1 eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformerne eller solvatet deraf, hvor Ri og R2 hver især uafhængigt af hinanden er 3-oxa-8-azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl eller NRaRb, og mindst ét af Ri og R2 er 3-oxa-8-azabicyclo[3.2.1]octanyl eller 8-oxa-3-azabicyclo[3.2.1]octanyl; hvor Ra og RB hver især uafhængigt af hinanden er H, C1-C3-alkyl, der er usubstitueret eller substitueret med C1-C3-alkoxy eller halogen, eller C1-C3-alkoxy, der er usubstitueret eller substitueret med halogen, eller RA og Rb sammen med N, til hvilket de er bundet, danner en nitrogenholdig mættet heterocyklisk gruppe med 6 til 7 ringatomer, der er usubstitueret eller substitueret med C1-C3-alkyl, C1-C3-alkoxy eller halogen.
- 3. Pyridopyrimidin- eller pyrimidopyrimidinforbindelse ifølge krav 1 eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf, hvor R-ι og R2 hver især uafhængigt af hinanden er 3-oxa-8-azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl eller NRARB, og mindst ét af Ri og R2 er 3-oxa-8-azabicyclo[3.2.1]octanyl eller 8-oxa-3-azabicyclo[3.2.1]octanyl; hvor Ra og RB sammen med N, til hvilket de er bundet, danner en morpholinring, der er usubstitueret eller substitueret med C1-C3-alkyl, C1-C3-alkoxy eller halogen.
- 4. Pyridopyrimidin- eller pyrimidopyrimidinforbindelsen ifølge krav 1, isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf, hvor
- 5. Pyridopyrimidin- eller pyrimidopyrimidinforbindelse ifølge krav 1 eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf, hvor Rc er H eller methyl.
- 6. Pyridopyrimidin- eller pyrimidopyrimidinforbindelsen ifølge krav 1 eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf, hvor forbindelsen angivet med formlen (I) er valgt fra gruppen bestående af følgende forbindelser:
- 7. Anvendelse af pyridopyrimidin- eller pyrimidopyrimidinforbindelsen ifølge et hvilket som helst af kravene 1 til 6, eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf som mTOR-inhibitor til behandling af en sygdom eller tilstand forårsaget af dysfunktion af PI3K-AKT-mTOR-signaleringsvejen.
- 8. Anvendelse ifølge krav 7, hvor sygdommen eller tilstanden forårsaget af dysfunktion af PI3K-AKT-mTOR-signaleringsvejen er en tumorsygdom.
- 9. Farmaceutisk præparat, der omfatter en terapeutisk effektiv mængde af pyridopyrimidin- eller pyrimidopyrimidinforbindelsen, isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf ifølge et hvilket som helst af kravene 1 til 6 og eventuelt en farmaceutisk acceptabel bærer eller excipiens. 10. mTOR-inhibitor, der omfatter en terapeutisk effektiv mængde af pyridopyrimidin- eller pyrimidopyrimidinforbindelsen, isomeren deraf, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf ifølge et hvilket som helst af kravene 1 til 6 og eventuelt en farmaceutisk acceptabel bærer eller excipiens.
- 11. Forbindelsen ifølge krav 1 eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf, hvor Ri er
- 12. Forbindelse ifølge krav 1 eller isomeren, det farmaceutisk acceptable salt, esteren, prodrugformen eller solvatet deraf, hvor R2 er
- 13. Forbindelser ifølge krav 1, der er valgt fra gruppen bestående af
- 14. Farmaceutisk præparat ifølge krav 9, hvor forbindelserne er valgt fra gruppen bestående af
- 15. Præparat ifølge krav 7, hvor forbindelserne er valgt fra gruppen bestående af
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310068888.8A CN103588792B (zh) | 2013-03-04 | 2013-03-04 | 吡啶并嘧啶或嘧啶并嘧啶类化合物、其制备方法、药物组合物及其用途 |
| PCT/CN2014/072678 WO2014135028A1 (zh) | 2013-03-04 | 2014-02-28 | 吡啶并嘧啶或嘧啶并嘧啶类化合物、其制备方法、药物组合物及其用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK2966079T1 true DK2966079T1 (da) | 2016-05-17 |
| DK2966079T3 DK2966079T3 (da) | 2022-02-14 |
Family
ID=50079144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK14760712.1T DK2966079T3 (da) | 2013-03-04 | 2014-02-28 | Pyridopyrimidin eller pyridopyrimidinforbindelse, fremgangsmåde til fremstilling, farmaceutisk sammensætning og anvendelse deraf |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9796732B2 (da) |
| EP (1) | EP2966079B1 (da) |
| JP (1) | JP2016510042A (da) |
| CN (1) | CN103588792B (da) |
| AU (1) | AU2014225155B2 (da) |
| CA (1) | CA2903072C (da) |
| DE (1) | DE14760712T1 (da) |
| DK (1) | DK2966079T3 (da) |
| ES (1) | ES2572105T3 (da) |
| HK (1) | HK1217197A1 (da) |
| RU (1) | RU2662713C2 (da) |
| WO (1) | WO2014135028A1 (da) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588792B (zh) | 2013-03-04 | 2016-03-23 | 中国科学院上海药物研究所 | 吡啶并嘧啶或嘧啶并嘧啶类化合物、其制备方法、药物组合物及其用途 |
| CN106008559B (zh) * | 2015-03-25 | 2020-10-16 | 中国科学院上海药物研究所 | 取代吡啶并嘧啶类化合物的合成工艺 |
| WO2017156350A1 (en) | 2016-03-09 | 2017-09-14 | K-Gen, Inc. | Methods of cancer treatment |
| CN111148747B (zh) * | 2017-11-07 | 2023-04-04 | 中国科学院上海药物研究所 | 吡啶并嘧啶类化合物的盐型和晶型及其制备方法 |
| CN109867667B (zh) * | 2017-12-05 | 2021-06-11 | 中国药科大学 | 含有吡啶并嘧啶结构的parp和pi3k双靶点抑制剂 |
| CN113825760B (zh) * | 2019-05-06 | 2022-08-19 | 南京明德新药研发有限公司 | 一种mTORC1/2双激酶活性抑制剂的盐型、晶型及其制备方法 |
| US20240208964A1 (en) * | 2020-06-03 | 2024-06-27 | Pyridopyrimidines And Methods Of Their Use | Pyridopyrimidines and methods of their use |
| WO2022061251A1 (en) * | 2020-09-18 | 2022-03-24 | Plexxikon Inc. | Compounds and methods for kras modulation and indications therefor |
| CN115260158A (zh) * | 2021-04-30 | 2022-11-01 | 上海医药集团股份有限公司 | 一种靶向蛋白调节剂的化合物及其应用 |
| CA3228579A1 (en) * | 2021-08-10 | 2023-02-16 | Amgen Inc. | Heterocyclic compounds and methods of use |
| AU2022325771A1 (en) * | 2021-08-10 | 2024-02-15 | Amgen Inc. | Heterocyclic compounds and methods of use |
| WO2023244600A1 (en) * | 2022-06-15 | 2023-12-21 | Mirati Therapeutics, Inc. | Prodrugs of pan-kras inhibitors |
| WO2024057013A1 (en) * | 2022-09-12 | 2024-03-21 | Exscientia Ai Limited | Nlrp3 modulators |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006217744A1 (en) * | 2005-02-25 | 2006-08-31 | Kudos Pharmaceuticals Limited | 2,4-diamino-pyridopyrimidine derivatives and their use as MTOR inhibitors |
| CN101360746B (zh) * | 2005-11-22 | 2013-12-11 | 库多斯药物有限公司 | 作为mTOR抑制剂的吡啶并-、吡唑并-和嘧啶并-嘧啶衍生物 |
| HUE035116T2 (hu) * | 2006-08-08 | 2018-05-02 | Chugai Pharmaceutical Co Ltd | PI3K inhibitor pirimidinszármazékok és alkalmazásuk |
| CN101558067B (zh) * | 2006-08-23 | 2014-05-28 | 库多斯药物有限公司 | 作为mtor抑制剂的2-甲基吗啉吡啶并、吡唑并和嘧啶并-嘧啶衍生物 |
| US20080233127A1 (en) * | 2007-03-21 | 2008-09-25 | Wyeth | Imidazolopyrimidine analogs and their use as pi3 kinase and mtor inhibitors |
| WO2010120987A1 (en) * | 2009-04-17 | 2010-10-21 | Wyeth Llc | Ring fused, ureidoaryl- and carbamoylaryl-bridged morpholino-pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
| CN102887895B (zh) * | 2011-07-22 | 2016-08-24 | 山东轩竹医药科技有限公司 | 吡啶并嘧啶类mTOR抑制剂 |
| CN102911172A (zh) * | 2011-08-04 | 2013-02-06 | 上海恒瑞医药有限公司 | 杂芳基并嘧啶类衍生物、其制备方法和用途 |
| CN103588792B (zh) * | 2013-03-04 | 2016-03-23 | 中国科学院上海药物研究所 | 吡啶并嘧啶或嘧啶并嘧啶类化合物、其制备方法、药物组合物及其用途 |
-
2013
- 2013-03-04 CN CN201310068888.8A patent/CN103588792B/zh active Active
-
2014
- 2014-02-28 RU RU2015140387A patent/RU2662713C2/ru active
- 2014-02-28 WO PCT/CN2014/072678 patent/WO2014135028A1/zh active Application Filing
- 2014-02-28 ES ES14760712T patent/ES2572105T3/es active Active
- 2014-02-28 CA CA2903072A patent/CA2903072C/en active Active
- 2014-02-28 AU AU2014225155A patent/AU2014225155B2/en not_active Ceased
- 2014-02-28 DK DK14760712.1T patent/DK2966079T3/da active
- 2014-02-28 DE DE14760712.1T patent/DE14760712T1/de active Pending
- 2014-02-28 JP JP2015560533A patent/JP2016510042A/ja active Pending
- 2014-02-28 EP EP14760712.1A patent/EP2966079B1/en active Active
-
2015
- 2015-09-01 US US14/842,682 patent/US9796732B2/en active Active
-
2016
- 2016-05-06 HK HK16105194.5A patent/HK1217197A1/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2016510042A (ja) | 2016-04-04 |
| HK1217197A1 (zh) | 2016-12-30 |
| WO2014135028A1 (zh) | 2014-09-12 |
| ES2572105T1 (es) | 2016-05-30 |
| AU2014225155A1 (en) | 2015-10-15 |
| CN103588792B (zh) | 2016-03-23 |
| EP2966079A4 (en) | 2016-11-09 |
| DK2966079T3 (da) | 2022-02-14 |
| US9796732B2 (en) | 2017-10-24 |
| ES2572105T3 (es) | 2022-04-13 |
| RU2662713C2 (ru) | 2018-07-27 |
| AU2014225155B2 (en) | 2017-11-23 |
| DE14760712T1 (de) | 2017-12-14 |
| RU2015140387A (ru) | 2017-03-30 |
| EP2966079A1 (en) | 2016-01-13 |
| EP2966079B1 (en) | 2021-11-24 |
| CA2903072C (en) | 2019-05-07 |
| CN103588792A (zh) | 2014-02-19 |
| US20150368274A1 (en) | 2015-12-24 |
| CA2903072A1 (en) | 2014-09-12 |
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