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HRP20211770T1 - 2-(morfolin-4-il)-1,7-naftiridini - Google Patents

2-(morfolin-4-il)-1,7-naftiridini Download PDF

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Publication number
HRP20211770T1
HRP20211770T1 HRP20211770TT HRP20211770T HRP20211770T1 HR P20211770 T1 HRP20211770 T1 HR P20211770T1 HR P20211770T T HRP20211770T T HR P20211770TT HR P20211770 T HRP20211770 T HR P20211770T HR P20211770 T1 HRP20211770 T1 HR P20211770T1
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general formula
intermediate compound
image
alkyl
phenyl
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HRP20211770TT
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Lars Wortmann
Ulrich LÜCKING
Julien LEFRANC
Hans Briem
Marcus Koppitz
Knut Eis
Franz Von Nussbaum
Benjamin Bader
Antje-Margret WENGNER
Gerhard Siemeister
Wilhelm Bone
Philip Lienau
Joanna Grudzinska-Goebel
Dieter Moosmayer
Uwe EBERSPÄCHER
Hans Schick
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Bayer Pharma Aktiengesellschaft
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
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    • A61K31/33Heterocyclic compounds
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    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53861,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541Non-condensed thiazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/675Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/22Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
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    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

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  • Nitrogen Condensed Heterocyclic Rings (AREA)
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  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (14)

1. Upotreba intermedijarnog spoja za dobivanje spoja opće formule (Ib) [image] naznačen time što: R1 predstavlja [image] pri čemu * označava točku vezanja navedene skupine s ostatkom molekule; R2 predstavlja vodik, halogen, -NR7R8, CN, C1-C6-alkil, C1-C4-alkoksi, 3- do 10-člani heterocikloalkoksi, C2-C4-alkenil, C3-C6-cikloalkil, 3- do 10-člani heterocikloalkil, 4- do 10-člani heterocikloalkenil, fenil, heteroaril, -(CO)NR7R8, -(SO2)R9, -(SO)R9, -SR9, -N=(SO)R9R10, -(PO)(OR7)2, -(PO)(OR7)R10, -(PO)(R10)2, pri čemu je svaki C1-C6-alkil, C1-C4-alkoksi, C3-C6-cikloalkil, 3- do 10-člani heterocikloalkil, fenil ili heteroaril po izboru supstituiran, jednom ili više puta, međusobno neovisno, s halogenom, OH, amino, -NR7R8, C1-C4-alkilom po izboru supstituiranim s hidroksilom ili fenilom, C1-C2-haloalkilom, C1-C3-alkoksi, C3-C6-cikloalkilom, 3- do 6-članim heterocikloalkilom, fenilom, -(CO)OR7, -(CO)NR7R8, -NR7(CO)R10, -NR8(CO)OR7, -(SO2)R9, -SR9, -NR7(SO2)R9, -((SO)=NR11)R10, -(PO)(OR7)2, -(PO)(OR7)R10, ili s heteroarilnom skupinom; pri čemu je svaki 4- do 10-člani heterocikloalkenil po izboru supstituiran, jednom ili više puta, međusobno neovisno, s metilom; R4 predstavlja vodik ili metil; R7, R8 predstavljaju, međusobno neovisno, vodik, C1-C6-alkil, C3-C6-cikloalkil ili fenil, navedeni fenil je po izboru supstituiran, jednom ili više puta, s halogenom; R9 predstavlja C1-C4-alkil ili fenil, pri čemu je svaki C1-C4-alkil ili fenil po izboru supstituiran, jednom ili više puta, međusobno neovisno, s R13; R10 predstavlja C1-C4-alkil; ili R9 i R10 zajedno, u slučaju skupine -N=(SO)R9R10 , predstavljaju 5- do 8-članu heterocikloalkilnu skupinu; R11 predstavlja vodik, C1-C4-alkil, -(CO)OR7, -(CO)NR7R8 ili CN; R13 predstavlja halogen, OH ili C1-C6-alkoksi, pri čemu je intermedijarni spoj odabran iz skupine koju čine: [image] [image] i [image] u kojoj R1 i R4 su kako je definirano za spoj opće formule (Ib); R3 predstavlja vodik; X predstavlja klor, brom ili jod; i Y predstavlja OH, -O-SO2-CF3, Cl, Br, I, SH ili -SO2Cl.
2. Postupak za dobivanje intermedijarnog spoja opće formule 5 [image] , naznačen time što spoj opće formule 4, u kojoj R3 i R4 predstavljaju, međusobno neovisno, vodik ili metil, reagira u organskom otapalu na temperaturi između -20°C i vrelišta otapala, poželjno između -5°C i 30°C, koristeći jaku bazu za dobivanje spoja opće formule 5.
3. Postupak prema patentnom zahtjevu 2, naznačen time što je jaka baza litijev bis(trimetilsilil)amid (LiHMDS), kalijev bis(trimetilsilil)amid (KHMDS), natrijev bis(trimetilsilil)amid (NaHMDS) ili litijev diizopropilamid (LDA).
4. Postupak prema patentnim zahtjevima 2 ili 3, naznačen time što je organsko otapalo aprotično organsko otapalo.
5. Postupak prema patentnom zahtjevu 4, naznačen time što je organsko otapalo tetrahidrofuran ili N, N-dimetilformamid.
6. Intermedijarni spoj opće formule 5 [image] naznačen time što R3 predstavlja H i R4 predstavlja metil.
7. Intermedijarni spoj opće formule 4 [image] naznačen time što R3 predstavlja H i R4 predstavlja metil.
8. Intermedijarni spoj opće formule 11 [image] naznačen time što R1, R3 i R4 su kako je definirano u zahtjevu 1 za intermedijarni spoj opće formule 11.
9. Intermedijarni spoj opće formule 12 [image] naznačen time što R1, R3 i R4 su kako je definirano u zahtjevu 1 za intermedijarni spoj opće formule 12 i u kojoj X predstavlja klor, brom ili jod.
10. Intermedijarni spoj opće formule 39 [image] naznačen time što Y predstavlja OH, -O-SO2-CF3, Cl, Br, I, SH ili -SO2Cl.
11. Intermedijarni spoj opće formule 39, naznačen time što Y predstavlja OH, -O-SO2-CF3 ili Cl.
12. Intermedijarni spoj opće formule 9 [image] naznačen time što R3 predstavlja H i R4 predstavlja metil.
13. Intermedijarni spoj opće formule 15 [image] naznačen time što R1, R3 i R4 su kako je definirano u zahtjevu 1 za intermedijarni spoj opće formule 15.
14. Intermedijarni spoj opće formule 16 [image] naznačen time što R1, R3 i R4 su kako je definirano u zahtjevu 1 za intermedijarni spoj opće formule 16.
HRP20211770TT 2014-08-04 2015-08-03 2-(morfolin-4-il)-1,7-naftiridini HRP20211770T1 (hr)

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EP14179692 2014-08-04
EP15159342 2015-03-17
EP18167649.5A EP3395818B1 (en) 2014-08-04 2015-08-03 2-(morpholin-4-yl)-1,7-naphthyridines

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Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI700283B (zh) * 2014-08-04 2020-08-01 德商拜耳製藥公司 2-(嗎啉-4-基)-1,7-萘啶
WO2016020295A1 (en) 2014-08-04 2016-02-11 Nuevolution A/S Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases
WO2017121684A1 (en) * 2016-01-14 2017-07-20 Bayer Pharma Aktiengesellschaft 5-substituted 2-(morpholin-4-yl)-1,7-naphthyridines
TWI794171B (zh) 2016-05-11 2023-03-01 美商滬亞生物國際有限公司 Hdac抑制劑與pd-l1抑制劑之組合治療
TWI808055B (zh) 2016-05-11 2023-07-11 美商滬亞生物國際有限公司 Hdac 抑制劑與 pd-1 抑制劑之組合治療
WO2018153975A1 (en) 2017-02-24 2018-08-30 Bayer As Combination therapy comprising a radiopharmaceutical and a dna-repair inhibitor
WO2018153972A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors and antiandrogens
CA3054247A1 (en) 2017-02-24 2018-08-30 Antje Margret Wengner Combination of atr kinase inhibitors with parp inhibitors
WO2018153971A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors
WO2018153970A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Solid forms of 2-[(3r)-3-methylmorpholin-4-yl]-4-(1-methyl-1h-pyrazol-5-yl)-8-(1h-pyrazol-5-yl)-1,7-naphthyridine
JOP20190197A1 (ar) * 2017-02-24 2019-08-22 Bayer Pharma AG مثبط كيناز ايه تي آر للاستخدام في طريقة لعلاج مرض فرط التكاثر
WO2018153969A1 (en) 2017-02-24 2018-08-30 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with radium-223 salt
WO2018206547A1 (en) 2017-05-12 2018-11-15 Bayer Pharma Aktiengesellschaft Combination of bub1 and atr inhibitors
US10421765B2 (en) 2017-05-26 2019-09-24 Board Of Regents, The University Of Texas System Tetrahydropyrido[4,3-d]pyrimidine inhibitors of ATR kinase
US10377591B2 (en) 2017-07-07 2019-08-13 Zebra Technologies Corporation Input handling for media processing devices
HUE066043T2 (hu) 2017-07-13 2024-07-28 Univ Texas A TR kináz beterociklusos inhibitorai
JOP20200024A1 (ar) 2017-08-04 2020-02-02 Bayer Ag مركبات ثنائي هيدروكساديازينون
EP3661917B1 (en) 2017-08-04 2022-05-11 Bayer Aktiengesellschaft 6-((3-trifluoromethyl)phenyl)-4,5-dihydropyridazin-3(2h)-one derivatives as pde3a and pde3b inhibitors for treating cancer
US11690911B2 (en) 2017-08-04 2023-07-04 Bayer Aktiengesellschaft Combination of ATR kinase inhibitors and PD-1/PD-L1 inhibitors
CN111886224B (zh) 2017-08-17 2024-07-23 德州大学系统董事会 Atr激酶的杂环抑制剂
WO2019057852A1 (en) 2017-09-22 2019-03-28 Bayer Aktiengesellschaft USE OF KAP1 AS A BIOMARKER FOR DETECTION OR MONITORING ATR INHIBITION IN A SUBJECT
EP3461480A1 (en) 2017-09-27 2019-04-03 Onxeo Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer
EP3720973A1 (en) * 2017-12-08 2020-10-14 Bayer Aktiengesellschaft Predictive markers for atr kinase inhibitors
EP3753937B1 (en) * 2018-02-07 2024-01-10 Wuxi Biocity Biopharmaceutics Co., Ltd. Atr inhibitor and application thereof
JP7341156B2 (ja) * 2018-03-16 2023-09-08 ボード オブ レジェンツ,ザ ユニバーシティ オブ テキサス システム Atrキナーゼの複素環式阻害剤
BR112021001309A2 (pt) * 2018-08-24 2021-04-27 Bayer Aktiengesellschaft método para a preparação da 2-[(3r)-3-metilmorfolin-4-il]-4-(1-metil-1h-pirazol-5-il)-8-(1h-pirazol-5-il)-1,7-naftiridina
EP3866805A1 (en) 2018-10-16 2021-08-25 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with 2,3-dihydroimidazo[1,2-c]quinazoline compounds
KR20210097124A (ko) * 2018-10-30 2021-08-06 리페어 세라퓨틱스 인크. 화합물, 약제 조성물, 및 화합물 제조 방법 및 atr 키나제 억제제로서의 이것들의 사용 방법
SG11202107698XA (en) 2019-02-11 2021-08-30 Bayer Ag The atr kinase inhibitor bay1895344 for use in the treatment of a hyper-proliferative disease
CN112142744A (zh) * 2019-06-28 2020-12-29 上海瑛派药业有限公司 取代的稠合杂芳双环化合物作为激酶抑制剂及其应用
KR20220035925A (ko) * 2019-07-22 2022-03-22 리페어 세라퓨틱스 인크. Atr 키나제 억제제로서의 치환된 2-모르폴리노피리딘 유도체
BR112022008000A2 (pt) * 2019-11-21 2022-07-12 Jiangsu Hengrui Medicine Co Derivado de pirazol-heteroarila, método de preparação para o mesmo e uso médico do mesmo
EP4072551A4 (en) * 2019-12-11 2023-11-15 Repare Therapeutics Inc. USE OF ATR INHIBITORS IN COMBINATION WITH PARP INHIBITORS
EP4076657A1 (en) 2019-12-20 2022-10-26 Nuevolution A/S Compounds active towards nuclear receptors
EP4126875A1 (en) 2020-03-31 2023-02-08 Nuevolution A/S Compounds active towards nuclear receptors
WO2021198955A1 (en) 2020-03-31 2021-10-07 Nuevolution A/S Compounds active towards nuclear receptors
EP4175948A4 (en) * 2020-07-03 2024-07-17 Antengene Discovery Limited ATR INHIBITORS AND USES THEREOF
KR20230039675A (ko) * 2020-07-13 2023-03-21 베이징 타이드 파마슈티컬 코퍼레이션 리미티드 Atr 키나제 억제제로 사용되는 피라졸로피리미딘 화합물
CN112110934B (zh) * 2020-09-23 2021-12-07 上海应用技术大学 一种基于azd9291的生物标记物及其制备方法与应用
US20240043419A1 (en) * 2020-09-27 2024-02-08 Medshine Discovery Inc. Class of 1,7-naphthyridine compounds and application thereof
EP4267581A4 (en) * 2020-12-25 2025-01-01 Impact Therapeutics Shanghai Inc SUBSTITUTED IMIDAZO[1,5-B]PYRIDAZINE COMPOUNDS AS KINASE INHIBITORS AND THEIR USE
US20240262823A1 (en) * 2021-05-21 2024-08-08 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Pharmaceutically acceptable salt of pyrazoloheteroaryl derivative and crystal form thereof
WO2023005928A1 (zh) 2021-07-27 2023-02-02 上海辉启生物医药科技有限公司 8-氧-3-氮杂二环[3.2.1]辛烷类化合物或其盐及其制备方法和用途
US20240317741A1 (en) * 2021-08-11 2024-09-26 Wigen Biomedicine Technology (shanghai) Co., Ltd. Naphthyridine derivative as atr inhibitor and method for preparing same
CN116283960A (zh) 2021-12-21 2023-06-23 上海安诺达生物科技有限公司 取代的稠杂环化合物及其制备方法与应用
CN116731011A (zh) * 2022-03-01 2023-09-12 武汉众诚康健生物医药科技有限公司 一种萘啶衍生物及其应用
KR20250023494A (ko) 2022-06-15 2025-02-18 아스트라제네카 아베 암 치료를 위한 병용 요법
WO2024188937A1 (en) 2023-03-13 2024-09-19 Bayer Aktiengesellschaft Combinations of atr kinase inhibitors and parp inhibitors to treat hyper-proliferative conditions e.g. cancer

Family Cites Families (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1307271A (en) 1970-06-25 1973-02-14 Shell Int Research Sulphoximine derivatives and their use in herbicidal compositions
US4008068A (en) * 1976-03-08 1977-02-15 Velsicol Chemical Corporation 1-Thiadiazolyl-5-morpholinoimidazolidinones
AU4007900A (en) 1999-03-11 2000-10-16 Neurogen Corporation Aryl fused 2,4-disubstituted pyridines: nk3 receptor ligands
DE10349423A1 (de) 2003-10-16 2005-06-16 Schering Ag Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
US20070054916A1 (en) 2004-10-01 2007-03-08 Amgen Inc. Aryl nitrogen-containing bicyclic compounds and methods of use
WO2007000445A1 (en) 2005-06-29 2007-01-04 Boehringer Ingelheim International Gmbh Glucopyranosyl-substituted benzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture
KR101464384B1 (ko) * 2005-11-22 2014-11-21 쿠도스 파마슈티칼스 리미티드 mTOR 억제제로서 피리도피리미딘, 피라조피리미딘 및피리미도피리미딘 유도체
DE102005062742A1 (de) 2005-12-22 2007-06-28 Bayer Schering Pharma Ag Sulfoximin substituierte Pyrimidine, Verfahren zu deren Herstellung und ihre Verwendung als Arzneimittel
EP1803723A1 (de) 2006-01-03 2007-07-04 Bayer Schering Pharma Aktiengesellschaft (2,4,9-triaza-1(2,4)-pyrimidina-3(1,3)-benzenacyclononaphan-3^4-yl)-sulfoximid derivate als selektive inhibitoren der aurora kinase zur behandlung von krebs
US7910747B2 (en) 2006-07-06 2011-03-22 Bristol-Myers Squibb Company Phosphonate and phosphinate pyrazolylamide glucokinase activators
ES2301380B1 (es) * 2006-08-09 2009-06-08 Laboratorios Almirall S.A. Nuevos derivados de 1,7-naftiridina.
MY148688A (en) * 2006-08-23 2013-05-31 Kudos Pharm Ltd 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors
AU2009289316A1 (en) * 2008-09-02 2010-03-11 Novartis Ag Bicyclic kinase inhibitors
EP2344490A2 (en) * 2008-10-03 2011-07-20 Merck Serono S.A. 4-morpholino-pyrido[3,2-d]pyrimidines active on pi3k
MX2011004953A (es) 2008-11-10 2011-12-14 Vertex Pharma Compuestos utiles como inhibidores de cinasa atr.
US20100144345A1 (en) 2008-12-09 2010-06-10 Microsoft Corporation Using called party mobile presence and movement in communication application
WO2010071837A1 (en) 2008-12-19 2010-06-24 Vertex Pharmaceuticals Incorporated Pyrazine derivatives useful as inhibitors of atr kinase
UY32351A (es) 2008-12-22 2010-07-30 Astrazeneca Ab Compuestos de pirimidinil indol para uso como inhibidores de atr
TW201111378A (en) 2009-09-11 2011-04-01 Bayer Schering Pharma Ag Substituted (heteroarylmethyl) thiohydantoins
WO2011143399A1 (en) 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011143422A1 (en) 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated 2 -aminopyridine derivatives useful as inhibitors of atr kinase
EP2569313A1 (en) 2010-05-12 2013-03-20 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011143425A2 (en) 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
EP2569286B1 (en) 2010-05-12 2014-08-20 Vertex Pharmaceuticals Inc. Compounds useful as inhibitors of atr kinase
US8962631B2 (en) 2010-05-12 2015-02-24 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
SA111320519B1 (ar) 2010-06-11 2014-07-02 Astrazeneca Ab مركبات بيريميدينيل للاستخدام كمثبطات atr
WO2011163527A1 (en) * 2010-06-23 2011-12-29 Vertex Pharmaceuticals Incorporated Pyrrolo- pyrazine derivatives useful as inhibitors of atr kinase
US20130090323A1 (en) * 2010-06-30 2013-04-11 Amgen Inc. Heterocyclic compounds and their uses
WO2012138938A1 (en) 2011-04-05 2012-10-11 Vertex Pharmaceuticals Incorporated Aminopyrazine compounds useful as inhibitors of tra kinase
US9096602B2 (en) 2011-06-22 2015-08-04 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-B]pyrazines as ATR kinase inhibitors
EP2723745A1 (en) 2011-06-22 2014-04-30 Vertex Pharmaceuticals Inc. Compounds useful as inhibitors of atr kinase
US9309250B2 (en) 2011-06-22 2016-04-12 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors
US8846656B2 (en) * 2011-07-22 2014-09-30 Novartis Ag Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators
CA3089792C (en) 2011-09-30 2023-03-14 Vertex Pharmaceuticals Incorporated Treating non-small cell lung cancer with atr inhibitors
WO2013049719A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2013049720A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8846686B2 (en) 2011-09-30 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
EP2776422A1 (en) 2011-11-09 2014-09-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8846917B2 (en) 2011-11-09 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8841449B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8841450B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013071094A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
LT2833973T (lt) 2012-04-05 2018-02-12 Vertex Pharmaceuticals Incorporated Junginiai, tinkami naudoti kaip atr kinazės inhibitoriai, ir jų kombinuotas gydymas
US8912198B2 (en) 2012-10-16 2014-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
SMT202100425T1 (it) 2012-12-07 2021-09-14 Vertex Pharma 2-ammino-n-(piperidin-1-il-piridin-3-il) pirazolo[1,5alpha]piirimidina-3-carbossiammide come inibitore di atr chinasi
WO2014109414A1 (ja) * 2013-01-11 2014-07-17 富士フイルム株式会社 含窒素複素環化合物またはその塩
WO2014143240A1 (en) 2013-03-15 2014-09-18 Vertex Pharmaceuticals Incorporated Fused pyrazolopyrimidine derivatives useful as inhibitors of atr kinase
TWI700283B (zh) 2014-08-04 2020-08-01 德商拜耳製藥公司 2-(嗎啉-4-基)-1,7-萘啶
WO2017121684A1 (en) * 2016-01-14 2017-07-20 Bayer Pharma Aktiengesellschaft 5-substituted 2-(morpholin-4-yl)-1,7-naphthyridines
CA3054247A1 (en) 2017-02-24 2018-08-30 Antje Margret Wengner Combination of atr kinase inhibitors with parp inhibitors
WO2018153971A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors
JOP20190197A1 (ar) 2017-02-24 2019-08-22 Bayer Pharma AG مثبط كيناز ايه تي آر للاستخدام في طريقة لعلاج مرض فرط التكاثر
WO2018153970A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Solid forms of 2-[(3r)-3-methylmorpholin-4-yl]-4-(1-methyl-1h-pyrazol-5-yl)-8-(1h-pyrazol-5-yl)-1,7-naphthyridine
WO2018153969A1 (en) 2017-02-24 2018-08-30 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with radium-223 salt
WO2018153972A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors and antiandrogens
WO2018153975A1 (en) 2017-02-24 2018-08-30 Bayer As Combination therapy comprising a radiopharmaceutical and a dna-repair inhibitor
WO2018206547A1 (en) 2017-05-12 2018-11-15 Bayer Pharma Aktiengesellschaft Combination of bub1 and atr inhibitors
AU2017420801A1 (en) 2017-06-28 2020-01-23 Corning Research & Development Corporation Multiports and devices having a connector port with a rotating securing feature
US11690911B2 (en) 2017-08-04 2023-07-04 Bayer Aktiengesellschaft Combination of ATR kinase inhibitors and PD-1/PD-L1 inhibitors
EP3720973A1 (en) 2017-12-08 2020-10-14 Bayer Aktiengesellschaft Predictive markers for atr kinase inhibitors
BR112021001309A2 (pt) 2018-08-24 2021-04-27 Bayer Aktiengesellschaft método para a preparação da 2-[(3r)-3-metilmorfolin-4-il]-4-(1-metil-1h-pirazol-5-il)-8-(1h-pirazol-5-il)-1,7-naftiridina
EP3860849A4 (en) 2018-10-05 2022-06-22 ISP Investments LLC SMOOTH HIGH SOLIDS FILM COATING COMPOSITION COMPRISING WATER-SOLUBLE CELLULOSE ETHER, AND METHOD FOR PREPARING THE SAME
EP3866805A1 (en) 2018-10-16 2021-08-25 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with 2,3-dihydroimidazo[1,2-c]quinazoline compounds
SG11202107698XA (en) 2019-02-11 2021-08-30 Bayer Ag The atr kinase inhibitor bay1895344 for use in the treatment of a hyper-proliferative disease

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