HRP20150146T1 - Derivati kromenona s protu tumourskom aktivnošä†u - Google Patents
Derivati kromenona s protu tumourskom aktivnošä†u Download PDFInfo
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- HRP20150146T1 HRP20150146T1 HRP20150146TT HRP20150146T HRP20150146T1 HR P20150146 T1 HRP20150146 T1 HR P20150146T1 HR P20150146T T HRP20150146T T HR P20150146TT HR P20150146 T HRP20150146 T HR P20150146T HR P20150146 T1 HRP20150146 T1 HR P20150146T1
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- alkyl
- pharmaceutically acceptable
- formula
- acceptable salt
- alkoxy
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- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical class C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title claims 4
- 230000000259 anti-tumor effect Effects 0.000 title 1
- 230000000694 effects Effects 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims 30
- 150000003839 salts Chemical class 0.000 claims 19
- 150000001875 compounds Chemical class 0.000 claims 18
- 125000003545 alkoxy group Chemical group 0.000 claims 17
- 229910052736 halogen Inorganic materials 0.000 claims 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims 11
- 150000002367 halogens Chemical class 0.000 claims 11
- -1 3-methoxypropyl Chemical group 0.000 claims 10
- 125000003342 alkenyl group Chemical group 0.000 claims 9
- 125000000304 alkynyl group Chemical group 0.000 claims 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 125000005843 halogen group Chemical group 0.000 claims 6
- 229910052717 sulfur Chemical group 0.000 claims 6
- 125000003282 alkyl amino group Chemical group 0.000 claims 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 239000001301 oxygen Substances 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims 3
- 239000011593 sulfur Chemical group 0.000 claims 3
- 125000004434 sulfur atom Chemical group 0.000 claims 3
- LMJFJIDLEAWOQJ-CQSZACIVSA-N 8-[(1r)-1-(3,5-difluoroanilino)ethyl]-n,n-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide Chemical compound N([C@H](C)C=1C2=C(C(C=C(O2)N2CCOCC2)=O)C=C(C=1)C(=O)N(C)C)C1=CC(F)=CC(F)=C1 LMJFJIDLEAWOQJ-CQSZACIVSA-N 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- LMJFJIDLEAWOQJ-UHFFFAOYSA-N 8-[1-(3,5-difluoroanilino)ethyl]-n,n-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide Chemical compound C=1C(C(=O)N(C)C)=CC(C(C=C(O2)N3CCOCC3)=O)=C2C=1C(C)NC1=CC(F)=CC(F)=C1 LMJFJIDLEAWOQJ-UHFFFAOYSA-N 0.000 claims 1
- JPRUSXLWICAZQV-UHFFFAOYSA-N 8-[1-(3,5-difluoroanilino)ethyl]-n-methyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide Chemical compound C=12OC(N3CCOCC3)=CC(=O)C2=CC(C(=O)NC)=CC=1C(C)NC1=CC(F)=CC(F)=C1 JPRUSXLWICAZQV-UHFFFAOYSA-N 0.000 claims 1
- 206010005949 Bone cancer Diseases 0.000 claims 1
- 208000018084 Bone neoplasm Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 230000002280 anti-androgenic effect Effects 0.000 claims 1
- 125000003725 azepanyl group Chemical group 0.000 claims 1
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 1
- 125000002393 azetidinyl group Chemical group 0.000 claims 1
- 208000026900 bile duct neoplasm Diseases 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 210000003679 cervix uteri Anatomy 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 230000001079 digestive effect Effects 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 210000003238 esophagus Anatomy 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 125000005961 oxazepanyl group Chemical group 0.000 claims 1
- 210000000496 pancreas Anatomy 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 210000003491 skin Anatomy 0.000 claims 1
- 238000012360 testing method Methods 0.000 claims 1
- 210000001550 testis Anatomy 0.000 claims 1
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 1
- 210000001685 thyroid gland Anatomy 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 210000003932 urinary bladder Anatomy 0.000 claims 1
- 210000004291 uterus Anatomy 0.000 claims 1
- 210000003905 vulva Anatomy 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/74—Benzo[b]pyrans, hydrogenated in the carbocyclic ring
-
- 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
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic 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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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (20)
1. Spoj s formulom I:
[image]
naznačen time da:
R1 je H ili (1-4C)alkil proizvoljno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, hidroksi ili (1-3C)alkoksi;
R2 je (1-4C)alkil ili (1-4C)alkoksi, bilo koji od njih može biti proizvoljno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, hidroksi, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi, cijano, (1-3C)alkilamino ili di-[(1-3C)alkil]amino; ili
R1 i R2 zajedno tvore 3 do 8 člani heterociklilni prstenasti sustav koji sadrži dušik, koji proizvoljno sadrži 1 ili 2 dodatna heteroatoma koji su odabrani od kisika, dušika i sumpora, pri čemu je atom sumpora u prstenu proizvoljno oksidiran tako da tvori S-oksid(e), te je navedeni prsten proizvoljno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, hidroksi, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi, okso, hidroksi-(1-3C)alkil, halogeno-(1-3C)alkil i (1-3C)alkoksi-(1-3C)alkil;
R3 je H ili (1-3C)alkil;
R4 i R5 su neovisno odabrani od H, halogena, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi i cijano; ili
R4 i R5 zajedno tvore fenilni prsten ili 5 ili 6 člani heterociklilni prsten ili 5 ili 6 člani heteroarilni prsten, pri čemu heterociklilni ili heteroarilni prsten sadrži 1, 2 ili 3 heteroatoma odabrana od kisika i dušika, te je navedeni fenilni, heterociklilni ili heteroarilni prsten proizvoljno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi i cijano;
R6, R7 i R8 su neovisno odabrani od H, halogena, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi i cijano;
n je 0, 1, 2, 3 ili 4;
svaka R9 skupina je (1-3C)alkil;
ili njegova farmaceutski prihvatljiva sol.
2. Spoj s formulom I prema zahtjevu 1, naznačen time da:
R1 je H ili (1-4C)alkil;
R2 je (1-4C)alkil proizvoljno supstituiran s halogeno, hidroksi, (1-3C)alkoksi, cijano, (1-3C)alkilamino ili di-[(1-3C)alkil]amino; ili
R1 i R2 zajedno tvore 4 do 7 člani heterociklilni prstenasti sustav koji sadrži dušik, koji proizvoljno sadrži 1 dodatni heteroatom koji je odabran od kisika, dušika i sumpora, pri čemu je atom sumpora u prstenu proizvoljno oksidiran tako da tvori S-oksid(e), te je navedeni prsten proizvoljno supstituiran s halogenom, hidroksi, (1-3C)alkil, (1-3C)alkoksi ili hidroksi-(1-3C)alkil;
ili njegova farmaceutski prihvatljiva sol.
3. Spoj s formulom I prema zahtjevu 1 ili 2, naznačen time da R3 je H ili metil; ili njegova farmaceutski prihvatljiva sol.
4. Spoj s formulom I prema bilo kojem od zahtjeva 1 do 3, naznačen time da R4 i R5 su neovisno odabrani od H, halogena, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi i cijano; ili njegova farmaceutski prihvatljiva sol.
5. Spoj s formulom I prema bilo kojem od zahtjeva 1 do 4, naznačen time da R6, R7 i R8 su neovisno odabrani od H, halogena, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi i cijano; ili njegova farmaceutski prihvatljiva sol.
6. Spoj s formulom I prema bilo kojem od zahtjeva 1 do 5, naznačen time da n je 1 i R9 je metil; ili njegova farmaceutski prihvatljiva sol.
7. Spoj s formulom I prema zahtjevu 1, naznačen time da:
R1 je H ili (1-4C)alkil;
R2 je (1-4C)alkil proizvoljno supstituiran s halogenom, hidroksi, (1-3C)alkoksi, cijano, (1-3C)alkilamino ili di-[(1-3C)alkil]amino; ili
R1 i R2 zajedno tvore 4 do 7 člani heterociklilni prstenasti sustav koji sadrži dušik, koji proizvoljno sadrži 1 dodatni heteroatom koji je odabran od kisika, dušika i sumpora, pri čemu je atom sumpora u prstenu proizvoljno oksidiran tako da tvori S-oksid(e), te je navedeni prsten proizvoljno supstituiran s halogenom, hidroksi, (1-3C)alkil, (1-3C)alkoksi ili hidroksi-(1-3C)alkil;
R3 je H ili metil;
R4 i R5 su neovisno odabrani od H, halogena, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi i cijano;
R6, R7 i R8 su neovisno odabrani od H, halogena, (1-3C)alkil, (2-3C)alkenil, (2-3C)alkinil, (1-3C)alkoksi i cijano;
n je 0;
ili njegova farmaceutski prihvatljiva sol.
8. Spoj s formulom I prema zahtjevu 1 naznačen time da:
R1 je H, metil ili etil;
R2 je (1-4C)alkil proizvoljno supstituiran s halogenom, hidroksi, (1-3C)alkoksi, cijano, (1-3C)alkilamino ili di-[(1-3C)alkil]amino; ili
R1 i R2 zajedno tvore heterociklilni prstenasti sustav koji sadrži dušik, odabran od iz skupine koja sadrži azepanil, oksazepanil, azetidinil, pirolidinil, morfolinil, tiomorfolinil, piperidinil i piperazinil, navedeni prsten je proizvoljno supstituiran s halogenom, hidroksi, (1-3C)alkilom, (1-3C)alkoksi ili hidroksi-(1-3C)alkilom;
R3 je H;
R4 i R5 su neovisno odabrani od H, fluoro ili kloro;
R6, R7 i R8 su neovisno odabrani od H ili halogena;
n je 0;
ili njegova farmaceutski prihvatljiva sol.
9. Spoj s formulom I prema zahtjevu 1 naznačen time da:
R1 je H, metil ili etil;
R2 je metil, etil, ciklopropilmetil, 2-fluoroetil, 2-hidroksietil, 2-metoksietil, 3-metoksipropil ili 2-(dimetilamino)etil; ili
R1 i R2 zajedno tvore proizvoljno supstituirani heterociklilni prstenasti sustav koji sadrži dušik, odabran od azepan-1-il, 1,4-oksazepan-4-il, azetidin-1-il, 3-fluoroazetidin-1-il, 3-hidroksiazetidin-1-il, pirolidin-1-il, (2R)-2-(hidroksimetil)pirolidin-1-il, (2S)-2-(hidroksimetil)pirolidin-1-il, morfolin-4-il, tiomorfolin-4-il, piperidin-1-il, 4-hidroksipiperidin-1-il, 4-metoksipiperidin-1-il, piperazin-1-il ili 4-metilpiperazin-1-il;
R3 je H ili metil;
R4 i R5 su neovisno odabrani od H, fluoro ili kloro;
R6, R7 i R8 su neovisno odabrani od H, fluoro ili kloro;
n je 0;
ili njegova farmaceutski prihvatljiva sol.
10. Spoj s formulom I, ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 5 i 7 do 9 naznačen time da je 8-((1R)-1-(3,5-difluorofenilamino)etil)-N,N-dimetil-2-morfolino-4-okso-4H-kromen-6-karboksamid.
11. Spoj s formulom I, ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 5 i 7 do 9 naznačen time da je 8-(1-(3,5-difluorofenilamino)etil)-N-metil-2-morfolino-4-okso-4H-kromen-6-karboksamid.
12. Spoj s formulom I, ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 11, naznačen time da je spoj jedan enantiomer koji je u enantiomernom suvišku (%ee) od ≥ 95.
13. Oblik B spoja s formulom I koji je (-)-8-(1-(3,5-difluorofenilamino)etil)-N,N-dimetil-2-morfolino-4-okso-4H-kromen-6-karboksamid prema zahtjevu 1, naznačen time da ima uzorak difrakcije X-zraka na prahu s barem dva specifična vrška kod oko 2-theta = 20.7° i 13.8° pri čemu navedene vrijednosti mogu biti plus ili minus 0.5° 2-theta.
14. Kombinacija pogodna za liječenje raka naznačena time da sadrži spoj s formulom I, ili njegovu farmaceutski prihvatljivu sol, prema zahtjevu 1 i antiandrogeni pripravak.
15. Kombinacija pogodna za liječenje raka koja sadrži spoj s formulom I, ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 10 i 12 naznačena time da je 8-((1R)-1-(3,5-difluorofenilamino)etil)-N,N-dimetil-2-morfolino-4-okso-4H-kromen-6-karboksamid i taksoid.
16. Farmaceutski pripravak, naznačen time da sadrži spoj s formulom I, ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 1 do 12 u kombinaciji s farmaceutski prihvatljivim razrjeđivačem ili nosačem.
17. Spoj s formulom I, ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 12 naznačen time da je za uporabu u liječenju.
18. Derivat kromenona prema formuli I, ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 12, naznačen time da je za uporabu kod sprečavanja ili liječenja tumora koji su osjetljivi na inhibiciju enzima PI 3-kinaze.
19. Derivat kromenona prema formuli I, ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 12, naznačen time da je za uporabu kod liječenja raka dojke, debelog crijeva, pluća i prostate.
20. Derivat kromenona prema formuli I, ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 12, naznačen time da je za uporabu kod liječenja raka žučovoda, kosti, mjehura, glave i vrata, bubrega, jetre, probavnog tkiva, jednjaka, jajnika, gušterače, kože, testisa, štitnjače, uterusa, grlića maternice i vulve, te leukemija, multiplog mijeloma i limfoma.
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| Application Number | Priority Date | Filing Date | Title |
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| EP09306017 | 2009-10-27 | ||
| PCT/GB2010/051788 WO2011051704A1 (en) | 2009-10-27 | 2010-10-25 | Chromenone derivatives with anti-tumour activity |
| EP10769052.1A EP2493870B1 (en) | 2009-10-27 | 2010-10-25 | Chromenone derivatives with anti -tumour activity |
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| HRP20150146TT HRP20150146T1 (hr) | 2009-10-27 | 2015-02-05 | Derivati kromenona s protu tumourskom aktivnošä†u |
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Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009155121A2 (en) | 2008-05-30 | 2009-12-23 | Amgen Inc. | Inhibitors of pi3 kinase |
| US8399460B2 (en) * | 2009-10-27 | 2013-03-19 | Astrazeneca Ab | Chromenone derivatives |
| US8530470B2 (en) | 2011-04-13 | 2013-09-10 | Astrazeneca Ab | Chromenone derivatives |
| CA2897279C (en) | 2013-01-23 | 2020-12-29 | Astrazeneca Ab | Aminopyrazine derivatives and pharmaceutical compositions thereof for use in the treatment of cancer |
| KR102222346B1 (ko) * | 2013-03-04 | 2021-03-02 | 아스트라제네카 아베 | 조합 치료 |
| KR20170015508A (ko) | 2014-06-13 | 2017-02-08 | 길리애드 사이언시즈, 인코포레이티드 | 포스파티딜이노시톨 3-키나제 억제제로서의 퀴나졸리논 유도체 |
| SG11201609540TA (en) | 2014-06-13 | 2016-12-29 | Gilead Sciences Inc | Phosphatidylinositol 3-kinase inhibitors |
| US10092563B2 (en) | 2014-06-13 | 2018-10-09 | Gilead Sciences, Inc. | Phosphatidylinositol 3-kinase inhibitors |
| WO2015191726A1 (en) | 2014-06-13 | 2015-12-17 | Gilead Sciences, Inc. | Phosphatidylinositol 3-kinase inhibitors |
| BR112016028814A2 (pt) | 2014-06-13 | 2017-08-22 | Gilead Sciences Inc | ?composição farmacêutica, métodos de tratamento de uma doença ou condição, de inibição de reações imunitárias ou crescimento excessivo ou destrutivo ou de proliferação de células cancerosas, kit, composto, um sal, um isômero, ou uma mistura farmaceuticamente aceitável do mesmo, e, uso de um composto, de um sal, de um isômero, ou de uma mistura farmaceuticamente aceitável do mesmo? |
| CN104744376A (zh) * | 2015-03-14 | 2015-07-01 | 长沙深橙生物科技有限公司 | 一种2-异丙基嘧啶衍生物的制备方法 |
| CN104803921A (zh) * | 2015-03-14 | 2015-07-29 | 长沙深橙生物科技有限公司 | 一种苯取代嘧啶衍生物的制备方法 |
| KR101766731B1 (ko) | 2015-06-23 | 2017-08-10 | 충남대학교산학협력단 | 강심 활성을 갖는 크로메논 유도체 및 이를 포함하는 심부전의 예방 또는 치료용 약학 조성물 |
| JP6912460B2 (ja) * | 2015-10-09 | 2021-08-04 | ヤンセン ファーマシューティカ エヌ．ベー． | ＰＩ３Ｋβ阻害剤としてのキノキサリンおよびピリドピラジン誘導体 |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| WO2018057808A1 (en) | 2016-09-23 | 2018-03-29 | Gilead Sciences, Inc. | Benzimidazole derivatives and their use as phosphatidylinositol 3-kinase inhibitors |
| AR121719A1 (es) * | 2020-04-03 | 2022-06-29 | Petra Pharma Corp | Inhibidores alostéricos de cromenona del fosfoinosítido 3-quinasa (pi3k) para el tratamiento de enfermedades |
| KR20210141214A (ko) * | 2020-05-15 | 2021-11-23 | 제이투에이치바이오텍 (주) | 3원환 화합물 및 이의 의약 용도 |
| US20240166617A1 (en) * | 2021-02-01 | 2024-05-23 | Geode Therapeutics Inc. | Phosphoinositide 3 kinase beta inhibitors and compositions and methods thereof |
| KR20240004744A (ko) * | 2021-05-03 | 2024-01-11 | 페트라 파마 코포레이션 | 질환의 치료를 위한 포스포이노시티드 3-키나제 (pi3k)의 알로스테릭 크로메논 억제제 |
| KR20240004865A (ko) | 2021-05-03 | 2024-01-11 | 페트라 파마 코포레이션 | 질환의 치료를 위한 포스포이노시티드 3-키나제 (pi3k)의 알로스테릭 크로메논 억제제 |
| JP2024520417A (ja) * | 2021-05-27 | 2024-05-24 | ペトラ・ファーマ・コーポレイション | がんの治療のためのホスホイノシチド３－キナーゼ（ｐｉ３ｋ）のアロステリッククロメノン阻害剤 |
| TW202329930A (zh) | 2021-09-30 | 2023-08-01 | 美商佩特拉製藥公司 | 用於治療疾病之磷酸肌醇3-激酶(pi3k)之異位色烯酮抑制劑 |
| WO2023104111A1 (en) * | 2021-12-08 | 2023-06-15 | Nanjing Zenshine Pharmaceuticals Co., Ltd. | Fused heterocyclic compounds as pi3kalpha inhibitors |
| WO2024003241A1 (en) | 2022-06-30 | 2024-01-04 | Astrazeneca Ab | Treatment for immuno-oncology resistant subjects with an anti pd-l1 antibody an antisense targeted to stat3 and an inhibitor of ctla-4 |
| WO2024081904A1 (en) * | 2022-10-14 | 2024-04-18 | Genesis Therapeutics, Inc. | Methods for treating cancer |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6027A (en) * | 1849-01-09 | Rotary blacksmith s twyer | ||
| HUT58310A (en) | 1988-12-21 | 1992-02-28 | Upjohn Co | Anti-atherosclerotic and anti-thrombotic 1-benzopyran-4-one- and 2-amino-1,3-benzoxazin-4-one derivatives, process for producing them and pharmaceutical compositions containing them |
| DK0525123T3 (da) | 1990-06-20 | 1998-05-04 | Upjohn Co | Antiatherosklerotiske og antithrombotiske 1-benzopyran-4-oner og 2-amino-1,3-benzoxazin-4-oner |
| DE4318756A1 (de) | 1993-06-05 | 1994-12-08 | Hoechst Ag | Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| ES2194181T3 (es) | 1996-02-13 | 2003-11-16 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de vegf. |
| DK0885198T3 (da) | 1996-03-05 | 2002-03-25 | Astrazeneca Ab | 4-Anilinoquinazolinderivater |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
| GB9900334D0 (en) | 1999-01-07 | 1999-02-24 | Angiogene Pharm Ltd | Tricylic vascular damaging agents |
| GB9900752D0 (en) | 1999-01-15 | 1999-03-03 | Angiogene Pharm Ltd | Benzimidazole vascular damaging agents |
| RU2262935C2 (ru) | 1999-02-10 | 2005-10-27 | Астразенека Аб | Производные хиназолина в качестве ингибиторов ангиогенеза |
| ES2286093T3 (es) | 2000-01-24 | 2007-12-01 | Astrazeneca Ab | Compuestos terapeuticos morfolino-sustituidos. |
| US7030123B2 (en) | 2000-05-31 | 2006-04-18 | Astrazeneca Ab | Indole derivatives with vascular damaging activity |
| UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| AU6623201A (en) | 2000-07-07 | 2002-02-05 | Angiogene Pharm Ltd | Colchinol derivatives as angiogenesis inhibitors |
| JP2004502766A (ja) | 2000-07-07 | 2004-01-29 | アンギオジェン・ファーマシューティカルズ・リミテッド | 血管損傷剤としてのコルヒノール誘導体 |
| EP1537102A4 (en) * | 2002-08-16 | 2010-12-08 | Astrazeneca Ab | INHIBITORS OF PHOSPHOINOSITIDE-3-KINASE BETA |
| AR053358A1 (es) * | 2005-04-15 | 2007-05-02 | Cancer Rec Tech Ltd | Inhibidores de adn - pk |
| EP1957475A1 (en) | 2005-10-21 | 2008-08-20 | Merz Pharma GmbH & Co.KGaA | Chromenones and their use as modulators of metabotropic glutamate receptors |
| CN101448505A (zh) * | 2006-04-04 | 2009-06-03 | 加利福尼亚大学董事会 | Pi3激酶拮抗剂 |
| WO2008064244A2 (en) | 2006-11-20 | 2008-05-29 | The Trustees Of Columbia University In The City Of New York | Phosphoinositide modulation for the treatment of neurodegenerative diseases |
| EP2112145A1 (en) | 2008-04-24 | 2009-10-28 | AxoGlia Therapeutics S.A. | Chromenone derivatives useful for the treatment of neurodegenerative diseases |
| WO2010134082A1 (en) | 2009-05-21 | 2010-11-25 | Proteologics Ltd | Chromenone derivatives for treatment of cancer |
| US8399460B2 (en) * | 2009-10-27 | 2013-03-19 | Astrazeneca Ab | Chromenone derivatives |
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