HRP20190908T1 - Spoj (6s,9as)-n-benzil-6-((4-hidroksifenil)metil)-4,7-diokso-8-((6-(3-(piperazin-1-il)azetidin-1-il)piridin-2-il)metil)-2-(prop-2-en-1-il)-oktahidro-1h-pirazino(2,1-c)(1,2,4)triazin-1-karboksamida - Google Patents
Spoj (6s,9as)-n-benzil-6-((4-hidroksifenil)metil)-4,7-diokso-8-((6-(3-(piperazin-1-il)azetidin-1-il)piridin-2-il)metil)-2-(prop-2-en-1-il)-oktahidro-1h-pirazino(2,1-c)(1,2,4)triazin-1-karboksamida Download PDFInfo
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- HRP20190908T1 HRP20190908T1 HRP20190908TT HRP20190908T HRP20190908T1 HR P20190908 T1 HRP20190908 T1 HR P20190908T1 HR P20190908T T HRP20190908T T HR P20190908TT HR P20190908 T HRP20190908 T HR P20190908T HR P20190908 T1 HRP20190908 T1 HR P20190908T1
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- octahydro
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- -1 (6S,9aS)-N-BENZYL-6-[(4-HYDROXYPHENYL)METHYL]-4,7-DIOXO-8-({6-[3-(PIPERAZINE-1-YL)AZETIDINE-1-YL]PYRIDINE-2-YL}METHYL)-2-(PROP-2-EN-1-YL)-OCTAHYDRO-1H-PYRAZINO[2,1-c][1,2,4]TRIAZINE-1-CARBOXAMIDE COMPOUND Chemical class 0.000 title claims 5
- 150000003839 salts Chemical class 0.000 claims 17
- 150000001875 compounds Chemical class 0.000 claims 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 5
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 5
- ZGNKNLOBYFTGRG-GIWKVKTRSA-N (6S,9aS)-N-benzyl-8-[[6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl]methyl]-6-[(2-fluoro-4-hydroxyphenyl)methyl]-4,7-dioxo-2-prop-2-enyl-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C1CN(CC)CCN1C1CN(C=2N=C(CN3C([C@H](CC=4C(=CC(O)=CC=4)F)N4[C@@H](N(N(CC=C)CC4=O)C(=O)NCC=4C=CC=CC=4)C3)=O)C=CC=2)C1 ZGNKNLOBYFTGRG-GIWKVKTRSA-N 0.000 claims 3
- SNDNPPITFPXTTR-GIWKVKTRSA-N (6S,9aS)-N-benzyl-8-[[6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl]methyl]-6-[(4-hydroxyphenyl)methyl]-4,7-dioxo-2-prop-2-enyl-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C(C1=CC=CC=C1)NC(=O)N1N(CC(N2[C@@H]1CN(C([C@@H]2CC2=CC=C(C=C2)O)=O)CC2=NC(=CC=C2)N2CC(C2)N2CCN(CC2)CC)=O)CC=C SNDNPPITFPXTTR-GIWKVKTRSA-N 0.000 claims 3
- MHZGAVWIXHVIET-UHFFFAOYSA-N N1(NC=NC=C1)C(=O)N Chemical compound N1(NC=NC=C1)C(=O)N MHZGAVWIXHVIET-UHFFFAOYSA-N 0.000 claims 3
- 229910052731 fluorine Chemical group 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- YEQDNBRCPJDLEK-UHFFFAOYSA-N 2h-triazine-1-carboxamide Chemical compound NC(=O)N1NN=CC=C1 YEQDNBRCPJDLEK-UHFFFAOYSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
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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
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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
- A61K31/53—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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- 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
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- 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
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
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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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic 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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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (17)
1. Spoj predstavljen formulom (1) ili njegova farmaceutski prihvatljiva sol:
naznačen time što R1 je skupina C1-6 alkil; R2 i R3 su isti ili međusobno različiti i svaki je vodikov atom ili skupina C1-6 alkil; X2, X3 i X4 su isti ili međusobno različiti i svaki je vodikov atom ili halogeni atom; i X5 je vodikov atom ili -P(=O)(OH)2.
2. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što R1 je metilna skupina, etilna skupina ili izopropilna skupina.
3. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što R2 i R3 su isti ili međusobno različiti i svaki je vodikov atom ili metilna skupina.
4. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što X2 je vodikov atom ili fluorov atom.
5. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što X3 je vodikov atom ili fluorov atom.
6. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što X4 je vodikov atom ili fluorov atom.
7. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1 naznačen time što je odabran iz niza koji čine:
(6S,9aS)-N-benzil-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2-fluoro-4-hidroksifenil)metil)-8-((6-(3-(4-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3S)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3R)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((2S)-2,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)-5-fluoropiridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((5-fluoro-6-(3-(4-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-8-((6-(3-(4-(propan-2-il)piperazin-1-il)azetidin-1-il)piridin-2-il)metil)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2-fluoro-4-hidroksifenil)metil)-8-((5-fluoro-6-(3-(4-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-8-((6-(3-(4-(propan-2-il)piperazin-1-il)azetidin-1-il)piridin-2-il)metil)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-8-((6-(3-(4-(propan-2-il)piperazin-1-il)azetidin-1-il)piridin-2-il)metil)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-(4-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-(-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-((3S)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-((2S)-2,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3S)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-3-((3R)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3S)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3R)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-((3S)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-((3R)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3R)-3,4-dimetilpiperazin-1-il)azetidin-1-il)-5-fluoropiridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
4-(((6S,9aS)-1-(benzilkarbamoil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino [2,1-c][1,2,4]triazin-6-il)metil)-3-fluorofenil dihidrogenfosfat , i,
4-(((6S,9aS)-1-(benzilkarbamoil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino [2,1-c][1,2,4]triazin-6-il)metil)fenil dihidrogenfosfat .
8. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1 naznačen time što je odabran iz niza koji čine:
(6S,9aS)-N-benzil-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino [2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino [2,1-c][1,2,4]triazin-1-karboksamid,
(6S, 9aS)-N-benzil-6-((2-fluoro-4-hidroksifenil)metil)-8-((6-(3-(4-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3S)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3R)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-(-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((5-fluoro-6-(3-(4-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-8-((6-(3-(4-(propan-2-il)piperazin-1-il)azetidin-1-il)piridin-2-il)metil)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en- 1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-(-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-((3S)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-((2S)-2,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino [2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-(3-((3S)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-8-((6-3-((3R)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
(6S,9aS)-N-benzil-6-((2,6-difluoro-4-hidroksifenil)metil)-8-((6-(3-((3S)-4-etil-3-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid,
4-(((6S,9aS)-1-(benzilkarbamoil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-6-il)metil)-3-fluorofenil dihidrogenfosfat , i
4-(((6S,9aS)-1-(benzilkarbamoil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-6-il)metil)fenil dihidrogenfosfat .
9. (6S,9aS)-N-Benzil-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
10. (6S,9aS)-N-Benzil-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
11. (6S,9aS)-N-Benzil-6-((2-fluoro-4-hidroksifenil)metil)-8-((6-(3-(4-metilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
12. (6S,9aS)-N-Benzil-8-((6-(3-((3S)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
13. (6S,9aS)-N-Benzil-8-((6-(3-((3R)-3,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((2-fluoro-4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
14. (6S,9aS)-N-Benzil-8-((6-(3-((2S)-2,4-dimetilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-6-((4-hidroksifenil)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-1-karboksamid ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
15. 4-(((6S,9aS)-1-(Benzilkarbamoil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil)-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-6-il)metil)-3-fluorofenil dihidrogenfosfat ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
16. 4-(((6S,9aS)-1-(Benzilkarbamoil)-8-((6-(3-(4-etilpiperazin-1-il)azetidin-1-il)piridin-2-il)metil-4,7-diokso-2-(prop-2-en-1-il)-oktahidro-1H-pirazino[2,1-c][1,2,4]triazin-6-il)metil)fenil dihidrogenfosfat ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1:
17. Farmaceutski pripravak, naznačen time što sadrži spoj ili njegovu farmaceutski prihvatljivu sol prema bilo kojem od patentnih zahtjeva 1 do 16.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2013267687 | 2013-12-25 | ||
| PCT/JP2014/083932 WO2015098853A1 (ja) | 2013-12-25 | 2014-12-22 | （６Ｓ，９ａＳ）－Ｎ－ベンジル－６－［（４－ヒドロキシフェニル）メチル］－４，７－ジオキソ－８－（｛６－［３－（ピペラジン－１－イル）アゼチジン－１－イル］ピリジン－２－イル｝メチル）－２－（プロプ－２－エン－１－イル）－オクタヒドロ－１Ｈ－ピラジノ［２，１－ｃ］［１，２，４］トリアジン－１－カルボキサミド化合物 |
| EP14873998.0A EP3088401B1 (en) | 2013-12-25 | 2014-12-22 | (6s,9as)-n-benzyl-6-((4-hydroxyphenyl)methyl)-4,7-dioxo-8-((6-(3-(piperazine-1-yl)azetidine-1-yl)pyridine-2-yl)methyl)-2-(prop-2-en-1-yl)-octahydro-1h-pyrazino(2,1-c)(1,2,4)triazine-1-carboxamide compound |
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| Publication Number | Publication Date |
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| HRP20190908T1 true HRP20190908T1 (hr) | 2019-08-09 |
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| HRP20190908TT HRP20190908T1 (hr) | 2013-12-25 | 2019-05-16 | Spoj (6s,9as)-n-benzil-6-((4-hidroksifenil)metil)-4,7-diokso-8-((6-(3-(piperazin-1-il)azetidin-1-il)piridin-2-il)metil)-2-(prop-2-en-1-il)-oktahidro-1h-pirazino(2,1-c)(1,2,4)triazin-1-karboksamida |
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| US (1) | US9174998B2 (hr) |
| EP (1) | EP3088401B1 (hr) |
| JP (1) | JP6085040B2 (hr) |
| KR (1) | KR102307053B1 (hr) |
| CN (1) | CN105873932B (hr) |
| AR (1) | AR098908A1 (hr) |
| AU (1) | AU2014371148B2 (hr) |
| BR (1) | BR112016013572B1 (hr) |
| CA (1) | CA2932435C (hr) |
| CL (1) | CL2016001419A1 (hr) |
| CY (1) | CY1122521T1 (hr) |
| DK (1) | DK3088401T3 (hr) |
| ES (1) | ES2728353T3 (hr) |
| HK (1) | HK1222656A1 (hr) |
| HR (1) | HRP20190908T1 (hr) |
| HU (1) | HUE044541T2 (hr) |
| IL (1) | IL245961A0 (hr) |
| JO (1) | JO3809B1 (hr) |
| LT (1) | LT3088401T (hr) |
| ME (1) | ME03391B (hr) |
| MX (1) | MX365376B (hr) |
| MY (1) | MY173946A (hr) |
| PE (1) | PE20160932A1 (hr) |
| PH (1) | PH12016501079A1 (hr) |
| PL (1) | PL3088401T3 (hr) |
| PT (1) | PT3088401T (hr) |
| RS (1) | RS58955B1 (hr) |
| RU (1) | RU2669805C2 (hr) |
| SG (1) | SG11201604496YA (hr) |
| SI (1) | SI3088401T1 (hr) |
| TR (1) | TR201908392T4 (hr) |
| TW (1) | TWI681961B (hr) |
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| US9945862B2 (en) | 2011-06-03 | 2018-04-17 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| PL3524595T3 (pl) | 2014-08-28 | 2022-10-31 | Eisai R&D Management Co., Ltd. | Pochodna chinoliny o wysokiej czystości i sposób jej wytwarzania |
| HUE064614T2 (hu) | 2015-02-25 | 2024-04-28 | Eisai R&D Man Co Ltd | Eljárás egy kinolin-származék keserû ízének elnyomására |
| KR20240064733A (ko) | 2015-03-04 | 2024-05-13 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| BR112017027227B1 (pt) * | 2015-06-16 | 2023-12-12 | Eisai R&D Management Co., Ltd | Agente anti-câncer |
| CA2986999C (en) | 2015-06-23 | 2023-08-08 | Eisai R&D Management Co., Ltd. | Crystal of (6s,9as)-n-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2h-pyrazino[2,1-c][1,2,4]triazine-1(6h)-carboxamide |
| CN108084067B (zh) * | 2016-11-22 | 2019-08-30 | 重庆圣华曦药业股份有限公司 | 一种立他司特中间体的制备方法 |
| CN110072528B (zh) | 2017-02-08 | 2022-04-26 | 卫材R&D管理有限公司 | 治疗肿瘤的药物组合物 |
| US20220409724A1 (en) | 2019-10-29 | 2022-12-29 | Eisai R&D Management Co., Ltd. | Combination of a pd-1 antagonist, a vegfr/fgfr/ret tyrosine kinase inhibitor and a cbp/beta-catenin inhibitor for treating cancer |
| US11655253B2 (en) | 2020-03-12 | 2023-05-23 | 3+2 Pharma, Llc | CBP/catenin signaling pathway inhibitors and uses thereof |
| WO2022092294A1 (ja) | 2020-10-30 | 2022-05-05 | 学校法人慶應義塾 | サルコペニア関連疾患等の新規治療および予防 |
| WO2023027888A1 (en) * | 2021-08-26 | 2023-03-02 | 3+2 Pharma, Llc | Pyrazole-containing cbp/catenin antagonists and uses thereof |
| CA3227813A1 (en) | 2021-09-08 | 2023-03-16 | Eisai R&D Management Co., Ltd. | Pharmaceutical composition for treating solid tumors |
| WO2023140369A1 (en) * | 2022-01-18 | 2023-07-27 | Prism BioLab Co., Ltd. | Phosphoric acid derivatives |
| WO2023190748A1 (ja) * | 2022-03-31 | 2023-10-05 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療用医薬組成物 |
| CN115784934A (zh) * | 2022-11-22 | 2023-03-14 | 上海吉奉生物科技有限公司 | 一种酪氨酸衍生物的合成方法 |
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| US8080657B2 (en) | 2001-10-12 | 2011-12-20 | Choongwae Pharma Corporation | Compounds of reverse turn mimetics and the use thereof |
| US7671054B1 (en) * | 2001-10-12 | 2010-03-02 | Choongwae Pharma Corporation | Reverse-turn mimetics and method relating thereto |
| ATE398129T1 (de) * | 2001-10-12 | 2008-07-15 | Choongwae Pharma Corp | Reverse-turn-mimetika und diese betreffendes verfahren |
| JP2009184924A (ja) | 2006-05-31 | 2009-08-20 | Eisai R & D Management Co Ltd | 生物学的試薬用化合物 |
| RU2512538C2 (ru) | 2008-06-06 | 2014-04-10 | Присм Байолэб Корпорейшн | Альфа-спиральные миметики и способы, связанные с ними |
| SG175045A1 (en) * | 2009-04-15 | 2011-11-28 | Jw Pharmaceutical Corp | Novel compounds of reverse-turn mimetics, method for manufacturing the same and use thereof |
| WO2012050393A2 (ko) * | 2010-10-14 | 2012-04-19 | 제이더블유중외제약 주식회사 | 리버스-턴 유사체의 신규한 화합물 및 그 제조방법과 용도 |
| CN103517904A (zh) * | 2011-02-25 | 2014-01-15 | 株式会社棱镜制药 | α-螺旋模拟物和与其相关的方法 |
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