MX2012005027A - Derivados de la cromenona con actividad anti-tumoral. - Google Patents
Derivados de la cromenona con actividad anti-tumoral.Info
- Publication number
- MX2012005027A MX2012005027A MX2012005027A MX2012005027A MX2012005027A MX 2012005027 A MX2012005027 A MX 2012005027A MX 2012005027 A MX2012005027 A MX 2012005027A MX 2012005027 A MX2012005027 A MX 2012005027A MX 2012005027 A MX2012005027 A MX 2012005027A
- Authority
- MX
- Mexico
- Prior art keywords
- carbon atoms
- ethyl
- chromene
- oxo
- morpholino
- Prior art date
Links
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical class C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title abstract description 79
- 230000000694 effects Effects 0.000 title description 57
- 230000000259 anti-tumor effect Effects 0.000 title description 10
- 238000000034 method Methods 0.000 claims abstract description 113
- 150000003839 salts Chemical class 0.000 claims abstract description 98
- 238000011282 treatment Methods 0.000 claims abstract description 54
- 238000004519 manufacturing process Methods 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- -1 3-methoxypropyl Chemical group 0.000 claims description 377
- 150000001875 compounds Chemical class 0.000 claims description 258
- 125000004432 carbon atom Chemical group C* 0.000 claims description 211
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 92
- 102000004190 Enzymes Human genes 0.000 claims description 91
- 108090000790 Enzymes Proteins 0.000 claims description 91
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 79
- 206010028980 Neoplasm Diseases 0.000 claims description 64
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 63
- 229910052736 halogen Inorganic materials 0.000 claims description 52
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims description 48
- 150000002367 halogens Chemical class 0.000 claims description 46
- 241001465754 Metazoa Species 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 230000005764 inhibitory process Effects 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 16
- 229910052717 sulfur Chemical group 0.000 claims description 16
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 239000003085 diluting agent Substances 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000003725 azepanyl group Chemical group 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 6
- 125000005961 oxazepanyl group Chemical group 0.000 claims description 6
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 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 description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 5
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 4
- 150000008371 chromenes Chemical class 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 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 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 230000008569 process Effects 0.000 abstract description 19
- 238000002360 preparation method Methods 0.000 abstract description 11
- 230000002062 proliferating effect Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 257
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
- 239000007787 solid Substances 0.000 description 125
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 118
- 238000001819 mass spectrum Methods 0.000 description 112
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 99
- 239000000243 solution Substances 0.000 description 91
- 229940088598 enzyme Drugs 0.000 description 88
- 229910001868 water Inorganic materials 0.000 description 88
- 239000000203 mixture Substances 0.000 description 83
- 238000000634 powder X-ray diffraction Methods 0.000 description 81
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 73
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
- 239000002904 solvent Substances 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
- 238000006243 chemical reaction Methods 0.000 description 68
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- 210000004027 cell Anatomy 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- 238000012360 testing method Methods 0.000 description 45
- 238000001914 filtration Methods 0.000 description 42
- 239000000725 suspension Substances 0.000 description 39
- 239000003112 inhibitor Substances 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 38
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 36
- 235000019341 magnesium sulphate Nutrition 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 32
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 30
- 238000003818 flash chromatography Methods 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 30
- 229910002027 silica gel Inorganic materials 0.000 description 30
- 239000012267 brine Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- 239000007858 starting material Substances 0.000 description 28
- 235000019441 ethanol Nutrition 0.000 description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- 201000011510 cancer Diseases 0.000 description 26
- 239000012043 crude product Substances 0.000 description 26
- 229960004132 diethyl ether Drugs 0.000 description 24
- 125000006083 1-bromoethyl group Chemical group 0.000 description 23
- 239000003054 catalyst Substances 0.000 description 23
- 125000006239 protecting group Chemical group 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 22
- 239000002585 base Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 20
- 108091008611 Protein Kinase B Proteins 0.000 description 20
- 108091000080 Phosphotransferase Proteins 0.000 description 19
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 19
- 229940093499 ethyl acetate Drugs 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 102000020233 phosphotransferase Human genes 0.000 description 19
- 229940002612 prodrug Drugs 0.000 description 19
- 239000000651 prodrug Substances 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- 238000010828 elution Methods 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- 239000003643 water by type Substances 0.000 description 18
- 230000001413 cellular effect Effects 0.000 description 17
- 238000001727 in vivo Methods 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 16
- 230000002401 inhibitory effect Effects 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- 238000002953 preparative HPLC Methods 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 210000004881 tumor cell Anatomy 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- 239000008096 xylene Substances 0.000 description 15
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 14
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 150000003857 carboxamides Chemical class 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 150000002148 esters Chemical class 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- 125000000524 functional group Chemical group 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000002246 antineoplastic agent Substances 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 230000035755 proliferation Effects 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 11
- 239000001099 ammonium carbonate Substances 0.000 description 11
- 235000012501 ammonium carbonate Nutrition 0.000 description 11
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- 125000002252 acyl group Chemical group 0.000 description 10
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- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- PSKDKFPIGKMDGE-UHFFFAOYSA-N 8-[1-(3,5-difluoroanilino)ethyl]-2-morpholin-4-yl-4-oxochromene-6-carboxylic acid Chemical compound C=1C(C(O)=O)=CC(C(C=C(O2)N3CCOCC3)=O)=C2C=1C(C)NC1=CC(F)=CC(F)=C1 PSKDKFPIGKMDGE-UHFFFAOYSA-N 0.000 description 9
- 241000208202 Linaceae Species 0.000 description 9
- 235000004431 Linum usitatissimum Nutrition 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 9
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
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- 108091008598 receptor tyrosine kinases Proteins 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 8
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- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
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- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 8
- MIIUCQQOKMDLDH-UHFFFAOYSA-N 8-[1-(3-chloro-2-fluoroanilino)ethyl]-2-morpholin-4-yl-4-oxochromene-6-carboxylic acid Chemical compound C=1C(C(O)=O)=CC(C(C=C(O2)N3CCOCC3)=O)=C2C=1C(C)NC1=CC=CC(Cl)=C1F MIIUCQQOKMDLDH-UHFFFAOYSA-N 0.000 description 7
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 7
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- 229910052786 argon Inorganic materials 0.000 description 6
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- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 6
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- 238000001816 cooling Methods 0.000 description 6
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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
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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
-
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- 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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- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09306017 | 2009-10-27 | ||
| PCT/GB2010/051788 WO2011051704A1 (en) | 2009-10-27 | 2010-10-25 | Chromenone derivatives with anti-tumour activity |
Publications (1)
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| MX2012005027A true MX2012005027A (es) | 2012-09-07 |
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| MX2012005027A MX2012005027A (es) | 2009-10-27 | 2010-10-25 | Derivados de la cromenona con actividad anti-tumoral. |
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| EP2307400B1 (en) | 2008-05-30 | 2014-04-23 | Amgen, Inc | Inhibitors of pi3 kinase |
| US8399460B2 (en) * | 2009-10-27 | 2013-03-19 | Astrazeneca Ab | Chromenone derivatives |
| UY34013A (es) | 2011-04-13 | 2012-11-30 | Astrazeneca Ab | ?compuestos de cromenona con actividad anti-tumoral?. |
| JP6307096B2 (ja) | 2013-01-23 | 2018-04-04 | アストラゼネカ アクチボラグ | 化合物 |
| KR102222346B1 (ko) * | 2013-03-04 | 2021-03-02 | 아스트라제네카 아베 | 조합 치료 |
| KR20170012560A (ko) | 2014-06-13 | 2017-02-02 | 길리애드 사이언시즈, 인코포레이티드 | 포스파티딜이노시톨 3-키나제 억제제 |
| JP6383810B2 (ja) | 2014-06-13 | 2018-08-29 | ギリアード サイエンシーズ， インコーポレイテッド | ホスファチジルイノシトール３−キナーゼ阻害剤としてのキナゾリノン誘導体 |
| AU2015274628B2 (en) | 2014-06-13 | 2018-03-15 | Gilead Sciences, Inc. | Phosphatidylinositol 3-kinase inhibitors |
| NZ726638A (en) | 2014-06-13 | 2018-04-27 | Gilead Sciences Inc | Phosphatidylinositol 3-kinase inhibitors |
| HK1231477A1 (zh) | 2014-06-13 | 2017-12-22 | 吉利德科学公司 | 磷脂酰肌醇3-激酶抑制剂 |
| 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 |
| AU2016335086B2 (en) * | 2015-10-09 | 2020-08-27 | Janssen Pharmaceutica Nv | Quinoxaline and pyridopyrazine derivatives as pI3Kbeta inhibitors |
| WO2018057808A1 (en) | 2016-09-23 | 2018-03-29 | Gilead Sciences, Inc. | Benzimidazole derivatives and their use as phosphatidylinositol 3-kinase inhibitors |
| 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 |
| 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 |
| 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 |
| CA3209581A1 (en) * | 2021-02-01 | 2022-08-04 | Geode Therapeutics Inc. | Phosphoinositide 3 kinase beta inhibitors and compositions and methods thereof |
| CR20230517A (es) * | 2021-05-03 | 2023-11-28 | Petra Pharma Corp | Inhibidores alostéricos de cromenona del fosfoinosítido 3-quinasa (pi3k) para el tratamiento de enfermedades |
| KR20240004744A (ko) * | 2021-05-03 | 2024-01-11 | 페트라 파마 코포레이션 | 질환의 치료를 위한 포스포이노시티드 3-키나제 (pi3k)의 알로스테릭 크로메논 억제제 |
| TWI829179B (zh) * | 2021-05-27 | 2024-01-11 | 美商佩特拉製藥公司 | 用於治療疾病之磷酸肌醇3-激酶(pi3k)異位色烯酮抑制劑 |
| 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 |
| EP4412606A4 (en) * | 2021-10-07 | 2025-09-24 | Relay Therapeutics Inc | PI3K-ALPHA INHIBITORS AND METHODS OF USE THEREOF |
| EP4444714A4 (en) * | 2021-12-08 | 2025-10-29 | Nanjing Zenshine Pharmaceuticals Co Ltd | CONDENSED HETEROCYCLIC COMPOUNDS USED AS PI3KALPHA INHIBITORS |
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| TW202506119A (zh) * | 2023-08-02 | 2025-02-16 | 大陸商鄭州同源康醫藥有限公司 | 稠環類化合物及其用途 |
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| FI912995A7 (fi) | 1988-12-21 | 1991-06-19 | Upjohn Co | Antiateroskleroottisia ja antitromboottisia 1-bentsopyran-4-oneja ja 2 -amino-1,3-bentsoksatsin-4-oneja |
| CA2081577A1 (en) | 1990-06-20 | 1991-12-21 | Ronald B. Gammill | Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1, 3-benzoxazine-4-ones |
| 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 |
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| CA2674803C (en) | 1999-02-10 | 2012-10-09 | Astrazeneca Ab | Quinazoline derivatives as angiogenesis inhibitors |
| CA2398163C (en) | 2000-01-24 | 2011-02-22 | Kinacia Pty Ltd. | Therapeutic morpholino-substituted compounds |
| CA2406979A1 (en) | 2000-05-31 | 2001-12-06 | 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 |
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| MXPA02012903A (es) | 2000-07-07 | 2004-07-30 | Angiogene Pharm Ltd | Derivados de colquinol como inhibidores de angiogenesis. |
| US7598377B2 (en) * | 2002-08-16 | 2009-10-06 | Astrazeneca Ab | Inhibition of phosphoinositide 3-kinase β |
| AR054438A1 (es) * | 2005-04-15 | 2007-06-27 | Kudos Pharm Ltd | Inhibidores de adn -pk |
| WO2007045876A1 (en) | 2005-10-21 | 2007-04-26 | Merz Pharma Gmbh & Co. Kgaa | Chromenones and their use as modulators of metabotropic glutamate receptors |
| SI2004654T1 (sl) * | 2006-04-04 | 2013-11-29 | The Regents Of The University Of California | Pirazolopirimidinski derivati za uporabo kot kinazni antagonisti |
| 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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