ES2331177T3 - Inhibidores de adam-10 humana. - Google Patents
Inhibidores de adam-10 humana. Download PDFInfo
- Publication number
- ES2331177T3 ES2331177T3 ES02784794T ES02784794T ES2331177T3 ES 2331177 T3 ES2331177 T3 ES 2331177T3 ES 02784794 T ES02784794 T ES 02784794T ES 02784794 T ES02784794 T ES 02784794T ES 2331177 T3 ES2331177 T3 ES 2331177T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- quad
- alkoxy
- substituted
- groups
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 108091007504 ADAM10 Proteins 0.000 title abstract description 17
- 102000036664 ADAM10 Human genes 0.000 title abstract description 17
- 239000003112 inhibitor Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 124
- 238000000034 method Methods 0.000 claims abstract description 35
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 7
- 230000033115 angiogenesis Effects 0.000 claims abstract description 7
- 201000011510 cancer Diseases 0.000 claims abstract description 7
- 206010003246 arthritis Diseases 0.000 claims abstract description 6
- 201000010099 disease Diseases 0.000 claims abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 219
- 125000000217 alkyl group Chemical group 0.000 claims description 170
- 229910052736 halogen Inorganic materials 0.000 claims description 170
- 150000002367 halogens Chemical class 0.000 claims description 170
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 136
- 229910052739 hydrogen Inorganic materials 0.000 claims description 87
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 79
- -1 C 1 -C 6 alkyl Chemical group 0.000 claims description 73
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 66
- 229910052757 nitrogen Inorganic materials 0.000 claims description 53
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 51
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 50
- 229910052799 carbon Inorganic materials 0.000 claims description 47
- 125000001188 haloalkyl group Chemical group 0.000 claims description 43
- 125000004076 pyridyl group Chemical group 0.000 claims description 41
- 239000000460 chlorine Substances 0.000 claims description 38
- 125000002757 morpholinyl group Chemical group 0.000 claims description 36
- 125000003386 piperidinyl group Chemical group 0.000 claims description 36
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 36
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 32
- 125000004414 alkyl thio group Chemical group 0.000 claims description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 31
- 125000001589 carboacyl group Chemical group 0.000 claims description 31
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 30
- 229910052731 fluorine Inorganic materials 0.000 claims description 28
- 125000001624 naphthyl group Chemical group 0.000 claims description 27
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 27
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 26
- 125000006542 morpholinylalkyl group Chemical group 0.000 claims description 26
- 125000004193 piperazinyl group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 25
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 24
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 125000005605 benzo group Chemical group 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 16
- 125000001544 thienyl group Chemical group 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 125000005046 dihydronaphthyl group Chemical group 0.000 claims description 14
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 14
- 125000005495 pyridazyl group Chemical group 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000003725 azepanyl group Chemical group 0.000 claims description 10
- 238000003786 synthesis reaction Methods 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 8
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- SZRDJHHKIJHJHQ-UHFFFAOYSA-N 3,4,5-trifluoroaniline Chemical compound NC1=CC(F)=C(F)C(F)=C1 SZRDJHHKIJHJHQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims 3
- 229910052751 metal Inorganic materials 0.000 claims 3
- 239000002184 metal Substances 0.000 claims 3
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 2
- 150000001448 anilines Chemical class 0.000 claims 2
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical group [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims 2
- 239000012954 diazonium Substances 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- 229910052792 caesium Inorganic materials 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 39
- 230000031018 biological processes and functions Effects 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 4
- 239000003937 drug carrier Substances 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 40
- 239000000243 solution Substances 0.000 description 37
- 239000007787 solid Substances 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
- 229940124530 sulfonamide Drugs 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 29
- 150000003456 sulfonamides Chemical class 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- 239000011347 resin Substances 0.000 description 22
- 229920005989 resin Polymers 0.000 description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 16
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 102100039673 Disintegrin and metalloproteinase domain-containing protein 10 Human genes 0.000 description 14
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 14
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 101000959356 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 10 Proteins 0.000 description 12
- 108010070047 Notch Receptors Proteins 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 12
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- 150000001413 amino acids Chemical class 0.000 description 11
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- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
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- 235000011152 sodium sulphate Nutrition 0.000 description 9
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 8
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- 125000000753 cycloalkyl group Chemical group 0.000 description 8
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- 238000000746 purification Methods 0.000 description 8
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- 230000014759 maintenance of location Effects 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- 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
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34017901P | 2001-12-14 | 2001-12-14 | |
| US340179P | 2001-12-14 |
Publications (1)
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|---|---|
| ES2331177T3 true ES2331177T3 (es) | 2009-12-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES02784794T Expired - Lifetime ES2331177T3 (es) | 2001-12-14 | 2002-12-13 | Inhibidores de adam-10 humana. |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US7498358B2 (enExample) |
| EP (1) | EP1461313B1 (enExample) |
| JP (1) | JP4427328B2 (enExample) |
| AT (1) | ATE438618T1 (enExample) |
| AU (1) | AU2002346724B2 (enExample) |
| CA (1) | CA2473938C (enExample) |
| DE (1) | DE60233261D1 (enExample) |
| ES (1) | ES2331177T3 (enExample) |
| WO (1) | WO2003051825A1 (enExample) |
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| WO2003051825A1 (en) * | 2001-12-14 | 2003-06-26 | Exelixis, Inc. | Human adam-10 inhibitors |
| AU2003239599B8 (en) | 2002-05-29 | 2008-08-14 | Merck Sharp & Dohme Corp. | Compounds useful in the treatment of anthrax and inhibiting lethal factor |
| EP2428509A1 (en) | 2002-06-12 | 2012-03-14 | Symphony Evolution, Inc. | Human adam-10 inhibitors |
| US8088737B2 (en) | 2003-04-04 | 2012-01-03 | Incyte Corporation | Compositions, methods and kits relating to Her-2 cleavage |
| GB0311228D0 (en) * | 2003-05-16 | 2003-06-18 | Celltech R&D Ltd | Assay |
| EP1493445A1 (en) * | 2003-07-04 | 2005-01-05 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibition of stress-induced ligand-dependent EGFR activation |
| US7163942B2 (en) | 2004-04-01 | 2007-01-16 | Pfizer Inc. | Sulfonamide compounds for the treatment of neurodegenerative disorders |
| JP2007537256A (ja) | 2004-05-11 | 2007-12-20 | メルク エンド カムパニー インコーポレーテッド | N−スルホン化アミノ酸誘導体調製のためのプロセス |
| EP1623995A1 (en) * | 2004-08-06 | 2006-02-08 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Inhibitors of L1 and ADAM10 for the treatment of carcinomas |
| EP1984500A2 (en) * | 2006-01-13 | 2008-10-29 | Vanderbilt University | Adam10 and its uses related to infection |
| WO2007103114A2 (en) | 2006-03-07 | 2007-09-13 | The Brigham & Women's Hospital, Inc. | Notch inhibition in the treatment or prevention of atherosclerosis |
| US9567396B2 (en) | 2006-03-07 | 2017-02-14 | Evonik Degussa Gmbh | Notch inhibition in the prevention of vein graft failure |
| JPWO2009096198A1 (ja) * | 2008-02-01 | 2011-05-26 | 一般社団法人ファルマIp | 新規ビアリール誘導体 |
| US20120129189A1 (en) * | 2009-07-17 | 2012-05-24 | Chulan Kwon | Methods of Controlling Cell Proliferation |
| EP2493497A4 (en) | 2009-11-01 | 2013-07-24 | Brigham & Womens Hospital | NOTCH INHIBITION IN THE TREATMENT AND PROPHYLAXIS OF ADIPOSITAS AND METABOLISM SYNDROME |
| EP2597084B1 (en) | 2010-07-08 | 2016-06-29 | Kaken Pharmaceutical Co., Ltd. | N-hydroxyformamide derivative and pharmaceutical containing same |
| WO2012064865A1 (en) | 2010-11-09 | 2012-05-18 | The University Of Chicago | Role of adam10 and its relevance to disease and therapeutics |
| EP2606884A1 (en) | 2011-12-21 | 2013-06-26 | Ecole Polytechnique Fédérale de Lausanne (EPFL) | Inhibitors of notch signaling pathway and use thereof in treatment of cancers |
| BR112020026148A2 (pt) | 2018-06-21 | 2021-03-16 | Cellestia Biotech Ag | Processo para fabricar éteres amino diarílicos e sais de cloridratos de éteres amino diarílicos |
| EP3823672A1 (en) | 2018-07-19 | 2021-05-26 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Combination for treating cancer |
| CN108947850B (zh) * | 2018-07-23 | 2021-05-18 | 蚌埠中实化学技术有限公司 | 一种3,4,5-三氟苯胺的制备方法 |
| EP4244391A1 (en) | 2020-11-16 | 2023-09-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for predicting and treating uveal melanoma |
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| US5985900A (en) | 1997-04-01 | 1999-11-16 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses |
| DE69836877D1 (de) | 1997-07-22 | 2007-02-22 | Shionogi & Co | Verwendung von Matrix- Metalloproteinase Inhibitoren zur Behandlung oder Vorbeugung von Glomerulopathie |
| EP1918278A1 (en) | 1998-02-04 | 2008-05-07 | Novartis AG | Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases |
| JPH11246527A (ja) | 1998-03-02 | 1999-09-14 | Shionogi & Co Ltd | Mmp−8阻害剤 |
| WO2000015213A1 (en) | 1998-09-11 | 2000-03-23 | Shionogi & Co., Ltd. | Remedal or preventive agent for congestive heart failure |
| WO2003051825A1 (en) * | 2001-12-14 | 2003-06-26 | Exelixis, Inc. | Human adam-10 inhibitors |
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2002
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- 2002-12-13 DE DE60233261T patent/DE60233261D1/de not_active Expired - Lifetime
- 2002-12-13 JP JP2003552713A patent/JP4427328B2/ja not_active Expired - Fee Related
- 2002-12-13 US US10/498,338 patent/US7498358B2/en not_active Expired - Fee Related
- 2002-12-13 AU AU2002346724A patent/AU2002346724B2/en not_active Ceased
- 2002-12-13 CA CA2473938A patent/CA2473938C/en not_active Expired - Fee Related
- 2002-12-13 AT AT02784794T patent/ATE438618T1/de not_active IP Right Cessation
- 2002-12-13 ES ES02784794T patent/ES2331177T3/es not_active Expired - Lifetime
- 2002-12-13 EP EP02784794A patent/EP1461313B1/en not_active Expired - Lifetime
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2009
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Also Published As
| Publication number | Publication date |
|---|---|
| ATE438618T1 (de) | 2009-08-15 |
| JP2005513065A (ja) | 2005-05-12 |
| EP1461313A1 (en) | 2004-09-29 |
| CA2473938C (en) | 2013-10-08 |
| EP1461313B1 (en) | 2009-08-05 |
| CA2473938A1 (en) | 2003-06-26 |
| AU2002346724B2 (en) | 2009-04-30 |
| AU2002346724A1 (en) | 2003-06-30 |
| EP1461313A4 (en) | 2006-03-01 |
| US7498358B2 (en) | 2009-03-03 |
| US20050227973A1 (en) | 2005-10-13 |
| JP4427328B2 (ja) | 2010-03-03 |
| DE60233261D1 (de) | 2009-09-17 |
| US7951972B2 (en) | 2011-05-31 |
| US20090143386A1 (en) | 2009-06-04 |
| WO2003051825A1 (en) | 2003-06-26 |
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