JP2001518469A - 三環式３−オキソ−プロパンニトリル化合物 - Google Patents
三環式３−オキソ−プロパンニトリル化合物Info
- Publication number
- JP2001518469A JP2001518469A JP2000513839A JP2000513839A JP2001518469A JP 2001518469 A JP2001518469 A JP 2001518469A JP 2000513839 A JP2000513839 A JP 2000513839A JP 2000513839 A JP2000513839 A JP 2000513839A JP 2001518469 A JP2001518469 A JP 2001518469A
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- methyl
- benzo
- propionitrile
- phenyl
- 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.)
- Withdrawn
Links
- ZMMOYIXZGHJMNI-UHFFFAOYSA-N 3-oxopropanenitrile Chemical class O=CCC#N ZMMOYIXZGHJMNI-UHFFFAOYSA-N 0.000 title description 3
- -1 nitro, amino Chemical group 0.000 claims abstract description 238
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical class 0.000 claims abstract description 16
- 108010033242 Kynurenine 3-monooxygenase Proteins 0.000 claims abstract description 15
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 12
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000000815 N-oxide group Chemical group 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims abstract description 5
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical class CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 239000011593 sulfur Substances 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 102
- 238000000034 method Methods 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 229940080818 propionamide Drugs 0.000 claims description 22
- 102100037652 Kynurenine 3-monooxygenase Human genes 0.000 claims description 13
- 125000004245 indazol-3-yl group Chemical group [H]N1N=C(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- OQMJRKXTDZRLLU-UHFFFAOYSA-N 2-(1-methylbenzo[g]indazole-3-carbonyl)-3-(3-methylphenyl)-3-oxopropanenitrile Chemical compound CC1=CC=CC(C(=O)C(C#N)C(=O)C=2C3=C(C4=CC=CC=C4C=C3)N(C)N=2)=C1 OQMJRKXTDZRLLU-UHFFFAOYSA-N 0.000 claims description 6
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 6
- 239000002532 enzyme inhibitor Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- 229940125532 enzyme inhibitor Drugs 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- MPLRHCMORQJNKM-UHFFFAOYSA-N 2-cyano-3-hydroxy-n-phenyl-3-(1-phenylbenzo[g]indazol-3-yl)prop-2-enamide Chemical compound N=1N(C=2C=CC=CC=2)C(C2=CC=CC=C2C=C2)=C2C=1C(O)=C(C#N)C(=O)NC1=CC=CC=C1 MPLRHCMORQJNKM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- GWPJEBQCCYGKPB-UHFFFAOYSA-N 2-(3-chlorobenzoyl)-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound ClC=1C=C(C(=O)C(C#N)C(=O)C2=NN(C3=C4C(=CC=C23)C=CC=C4)C)C=CC1 GWPJEBQCCYGKPB-UHFFFAOYSA-N 0.000 claims description 3
- BLHVIFWVNGVTOT-UHFFFAOYSA-N 2-(3-chlorophenyl)sulfonyl-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound C12=CC=C3C=CC=CC3=C2N(C)N=C1C(=O)C(C#N)S(=O)(=O)C1=CC=CC(Cl)=C1 BLHVIFWVNGVTOT-UHFFFAOYSA-N 0.000 claims description 3
- BSQQQFRDYQRUDT-UHFFFAOYSA-N 2-(4-fluorobenzoyl)-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound C12=CC=C3C=CC=CC3=C2N(C)N=C1C(=O)C(C#N)C(=O)C1=CC=C(F)C=C1 BSQQQFRDYQRUDT-UHFFFAOYSA-N 0.000 claims description 3
- QGDGTJGVPSNWOJ-UHFFFAOYSA-N 2-(4-methoxybenzoyl)-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound C1=CC(OC)=CC=C1C(=O)C(C#N)C(=O)C1=NN(C)C2=C1C=CC1=CC=CC=C21 QGDGTJGVPSNWOJ-UHFFFAOYSA-N 0.000 claims description 3
- GXCFLNZAMCFLMB-UHFFFAOYSA-N 2-(benzenesulfonyl)-3-(9-chloro-1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound C12=CC=C3C=CC=C(Cl)C3=C2N(C)N=C1C(=O)C(C#N)S(=O)(=O)C1=CC=CC=C1 GXCFLNZAMCFLMB-UHFFFAOYSA-N 0.000 claims description 3
- QHHKDGKZJTWVQY-UHFFFAOYSA-N 2-benzoyl-3-(9-chloro-1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound C12=CC=C3C=CC=C(Cl)C3=C2N(C)N=C1C(=O)C(C#N)C(=O)C1=CC=CC=C1 QHHKDGKZJTWVQY-UHFFFAOYSA-N 0.000 claims description 3
- NDGDQWFVASUKKA-UHFFFAOYSA-N 2-benzoyl-3-(9-methoxy-1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound N=1N(C)C2=C3C(OC)=CC=CC3=CC=C2C=1C(=O)C(C#N)C(=O)C1=CC=CC=C1 NDGDQWFVASUKKA-UHFFFAOYSA-N 0.000 claims description 3
- RAOUEEULHQCXNH-UHFFFAOYSA-N 2-cyano-3-(1-methylbenzo[g]indazol-3-yl)-3-oxo-n-[3-(trifluoromethyl)phenyl]propanamide Chemical compound C12=CC=C3C=CC=CC3=C2N(C)N=C1C(=O)C(C#N)C(=O)NC1=CC=CC(C(F)(F)F)=C1 RAOUEEULHQCXNH-UHFFFAOYSA-N 0.000 claims description 3
- QXBYKIXIRWTCSQ-UHFFFAOYSA-N 2-cyano-3-(1-methylbenzo[g]indazol-3-yl)-n-(3-methylphenyl)-3-oxopropanamide Chemical compound CC1=CC=CC(NC(=O)C(C#N)C(=O)C=2C3=C(C4=CC=CC=C4C=C3)N(C)N=2)=C1 QXBYKIXIRWTCSQ-UHFFFAOYSA-N 0.000 claims description 3
- GDZLLIFFIRSBRR-UHFFFAOYSA-N 2-cyano-3-(8-fluoro-1-methylbenzo[g]indazol-3-yl)-3-oxo-n-phenylpropanamide Chemical compound C12=CC=C3C=CC(F)=CC3=C2N(C)N=C1C(=O)C(C#N)C(=O)NC1=CC=CC=C1 GDZLLIFFIRSBRR-UHFFFAOYSA-N 0.000 claims description 3
- SKVAJSWMJNECDY-UHFFFAOYSA-N 2-cyano-3-oxo-n-phenyl-3-(1-phenylpyrazolo[4,3-c]quinolin-3-yl)propanamide Chemical compound N=1N(C=2C=CC=CC=2)C(C2=CC=CC=C2N=C2)=C2C=1C(=O)C(C#N)C(=O)NC1=CC=CC=C1 SKVAJSWMJNECDY-UHFFFAOYSA-N 0.000 claims description 3
- SLMORSISRMMWPG-UHFFFAOYSA-N 3-(1-methylbenzo[g]indazol-3-yl)-2-(3-methylphenyl)sulfonyl-3-oxopropanenitrile Chemical compound CC1=CC=CC(S(=O)(=O)C(C#N)C(=O)C=2C3=C(C4=CC=CC=C4C=C3)N(C)N=2)=C1 SLMORSISRMMWPG-UHFFFAOYSA-N 0.000 claims description 3
- URUSBDVAJNDMDO-UHFFFAOYSA-N 3-(1-methylbenzo[g]indazol-3-yl)-3-oxo-2-[3-(trifluoromethyl)phenyl]sulfonylpropanenitrile Chemical compound C12=CC=C3C=CC=CC3=C2N(C)N=C1C(=O)C(C#N)S(=O)(=O)C1=CC=CC(C(F)(F)F)=C1 URUSBDVAJNDMDO-UHFFFAOYSA-N 0.000 claims description 3
- VRHBWEPBFZWPHW-UHFFFAOYSA-N 3-(9-chloro-1-methylbenzo[g]indazol-3-yl)-2-cyano-3-oxo-n-phenylpropanamide Chemical compound C12=CC=C3C=CC=C(Cl)C3=C2N(C)N=C1C(=O)C(C#N)C(=O)NC1=CC=CC=C1 VRHBWEPBFZWPHW-UHFFFAOYSA-N 0.000 claims description 3
- OFZFFIDUIUEPIB-UHFFFAOYSA-N 3-oxopropanamide Chemical compound NC(=O)CC=O OFZFFIDUIUEPIB-UHFFFAOYSA-N 0.000 claims description 3
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- JXYKHUPUBIZYQD-UHFFFAOYSA-N n-benzyl-2-cyano-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanamide Chemical compound C12=CC=C3C=CC=CC3=C2N(C)N=C1C(=O)C(C#N)C(=O)NCC1=CC=CC=C1 JXYKHUPUBIZYQD-UHFFFAOYSA-N 0.000 claims description 3
- FFIIZQVSQWOTCS-UHFFFAOYSA-N n-butyl-2-cyano-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanamide Chemical compound C1=CC2=CC=CC=C2C2=C1C(C(=O)C(C#N)C(=O)NCCCC)=NN2C FFIIZQVSQWOTCS-UHFFFAOYSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- XMGZVOWVGXXOOT-UHFFFAOYSA-N 2-(4-methoxyphenyl)sulfonyl-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C(C#N)C(=O)C1=NN(C)C2=C1C=CC1=CC=CC=C21 XMGZVOWVGXXOOT-UHFFFAOYSA-N 0.000 claims description 2
- LVZOPUMRCOJXLU-UHFFFAOYSA-N 2-benzoyl-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanenitrile Chemical compound C12=CC=C3C=CC=CC3=C2N(C)N=C1C(=O)C(C#N)C(=O)C1=CC=CC=C1 LVZOPUMRCOJXLU-UHFFFAOYSA-N 0.000 claims description 2
- SYMDSKWDJXMMTD-UHFFFAOYSA-N 2-cyano-3-(1-methylpyrazolo[4,3-c]quinolin-3-yl)-3-oxo-n-phenylpropanamide Chemical compound C12=CN=C3C=CC=CC3=C2N(C)N=C1C(=O)C(C#N)C(=O)NC1=CC=CC=C1 SYMDSKWDJXMMTD-UHFFFAOYSA-N 0.000 claims description 2
- AVXFRLISNAOUOU-UHFFFAOYSA-N 2-cyano-3-hydroxy-3-(1-methylbenzo[g]indazol-3-yl)-n-phenylprop-2-enamide Chemical compound C12=CC=C3C=CC=CC3=C2N(C)N=C1C(O)=C(C#N)C(=O)NC1=CC=CC=C1 AVXFRLISNAOUOU-UHFFFAOYSA-N 0.000 claims description 2
- GSZLNOJRGIROOV-UHFFFAOYSA-N 2-cyano-n-(4-methoxyphenyl)-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanamide Chemical compound C1=CC(OC)=CC=C1NC(=O)C(C#N)C(=O)C1=NN(C)C2=C1C=CC1=CC=CC=C21 GSZLNOJRGIROOV-UHFFFAOYSA-N 0.000 claims description 2
- 229940122439 Hydroxylase inhibitor Drugs 0.000 claims description 2
- BMRUICICTSXZBC-UHFFFAOYSA-N N-(3-chlorophenyl)-2-cyano-3-(1-methylbenzo[g]indazol-3-yl)-3-oxopropanamide Chemical compound C(#N)C(C(=O)NC1=CC(=CC=C1)Cl)C(=O)C1=NN(C2=C3C(=CC=C12)C=CC=C3)C BMRUICICTSXZBC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- DOZZSWAOPDYVLH-UHFFFAOYSA-N 2-phenylpropanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1 DOZZSWAOPDYVLH-UHFFFAOYSA-N 0.000 claims 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 1
- 230000002981 neuropathic effect Effects 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 125000001769 aryl amino group Chemical group 0.000 abstract 1
- 159000000000 sodium salts Chemical class 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- 125000004494 ethyl ester group Chemical group 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 239000000243 solution Substances 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- YGPSJZOEDVAXAB-UHFFFAOYSA-N kynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-UHFFFAOYSA-N 0.000 description 15
- HCZHHEIFKROPDY-UHFFFAOYSA-N kynurenic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 HCZHHEIFKROPDY-UHFFFAOYSA-N 0.000 description 14
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- WJXSWCUQABXPFS-UHFFFAOYSA-N 3-hydroxyanthranilic acid Chemical compound NC1=C(O)C=CC=C1C(O)=O WJXSWCUQABXPFS-UHFFFAOYSA-N 0.000 description 4
- VCKPUUFAIGNJHC-UHFFFAOYSA-N 3-hydroxykynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC(O)=C1N VCKPUUFAIGNJHC-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229960004793 sucrose Drugs 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- HALAYLPVVOEUTG-UHFFFAOYSA-N 1-methylbenzo[g]indazole-3-carboxylic acid Chemical compound C1=CC=CC2=C3N(C)N=C(C(O)=O)C3=CC=C21 HALAYLPVVOEUTG-UHFFFAOYSA-N 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9720899.5 | 1997-10-01 | ||
| GBGB9720899.5A GB9720899D0 (en) | 1997-10-01 | 1997-10-01 | Condensed heterocyclic compounds |
| PCT/EP1998/006051 WO1999016753A2 (fr) | 1997-10-01 | 1998-09-23 | Composes 3-oxo-propanenitrile tricycliques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001518469A true JP2001518469A (ja) | 2001-10-16 |
Family
ID=10819928
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000513839A Withdrawn JP2001518469A (ja) | 1997-10-01 | 1998-09-23 | 三環式３−オキソ−プロパンニトリル化合物 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1019380A2 (fr) |
| JP (1) | JP2001518469A (fr) |
| AU (1) | AU1334399A (fr) |
| CA (1) | CA2302025A1 (fr) |
| GB (1) | GB9720899D0 (fr) |
| WO (1) | WO1999016753A2 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009539773A (ja) * | 2006-06-02 | 2009-11-19 | イーラン ファーマスーティカルズ、インコーポレイテッド | 溶融三環系スルホンアミドγセクレターゼ阻害剤 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10021900A1 (de) | 2000-05-08 | 2001-11-15 | Bayer Ag | Phenyl-substituierte 2-Enamino-Ketonitrile |
| CN116535386A (zh) * | 2023-04-19 | 2023-08-04 | 西南大学 | 氰乙烯磺酰苯胺类化合物及其制备方法和医药应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3842099A (en) * | 1969-10-06 | 1974-10-15 | Teikoku Hormune Mfg Co Ltd | Naphtho(2,1-d)isoxazole derivatives |
| IL60269A (en) * | 1979-06-11 | 1983-12-30 | Ciba Geigy | Alpha-carbamoyl-pyrrolpropionitriles,their preparation and pharmaceutical compositions containing them |
| US4435407A (en) * | 1982-01-07 | 1984-03-06 | Ciba-Geigy Corporation | Certain substituted β-oxo-α-carbamoylpyrrolepropionitriles |
| GB2127809B (en) * | 1982-09-28 | 1986-03-12 | Ciba Geigy Ag | Certain b-oxo-a-carbamoyl-pyrrolepropionitriles |
| US4816467A (en) * | 1987-01-09 | 1989-03-28 | Farmitalia Carlo Erba S.R.L | Heteroaryl 3-oxo-propanenitrile derivatives, pharmaceutical compositions and use |
| GB8814586D0 (en) * | 1988-06-20 | 1988-07-27 | Erba Carlo Spa | Tricyclic 3-oxo-propanenitrile derivatives & process for their preparation |
| IL92508A0 (en) * | 1988-12-08 | 1990-08-31 | Ciba Geigy Ag | Novel alpha-cyano-beta-oxopropionamides |
| GB2227741B (en) * | 1989-02-06 | 1992-08-05 | Erba Carlo Spa | Condensed 3-oxo-propanenitrile derivatives and process for their preparation |
| GB8916290D0 (en) * | 1989-07-17 | 1989-08-31 | Erba Carlo Spa | Heteroaryl-3-oxo-propanenitrile derivatives useful in stimulating myelopoiesis |
| JP3148960B2 (ja) * | 1993-04-12 | 2001-03-26 | コニカ株式会社 | 写真用シアンカプラー |
| JP3542826B2 (ja) * | 1994-07-11 | 2004-07-14 | 帝国臓器製薬株式会社 | 新規な二環式化合物縮合［２，１−ｄ］イソキサゾール−３−カルボン酸誘導体 |
-
1997
- 1997-10-01 GB GBGB9720899.5A patent/GB9720899D0/en not_active Ceased
-
1998
- 1998-09-23 CA CA002302025A patent/CA2302025A1/fr not_active Abandoned
- 1998-09-23 WO PCT/EP1998/006051 patent/WO1999016753A2/fr not_active Application Discontinuation
- 1998-09-23 JP JP2000513839A patent/JP2001518469A/ja not_active Withdrawn
- 1998-09-23 AU AU13343/99A patent/AU1334399A/en not_active Abandoned
- 1998-09-23 EP EP98956836A patent/EP1019380A2/fr not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009539773A (ja) * | 2006-06-02 | 2009-11-19 | イーラン ファーマスーティカルズ、インコーポレイテッド | 溶融三環系スルホンアミドγセクレターゼ阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999016753A3 (fr) | 1999-05-20 |
| CA2302025A1 (fr) | 1999-04-08 |
| GB9720899D0 (en) | 1997-12-03 |
| WO1999016753A2 (fr) | 1999-04-08 |
| EP1019380A2 (fr) | 2000-07-19 |
| AU1334399A (en) | 1999-04-23 |
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