SK232000A3 - Pyridine derivatives and pharmaceutical composition containing them - Google Patents
Pyridine derivatives and pharmaceutical composition containing them Download PDFInfo
- Publication number
- SK232000A3 SK232000A3 SK23-2000A SK232000A SK232000A3 SK 232000 A3 SK232000 A3 SK 232000A3 SK 232000 A SK232000 A SK 232000A SK 232000 A3 SK232000 A3 SK 232000A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- carboxy
- alkyl
- alkoxy
- methyl
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
- 150000003222 pyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 68
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract description 8
- 230000001404 mediated effect Effects 0.000 claims abstract description 8
- -1 piperidino, carboxy Chemical group 0.000 claims description 148
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000003282 alkyl amino group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 230000000848 glutamatergic effect Effects 0.000 claims description 6
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 5
- 125000004419 alkynylene group Chemical group 0.000 claims description 5
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000008054 signal transmission Effects 0.000 claims description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- KYJSGWVPWUBKGL-UHFFFAOYSA-N 2-methyl-6-(2-pyridin-3-ylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=NC=CC=2)=N1 KYJSGWVPWUBKGL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 2
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 239000003446 ligand Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims 3
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 claims 1
- 150000001204 N-oxides Chemical class 0.000 claims 1
- 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims 1
- 108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 claims 1
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 abstract description 6
- 239000003921 oil Substances 0.000 description 44
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- 229920002554 vinyl polymer Polymers 0.000 description 31
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- 150000003840 hydrochlorides Chemical class 0.000 description 13
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 9
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 9
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- HHOFXGSYOXBLCK-UHFFFAOYSA-N 2-[2-(3-bromophenyl)ethynyl]-6-methylpyridine Chemical compound CC1=CC=CC(C#CC=2C=C(Br)C=CC=2)=N1 HHOFXGSYOXBLCK-UHFFFAOYSA-N 0.000 description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 3
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 208000004454 Hyperalgesia Diseases 0.000 description 3
- 208000035154 Hyperesthesia Diseases 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 3
- 150000003973 alkyl amines Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 230000036461 convulsion Effects 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229910052751 metal Chemical group 0.000 description 3
- 239000002184 metal Chemical group 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- XHPPWPVROZXXSG-UHFFFAOYSA-N 2-[1,2-dibromo-2-(3-bromophenyl)ethyl]-6-methylpyridine Chemical compound CC1=CC=CC(C(Br)C(Br)C=2C=C(Br)C=CC=2)=N1 XHPPWPVROZXXSG-UHFFFAOYSA-N 0.000 description 2
- XWLGPZHIBIDKMI-UHFFFAOYSA-N 2-[2-(3-bromophenyl)ethenyl]-6-methylpyridine Chemical compound CC1=CC=CC(C=CC=2C=C(Br)C=CC=2)=N1 XWLGPZHIBIDKMI-UHFFFAOYSA-N 0.000 description 2
- MDKKZIPYNIZWGB-UHFFFAOYSA-N 2-[2-(6-methylpyridin-2-yl)ethenyl]benzonitrile Chemical compound CC1=CC=CC(C=CC=2C(=CC=CC=2)C#N)=N1 MDKKZIPYNIZWGB-UHFFFAOYSA-N 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- CZLNWHQVWWRKHG-UHFFFAOYSA-N 2-methyl-6-(2-naphthalen-2-ylethenyl)pyridine Chemical compound CC1=CC=CC(C=CC=2C=C3C=CC=CC3=CC=2)=N1 CZLNWHQVWWRKHG-UHFFFAOYSA-N 0.000 description 2
- SISOFUCTXZKSOQ-UHFFFAOYSA-N 2-methyl-6-(2-phenylethenyl)pyridine Chemical compound CC1=CC=CC(C=CC=2C=CC=CC=2)=N1 SISOFUCTXZKSOQ-UHFFFAOYSA-N 0.000 description 2
- GDYSBRVYTYYALX-UHFFFAOYSA-N 2-methyl-6-[2-(2-methylphenyl)ethenyl]pyridine Chemical compound CC1=CC=CC(C=CC=2C(=CC=CC=2)C)=N1 GDYSBRVYTYYALX-UHFFFAOYSA-N 0.000 description 2
- VBUCDUWZPMKSPT-UHFFFAOYSA-N 3-[2-(6-methylpyridin-2-yl)ethenyl]benzonitrile Chemical compound CC1=CC=CC(C=CC=2C=C(C=CC=2)C#N)=N1 VBUCDUWZPMKSPT-UHFFFAOYSA-N 0.000 description 2
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- OVFQFWCPZCVGHK-UHFFFAOYSA-N (4-fluorophenyl)-[1-[2-[2-(3-fluorophenyl)ethynyl]-6-methylpyridine-4-carbonyl]piperidin-4-yl]methanone Chemical compound N=1C(C)=CC(C(=O)N2CCC(CC2)C(=O)C=2C=CC(F)=CC=2)=CC=1C#CC1=CC=CC(F)=C1 OVFQFWCPZCVGHK-UHFFFAOYSA-N 0.000 description 1
- DNNGRDHVSYGNCR-UHFFFAOYSA-N (4-fluorophenyl)-[1-[6-[2-(3-fluorophenyl)ethenyl]-2-methylpyridine-3-carbonyl]piperidin-4-yl]methanone Chemical compound C=1C=C(C(=O)N2CCC(CC2)C(=O)C=2C=CC(F)=CC=2)C(C)=NC=1C=CC1=CC=CC(F)=C1 DNNGRDHVSYGNCR-UHFFFAOYSA-N 0.000 description 1
- OQCKLVPQCCOFIM-UHFFFAOYSA-N (4-fluorophenyl)-[1-[6-[2-(3-fluorophenyl)ethynyl]-2-methylpyridine-3-carbonyl]piperidin-4-yl]methanone Chemical compound CC1=NC(C#CC=2C=C(F)C=CC=2)=CC=C1C(=O)N(CC1)CCC1C(=O)C1=CC=C(F)C=C1 OQCKLVPQCCOFIM-UHFFFAOYSA-N 0.000 description 1
- YSWYUAZDUVLSKW-UHFFFAOYSA-N (4-fluorophenyl)-[1-[6-[2-(3-fluorophenyl)ethynyl]pyridine-3-carbonyl]piperidin-4-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(C(=O)C=2C=NC(=CC=2)C#CC=2C=C(F)C=CC=2)CC1 YSWYUAZDUVLSKW-UHFFFAOYSA-N 0.000 description 1
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- HKFPYLGHMOOBIW-UHFFFAOYSA-N ethyl 6-[2-(3-fluorophenyl)ethynyl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC=C1C#CC1=CC=CC(F)=C1 HKFPYLGHMOOBIW-UHFFFAOYSA-N 0.000 description 1
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- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
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- 238000000338 in vitro Methods 0.000 description 1
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
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- VAUZRJZXZWKUCY-UHFFFAOYSA-N methyl 2-[[6-[2-(3-fluorophenyl)ethynyl]-2-methylpyridine-3-carbonyl]amino]-2-phenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)OC)NC(=O)C(C(=N1)C)=CC=C1C#CC1=CC=CC(F)=C1 VAUZRJZXZWKUCY-UHFFFAOYSA-N 0.000 description 1
- AGKCNDHYPPNDIG-UHFFFAOYSA-N methyl 3-[2-(6-methylpyridin-2-yl)ethenyl]benzoate Chemical compound COC(=O)C1=CC=CC(C=CC=2N=C(C)C=CC=2)=C1 AGKCNDHYPPNDIG-UHFFFAOYSA-N 0.000 description 1
- VAQRTIKBWDNDIC-UHFFFAOYSA-N methyl 4-[2-(6-methylpyridin-2-yl)ethenyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C=CC1=CC=CC(C)=N1 VAQRTIKBWDNDIC-UHFFFAOYSA-N 0.000 description 1
- HCNBYHFDQJDQLV-UHFFFAOYSA-N methyl 6-(2-phenylethenyl)pyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(C=CC=2C=CC=CC=2)=N1 HCNBYHFDQJDQLV-UHFFFAOYSA-N 0.000 description 1
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- LWAHKNCLKDKOGE-UHFFFAOYSA-N n-[3-[2-(6-methylpyridin-2-yl)ethenyl]phenyl]thiophene-2-carboxamide Chemical compound CC1=CC=CC(C=CC=2C=C(NC(=O)C=3SC=CC=3)C=CC=2)=N1 LWAHKNCLKDKOGE-UHFFFAOYSA-N 0.000 description 1
- FSFBWPSVWXMWKM-UHFFFAOYSA-N n-[3-[2-(6-methylpyridin-2-yl)ethynyl]phenyl]-2-phenylacetamide Chemical compound CC1=CC=CC(C#CC=2C=C(NC(=O)CC=3C=CC=CC=3)C=CC=2)=N1 FSFBWPSVWXMWKM-UHFFFAOYSA-N 0.000 description 1
- CRYBQCTZQHNFKT-UHFFFAOYSA-N n-[3-[2-(6-methylpyridin-2-yl)ethynyl]phenyl]thiophene-2-carboxamide Chemical compound CC1=CC=CC(C#CC=2C=C(NC(=O)C=3SC=CC=3)C=CC=2)=N1 CRYBQCTZQHNFKT-UHFFFAOYSA-N 0.000 description 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 description 1
- YQWXDBJCHHLIPH-UHFFFAOYSA-N n-[4-[2-(6-methylpyridin-2-yl)ethenyl]phenyl]-2-phenylacetamide Chemical compound CC1=CC=CC(C=CC=2C=CC(NC(=O)CC=3C=CC=CC=3)=CC=2)=N1 YQWXDBJCHHLIPH-UHFFFAOYSA-N 0.000 description 1
- MCSRDAAOPHMWRQ-UHFFFAOYSA-N n-ethyl-3-[2-(6-methylpyridin-2-yl)ethenyl]aniline Chemical compound CCNC1=CC=CC(C=CC=2N=C(C)C=CC=2)=C1 MCSRDAAOPHMWRQ-UHFFFAOYSA-N 0.000 description 1
- LFWVZVCRTMFSFL-UHFFFAOYSA-N n-hexyl-6-(2-phenylethenyl)pyridine-2-carboxamide Chemical compound CCCCCCNC(=O)C1=CC=CC(C=CC=2C=CC=CC=2)=N1 LFWVZVCRTMFSFL-UHFFFAOYSA-N 0.000 description 1
- QZKHLLJITABEHV-UHFFFAOYSA-N n-tert-butyl-6-(2-phenylethenyl)pyridine-2-carboxamide Chemical compound CC(C)(C)NC(=O)C1=CC=CC(C=CC=2C=CC=CC=2)=N1 QZKHLLJITABEHV-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
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- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
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- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 239000000047 product Substances 0.000 description 1
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- 125000006308 propyl amino group Chemical group 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
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- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- 241000894007 species Species 0.000 description 1
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- 230000004083 survival effect Effects 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- IULOCEKPADTWDT-UHFFFAOYSA-N tert-butyl 2-[2-(3-fluorophenyl)ethynyl]-6-methylpyridine-4-carboxylate Chemical compound CC1=CC(C(=O)OC(C)(C)C)=CC(C#CC=2C=C(F)C=CC=2)=N1 IULOCEKPADTWDT-UHFFFAOYSA-N 0.000 description 1
- FJRRKHJUPGGVLO-UHFFFAOYSA-N tert-butyl 4-[6-[2-(3-fluorophenyl)ethynyl]-2-methylpyridine-3-carbonyl]piperazine-1-carboxylate Chemical compound CC1=NC(C#CC=2C=C(F)C=CC=2)=CC=C1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1 FJRRKHJUPGGVLO-UHFFFAOYSA-N 0.000 description 1
- FAJFHFNHZWPFBE-UHFFFAOYSA-N tert-butyl 6-[2-(3-fluorophenyl)ethynyl]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC(C)(C)C)=CC=C1C#CC1=CC=CC(F)=C1 FAJFHFNHZWPFBE-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- AUKNAUAVKQLRGA-UHFFFAOYSA-N tert-butyl n-[1-[3-[2-(6-methylpyridin-2-yl)ethenyl]anilino]-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound CC1=CC=CC(C=CC=2C=C(NC(=O)C(CC=3C=CC=CC=3)NC(=O)OC(C)(C)C)C=CC=2)=N1 AUKNAUAVKQLRGA-UHFFFAOYSA-N 0.000 description 1
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- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- WZHDDGLXLMYETM-UHFFFAOYSA-N trimethyl-[2-[3-[2-(6-methylpyridin-2-yl)ethenyl]phenyl]ethynyl]silane Chemical compound CC1=CC=CC(C=CC=2C=C(C=CC=2)C#C[Si](C)(C)C)=N1 WZHDDGLXLMYETM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/02—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
- 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
- C07D213/06—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
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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
- C07D213/02—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
- 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
- C07D213/06—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
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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
- C07D213/02—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
- 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
- C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/02—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
- 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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- 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
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89068997A | 1997-07-11 | 1997-07-11 | |
| US89169197A | 1997-07-11 | 1997-07-11 | |
| PCT/EP1998/004266 WO1999002497A2 (en) | 1997-07-11 | 1998-07-09 | Pyridine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK232000A3 true SK232000A3 (en) | 2000-06-12 |
Family
ID=27128958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK23-2000A SK232000A3 (en) | 1997-07-11 | 1998-07-09 | Pyridine derivatives and pharmaceutical composition containing them |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6656957B1 (de) |
| EP (1) | EP0998459B1 (de) |
| JP (1) | JP3481208B2 (de) |
| KR (1) | KR20010021712A (de) |
| CN (1) | CN1203060C (de) |
| AR (1) | AR016314A1 (de) |
| AT (1) | ATE393145T1 (de) |
| AU (1) | AU738973B2 (de) |
| BR (1) | BR9811685A (de) |
| CA (1) | CA2295678C (de) |
| DE (1) | DE69839398T2 (de) |
| ES (1) | ES2308811T3 (de) |
| HU (1) | HUP0004225A3 (de) |
| ID (1) | ID23889A (de) |
| IL (1) | IL133904A0 (de) |
| MY (1) | MY119800A (de) |
| NO (1) | NO20000124L (de) |
| NZ (1) | NZ502210A (de) |
| PE (1) | PE97799A1 (de) |
| PL (1) | PL343865A1 (de) |
| PT (1) | PT998459E (de) |
| RU (1) | RU2203889C2 (de) |
| SK (1) | SK232000A3 (de) |
| TR (1) | TR200000059T2 (de) |
| TW (1) | TW544448B (de) |
| WO (1) | WO1999002497A2 (de) |
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| AU4226493A (en) | 1992-05-01 | 1993-11-29 | Smithkline Beecham Corporation | Leukotriene antagonists |
| GB9515412D0 (en) * | 1995-07-27 | 1995-09-27 | Pharmacia Spa | 2-(4-substituted)-benzylamino-2-methyl-propanamide derivatives |
| JPH11509847A (ja) * | 1995-07-31 | 1999-08-31 | ノボ ノルディスク アクティーゼルスカブ | ヘテロ環式化合物、それらの調製及び使用 |
| IT1276153B1 (it) * | 1995-11-17 | 1997-10-27 | Roberto Pellicciari | Derivati di glicina ad attivita' antagonista dei recettori metabotropi del glutammato |
-
1998
- 1998-07-06 TW TW087110887A patent/TW544448B/zh not_active IP Right Cessation
- 1998-07-08 AR ARP980103330A patent/AR016314A1/es unknown
- 1998-07-09 CN CNB988070502A patent/CN1203060C/zh not_active Expired - Fee Related
- 1998-07-09 KR KR1020007000271A patent/KR20010021712A/ko not_active Ceased
- 1998-07-09 EP EP98941308A patent/EP0998459B1/de not_active Expired - Lifetime
- 1998-07-09 JP JP2000502025A patent/JP3481208B2/ja not_active Expired - Fee Related
- 1998-07-09 NZ NZ502210A patent/NZ502210A/en unknown
- 1998-07-09 AU AU89743/98A patent/AU738973B2/en not_active Ceased
- 1998-07-09 DE DE69839398T patent/DE69839398T2/de not_active Expired - Lifetime
- 1998-07-09 HU HU0004225A patent/HUP0004225A3/hu unknown
- 1998-07-09 TR TR2000/00059T patent/TR200000059T2/xx unknown
- 1998-07-09 SK SK23-2000A patent/SK232000A3/sk unknown
- 1998-07-09 ID IDW20000009A patent/ID23889A/id unknown
- 1998-07-09 BR BR9811685-1A patent/BR9811685A/pt not_active IP Right Cessation
- 1998-07-09 CA CA2295678A patent/CA2295678C/en not_active Expired - Fee Related
- 1998-07-09 IL IL13390498A patent/IL133904A0/xx unknown
- 1998-07-09 PL PL98343865A patent/PL343865A1/xx unknown
- 1998-07-09 AT AT98941308T patent/ATE393145T1/de not_active IP Right Cessation
- 1998-07-09 RU RU2000102667/04A patent/RU2203889C2/ru not_active IP Right Cessation
- 1998-07-09 WO PCT/EP1998/004266 patent/WO1999002497A2/en not_active Ceased
- 1998-07-09 PT PT98941308T patent/PT998459E/pt unknown
- 1998-07-09 ES ES98941308T patent/ES2308811T3/es not_active Expired - Lifetime
- 1998-07-09 PE PE1998000606A patent/PE97799A1/es not_active Application Discontinuation
- 1998-07-10 MY MYPI98003161A patent/MY119800A/en unknown
-
2000
- 2000-01-10 NO NO20000124A patent/NO20000124L/no not_active Application Discontinuation
- 2000-11-27 US US09/722,803 patent/US6656957B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE393145T1 (de) | 2008-05-15 |
| DE69839398T2 (de) | 2009-05-28 |
| TW544448B (en) | 2003-08-01 |
| AU738973B2 (en) | 2001-10-04 |
| ID23889A (id) | 2000-05-25 |
| EP0998459B1 (de) | 2008-04-23 |
| AU8974398A (en) | 1999-02-08 |
| JP2001509504A (ja) | 2001-07-24 |
| WO1999002497A3 (en) | 1999-04-01 |
| NZ502210A (en) | 2002-07-26 |
| JP3481208B2 (ja) | 2003-12-22 |
| WO1999002497A2 (en) | 1999-01-21 |
| RU2203889C2 (ru) | 2003-05-10 |
| PE97799A1 (es) | 1999-11-08 |
| AR016314A1 (es) | 2001-07-04 |
| HUP0004225A3 (en) | 2001-06-28 |
| TR200000059T2 (tr) | 2000-06-21 |
| DE69839398D1 (de) | 2008-06-05 |
| US6656957B1 (en) | 2003-12-02 |
| CA2295678C (en) | 2010-04-13 |
| BR9811685A (pt) | 2000-09-19 |
| MY119800A (en) | 2005-07-29 |
| KR20010021712A (ko) | 2001-03-15 |
| HUP0004225A2 (hu) | 2001-05-28 |
| PL343865A1 (en) | 2001-09-10 |
| ES2308811T3 (es) | 2008-12-01 |
| NO20000124D0 (no) | 2000-01-10 |
| CA2295678A1 (en) | 1999-01-21 |
| EP0998459A2 (de) | 2000-05-10 |
| CN1262676A (zh) | 2000-08-09 |
| IL133904A0 (en) | 2001-04-30 |
| PT998459E (pt) | 2008-07-31 |
| NO20000124L (no) | 2000-03-02 |
| CN1203060C (zh) | 2005-05-25 |
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