UA75871C2 - 1,2,4-oxadiazole derivatives and use thereof as antagonists at metabotropic glutamate receptors - Google Patents

Info

Publication number

UA75871C2

UA75871C2 UA2002032079A UA2002032079A UA75871C2 UA 75871 C2 UA75871 C2 UA 75871C2 UA 2002032079 A UA2002032079 A UA 2002032079A UA 2002032079 A UA2002032079 A UA 2002032079A UA 75871 C2 UA75871 C2 UA 75871C2

Authority

UA

Ukraine

Prior art keywords

oxadiazole

pyridyl

group

cyanophenyl

chloro

Prior art date

1999-08-19

Links

• Espacenet
• Global Dossier
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• 102000016193 Metabotropic glutamate receptors Human genes 0.000 title claims abstract description 13
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 title claims abstract description 13
• 150000005071 1,2,4-oxadiazoles Chemical class 0.000 title claims description 33
• 239000005557 antagonist Substances 0.000 title abstract description 21
• 150000001875 compounds Chemical class 0.000 claims abstract description 55
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 13
• 208000025966 Neurological disease Diseases 0.000 claims abstract description 12
• 125000003118 aryl group Chemical group 0.000 claims abstract description 11
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
• 102000005962 receptors Human genes 0.000 claims description 32
• 108020003175 receptors Proteins 0.000 claims description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
• 201000010099 disease Diseases 0.000 claims description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 11
• 208000035475 disorder Diseases 0.000 claims description 11
• 229930195712 glutamate Natural products 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 10
• 229910052700 potassium Inorganic materials 0.000 claims description 8
• OTAZWJWYCGCZPY-UHFFFAOYSA-N 3-pyridin-2-yl-5-(2,3,6-trifluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=C(F)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1F OTAZWJWYCGCZPY-UHFFFAOYSA-N 0.000 claims description 7
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• KZOBYFBUONCLFZ-UHFFFAOYSA-N 3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 KZOBYFBUONCLFZ-UHFFFAOYSA-N 0.000 claims description 6
• JWGWZTPLPSOQLP-UHFFFAOYSA-N 5-(2,5-difluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC=C(F)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 JWGWZTPLPSOQLP-UHFFFAOYSA-N 0.000 claims description 6
• NGKWCJCCZGCLID-UHFFFAOYSA-N 5-(2-chlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=NO1 NGKWCJCCZGCLID-UHFFFAOYSA-N 0.000 claims description 6
• QAWYDHMYEBUWOI-UHFFFAOYSA-N 5-(3-chloro-5-fluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC(Cl)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 QAWYDHMYEBUWOI-UHFFFAOYSA-N 0.000 claims description 6
• 230000006378 damage Effects 0.000 claims description 6
• GELAFISMURFRCA-UHFFFAOYSA-N 3-fluoro-5-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound FC1=CC(C#N)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 GELAFISMURFRCA-UHFFFAOYSA-N 0.000 claims description 5
• IBIPNEKWIOPNFP-UHFFFAOYSA-N 5-(2,3-dichlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1Cl IBIPNEKWIOPNFP-UHFFFAOYSA-N 0.000 claims description 5
• HSLAPYCDJGEODS-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC(Cl)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 HSLAPYCDJGEODS-UHFFFAOYSA-N 0.000 claims description 5
• PREUPKHXEHMSKI-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=C(Cl)C=C1C1=NC(C=2N=CC=CC=2)=NO1 PREUPKHXEHMSKI-UHFFFAOYSA-N 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 208000020016 psychiatric disease Diseases 0.000 claims description 5
• ACEMLHPTBCVQEO-UHFFFAOYSA-N 3-[3-(3-fluoropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound FC1=CC=CN=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 ACEMLHPTBCVQEO-UHFFFAOYSA-N 0.000 claims description 4
• JTCHHBMKZRITLW-UHFFFAOYSA-N 3-[3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(F)=CC=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 JTCHHBMKZRITLW-UHFFFAOYSA-N 0.000 claims description 4
• BRSJLLPXGUAIGO-UHFFFAOYSA-N 3-[3-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound ClC1=CC(C(F)(F)F)=CN=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 BRSJLLPXGUAIGO-UHFFFAOYSA-N 0.000 claims description 4
• NEBUBOGLNXERLF-UHFFFAOYSA-N 3-chloro-5-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound ClC1=CC(C#N)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NEBUBOGLNXERLF-UHFFFAOYSA-N 0.000 claims description 4
• RBSPCALDSNXWEP-UHFFFAOYSA-N 3-fluoro-5-[3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(F)=CC=C1C1=NOC(C=2C=C(C=C(F)C=2)C#N)=N1 RBSPCALDSNXWEP-UHFFFAOYSA-N 0.000 claims description 4
• MWFUWMAFXIIDOK-UHFFFAOYSA-N 5-(3,5-difluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC(F)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 MWFUWMAFXIIDOK-UHFFFAOYSA-N 0.000 claims description 4
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• 206010019196 Head injury Diseases 0.000 claims description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 4
• 206010015037 epilepsy Diseases 0.000 claims description 4
• YWSNJWSAQDJCBJ-UHFFFAOYSA-N 5-(3-bromophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound BrC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 YWSNJWSAQDJCBJ-UHFFFAOYSA-N 0.000 claims description 3
• IMLLSKDXLVDFRH-UHFFFAOYSA-N 5-(3-chlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 IMLLSKDXLVDFRH-UHFFFAOYSA-N 0.000 claims description 3
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• 230000036407 pain Effects 0.000 claims description 3
• 201000000980 schizophrenia Diseases 0.000 claims description 3
• NPHDXXRKYHPQLD-UHFFFAOYSA-N 5-(3-methylphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound CC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NPHDXXRKYHPQLD-UHFFFAOYSA-N 0.000 claims description 2
• 208000013016 Hypoglycemia Diseases 0.000 claims description 2
• 230000002218 hypoglycaemic effect Effects 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• VMDCHMHYENMYCK-UHFFFAOYSA-N 5-phenyl-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound C1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=NO1 VMDCHMHYENMYCK-UHFFFAOYSA-N 0.000 claims 2
• 208000020401 Depressive disease Diseases 0.000 claims 1
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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 125000000623 heterocyclic group Chemical group 0.000 abstract description 15
• 125000005842 heteroatom Chemical group 0.000 abstract description 8
• 229910002091 carbon monoxide Inorganic materials 0.000 abstract description 3
• 229910052757 nitrogen Inorganic materials 0.000 abstract description 2
• 229910052760 oxygen Inorganic materials 0.000 abstract description 2
• 229910052717 sulfur Inorganic materials 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 82
• 238000000034 method Methods 0.000 description 68
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• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 56
• 239000000243 solution Substances 0.000 description 52
• 238000003786 synthesis reaction Methods 0.000 description 48
• -1 2-oxazole Chemical compound 0.000 description 45
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 41
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