CZ2002599A3 - Heteropolycyklické sloučeniny a jejich pouľití jako antagonistů metabotropního receptoru glutamátu - Google Patents

Info

Publication number

CZ2002599A3

CZ2002599A3 CZ2002599A CZ2002599A CZ2002599A3 CZ 2002599 A3 CZ2002599 A3 CZ 2002599A3 CZ 2002599 A CZ2002599 A CZ 2002599A CZ 2002599 A CZ2002599 A CZ 2002599A CZ 2002599 A3 CZ2002599 A3 CZ 2002599A3

Authority

CZ

Czechia

Prior art keywords

pyridyl

oxadiazole

oxazole

group

cyanophenyl

Prior art date

1999-08-19

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• 102000016193 Metabotropic glutamate receptors Human genes 0.000 title claims abstract description 54
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 title claims abstract description 54
• 239000003825 glutamate receptor antagonist Substances 0.000 title 1
• 125000004585 polycyclic heterocycle group Chemical group 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 70
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 27
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 15
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 14
• 125000003118 aryl group Chemical group 0.000 claims abstract description 14
• 208000025966 Neurological disease Diseases 0.000 claims abstract description 13
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 9
• 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 6
• -1 CH 3 Inorganic materials 0.000 claims description 79
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 42
• 238000000034 method Methods 0.000 claims description 38
• 239000000203 mixture Substances 0.000 claims description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
• 201000010099 disease Diseases 0.000 claims description 16
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
• VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 claims description 15
• 150000003839 salts Chemical class 0.000 claims description 10
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 9
• 208000035475 disorder Diseases 0.000 claims description 9
• CQXOVXIKDZNZMV-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 CQXOVXIKDZNZMV-UHFFFAOYSA-N 0.000 claims description 8
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 7
• 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
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 7
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 claims description 7
• FKZJTFVDFGPXSB-UHFFFAOYSA-N 3-(3-quinolin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2ON=C(N=2)C=2N=C3C=CC=CC3=CC=2)=C1 FKZJTFVDFGPXSB-UHFFFAOYSA-N 0.000 claims description 6
• XZDUVAVPEQYRJT-UHFFFAOYSA-N 3-(4-pyridin-2-yl-1,3-oxazol-2-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 XZDUVAVPEQYRJT-UHFFFAOYSA-N 0.000 claims description 6
• SQUAEZRORGDMPG-UHFFFAOYSA-N 3-[3-(5-chloropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(Cl)=CC=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 SQUAEZRORGDMPG-UHFFFAOYSA-N 0.000 claims description 6
• 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 6
• FZTXNLFUEFOVRO-UHFFFAOYSA-N 3-pyridin-2-yl-5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 FZTXNLFUEFOVRO-UHFFFAOYSA-N 0.000 claims description 6
• 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 6
• NFNZGNPPPSUBSN-UHFFFAOYSA-N 5-(3,5-dimethoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC(OC)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NFNZGNPPPSUBSN-UHFFFAOYSA-N 0.000 claims description 6
• UTVLFQJTGRGDDM-UHFFFAOYSA-N 5-(3-methoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 UTVLFQJTGRGDDM-UHFFFAOYSA-N 0.000 claims description 6
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• HFGWLRAJYOVQAY-UHFFFAOYSA-N 2-(3-bromophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound BrC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 HFGWLRAJYOVQAY-UHFFFAOYSA-N 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 5
• BNBQQYFXBLBYJK-UHFFFAOYSA-N 2-pyridin-2-yl-1,3-oxazole Chemical compound C1=COC(C=2N=CC=CC=2)=N1 BNBQQYFXBLBYJK-UHFFFAOYSA-N 0.000 claims description 5
• 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 5
• XKZXZXODZDSMKN-UHFFFAOYSA-N 3-[3-(5-methoxypyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(OC)=CC=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 XKZXZXODZDSMKN-UHFFFAOYSA-N 0.000 claims description 5
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
• GIHMKZCHBTWVSO-UHFFFAOYSA-N 5-(2,3-difluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1F GIHMKZCHBTWVSO-UHFFFAOYSA-N 0.000 claims description 5
• XUZXZGGCOASVTJ-UHFFFAOYSA-N 5-(2-bromo-5-methoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=C(Br)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 XUZXZGGCOASVTJ-UHFFFAOYSA-N 0.000 claims description 5
• 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 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
• 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 5
• 208000024827 Alzheimer disease Diseases 0.000 claims description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 5
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 125000004435 hydrogen atom Chemical class [H]* 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
• FPYLVHWPDOYNOI-UHFFFAOYSA-N 4-pyridin-2-yl-2-(2,3,6-trifluorophenyl)-1,3-oxazole Chemical compound FC1=CC=C(F)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1F FPYLVHWPDOYNOI-UHFFFAOYSA-N 0.000 claims description 4
• 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 4
• 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 4
• 239000001257 hydrogen Substances 0.000 claims description 4
• YXDVCVJVOFDWQF-UHFFFAOYSA-N 2-(2-chlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=CO1 YXDVCVJVOFDWQF-UHFFFAOYSA-N 0.000 claims description 3
• ASQZRZJOTGTSSV-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC(Cl)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 ASQZRZJOTGTSSV-UHFFFAOYSA-N 0.000 claims description 3
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• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
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