BRPI0611423A2 - derivados de oxadiazol substituìdos como moduladores alostéricos positivos de receptores de glutamato metabotrópicos e seus usos - Google Patents

Info

Publication number

BRPI0611423A2

BRPI0611423A2 BRPI0611423-7A BRPI0611423A BRPI0611423A2 BR PI0611423 A2 BRPI0611423 A2 BR PI0611423A2 BR PI0611423 A BRPI0611423 A BR PI0611423A BR PI0611423 A2 BRPI0611423 A2 BR PI0611423A2

Authority

BR

Brazil

Prior art keywords

alkyl

piperidin

oxadiazol

methanone

phenyl

Prior art date

2005-05-18

Links

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• 230000003281 allosteric effect Effects 0.000 title claims abstract description 24
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 title abstract description 10
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 title abstract description 10
• 150000004866 oxadiazoles Chemical class 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 212
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
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• 238000000034 method Methods 0.000 claims description 190
• -1 hydroxy, amino Chemical group 0.000 claims description 100
• 125000000217 alkyl group Chemical group 0.000 claims description 71
• 125000003118 aryl group Chemical group 0.000 claims description 54
• 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims description 46
• 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims description 46
• 125000001072 heteroaryl group Chemical group 0.000 claims description 46
• 239000001257 hydrogen Substances 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 39
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 29
• 239000000203 mixture Substances 0.000 claims description 29
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 14
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 14
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
• 201000000980 schizophrenia Diseases 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 14
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 13
• 229940025084 amphetamine Drugs 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 150000002367 halogens Chemical class 0.000 claims description 13
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 12
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 230000002265 prevention Effects 0.000 claims description 10
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• 238000002360 preparation method Methods 0.000 claims description 8
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
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• 125000004429 atom Chemical group 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
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• 150000004677 hydrates Chemical class 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 6
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
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• 238000003384 imaging method Methods 0.000 claims description 4
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• KTYBDZDFPFJRBT-NSHDSACASA-N [(3s)-3-(5-pyridin-2-yl-1,2,4-oxadiazol-3-yl)piperidin-1-yl]-(2,4,6-trifluorophenyl)methanone Chemical compound FC1=CC(F)=CC(F)=C1C(=O)N1C[C@@H](C=2N=C(ON=2)C=2N=CC=CC=2)CCC1 KTYBDZDFPFJRBT-NSHDSACASA-N 0.000 claims description 3
• 125000000623 heterocyclic group Chemical group 0.000 claims description 3
• FVLYACNSOCNXOP-UHFFFAOYSA-N (2,4-difluorophenyl)-[3-[5-(2,4-difluorophenyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound FC1=CC(F)=CC=C1C(=O)N1CC(C=2N=C(ON=2)C=2C(=CC(F)=CC=2)F)CCC1 FVLYACNSOCNXOP-UHFFFAOYSA-N 0.000 claims description 2
• QHJPIBZJKPKBGD-UHFFFAOYSA-N (2,4-difluorophenyl)-[3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound FC1=CC(F)=CC=C1C(=O)N1CC(C=2N=C(ON=2)C=2C(=CC=CC=2)F)CCC1 QHJPIBZJKPKBGD-UHFFFAOYSA-N 0.000 claims description 2
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• BMOHUBRAWYJENF-OAHLLOKOSA-N (4-fluorophenyl)-[(3r)-3-[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@H](C=2N=C(ON=2)C=2C=CC(F)=CC=2)CCC1 BMOHUBRAWYJENF-OAHLLOKOSA-N 0.000 claims description 2
• QLNWFLZYUUILOY-ZDUSSCGKSA-N (4-fluorophenyl)-[(3s)-3-[5-(3-fluoropyridin-4-yl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2N=C(ON=2)C=2C(=CN=CC=2)F)CCC1 QLNWFLZYUUILOY-ZDUSSCGKSA-N 0.000 claims description 2
• BMOHUBRAWYJENF-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2N=C(ON=2)C=2C=CC(F)=CC=2)CCC1 BMOHUBRAWYJENF-HNNXBMFYSA-N 0.000 claims description 2
• IYGYBNPIOYQURC-UHFFFAOYSA-N (5-methyl-1,2-oxazol-4-yl)-[3-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl)piperidin-1-yl]methanone Chemical compound O1N=CC(C(=O)N2CC(CCC2)C=2N=C(ON=2)C=2C=CN=CC=2)=C1C IYGYBNPIOYQURC-UHFFFAOYSA-N 0.000 claims description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 125000006718 (C3-C7) heterocycloalkenyl group Chemical group 0.000 claims description 2
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• OAXMEKMRFCINDX-AWEZNQCLSA-N [(3s)-3-[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]-(2-fluoropyridin-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)N=CC=2)=NO1 OAXMEKMRFCINDX-AWEZNQCLSA-N 0.000 claims description 2
• JFFWTUODKSBWNY-ZDUSSCGKSA-N [(3s)-3-[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]-(5-fluoropyridin-2-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NC([C@@H]2CN(CCC2)C(=O)C=2N=CC(F)=CC=2)=NO1 JFFWTUODKSBWNY-ZDUSSCGKSA-N 0.000 claims description 2
• RSTNDKZTQBZOCY-UHFFFAOYSA-N [3-[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]-(6-fluoropyridin-3-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NC(C2CN(CCC2)C(=O)C=2C=NC(F)=CC=2)=NO1 RSTNDKZTQBZOCY-UHFFFAOYSA-N 0.000 claims description 2
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• CHNUNORXWHYHNE-UHFFFAOYSA-N Oxadiazon Chemical compound C1=C(Cl)C(OC(C)C)=CC(N2C(OC(=N2)C(C)(C)C)=O)=C1Cl CHNUNORXWHYHNE-UHFFFAOYSA-N 0.000 claims 1
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