BRPI0610067A2 - compostos heterocìclicos como moduladores alostéricos positivos de receptores de glutamato metabotrópico, composição farmacêutica e uso - Google Patents

Info

Publication number

BRPI0610067A2

BRPI0610067A2 BRPI0610067-8A BRPI0610067A BRPI0610067A2 BR PI0610067 A2 BRPI0610067 A2 BR PI0610067A2 BR PI0610067 A BRPI0610067 A BR PI0610067A BR PI0610067 A2 BRPI0610067 A2 BR PI0610067A2

Authority

BR

Brazil

Prior art keywords

alkyl

cycloalkyl

alkenyl

alkynyl

alkylcycloalkyl

Prior art date

2005-05-18

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• 230000003281 allosteric effect Effects 0.000 title claims abstract description 25
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• 108010010914 Metabotropic glutamate receptors Proteins 0.000 title claims abstract description 12
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
• 150000002391 heterocyclic compounds Chemical class 0.000 title abstract description 4
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• 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract description 43
• 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims abstract description 43
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• 125000000217 alkyl group Chemical group 0.000 claims description 550
• 125000003118 aryl group Chemical group 0.000 claims description 251
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 225
• 125000001072 heteroaryl group Chemical group 0.000 claims description 193
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 167
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 143
• -1 hydroxy, amino Chemical group 0.000 claims description 123
• 238000000034 method Methods 0.000 claims description 106
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• 125000001424 substituent group Chemical group 0.000 claims description 89
• 150000002367 halogens Chemical class 0.000 claims description 85
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 85
• 239000001257 hydrogen Substances 0.000 claims description 84
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• 125000003710 aryl alkyl group Chemical group 0.000 claims description 79
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 61
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 60
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 60
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 53
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• 150000002431 hydrogen Chemical class 0.000 claims description 37
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 36
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 35
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 33
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• 239000012453 solvate Substances 0.000 claims description 22
• 150000004677 hydrates Chemical class 0.000 claims description 21
• 125000004429 atom Chemical group 0.000 claims description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
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• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
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• AHHDFYLXGGNZPQ-FUHWJXTLSA-N (4-fluorophenyl)-[(3s)-3-[5-[(r)-hydroxy(phenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C([C@@H](C1)C=2N=C(ON=2)[C@H](O)C=2C=CC=CC=2)CCN1C(=O)C1=CC=C(F)C=C1 AHHDFYLXGGNZPQ-FUHWJXTLSA-N 0.000 claims description 4
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• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 4
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• HDOANYBDYVEKAB-HNNXBMFYSA-N (3,4-difluorophenyl)-[(3s)-3-[3-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 HDOANYBDYVEKAB-HNNXBMFYSA-N 0.000 claims description 3
• AHHDFYLXGGNZPQ-WMZOPIPTSA-N (4-fluorophenyl)-[(3s)-3-[5-[(s)-hydroxy(phenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C([C@@H](C1)C=2N=C(ON=2)[C@@H](O)C=2C=CC=CC=2)CCN1C(=O)C1=CC=C(F)C=C1 AHHDFYLXGGNZPQ-WMZOPIPTSA-N 0.000 claims description 3
• NHISSLTUUYENPE-HNNXBMFYSA-N [(3s)-3-(5-anilino-1,2,4-oxadiazol-3-yl)piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2N=C(NC=3C=CC=CC=3)ON=2)CCC1 NHISSLTUUYENPE-HNNXBMFYSA-N 0.000 claims description 3
• CYINQQLYAWDDKD-ZDUSSCGKSA-N (3,4-dichlorophenyl)-[(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=C(Cl)C(Cl)=CC=2)=C1 CYINQQLYAWDDKD-ZDUSSCGKSA-N 0.000 claims description 2
• DHKSPUYDGMLYJN-HNNXBMFYSA-N (3,4-difluorophenyl)-[(3s)-3-[5-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=NO1 DHKSPUYDGMLYJN-HNNXBMFYSA-N 0.000 claims description 2
• WTOGNIYSSZSJPM-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-[3-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 WTOGNIYSSZSJPM-INIZCTEOSA-N 0.000 claims description 2
• OGLUZYAARIAUIK-YJBOKZPZSA-N (4-fluorophenyl)-[(3s)-3-[5-[(1s)-1-phenylethyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C([C@@H](C1)C=2N=C(ON=2)[C@@H](C)C=2C=CC=CC=2)CCN1C(=O)C1=CC=C(F)C=C1 OGLUZYAARIAUIK-YJBOKZPZSA-N 0.000 claims description 2
• XNZSOPFYWVTZAN-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-[5-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=NO1 XNZSOPFYWVTZAN-INIZCTEOSA-N 0.000 claims description 2
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
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• IDRSRZPBOJJRRM-LBPRGKRZSA-N [(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-(1,3-thiazol-5-yl)methanone Chemical compound N=1OC([C@H]2CCCN(C2)C(=O)C=2SC=NC=2)=NC=1OC1=CC=CC=C1 IDRSRZPBOJJRRM-LBPRGKRZSA-N 0.000 claims description 2
• CZUMPSXIWUNCLN-UHFFFAOYSA-N [3-[3-(4-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1OC1=NOC(C2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 CZUMPSXIWUNCLN-UHFFFAOYSA-N 0.000 claims description 2
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• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 2
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